Pulmonary hypertension is associated with poor prognosis in heart failure.However, non-invasive diagnosis is still challenging in clinicalpractice.We sought to assess the prognostic utility of non-invasive estimation ofpulmonary vascular resistances (PVR) by cardiovascular magnetic resonance topredict adverse cardiovascular outcomes in heart failure with reducedejection fraction (HFrEF).Prospective registry of patients with left ventricular ejection fraction(LVEF) < 40% and recently admitted for decompensated heart failure duringthree years. PVRwere calculated based on right ventricular ejection fractionand average velocity of the pulmonary artery estimated during cardiacmagnetic resonance. Readmission for heart failure and all-cause mortalitywere considered as adverse events at follow-up.105 patients  wereincluded. Patients with adverse events at long-term follow-up had highervalues of PVR (6.93 ± 1.9 vs. 4.6 ± 1.7estimated Wood Units(eWu), p < 0.001). In multivariate Cox regression analysis, PVR ≥5 eWu was independently associated withincreased risk of adverse events at 9 months follow-up .In patients with HFrEF, the presence of PVR ≥ 5.0 Wu is associatedwith significantly worse clinical outcome at follow-up. Non-invasiveestimation of PVR by cardiac magnetic resonance might be useful for riskstratification in HFrEF, irrespective of etiology, presence of lategadolinium enhancement or LVEF. Only were included in this analysis those patients with a leftventricular ejection fraction (LVEF) ≤ 40% estimated by CMR. Diagnosis ofHF was achieved as recommended by current guidelines.15Written informed consent was obtained before CMR in each patient.We prospectively enrolled 105 consecutive patients  referred to our cardiac imaging unit between March 2011and April 2014. Of these patients, 84 come from our previous analysis in HFpatients with both reduced and preserved ejection fraction.Medical history was examined in all patients, recording cardiovascular riskfactors and medication. Relevant blood tests values (hemoglobin and creatinineat admission) were also recorded as well as significant electrocardiographicparameters .16 criteria: history ofmyocardial infarction or revascularization, ≥ 75% stenosis of left mainor proximal left anterior descending artery, or ≥ 75% stenosis of two ormore epicardial vessels.All patients underwent coronary angiography at our institution as referralhospital during current admission or previously. Data from coronariography wererecorded to define ischemic etiology of HF according Felker et al.Echocardiographic data for analysis were recorded from studies during admission.LVEF, left ventricular end-diastolic and end-systolic diameters, tricuspidannular plane systolic excursion, E/e' ratio and sPAP were examined, althoughLVEF was the only parameter recorded in medical history in all patients. Theother variables were considered when available.17 acquiredafter intravenous injection (0.15 mL/kg) of dimeglubine gadobenate 0.5 M. Theareas of necrosis or fibrosis were assessed using inversion recovery-SSFPsequences  ten minutes after contrast administrationadjusting the inversion time  to null normalmyocardium. Flow imaging was performed perpendicular to the PA trunk with avelocity-encoded gradient echo sequence using an upper velocity limit of 150cm/s . Two double-obliqueorthogonal views oriented along the main PA were acquired with SSFP cinesequence and used as the reference to prescribe the plane perpendicular to thePA trunk for the acquisition of phase-contrast images. These parameters wereapplied as usually: repetition time/echo time 5.9-7.5/3.1-6.5 ms, slicethickness 6 mm, in-plane resolution 1.5-3 mm, 20 reconstructed cardiac phases,and temporal resolution 55-105 ms.CMR was performed with a 1.5 T unit . For cine imaging, breath-holding ECG-gated steady-state freeprecession (SSFP) sequences were used as normally to acquire long and short axisslices, and hence evaluate ventricular volumes and function. A standard17-segmented cardiac-model was used for segmentation and assessing areas of LGEimages,®, Siemens, Erlangen, Germany). Shortaxis slices were used to calculate ejection fractions and ventricular volumesusing Simpson's method. LGE of the myocardium was visually identified by the CMRexpert blinded to hemodynamic and echocardiographic data, considering both thepresence (ischemic and non-ischemic patterns) as distribution of LGE . PA cross-section were outlined in each cardiacphase to estimate PA area and flow, and calculate peak and average velocitiesduring the complete cardiac cycle, minimum and maximum areas, and PA net forwardvolume  = 19.38 - [4.62 x ln PA average velocity (in cm/s)] - [0.08 x rightventricular ejection fraction (RVEF) (in %)].Readmission for HF and all-cause mortality were considered as major adverseevents at follow-up. Combination of both outcomes constitutes the primaryendpoint. Data were collected from electronic centralized medical history,shared by all hospitals involved.Categorical values were expressed as absolute number and percentages, andcontinuous variables as mean ± standard deviation. Kolmogorov-Smirnovtest was used for normality of the distribution. Patients were initially dividedinto tertiles according to the value of PVR on CMR. Comparisons between groupswere made using analysis of variance , and its prognostic role was assessed byconstruction of Kaplan-Meier survival curve. Subsequently, the sample wasdivided in two groups according to the optimal cut-off value of PVR calculatedby receiver operating characteristic (ROC) curve to predict primary endpoint atfollow up. Comparisons between both groups were made by Chi-Square test orunpaired t-Student test as appropriate.A multivariate Cox regression model was performed with all variables with a pvalue < 0.10 in the univariate analysis to define the prognostic utility ofPVR. Survival curves according PVR cut-off point were again constructed with theKaplan-Meier method and compared by Log-rank test.®software (version 17.0).All tests were two-tailed and p value < 0.05 was considered statisticallysignificant. Statistical analyses were performed using SPSS Baseline characteristics of patients according to tertiles of PVR are presentedin Worse ventricular function and higher ventricular diameters and volumes estimatedby CMR were found in patients in upper tertiles . A signiPatients with primary endpoint at long-term follow-up had higher values of PVRcalculated by CMR .When we analyze the probability of survival free of readmission for heartfailure and all-cause mortality according to tertiles of PVR, patients in uppertertiles were significantly more likely to reach the composite adverse event.Univariate analysis of all cardiovascular risk factors and parameters ofechocardiography and CMR are reported in In order to establish the optimal cutoff value of PVR to predict adverse eventsat follow-up, a ROC curve was carry out considering the primary endpoint asclinical outcome . General characteristics of bothgroups according to this cutoff value are summarized in To assess whether this cutoff value of PVR had an independent prognostic impactat follow-up, a Cox proportional hazard analysis was performed including allsignificant factors in univariate analysis . After tAt a mean follow-up of 9.1 (1-38) months, patients with PVR ≥ 5.0 eWu hada significantly worse prognosis, as indicated in Kaplan-Meier survival curves,both for readmission to HF  as for all-cause mortality and risk to reach the primary endpoint  .The main body of cardiac events during follow-up in these patients wasrepresented by readmissions for HF, as follows: 5 readmissions for HF with nodeaths in patients with lower PVR, and 28 readmissions for HF with 5 deaths inthose with PVR ≥ 5.0 eWu. Of these total fatal events, 3 patients werepreviously admitted for acute decompensated HF.Following the publication of the prognostic utility of PVR estimated by CMR topredict adverse events in chronic HF, the results of this study reinforce theprognostic value of this technique in the selected group of patients with systolicdysfunction. Thereby, we could observe that increased PVR by CMR remained as anindependent predictor of worse prognosis at long-term follow up as well assemiquantitative size of LGE, and interestingly, irrespective of the presence ofLGE. In clinical practice, routine use of this parameter could therefore provideadditional valuable prognostic information for patients with HFrEF.Diagnosis of PH in chronic HF remains challenging, because of inconsistency ofechocardiography and risks derived from right heart catheterization, usuallyreserved for selected cases. Even so, in clinical practice, sPAP is oftencalculated by echocardiography from the velocity of the tricuspid regurgitantjet as an indirect estimation of the presence of PH, although as known remains amethod with widely varying results and therefore unreliable in patients withsuspected PH.22Indeed, in our study with data recorded from real clinical practice, sPAP wascalculated only in 48 of 105 patients, either because there was no significanttricuspid regurgitation or because inadequate visualization of right ventricle.This means, as shown, a major limitation of echocardiography.Other more accurate methods such as pulmonary artery acceleration time, rightventricular isovolumic relaxation time, or PVR itself, have been also describedalthough systematically neglected in routine practice.12 using an equation with onlytwo variables: RVEF and PA average velocity. This method showed a good limits ofagreement with PVR quantified by right heart catheterization and allowedidentify accurately those patients with increased PVR (considered as > 3eWu). In addition, this model has also demonstrated its ability to monitor acuteand chronic changes of PVR in a well-designed study that included: anexperimental phase in pigs to evaluate acute changes after pulmonaryembolization; serial changes in patients with chronic PH; and acute changes inPVR during vasodilator testing.23 This capability could therefore be valuable to noninvasiveassessment and follow-up of patients with PH.A promising novel tool in this regard comes from CMR, which allows an accuratenon-invasive estimation of PVR, as reported in previous studies. In our study,we employed the model proposed by Garcia-Alvarez et al.,14 In orderto confirm the potential prognostic role of PVR in the group of patients withreduced LVEF, those referred to our cardiac imaging unit were long-termfollowed. We found that optimally medicated patients with increased PVR,according to optimal value calculated with ROC curve, had worse left and rightventricular systolic function and higher ventricular volumes, and showed anincreased risk to achieve the primary endpoint at follow-up. This incrementalrisk was tested in univariate and multivariate analyses with other well-knownprognostic factors such as LVEF, RVEF, presence and size of LGE or atrialfibrillation, and PVR remained as a solid predictor.In patients with HFrEF, in which CMR is routinely used to define aetiology andclinical management, regular inclusion of PVR measurement could provideadditional prognostic information in this respect, as previouslydescribed.25 few studies have assessed the relationship betweendifferent PH subtypes and clinical outcomes. In this regard, the presence of anelevated transpulmonary gradient (> 12 mmHg) which reflects a significantcontribution of pre-capillary component, appears to identify a subgroup ofparticular worse prognosis.5 This type of reactive PH iscommon among patients with acute decompensated HF, and therefore, taking intoconsideration the increased mortality rates observed in this subgroup ofpatients, it is essential to distinguish them at an early stage. Therefore,non-invasive estimation of PVR by CMR could emerge as a novel clinical tool inthis context.Although prognostic relevance of PH in chronic HF is well known,26Both in our previous study14as in this, we could indirectly evaluate the pre-capillary contribution to PHthrough the estimation of PVR which are closely related to increased pulmonaryvascular tone. Thereby, we found that PVR by CMR were superior to predictadverse outcomes at long-term follow up when compared to sPAP byechocardiography and other consolidated risk factors such as LVEF, presence ofLGE, or atrial fibrillation. As well as assessment of LGE on CMR has become anessential tool in the evaluation of HF patients in lasts years, among othervariables with firmly established prognostic value such as LVEF, QRS duration orNew York Heart Association functional class, our resultssuggest that inclusion of PVR measurement in standard CMR protocol couldcontribute to prognostic stratification of patients with HFrEF.Since the majority of previous studies assessing the relationship between PH andadverse outcomes have normally used noninvasive parameters such as sPAP, thedifferent contributions of pre- and post-capillary components could not beproperly assessed so far.The main limitation of the study is determined by the process of enrollingpatients and subsequent analysis of clinical and echocardiographic data.Although inclusion was prospective, patients came referred from differentcenters to our cardiac imaging unit and therefore, there was no protocol on datarecord regarding blood tests, echocardiography or clinical management. Thisprocess caused data loss in some important echocardiographic parameters, andconsequently were not included in univariate nor multivariate analysis, asindicated in methods.In this regard, another important limitation comes from semiquantitativeestimation of necrosis size by CMR. Thus, estimating the extent of LGE by numberof segments and not by percentage with respect total myocardial mass probablyconditioned the results of univariate analysis, knowing the solid prognosticvalue of LGE extent in this context. In order to minimize this issue, thisvariable was included in multivariate analysis despite being non-significant inthe univariate.Since right heart catheterization is still the reference test for diagnosis andfollow-up of patients with PH, the absence of hemodynamic data could also beconsidered a limitation of the study.Other important limitations are the reduced size of study population, the limitedfollow-up period and the fact of considering all-cause mortality, rather thancardiac mortality, as fatal event in the primary endpoint. Further studies willbe therefore necessary to consolidate the prognostic value of PVR by CMR inpatients with HFrEF.In patients with HFrEF, the presence of PVR ≥ 5.0 eWu on CMR is associatedwith significantly worse clinical outcome, considering both readmission for HF andall-cause mortality. Non-invasive estimation of PVR by CMR might be useful for riskstratification in HFrEF, irrespective of etiology, presence of LGE or LVEF.


P < 0.05). The extent of P2 prolapse was under or overestimated in 5 patients with 2D xPlane and in 9 patients with 3D TTE. 2D xPlane imaging is an accurate, easy to use (compared to 3D TTE) and easy to interpret (compared to 2D and 3D TTE) imaging modality to study the site and the extent of MV prolapse.This study sought to assess the value of two-dimensional (2D) transthoracic echocardiography (TTE), 2D xPlane imaging and three-dimensional (3D) TTE for the definition of the site and the extent of mitral valve (MV) prolapse. Fifty patients underwent transthoracic 2D, 2D xPlane and 3D echocardiography. With 2D xPlane a segmental analysis of the MV was performed, by making a lateral sweep across the MV coaptation line as seen in the parasternal short-axis view. Inter-observer agreement for specific scallop prolapse was for 2D xPlane excellent  and for 3D TTE moderate . The respective sensitivities of standard 2D TTE, 2D xPlane, and 3D TTE for the identification of the precise posterior scallop prolapse were for P1 92, 85, and 92 %, for P2 96, 96, and 82 %, and for P3 86, 81, and 71 %. In total, 5 (8 %) prolapsing MV scallops were missed by 2D TTE, 7 (12 %) by 2D xPlane, and 12 (20 %) by 3D TTE. The sensitivity of 3D TTE was significantly lower than standard 2D imaging (80 % versus 93 %,  Mitral valve (MV) prolapse (MVP) is one of the most common valvular abnormalities in industrialized countries . The sitBetween May 2012 and August 2013, 57 consecutive patients with MVP were referred to our center for surgical MV repair because of isolated severe mitral regurgitation (MR). The institutional review board approved the study and informed consent was obtained from all patients.Prior to surgery a transthoracic 2D, 2D xPlane and 3D echocardiogram in harmonic imaging was performed using an iE33 ultrasound system  equipped with an X5-1 matrix probe composed of 3040 elements, with a 1–5 MHz extended operating frequency range, with the patient in the left lateral decubitus position.As recommended, four standard 2D imaging planes were used: the parasternal long-axis and short-axis views and the apical four- and two-chamber views .A segmental analysis of the MV was performed with SMPI in xPlane mode, by making a lateral sweep across the MV coaptation line as seen in the parasternal short-axis view Fig. . In the In patients in sinus rhythm a full-volume data set from four to six R-wave gated sub-volumes during a single end-expiratory breath-hold was acquired and in patients with atrial fibrillation a live 3D data set was acquired to avoid the concerns about stitching artefacts. All full-volume and live 3D data sets were taken from a parasternal or an apical window , 12. TheA senior cardiologist with extensive experience in 2D and 3D echocardiography and MV disease analyzed all echocardiographic data sets blinded to other patient information with at least 10 days between each specific analysis in a random order. MV prolapse and segmental visualization of the affected scallop was classified according to the Carpentier nomenclature . The extThe sensitivity of scoring a P1, P2 or P3 prolapse was calculated as the positive findings of the different modalities divided by the positive surgical findings. The specificity was calculated as the negative findings of the different modalities divided by the negative surgical findings.The identification of the extent of the P2 prolapse examined with 2D xPlane and 3D TTE was split up into five categories and compared with the surgical finding. The five categories are; Barlow disease (including P1 and P3 prolapse), broad P2 , small P2 , asymmetric P2  and edge P2 .Prolapse site sensitivity and specificity were calculated according to standard formulas.The degree of inter-observer agreement between the two blinded observers (MLG and JSMcG) for specific scallop prolapse using 2D xPlane and 3D echocardiography was assessed by calculating the Kappa coefficient .Of the 57 patients referred for surgical repair, 7 patients (12 %) were excluded because a 3D TTE was not possible due to inadequate 2D image quality. In the remaining 50 patients mean age was 61 ± 16 years and 33 (66 %) were men. Forty (80 %) patients were in sinus rhythm and 10 (20 %) in atrial fibrillation. Eleven patients (22 %) had Barlow’s disease involving both the anterior and posterior mitral valve leaflet. In 24 patients (48 %) the prolapse was confined to one or more posterior mitral valve scallops . In the remaining 15 patients (30 %) no prolapse was seen and MR was due to mitral annular dilatation with or without retraction in 10 patients (20 %), endocarditis in 3 patients (6 %), and rheumatic disease in 2 patients (4 %).In 16 patients, a prolapsing anterior MV leaflet was seen. In the eleven patients with Barlow disease all prolapsing anterior MV leaflets were recognized with all techniques, apart from one patient in which 3D echocardiography missed the prolapse. In the 5 remaining patients the prolapse was confined to the A2 part in one patient, the A2–A3 part in one patient and the A3 part in three patients. Standard 2D analysis detected anterior MV leaflet prolapse in all patients although distinction between the specific scallops was problematic. 2D xPlane identified the specific prolapse part in all patients where as 3D echocardiography missed the prolapse in two patients with A3 prolapse.P < 0.05). As seen in Fig. As seen in Fig. The results of 2D xPlane and 3D TTE for accurately diagnosing the extent of the P2 prolapse are shown in Table Seven additional 3D TTE were excluded because the second observer determined the 3D quality too poor to reliably assess the site of MV prolapse. Inter-observer agreement for specific scallop prolapse is shown in Fig. In this study we sought to assess the relative value of transthoracic standard 2D imaging, 2D xPlane imaging, and 3D imaging for the definition of the site and extent of MV prolapse. The main results of the study are (1) transthoracic 2D imaging has excellent diagnostic value in detection of the prolapsing MV scallop, (2) 2D xPlane and 3D imaging do not improve detection of the prolapsing MV scallop, (3) the extent and asymmetry of P2 prolapse can, however, only be assessed by xPlane and 3D imaging, and (4) 2D xPlane imaging may be superior to en-face 3D imaging in this latter aspect because it is (a) easier to implement as it is a 2D technique, (b) has a better interobserver agreement, and (c) misses less prolapsing MV scallop parts because of less artifacts (dropouts and side-lobe artifacts) and better spatial resolution.The definition of the site and extent of MV prolapse plays a crucial role not only in surgical referral but also for the operative plan since different pathology require different levels of surgical expertise based on the complexity of lesions seen with echocardiography , 15. SomIn contrast, Monin et al. reported sensitivities of 95 and 93 % for respectively the central P2 prolapse and the not centrally-located P1 and P3 scallops based on a similar 2D analysis. Our results of sensitivities of 92, 96, and 86 % for respectively P1, P2, and P3 prolapse are in line with these results of Monin et al. Of note, like in our study the echo studies were performed by dedicated “senior” sonographers and analyzed by a cardiologist with extensive experience in MV assessment. As a result of the excellent transthoracic 2D diagnostic results 2D xPlane and 3D imaging was not able to add diagnostic value. On the contrary, 2D-xPlane imaging and in particular 3D imaging resulted in more false negative results.In the literature there is some controversy over the accuracy of 3D TTE for the evaluation of the site and extent of the MV prolapse. All investigators stated that 3D TTE is a feasible technique in the majority of patients. This was confirmed in our study as in only 7 patients (12 %) the 3D images were deemed not possible because of image quality by the sonographer and in another 7 patients the 3D image quality was found to be inadequate for analysis by one of the two observers. Several investigators stated that the accuracy of 3D TTE for the identification of scallop prolapse is high –20 and mThe identification of 3D volume-rendered images may be difficult even for the experienced observer since a prolapsing scallop should be identified as a convexity or bulge, and often as a bright area when compared with the rest of the mitral valve. Despite exclusion of patients with poor echocardiographic images, the current spatial and temporal resolution of 3D transthoracic transducers in our opinion still limits the interpretation of images. This was evidenced not only by the 12 missed prolapsing scallops (compared to 5 and 7 with respectively 2D TTE and 2D xPlane), but also by the underestimation of P2 scallop extent by 3D.With the introduction of 2D xPlane imaging it is possible to identify not only a prolapsing MV leaflet but also to assess, like 3D imaging, in a systematic manner the extent of MV prolapse. It is important to realize that the xPlane technique in fact mimics the 3D multiplane reconstruction with as opposite to 3D imaging only a minimal impact on spatial resolution compared to standard 2D imaging with a 2D transducer. Compared to the surgical findings 2D xPlane was a sensitive technique  to identify MV prolapse and the inter-observer agreement for identification of the prolapsing MV scallop was excellent. Also, the sensitivity of 2D xPlane imaging for the identification of MV prolapse was not lower than standard 2D imaging, whereas 3D TTE was significantly lower compared to standard 2D imaging. In addition, good results were seen in the identification of the extent of P2 prolapse.Any sonographer will be able to perform an accurate, rapid, online segmental analysis of the entire coaptation line of the MV with xPlane imaging. Virtually the images do not suffer from a loss in spatial resolution and rhythm irregularities will not affect the data. Although in the present study the identification of MV prolapse presence was not superior to standard 2D imaging it should be realized that the 2D images were interpreted by a senior cardiologist highly experienced in MV evaluation.Although not discussed in this article, 2D and 3D TEE imaging are excellent imaging tools to describe the MV geometry and mechanism of regurgitation and to guide the surgical approach. However, TEE is a semi-invasive imaging technique not totally without procedural risk.  Because The spatial resolution of the X5-1 matrix transthoracic probe remains somewhat inferior to the stand-alone 2D transducer and in addition the frame rate  drops by half when entering the xPlane mode. This drop in temporal resolution however, does not seem very important in the assessment of the site and extent of MV prolapse and can be brought to a minimum by ensuring that the smallest sector able to encompass the MV is used.Care must be taken with the interpretation of the extent of prolapse from the standard parasternal short axis view analysis since the motion of the heart throughout the cardiac cycle may result in the reference line not transecting the same region of interest at any time point in the heart cycle.The echo studies were performed by dedicated “senior” sonographers and analyzed by a cardiologist with extensive experience in MV assessment. Therefore, our results may not be generalized to less experienced centers. In addition, TEE imaging was not considered in the design of the study because the aim of the study was to assess the relative value of transthoracic standard 2D imaging, transthoracic 2D xPlane imaging, and transthoracic 3D imaging for the definition of the site and extent of MV prolapse defined by the surgical standard.Finally, the anatomical findings at surgery served as the gold standard. It should be recognized that surgeons assess an immobile valve in a flaccid heart whereas echocardiography assesses a dynamic valve. Unfortunately, there is no practical alternative to this approach.2D xPlane imaging is an accurate, easy to use (compared to 3D TTE) and easy to interpret (compared to 2D and 3D TTE) imaging modality to study the site and the extent of MV prolapse.


With the expanding use of vasodilator stress CMR, there has been a parallel rise in the use of regadenoson as a pharmacological stress agent. To date, however, prognostic data for stress CMR has focused on the use of adenosine or dipyridamole while prognostic data regarding the use of regadenoson is limited. We therefore sought to identify the prognostic value of regadenoson vasodilator stress CMR on clinical events in patients with known or suspected coronary artery disease.We prospectively studied 346 consecutive patients clinically referred for CMR assessment of myocardial viability/ischemia over the course of 36 months. The CMR protocol consisted of: (1) cine SSFP functional imaging in multiple imaging planes, (2) stress perfusion imaging after administration of Regadenoson and a bolus injection of 0.1 mmol/kg intravenous gadolinium-DPTA; (3) late gadolinium enhancement imaging. Clinical follow-up was obtained via mailed questionnaire, review of electronic medical records, contact with the patients' cardiologist, and/or telephone contact with the patients. We used a primary composite endpoint of cardiovascular death or acute myocardial infarction.A total of 346 patients were prospectively followed for a median time of 1.9 years. There were 7 cardiac deaths and 8 acute myocardial infarctions during the follow-up period. By univariable Cox regression modeling, the presence of inducible ischemia was associated with a near-7-fold increased risk of the primary outcome . Patients with absence of inducible ischemia experienced a low annualized cardiac event rate of 0.6% per patient year. To the contrary, patients with inducible ischemia had an annualized rate of cardiac event of 3.2% per patient year.Regadenoson stress CMR is a prognostically useful examination in which a negative study is linked to a low risk of adverse cardiovascular outcomes in a prospective cohort of 346 patients followed for nearly 1½ years. In addition, a positive regadenoson stress CMR is associated with a significantly higher annualized rate of adverse cardiovascular events in patients referred for known or suspected CAD, even after adjustment for clinical and demographic characteristics.Astellas Pharma US, Inc.


While echocardiographic grading of left ventricular (LV) diastolic dysfunction (DD) is used every day, the relationship between echocardiographic DD grade and hemodynamic abnormalities is uncertain.We identified 460 consecutive patients who underwent transthoracic echocardiography within 24 h of elective left heart catheterization and had: normal sinus rhythm, no confounding structural heart disease, no change in medications between catheterization and echo, and complete echocardiographic data. Patients were grouped based on echocardiographic DD grade. Hemodynamic tracings were used to determine time constant of isovolumic pressure decay (Tau), LV end-diastolic pressure (LVEDP) and end-diastolic volume index at a pressure of 20 mmHg (EDVi20).Normal diastolic function was found in 55 (12.0 %) patients, while 132 (28.7 %) patients had grade 1, 156 (33.9 %) grade 2 and 117 (25.4 %) grade 3 DD. The median value for Tau was 46.9 ms for the overall population (interquartile range 38.6-58.1 ms), with a prevalence of a prolonged Tau (>48 ms) of 47.5 %. While there was an association between DD grade and Tau (p = 0.003), LV dysfunction (ejection fraction <50 %) was more strongly associated with increased Tau (p < 0.001) than was DD grade (p = 0.19). There was also an association between DD grade and LVEDP (p < 0.001), with both LV dysfunction (p = 0.029) and DD grade (p < 0.001) independently associated with LVEDP. Calculated EDVi20 was related to DD grade, but this relationship was driven by findings of paradoxically increased compliance in patients with severe DD.Although echocardiographic grading of DD was related to invasive hemodynamics in this population, the relationship was modest. It is generally accepted that mild impairments of left ventricular diastolic function manifest as delayed early relaxation. The adequacy of the initial phase of diastole is reflected by Tau, the time constant of ventricular pressure decay , 2. The On the opposite end of the spectrum, severe impairments of diastolic function result in reduced chamber compliance with ‘restrictive’ ventricular filling. This is best characterized invasively using pressure-volume loop analysis. Due to technical, cost and safety issues, it is commonly assessed by measurement of left ventricular end-diastolic pressure (LVEDP). An alternative approach has been reported to estimate chamber compliance using extrapolation of end-diastolic volume index at a pressure of 20 mmHg , 4. The The prognostic importance of the DD grading system has been shown in a variety of populations –9. In kePatients undergoing left heart catheterization and trans-thoracic echocardiography within 24 h were identified by retrospective review of echocardiography and catheterization databases at the Cleveland Clinic from Jan 2008 until Oct 2010. Patients with poor echo image quality  or incomplete mitral inflow or tissue Doppler data were excluded. Further exclusion criteria included atrial fibrillation, heart rate > 100 beats per minute, mitral stenosis or severe mitral annular calcification, severe mitral or aortic regurgitation, acute coronary syndrome, and prior heart transplantation. Manual review of electronic medical records was used to determine any change in diuretics or vasodilators between cardiac catheterization and echocardiography, which was also considered an exclusion criterion.Trans-thoracic echocardiograms were completed according to laboratory protocol. Archived images were re-analyzed by three blinded investigators with re-measurement of all relevant parameters. These included left atrial volume measurements, peak early (E) and atrial (A) velocities of mitral inflow, A wave duration, early mitral inflow deceleration time (DT), septal and lateral mitral annular e’ velocities, pulmonary vein A wave reversal duration, isovolumic relaxation time (IVRT), and time difference between the onset of the E wave and e’. Where possible, each measurement was averaged over multiple cardiac cycles.Diastolic function grading was assigned based on current guidelines  see Fig. In caseSubjects underwent left heart catheterization by a standard approach in a fasting state. All measurements were made using fluid-filled catheters. Left ventricular end-diastolic pressure (LVEDP) was determined post-A wave. The time constant of isovolumic pressure decay (Tau) was estimated with a zero asymptote assumption as follows :\documensystolic peak LV systolic pressure and LVEDP LV end-diastolic pressure. Projected end-diastolic volume index at a pressure of 20 mmHg (EDVi20) was calculated as previously reported [Where IVRT is isovolumic relaxation time by Doppler echocardiography, Preported , 4.Patients were grouped according to echocardiographic diastolic function grade. Categorical variables were compared between groups with chi-squared analysis. Continuous variables were compared between groups using analysis of variance (ANOVA) or Kruskal-Wallis where appropriate.2.The influence of DD grade on each of Tau, LVEDP and EDVi20 was tested in the entire population, and then separately in those with impaired (LVEF <0.50) and preserved (LVEF ≥ 0.50) left ventricular systolic function. The same relationships were then assessed with multivariable analysis using DD grade and LV dysfunction (again defined as LVEF <0.50) as independent factors. Statistical analyses were repeated after excluding all patients with abnormal septal or lateral e’ velocity but left atrial volume index <34 mL/mA p value of <0.05 was considered statistically significant. Analyses were performed using SPSS Statistics 19.0 .From 2008 to 2010, a total of 1204 patients underwent an elective transthoracic echocardiogram within 24 h of left heart catheterization at our institution. Thirteen studies were excluded for poor image quality and 316 due to incomplete Doppler or other data. A further 415 patients were excluded for clinical reasons  had normal diastolic function, 132 (28.7 %) had grade 1, 156 (33.9 %) grade 2 and 117 (25.4 %) grade 3 DD . In multivariable analysis, LV dysfunction was associated with increased Tau , but DD grade was not . Post hoc analysis of patients without LV dysfunction showed patients with Grade 1 DD to have higher Tau than any other subgroup . In contrast, there was no difference between DD subgroups in patients with LV dysfunction , with a prevalence of a prolonged Tau (>48 ms) of 47.5 %. There was an association between DD grade and Tau by Kruskal-Wallis analysis (p = 0.003) as depicted in Table ion Fig. .Fig. 4a2, there was no association between DD grade and LVEDP (p = 0.089). In multivariable analysis, LV dysfunction  and DD grade  were independently associated with LVEDP . There was an association between DD grade and LVEDP by Kruskal-Wallis (p < 0.001). Post-hoc analysis showed a difference in LVEDP between grade 3 DD patients and those with normal diastolic function (p = 0.034), grade 1 DD (p = 0.003) and grade 2 DD (p < 0.001) Fig. . When thEDP Fig. .Fig. 5a2 (interquartile range 39.0 to 55.8 mL/m2). There was an association between DD grade and EDVi20 by ANOVA (p = 0.001). This was driven by grade 3 DD patients representing a distinct group  and grade 3 DD (p = 0.004) groups greater than normals). Multivariate analysis showed LV dysfunction  but not DD grade  to be associated with EDVi20. No subgroup differences were found when patients were broken down by LV function.The median value for EDVi20 was 47.5 mL/moup Fig. , with EDAn association was seen between B-type natriuretic peptide levels and DD grade (p < 0.001). On post-hoc analysis, the only distinct group was that of patients with grade 3 DD. This group differed from patients with normal diastolic function (p < 0.001), grade 1 DD (p < 0.001), and grade 2 DD (p = 0.006).This study was an observational comparison of echocardiographic grading of diastolic dysfunction (DD) as recommended by major echocardiography societies , 21, witWe proposed a Tau of greater than 48 ms as prolonged, , 21 withAt issue is the fact that no single echocardiographic parameter captures all the features of early relaxation. As early relaxation is impaired, IVRT increases, mitral annular movement is delayed and its velocity (e’) decreases, and mitral inflow changes, with a reduction in E wave height and lengthening of deceleration time. However, these parameters are all influenced by other factors. IVRT is dependent on the rate of relaxation, but also on the difference between aortic blood pressure and left atrial pressure. E wave height is affected by LVEDP, LV compliance, atrial conduit and booster pump function. Mitral annular e’ velocity is related to early relaxation, but is also heavily dependent on systolic function , 27.LV stiffness and LVEDP are linked, as the diastolic rise in pressure is more pronounced in a less compliant ventricle. While there may be discrepancy between LVEDP and LV stiffness in the setting of acute changes of load, LVEDP would be expected to track LV stiffness in stable heart disease. Mitral inflow deceleration time (DT) has been shown to be inversely correlated with the operative stiffness of the LV (the change in ventricular pressure for a given change in volume) –30, and higher (not lower as would be expected) in patients with more advanced DD.In our study, LVEDP was increased in comparison to those with normal diastolic function among grade 3 DD, but not grade 2 DD patients. Indeed, using a cutoff of 16 mmHg , 24, 25,Therefore, if grade 2 DD is meant to imply raised filling pressures beyond those seen in grade 1 DD and normal diastolic function, the accuracy of DD grading in describing filling pressures in this study was limited. Furthermore, grade 3 DD was associated with increased filling pressures and elevated BNP, but the ancillary measure of EDVi20 suggests that these patients do not as a rule have reduced ventricular compliance. Multivariate analysis suggests that the relationship between EDVi20 and DD grade may actually be driven by differences in LV systolic function.Only 76 out of 405 patients with diastolic dysfunction (18.8 %) had unambiguous DD grading. We elected to assign patients to the DD category for which they had the greatest number of parameters, but this issue is not addressed in current guidelines . AnotherOn the other hand, findings that could be expected in patients with diastolic impairment are not universally seen by echocardiography. One important example would be left atrial enlargement. In our study, left atrial volume index (LAVi) was increased in patients with grade 3 but not grades 1 or 2 DD. This is in keeping with with the unexpectedly low LVEDP in patients with grade 2 DD in our cohort. It is also consistent with prior studies showing normal LAVi  or left We elected to study patients with both preserved and reduced ejection fraction. The diastolic function grading system in the current guidelines does not make a distinction between these two groups. Since they do have separate algorithms for estimating filling pressure in normal and depressed ejection fraction , there iThe patients in this report belong to a population with a high prevalence (88.1 %) of DD. However, the finding of prolonged Tau > 48 ms in only 47.5 % of patients, suggests a lower than expected rate of impaired relaxation. Previous investigators have also failed to show significant prolongation of Tau in patients with other markers of diastolic dysfunction . While gAdditionally, LVEDP was not found to be increased in grade 2 patients. Failure to show a clear stepwise increase in LVEDP with progressive grades of DD beyond grade 1 is consistent with previous reports showing no difference between resting filling pressures of patients with diastolic heart failure and those of control subjects , 19.The findings of this study question the notion that DD is a predictable, progressive process beginning with impaired relaxation followed by reduced compliance and increased filling pressures. The prognostic value of echo graded DD may relate more to its reflection of intrinsic properties of the left ventricle, or to exercise hemodynamics  than to An important technical limitation of this study is that echo images and catheterization tracings were not obtained simultaneously. This could lead to significant underestimation of the relationship beween invasive hemodynamics and echo parameters. However, echocardiographic DD is frequently reported and used clinically, with an expectation that it has diagnostic and prognostic value well outside of a 24 h timeframe. We used the electronic medical record to exclude patients in whom the use of diuretics, the provision of intravenous fluids, or a change in vasodilator therapy could have influenced hemodynamics.We were only able to use a semi-invasive estimate of Tau because high fidelity pressure measurements were not made at the time of catheterization. Nevertheless, the assumptions used have been validated , assuminA large percentage of cases were excluded, resulting in a fairly select group of patients in the final analysis. This was done to ensure that conditions affecting LV filling other than diastolic function were excluded. We feel that this is critical when evaluating DD, as supported by the guidelines .Even with careful reanalysis of primary data, there is the possibility of misclassification of DD grade based on the echocardiographic data . We atteAlthough echocardiographic grading of diastolic function was significantly related to invasive hemodynamics in this population, the relationship was modest. Impaired relaxation was not a universal finding in DD, not significantly differentiating patients with normal diastolic function by echocardiography from patients with grade 2 or 3 DD. No influence of DD grade on early relaxation was found after controlling for systolic dysfunction. Additionally, abnormally increased filling pressures were frequently seen among patients with normal invasive measures of early relaxation, questioning the current paradigm of diastolic function progression.


Aims. To detect anatomical and intrinsic histopathological features of the ascending aorta and left ventricular (LV) myocardium and evaluate right ventricular (RV) function in fetuses with hypoplastic left heart syndrome (HLHS). Methods. Twenty-five fetuses diagnosed with HLHS were followed up in the antenatal and postpartum periods. 12 necropsy heart specimens were analyzed for morphological and histological changes. Results. Prenatal echocardiography and pathologic anatomy displayed the typical characteristics of HLHS as a severe underdevelopment of the LV in the form of mitral stenosis or atresia or as aortic atresia or stenosis, with a decreased ratio of aortic diameter to pulmonary artery diameter  and a higher ratio of RV diameter to LV diameter . The RV volume, stroke volume, and cardiac output in HLHS fetuses were increased compared with the gestational age-matched normal controls (p < 0.01). Histological changes in the 12 HLHS specimens included LV myocardial fibrosis, aortic elastic fragmentation, and fibrosis. Conclusions. In addition to severe anatomical deformity, distinct histological abnormalities in the LV myocardium and aortic wall were identified in the fetuses with HLHS. RV function damage may be potentially exists. Hypoplastic left heart syndrome (HLHS) is a rare congenital heart disease that is characterized by the presentation of left ventricular (LV) inlet and outflow tract hypoplasia; it was first described by Lev in 1952 and termed “HLHS” by Noonan and Nadas , 4. AlthTwenty-five fetuses with LV hypoplasia, mitral stenosis or atresia, or aortic stenosis or atresia and 25 gestational age-matched normal controls were evaluated by prenatal echocardiography at Xinqiao Hospital, Chongqing, between February 1, 2006, and December, 31, 2012. We did not include fetuses with exclusive coarctation of the aorta (CoA). Through the kind efforts of the dedicated families who signed the donation agreements, 12 formalin-fixed heart specimens from HLHS fetuses  and 6 normal control heart specimens  were obtained from the Department of Pathology at Xinqiao Hospital. These specimens were suitable for both macroscopic and microscopic study. Sections of the LV myocardium and the aortic walls were labeled using hematoxylin and eosin (HE), Masson's trichrome, and elastic van Gieson (EVG) stains. Each section was examined by two independent pathologists. In instances where there was a discrepancy, the specimens were reevaluated by both pathologists and by a third pathologist to reach a consensus. Follow-ups in the antenatal and postpartum periods were performed for six live births; they included clinical interventions and changes in echocardiographic characteristics. Another seven cases were lost to follow-up. This study was performed in accordance with a protocol that was approved by the Xinqiao Hospital Committee for Clinical Investigations.All fetal patients underwent at least 1 detailed prenatal echocardiogram, and 6 neonates received echo examinations each month following birth. Echocardiography was performed using a Philips IE33 unit , equipped with the latest version of QLAB analysis software, with S8-3, C5-1 probe, and X5-1 matrix probe. Multiple parameters, including cardiovascular anatomic structure and Doppler blood flow, were assessed. Specifically, the anatomic assessment included the measurement of the following structures, in accordance with the cardiac segmental approach: left atrial (LA) and right atrial (RA) dimensions, LV and right ventricular (RV) end-diastolic width diameters, and ascending aorta (AA) and pulmonary trunk (PT) diameters. The mitral valve (MV) was described as either anatomically normal or abnormal. Mitral valve stenosis (MS) was defined as a pathologically decreased diameter of the mitral valve annulus, where color Doppler imaging demonstrated minimal forward flow across the mitral valve. The diameter of the foramen ovale (FO) was also recorded. Cardiac Doppler evaluation included measurements of the MV and the tricuspid valve (TV) flow patterns, the MV and TV color Doppler regurgitant jet areas, and the velocities and flow patterns in the AA and PT. The direction of FO flow was further described. Real time three-dimensional echocardiography (RT-3DE) was used to measure RV end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), cardiac output (CO), and ejection fraction (EF). All direct measurements were performed by a single experienced investigator. The investigator was blinded to the patient information when measuring these parameters.When performing autopsies, the right atrial appendage and RV were opened along the lateral wall to the RV apex and along the interventricular septum to the pulmonary valve. The left side of the heart was similarly opened according to the path of blood flow . Excisedt-test to analyze ecological parameters between our echocardiographic results and normal reference standards. Data are presented as the median (range). Only p ≤ 0.01 was considered to be statistically significant.The data are primarily presented in a descriptive fashion due to the small number of fetuses and infants included in our study. Statistical analyses were performed using a sample Twenty-five fetuses with HLHS, whose mothers underwent prenatal echocardiography at a gestational age of 28.0 ± 7.1 weeks (range 23.9 to 36.4 weeks) and 25 controls with a gestational age of 27.5 ± 2.9 weeks (range 24.3 to 35 weeks) were included in our study. None of the patients had a confirmed family history of HLHS. During follow-up, 11 parents elected to terminate the pregnancy after considering the poor prognosis for a fetal heart condition . One fetus died at 32.6 weeks . Six of the fetuses were born alive and presented to Xinqiao Hospital due to progressive heart failure, delayed development, or pulmonary infection at a median age of 12.5 days (range 1.0 to 35.0 days). These six infants were all male. One died at 126 days of age, 1 day after a selective angiocardiography catheterization was performed during hospitalization. One died at 89 days of age, one week after computed-tomography angiography was performed. There were 4 twins (2 sets). Of these, 1 set of twins died . The other set of twins was healthy .http://dx.doi.org/10.1155/2016/2616729), no blood flow through the mitral valve during diastolic filling (Video 2), a restrictive atrial septum bulging from left to right, or an intact atrial septum. The ratio of the diameter of the aortic root to the diameter of the pulmonary artery was decreased, with a median of 0.49 and a range of 0.24 to 0.69, compared to the normal range at the same gestational age of 0.75 to 1.02 [p < 0.01). The RV EF showed no significant difference between HLHS fetuses and the controls (p > 0.05)  . In the  > 0.05) .Six fetuses had either mild or severe left ventricular outflow tract (LVOT) obstruction. During the postnatal follow-up of the infants, one presented with progressive biventricular hypertrophy within a short period of time after birth (from 6 mm to 12 mm over three months) Figures ; this paHistomorphological and histopathological examinations of fetuses with HLHS were performed in the 12 induced cases. Among the autopsy specimens, 12 displayed a decreased ratio of the diameter of the aortic (AO) to the diameter of the pulmonary artery (PA) , and allHLHS has been recognized as a congenital heart disease with a high mortality rate following birth. However, little is known about the histopathological features of the aorta and LV myocardium during the fetal stages of the disease. This study reports the histopathological features of HLHS specimens from patients who presented with severe LV dysplasia, aortic stenosis or aortic atresia, mitral stenosis or mitral atresia, restrictive or intact atrial septum, and CoA. We hypothesized that these abnormalities might be a complex set of defects that should be considered as a distinct clinical entity.A small proportion of infants with HLHS have either an intact or a restrictive atrial septum. Their neonatal mortality is particularly high, even following successful atrial decompression . An intaHowever, the best timing for intervention and the possible feasibility of such a maneuver in a fetus remain speculative at this time. The favorable consequences, however, appear to increase the chances of successful postnatal biventricular physiology. Disappointingly, intervention during the second trimester has not been shown to improve the growth and development of LV dimensions . The reaNormal cardiac morphogenesis requires blood-flow directed remodeling in addition to intrinsic patterning. Blood-flow directed remodeling contributes to the secondary development and differentiation of structures as a result of the effects of shear stress and the dynamics of blood flow within the structures . LV hypoCellular proliferation (hyperplasia) is confirmed to be an obligatory process during embryogenesis. In contrast, the developing human heart mainly results from cardiomyocyte hypertrophy and not from hyperplasia. Therefore, at some point during heart development, the ventricular muscle may undergo a switch in potential from hyperplasia to hypertrophy. This switch in myogenic potential may have important implications for ventricular remodeling in neonates with LVOT obstruction . The resIn some congenital heart diseases, in addition to abnormal cardiac anatomy, myocardial histopathological changes can be discerned at an early developmental stage during the fetal period; such changes include noncompaction, fibrosis, and endocardial fibroelastosis (EFE) . The chaE/A ratios, higher E/e′ ratios, and higher right ventricular myocardial performance indices [Because of severe left ventricular dysfunction being unable to maintain the circulation of blood perfusion in neonates with HLHS, RV is actually functional single ventricle and assumes the pulmonary circulation and blood circulation spring function. Therefore, an accurate assessment of right ventricular function in fetuses with HLHS would have given a more meaningful message on prenatal counseling, intrauterine intervention surgical treatment options, and prognosis after birth. Our results displayed that the RV volume, SV, and CO in HLHS fetuses were increased compared with the gestational age-matched normal controls, which indicates the compensated contraction of right ventricle. The RV EF showed no significant difference between HLHS fetuses and the controls. RV EF reflects the percentage of RV SV accounted for RV EDV. RV SV increases with the increase of RV EDV; both of them adapt to each other, thus leading to RV EF values remaining within a certain range of fluctuations in HLHS fetuses. Natarajan et al. showed that fetuses with endocardial fibroelastosis (EFE) of the left ventricle and HLHS presented with marked abnormal RV myocardial function by lower tricuspid  indices . Fetal HDespite significant improvements in medical resources and therapies, the lifespan of patients with HLHS remains short. We hypothesized that the changes in cardiac function in these patients may be related to cardiac pathological changes. Cardiac morphogenesis and myocardial tissue structure changed significantly during the fetal period and in the first years after birth. Some related studies have reported the ultrasound and MRI characteristics of patients with HLHS, but few histopathological observations have been reported. With the support of the patients and Xinqiao Hospital, we were able to observe preliminary histopathological features in these patients. However, our case series contains only a limited number of patients. Large histopathological studies that include the right ventricle and pulmonary artery in HLHS specimens are needed to further understand the pathophysiologic features of HLHS patients.In addition to severe anatomical deformity, distinct histological abnormalities in the LV myocardium and aortic wall were identified in the fetuses with HLHS. These changes suggest that structural abnormalities of the heart may be intrinsic in HLHS. RV function damage may potentially exist.Video 1: Doppler color flow image in the aortic arch view demonstrating a ductus arteriosus-dependent retrograde flow in the transverse aortic arch (white arrow).Video 2: Doppler color flow image in a 4-chamber view demonstrating mitral atresia without blood filling, while blood flow filling normally through the tricuspid during diastole.


Dyslipidemia and obesity are considered strong risk factors for premature atherosclerotic cardiovascular disease and increased morbidity and mortality and may have a negative impact on myocardial function.Our purpose was to assess the presence of early myocardial deformation abnormalities in dyslipidemic children free from other cardiovascular risk factors, using 2-dimensional speckle tracking echocardiography (2DSTE) and 3-dimensional speckle tracking echocardiography (3DSTE).We studied 80 consecutive nonselected patients (6–18 years of age) with hypercholesterolemia (low-density lipoprotein [LDL] cholesterol levels >95th percentile for age and sex). Forty of them had normal weight and 40 were obese (body mass index >95th percentile for age and sex). Forty healthy age-matched children were selected as controls. Left ventricular (LV) global longitudinal, circumferential, and radial strains were calculated by 2DSTE and 3DSTE. Global area strain (GAS) was calculated by 3DSTE as percentage of variation in surface area defined by the longitudinal and circumferential strain vectors. Right ventricular (RV) global and free-wall longitudinal strain and LV and RV diastolic strain rate parameters were obtained. Data analysis was performed offline.LV global longitudinal strain and GAS were lower in normal-weight and obese dyslipidemic children compared with normal controls and reduced in obese patients compared with normal-weight dyslipidemic children. LV early diastolic strain rate was lower compared with normals. RV global and free-wall longitudinal strain was significantly reduced in obese patients when compared with the control group. A significant inverse correlation was found between LV strain, LDL cholesterol levels, and body mass index.2DSTE and 3DSTE show LV longitudinal strain and GAS changes in dyslipidemic children and adolescents free from other cardiovascular risk factors or structural cardiac abnormalities. Obesity causes an additive adverse effect on LV strain parameters and RV strain impairment. Forty of them had normal weight and 40 were obese (body mass index >95th percentile for age and sex). Mean age was 10.48 ± 3.42 and 10.74 ± 3.67 years in the normal-weight and obese groups, respectively. None of them had any other cardiovascular risk factors. Children with thyroid dysfunction, nephrotic syndrome, autoimmune disease, liver disease, primary biliary cirrhosis, and sleep apnea (according to parents’ information) were excluded. Forty healthy children matched for age and sex were also recruited. Systolic and diastolic blood pressures were systematically measured during the echocardiographic studies. The study was approved by the local ethics committee, and written informed consent was obtained from all subjects.13 Peak early (E) and late (A) diastolic velocities, deceleration time, LV isovolumic relaxation time, myocardial performance index, and right ventricular (RV) systolic pressure were obtained using standard Doppler practices. Mitral annular velocities  were measured on the transthoracic 4-chamber views.Patients were examined in the left lateral decubitus position using a Vivid E9 commercial ultrasound scanner  with an active matrix single-crystal phased-array transducer . Grayscale recordings were optimized at a mean frame rate of ≥50 frames/s. Measurements of cardiac chambers were made by transthoracic echocardiography according to established criteria.STE) was used for calculating the E/E′STE. Manual readjustments were made only when necessary to ensure accurate tracking.LV 2D longitudinal strain Figure  was calcSTE). Global strain and strain rate were calculated by averaging local strains along the entire right ventricle, using software .To assess regional and global RV systolic function in the longitudinal direction, we adopted a 6-segment RV model . Peak systolic strain was recorded for the 3 RV myocardial free-wall and septal segments and the entire RV wall Figure . The folA fully sampled matrix-array transducer with almost 3000 active elements was used . The acquisition of 3-dimensional echocardiography (3DE) data was obtained in an adjustable volume divided into 6 subvolumes. By keeping the ultrasonic transducer in a stable position, the acquisition of subvolumes was steered electronically and triggered to the ECG R wave on consecutive heartbeats. Acquisitions were recorded at the LV apex during end-expiration breath-hold with a mean volume rate of ≥30 vol/s and a 6-beat acquisition to obtain a correct spatial registration of all subvolumes and optimal temporal–spatial resolution. To optimize the acquisition frame rate ≥30 Hz (30 frames/s), depth was minimized to include only the left ventricle.. 3DSTE was used to determine at end-systole global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS). GAS was determined as the percentage of decrease in the size of endocardial surface area defined by the vectors of longitudinal and circumferential deformations. Following a frame-by-frame analysis, a final 17-segment Bullseye map of strain values was displayed , using the original raw data from 3-dimensional data sets. Alignment was performed with the presentation of 4-chamber, 2-chamber, and 3-chamber apical views, as well as short-axis views. For the end-diastolic volumes, the operator placed one point in the middle of the mitral annular plane and a second point at the LV apex, generating an end-diastolic endocardial border tracing and including the papillary muscles within the LV cavity. For the end-systolic volumes, the same process was repeated in end-systole, and acquisition of LV volumes and left ventricular ejection fraction (LVEF) was obtained. The correct alignment of the endocardial contours during the cardiac cycle was checked to obtain the volume waveform. A second semiautomated epicardial tracking was made to delineate the region of interest for strain analysis (3DSTE)P < 0.1 or less on univariate analysis was entered into the model. Variance inflation factor approach was used to identify collinearity among explanatory variables. Variables were compared among groups by Student t test. Differences were considered statistically significant if the P value was <0.05. Intraobserver and interobserver variabilities of strain measurements were evaluated in 10 randomly selected patients. To analyze intraobserver variability, measurements of strain parameters were made at multiple sites in different patients on 2 different occasions. For interobserver variability, a second investigator randomly made measurements at the above different sites without knowledge of other echocardiographic parameters. The intraobserver and interobserver variabilities were determined as the difference between the 2 sets of observations divided by the mean of the observations and expressed as a percentage. Beat-to-beat variability was assessed by the analysis of multiple 2D and 3D loops in a subset of 10 randomly selected normal subjects. Acquisition variability was assessed by repeating the test with a different operator within 1 hour after the first study without alteration of hemodynamics or therapy and analyzing by separate observers the measurements of the same strain parameters obtained in the 2 different acquisitions.Data are presented as mean value ± SD. Linear correlations and univariate and multivariate analyses were used for comparisons. Multivariate analyses were performed using a stepwise forward regression model in which each variable with STE, and 6.7% ± 3.2% for RVLS, and interobserver variability was 6.9% ± 3.2% for FW-RVLS, 8.6% ± 3.9% for GLS, 9.7% ± 3.7% for GCS, 12.9% ± 4.5% for GRS, 7.9% ± 3.6% for E′STE, and 7.3% ± 3.4% for RVLS. For 3DSTE, intraobserver variability was 6.6% ± 2.3% for GLS, 7.8% ± 2.7% for GCS, 5.7% ± 2.4% for GAS, and 9.7% ± 4.1% for GRS, and interobserver variability was 7.3% ± 2.8% for GLS, 8.4% ± 2.9% for GCS, 6.1% ± 2.6% for GAS, and 10.2% ± 3.9% for GRS. Beat-to-beat variability on average had a coefficient of variance <10%. Acquisition variability for 2DSTE was 8.2% ± 4.1% for GLS, 9.8% ± 3.9% for GCS, 11.8% ± 5.2% for GRS, 8.1% ± 3.3% for E′STE, 6.8% ± 3.5% for FW-RVLS, and 6.9% ± 3.7% for RVLS, and for 3DSTE was 7.1% ± 2.2% for GLS, 8.5% ± 2.9% for GCS, 6.3% ± 2.4% for GAS, and 10.1% ± 4.1% for GRS.Eighty out of 91 initially evaluated patients were included in the study. Eleven patients were excluded due to inadequate myocardial tracking  or rhythm abnormalities (n = 1). Global feasibility of the study was 88%. The intraobserver and interobserver variabilities were slightly higher for 2D GLS, GCS, and GRS compared with the corresponding 3D strain values. For 2DSTE, intraobserver variability was 6.3% ± 3.1% for FW-RVLS, 7.4% ± 3.5% for GLS, 8.9% ± 3.4% for GCS, 11.5% ± 4.6% for GRS, 7.1% ± 3.2% for E′P = 0.078).The baseline characteristics of patients and controls are listed in Table Dyslipidemic children had increased LV-wall thickness and mass index compared with controls Table . LVEF waSTE was lower compared with normals both in normal-weight and obese dyslipidemic patients. E/E′STE was higher only in the obese group . Both image acquisition time  and offline analysis time  were significantly faster for 3DSTE compared with 2DSTE. Analysis time included calculation of LV volumes, LVEF, and all 3 (2D) or 4 (3D) strains from a single vendor-specific algorithm.The total duration of 3D data analysis averaged 9.1 ± 1.5 minutes, which was 49% less than the time used for 2D analyses . No significant correlation between global RS extracted from 3DSTE and 2DSTE was found. The 3DSE approach gave lower values than 2DSTE for both global LS and CS components (Table P < 0.01) for LS and 0.44 (P < 0.05) for CS. When comparing segmental LS measured with 2D and 3D methods at ventricular levels, the smallest differences were found in the midventricular segments (P = ns), whereas significantly larger differences were obtained in the basal (P < 0.01) and apical (P < 0.05) segments.Global LS and CS measured by 2DSTE and 3DSTE showed significant correlations between both methods , LDL cholesterol levels and 3D-derived longitudinal strain , LDL cholesterol levels and GAS , body mass index and 2D-derived longitudinal strain , body mass index and 3D-derived longitudinal strain , and body mass index and GAS . By multivariate analysis, 2D-GLS (P = 0.038), 3D-GLS (P = 0.044) and GAS (P = 0.012) were independently associated with hypercholesterolemia , GAS might decrease the tracking error and emphasize synergistically the magnitude of deformation; thus, it is reasonable to expect that deteriorated LV function can be detected at an earlier stage by using 3D speckle tracking analysis in comparison with one-directional strain. Among the 4 measured strains , we found that GAS had the best correlation with LDL cholesterol level and the highest discriminating power compared with normal controls, and this suggests a superiority of GAS over the conventional strain parameters in detecting early LV systolic dysfunction.A significant inverse correlation was found between longitudinal deformation and LDL cholesterol level, and a significant higher correlation was found between GAS obtained by 3DSTE and LDL cholesterol level. Several studies have validated 3DSTE, both in vitro and in vivo, against reference techniques such as sonomicrometry and magnetic resonance imaging tagging.26 we had a satisfactory correlation between 2DSTE and 3DSTE for GLS and GCS, but the correlation was poor for GRS. One reason may be that GRS values show a greater variability because they are calculated by both endocardial and epicardial speckle tracking data, whereas GLS and GCS are estimated only by endocardial tracking. Another reason might be the fact that the spatial motion gradient is calculated over a small region due to the limited wall thickness in combination with limited spatial resolution of the image.As in previous reports,28 The superiority of 3DSTE over 2DSTE for the evaluation of all 3 components of LV deformation  has been questioned.29 The 3D mode avoids foreshortening of apical views, consumes less time in data acquisition, helps to solve the problem of out-of-plane motion present in the 2D modality tracking motion of speckles in all 3 dimensions, and has good reproducibility as an automated method as shown by lower intraobserver and interobserver variabilities. However, this advantage is achieved at the expense of lower volume rate that might alter the correlations with measurements obtained by 2DSTE.Both 2DSTE and 3DSTE showed to be more sensitive to the detection of subtle myocardial damage compared with conventional indices of LV function.30 longitudinal and circumferential strain values that are comparable with the ones obtained from 2DSTE, even though they are not interchangeable with each other for various reasons. First, GLS was smaller on 3DE than 2DE imaging, and the lower longitudinal strain values may be explained by the twisting of the heart and out-of-plane rotation of myocardial segments on 2DE imaging.30 Second, the differences of strain values between the 2 methods were higher in the basal and apical segments than in the midventricular ones. These findings can be attributed to the diverging ultrasound beams toward the base that cause worse spatial resolution. In addition, these segments move at the highest velocities during the cardiac cycle, and this affects the accuracy of measurements due to the low frame rate of the current 3D echocardiography data sets. The problems of tracking in terms of apical segments can likely be attributed to the near-field artifacts or falling out of the field of view30 as it occurs in very lean subjects where the heart is close to the chest wall and further increasing the field of view is not possible unless decreasing frame rate which is unacceptable.Our study is in keeping with previous reports showing that 3DSTE provides global and regional33 The mechanisms of cardiac remodeling with obesity are complex,32 and a major obstacle in attempts to characterize “obesity cardiomyopathy” is the prevalence of comorbid disorders such as insulin resistance, systemic hypertension, obstructive sleep apnea, type 2 diabetes mellitus, and physical inactivity. However, long-term follow-up studies found that obesity was associated with coronary artery disease independently of other cardiovascular risk factors,34 and other data suggested that overweight and obesity in young adults accelerate the progression of atherosclerosis before the appearance of clinical manifestations.35 The underlying pathophysiologic mechanisms that could lead to an increased risk for coronary artery disease include obesity-mediated free fatty acid turnover,34 obesity-mediated reduction in insulin sensitivity,34 induction of a hypercoagulable and hyperinflammatory state,36 and increased endothelial prostanoid-mediated vasoconstriction.37We also showed a correlation between deformation indexes and body mass index. Several mechanisms have been proposed to explain ventricular dysfunction in obesity, such as an increased mass in response to a larger intravascular volume, increased preload, and increased afterload.34 Subclinical changes in LV systolic and diastolic function have been described in obese adults38 and children.9 Children may show early cardiovascular dysfunction as a result of their excess adiposity, independently of other obesity-related comorbidities such as insulin resistance and dyslipidemia.1 Our data found LV systolic and diastolic abnormalities in obese dyslipidemic children. Systolic strain impairment was higher in the obese group compared with normal-weight hypercholesterolemic patients, indicating that this metabolic abnormality exerts an independent effect on LV function. Early diastolic strain rate is recognized as one of the markers of diastolic dysfunction and was lower in the hypercholesterolemic patients compared with controls, suggesting an incipient abnormal relaxation pattern. Because an abnormal E/E′STE ratio is associated with elevated filling pressure, it is not surprising that this ratio remained within the normal range in normal-weight hypercholesterolemic children and adolescents and was higher in the obese group in whom increased mass and LV impairment were more severe.Obesity showed an additive adverse effect on LV strain parameters in our young patients with lipid abnormalities, and this is reasonable on the basis of the above considerations. Previous studies in obese dyslipidemic children reported reduced systolic LV deformation characteristics, early vessel wall changes, and increased arterial stiffness suggesting an abnormal ventricular–vascular interaction.40 In the pediatric population, the few papers that have analyzed RV in obesity showed different results. Potential reasons for this discrepancy may include the echocardiographic methods used, the differences in sample size, and the severity and duration of obesity. In the present study, we found a decreased RV free-wall strain and strain rate compared with controls, and these results are similar to those reported in nonhypertensive obese children using strain rate TDI.39 Other authors9 have described significantly higher RV strain and SR values in the obese patients, and it was speculated that, different from the LV function, systolic RV function was not an early abnormality in obesity and can be initially masked by the hypervolaemia state present in obesity because of an increase in preload, which would influence RV strain and strain rate.An incipient RV dysfunction has also been shown in obese adults and children.Our study shows the presence of LV deformation abnormalities in hypercholesterolemic children and adolescents and an accentuation of LV changes as well as an additional RV involvement in obese patients. We have also shown that 3DSTE allowed more rapid image acquisition and analysis because a single volumetric acquisition is required for this type of analysis, and this is convenient for any method to be applied clinically. Although 2D techniques require multiplane acquisitions for analysis, 3DSTE allows a reduction in acquisition time through the acquisition of the entire 3D volume data set from a single apical view over several cardiac cycles, and the postprocessing analysis performed allows derivation of all 4 components of 3D strain from a single analysis. Moreover, a further advantage of 3D-STE is the use of area strain for global LV function assessment, which is a novel index in addition to conventional strain parameters. However, 2D strain modalities are preferable whenever wall tracking tends to be suboptimal as well as in the assessment of RV function. Thus, our 2DSTE and 3DSTE data can be useful to critically assess not only the potentialities but also the actual limitations of speckle tracking echocardiography in the daily clinical practice. Overall, these findings provide additional evidence to induce physicians to manage hypercholesterolemia and obesity even at a young age and look for early detection of cardiac dysfunction in view of its potential reversibility.Currently, 2 important technical limitations of 3DSTE are that the speckle tracking analysis is highly dependent on image quality, especially endocardial boundary delineation, and its low frame rate may lead to miscorrelation among frames and affect strain data accuracy. The low temporal resolution affects the ability to track anatomic details frame by frame and requires multibeat (6 beats) acquisitions. Although single-beat 3-dimensional STE data sets could have been acquired, image quality of single-beat acquisitions is not currently on an equal level with image quality of the multibeat acquisitions. Further research leading to improvements in both hardware and software is required to assess the feasibility of 3DSTE and the relative importance of current limitations such as low frame rates and suboptimal image quality.The sources of variability are a further limitation, because the contribution to the overall coefficient of variation is not only related to the reader or the operator but also to beat-to-beat variability in single-beat and multibeat acquisitions. Consequently, efforts should be directed to utilize this information in developing more robust acquisition techniques and strategies.41 The use of a single vendor is appropriate for early research applications, but prevents widespread clinical applications in large populations across multiple imaging platforms and institutions.Moreover, there is only limited experience cross-comparing intervendor differences in 3DSTE measurements.Additionally, this was a relatively small observational study in a single-center protocol; thus, the prognostic implications of this mild LV dysfunction in order to improve the risk stratification of this subpopulation were not assessed and a larger study is required to confirm our findings.Dyslipidemia and obesity are associated with myocardial deformation changes as assessed by 2DSTE and 3DSTE in patients with no other cardiovascular risk factors or structural cardiac abnormalities. Obese dyslipidemic children and adolescents present greater impairment in LV strain parameters and impairment in RV strain compared with normal-weight dyslipidemic patients. Larger long-term studies are necessary to confirm the clinical importance of these results.


The present study proposes arousal as an important mechanism driving buying impulsiveness. We examined the effect of buying impulsiveness on arousal in non-shopping and shopping contexts. In an eye-tracking experiment, we measured pupil dilation while participants viewed and rated pictures of shopping scenes and non-shopping scenes. The results demonstrated that buying impulsiveness is closely associated with arousal as response to viewing pictures of shopping scenes. This pertained for hedonic shopping situations as well as for utilitarian shopping situations. Importantly, the effect did not emerge for non-shopping scenes. Furthermore, we demonstrated that arousal of impulsive buyers is independent from cognitive evaluation of scenes in the pictures. Buying impulsiveness is consumers' tendency to engage repeatedly in spontaneous, “on-the-spot” purchases, without consideration of potential consequences Research on impulsive buying commonly uses questionnaires or self-ratings. Thus, it often neglects consumers' physiological reactions, though these reactions might represent an important link between individual traits and behavior An expression used to indicate a state of arousal, as well as that of excitement and joy, is “wide-eyed.” However, “wide-eyed” may be more than just a phrase: Previous research suggests that our eyes literally widen in situations in which individuals experience arousal, as demonstrated by physiological literature using pupil responses. Task-evoked pupil dilation is a common measure in psychophysiology There might be two reasons why shopping situations trigger arousal in impulsive buyers: self-control conflicts and affective responses. Most theories agree that failures in self-control play an important role in buying impulsiveness Impulsive buying is related not only to a lack of self-control, but also to increased affective responses Furthermore, we assume that arousal in impulsive buyers is domain-specific. Recent research has demonstrated that temptations in self-control conflicts are largely idiosyncratic and domain-specific The present study is the first to use a physiological measure to examine processes that underlie buying impulsiveness. Specifically, we suggest arousal to be a crucial mechanism underlying buying impulsiveness. In order to address the role of arousal in shopping situations, we measured pupil dilation while participants viewed pictures of non-shopping and shopping scenes. To demonstrate the effect across a variety of shopping situations, we used pictures of shopping scenes that are typically considered hedonic, such as apparel shopping, and shopping scenes that are typically considered as utilitarian, such as grocery shopping According to the Austrian Universities Act 2002 (UG2002), which was in place at the time the study was carried out, only medical universities were required to appoint ethics committees for clinical tests, application of medical methods, and applied medical research. Consequently, no ethical approval for this specific study was required.Nevertheless, the present study was part of a project that was funded by a European Union Marie Curie FP7 Integration Grant, and the project received ethical approval. As there was no institutional review board in charge at the time the project proposal was submitted, it was approved by an independent expert .The present study was conducted in accordance with the Declaration of Helsinki (revised 1983) and local guidelines of the Faculty of Psychology, University of Vienna. Written informed consent was given by all participants, who could also withdraw at any time during the experiment without further consequences. At the end of the experiment, participants were debriefed in detail.Fifty participants completed the study, and each received six euros as compensation. We recruited participants, without exclusion criteria, from the local subject pool. The subject pool consists of volunteers who are recruited online, as well as via flyers and posters, at the university. As studies that are conducted in our lab regularly involve paradigms from psychological research, psychology students are not included in the subject pool, in order to avoid demand effects that result from prior knowledge of these paradigms.Mage = 25.4, SDage = 5.3, 31 women).Participants were unaware that physiological reaction to picture content was the focus of the study, and they were not familiar with the stimulus material. We removed one participant due to missing values in the rating task, resulting in a sample of 49 participants (We used 40 different pictures that belonged to one of four categories: (a) hedonic shopping context, (b) utilitarian shopping context, (c) positive non-shopping context, and (d) neutral non-shopping context. Pictures in the shopping context depicted situations in various stores. For instance, the hedonic shopping context included pictures of the interior of apparel stores and of shopping bags with clothing. The utilitarian shopping context, on the other hand, included pictures of the interior of grocery stores and carts containing groceries. As stimuli for the non-shopping situations, we used a subset of pictures used in a previous study measuring pupil dilation In order to rule out the possibility that visual aspects influenced pupil dilatation, the pictures were transformed to 8-bit greyscale. Each picture had the same mean luminosity .Mage = 24.3, SDage = 4.1) with the sample of the main study . The proportion of women in the pretest (86%) was higher than that of the main study (63%), but as the pretest did not find any gender effects regarding picture rating this difference is negligible.A pretest ensured adequate picture selection, and confirmed the comparability of visual aspects: there were no differences regarding perceived complexity and contrast between the four categories of pictures. Additionally, participants in the pretest rated positive pictures as more pleasant compared to pictures in all other categories, and shopping pictures as more strongly related to shopping compared to pictures of non-shopping scenes. The sample used in the pretest was comparable regarding age  they would see a cross in the middle of the screen, (b) the cross disappears when they look at it, (c) the picture is presented for a few seconds, and (d) they would be asked for their rating.The presentation screen was a 22-inch monitor with a resolution of 1680×1050 pixels and a refresh rate of 60 Hz. Participants were seated approximately 60 cm away from the monitor. Lighting was kept constant and the participants wore headphones to control for background noises. The grey background during the task was equal to the mean luminosity of the pictures .The experiment consisted of 40 trials. Each trial started with a fixation cross in the location where the pictures were later presented. After participants had fixated on the cross for 1,500 ms, a blank screen was presented for 500 ms. Then, one of the 40 pictures from the four categories  was presented on the screen for 4,000 ms. The order of the pictures was fully randomized. During the picture presentation, we assessed pupil diameter using an SMI RED 500 remote eye-tracker  with a sampling rate of 250 Hz. After the presentation of each picture, the participants rated how much they liked the picture  and how positively they perceived the scene presented in the picture .buying impulsiveness scale  from Rook and Fisher M = 18.3, SD = 6.1).After the 40 trials, the participants answered a questionnaire that contained questions on demographics and the We corrected for artifacts and calculated tasked-evoked pupil dilation according to standard procedures We hypothesized that context (non-shopping vs. shopping) moderates the influence of buying impulsiveness on arousal. We conducted a general linear model analysis with pupil dilation as the dependent variable; the context was a within-subject factor, and buying impulsiveness was a continuous between-subject predictor.F  = 16.18, p<.001, whereas the effect of buying impulsiveness was not, F = 2.58, p = .12. The respondents' pupils became more dilated while viewing shopping scenes compared to non-shopping scenes. In line with our expectation, a significant Context x Buying Impulsiveness interaction, F = 5.81, p = .02, indicated a differential influence of buying impulsiveness in each context  = 67.42, p<.001, and rated scenes in non-shopping pictures as more positive, F = 93.00, p<.001. However, neither liking, F = 0.02, p = .90, nor valence, F =  0.13, p = .72, were influenced by buying impulsiveness. In addition, the analyses revealed no effects of the Context x Buying Impulsiveness interaction neither for liking, F = 0.32, p = .57, nor for valence, F = 1.32, p = .26. Additionally, pupil dilation did not correlate with liking or valence, neither in the shopping context, r(47)s<−.10, ps>.50, nor the non-shopping context, r(47)s<.14, ps>.33. Taken together, these findings indicate that buying impulsiveness did not influence physiological arousal through cognitive evaluations of the scenes in the pictures.In order to examine whether the arousal was independent from cognitive evaluation of the shown scenes, we analyzed whether buying impulsiveness influenced the picture ratings. We conducted two general linear model analyses, with liking of the pictures and valence of the scenes depicted in the pictures as dependent variables, respectively. Context was a within-subject factor and buying impulsiveness was a continuous between-subject predictor. Overall, the participants liked the non-shopping pictures more, The present study is the first to analyze the effect of buying impulsiveness on arousal using a physiological measure. While participants viewed and rated pictures of shopping and non-shopping scenes we measured pupil dilation, representing arousal. For pictures depicting shopping scenes, high buying impulsiveness was accompanied by an increased intensity of arousal, as reflected in the participants' pupil dilation. Importantly, for non-shopping scenes the intensity of arousal was not correlated with buying impulsiveness. This specificity of reaction is in line with research indicating that impulsivity is idiosyncratic and domain-specific Previous research has shown that the act of purchasing is linked to arousal The finding that shopping situations, in and of themselves, trigger arousal is substantiated by the fact that the type of the shopping scene did not have an effect. Arousal of highly impulsive buyers was not restricted to specific shopping scenes; but buying impulsiveness is linked to intensity of arousal in a wide range of shopping scenes, e.g. grocery shopping or apparel shopping. This implies that physiological arousal triggered by shopping situations is independent from the type of shopping situation.Furthermore, we found that the self-reported evaluation of the shopping scenes was independent from buying impulsiveness. This suggests that the correlation between buying impulsiveness and arousal is independent from cognitive evaluations. We assessed how much participants liked the pictures, and whether the scene in the pictures was positive or negative. Impulsive buyers rated shopping scenes equally to non-impulsive buyers. Thus, pupil dilation was not related to evaluation of the scenes depicted in the pictures. Hence, evaluation cannot be a mediating factor for the moderated effect of buying impulsiveness and context on arousal. This fact further stresses our argument that shopping situations trigger arousal in and of themselves.Based on the physiological reactions of impulsive buyers on pictures of shopping scenes, we conclude that impulsive buyers feel aroused just by entering a shopping environment and that the act of purchasing is not necessary to stimulate an aroused state in impulsive buyers. Moreover, the results indicate that this arousal of impulsive buyers is a basic physiological reaction that is independent from cognitive evaluations of the shopping scene.