P = 0.003), prolonged mechanical ventilation  and longer hospitalization . In patients with TOF, Ea and Ees reduced post-operatively; however, VAC remained unchanged and was not associated with post-operative outcomes. Despite of different loading condition, preoperative VAC maintained in both of VSD and TOF. However, particularly in VSD patients, abrupt increase in post-operative loading state induces contractility-load decoupling, which leads to worse post-operative outcomes.Ventricular performance and its loading condition change drastically after surgical correction of congenital heart defect. Pressure–volume loops analysis can provide quantitative information about ventriculo-arterial coupling (VAC) indicating the interaction between ventricular contractility and loading condition. Therefore, we investigated changes in VAC after corrective surgery for ventricular septal defect (VSD)/tetralogy of Fallot (TOF), and implication of ventriculo-arterial decoupling as a prognostic factor of post-operative outcomes. In children with VSD/TOF, pre- and post-operative arterial elastance (Ea), end-systolic ventricular elastance (Ees) and VAC (Ea/Ees) were non-invasively estimated using echocardiographic parameters. Post-operative outcomes included maximum vasoactive-inotropic score, the duration of mechanical ventilation and hospital stay. Preoperatively, patients with VSD had significantly lower Ea and Ees than patients with TOF; however, VAC were preserved in both. In patients with VSD, post-operative Ea increased disproportionately to change in Ees, resulting in increased VAC. Post-operative higher VAC in patients with VSD was independently associated with maximum vasoactive-inotropic score  contains supplementary material, which is available to authorized users. In children with congenital heart defects (CHDs), intra- or extra-cardiac shunt is associated with the pressure or volume overloading of ventricles, which influences alterations in ventricular structures and mechanics . The hemA pressure–volume (P–V) relationship analysis is generally used to comprehensively assess ventricular performance during a cardiac cycle , 3. GiveSenzaki et al. showed the characteristics of P–V relationship according to various loading conditions in specific types of CHDs , 11. TheIn this study, we investigated the alterations in P–V relationship including Ees, Ea and VAC according to different loading conditions in children undergoing cardiac surgery for VSD and TOF, using non-invasive echocardiographic estimation. Additionally, we examined whether post-operative changes in Ees, Ea or VAC had any prognostic significance following corrective surgery.This retrospective cohort study was approved by the Institutional Review Board and Institutional Ethics Committee of Asan Medical Center, Seoul, Korea in July 2017. The need for an informed consent from patients was waived by the Institutional Review Board. Electronic medical records of pediatric patients younger than 6 years with diagnoses of CHDs, who underwent cardiac surgery with cardiopulmonary bypass (CPB) between January 2011 and December 2016, were retrospectively reviewed. VSD and TOF having representative hemodynamic features of left ventricular volume overloading and underloading, respectively, were selected for the grouping of CHDs , 12. Pedmax) after weaning from CPB. Post-operative variables included the duration of stay in the intensive care unit, mechanical ventilation, post-operative VISmax during the first 48 h and post-operative complications. The VIS was calculated as described by Gaies et al. [Demographic variables included age, sex, weight, height, history of prematurity and birth weight. Intra-operative variables were anesthesia time, operation time, CPB time, aorta cross-clamp time and maximum vasoactive-inotropic score  examination using a commercially available ultrasound system  was performed by an experienced sonographer to determine the cardiac structures and function according to the American Society of Echocardiography recommendations , and attRegarding arterial load, Ea was represented as the slope of ESP versus SVI in the PV loop . To quanχ2 test or Fisher’s exact test, while continuous variables were analyzed using Student’s t-test or Mann–Whitney U test. One-way analysis of variance and Kruskal–Wallis test were applied to determine the differences between the groups, followed by a post-hoc Bonferroni test. The statistical significance of the change in the PV relationship before and after operation was determined using the paired t-test and Wilcoxon signed-rank test. Univariate logistic regression analysis was performed to determine the relationship between worse post-operative outcomes and PV loop variables. Worse post-operative outcomes were defined as post-operative VISmax > 5, the duration of mechanical ventilation > 15 h and post-operative hospitalization > 7 days. Multivariable logistic regression analysis was performed, adjusting for the clinical variables that showed significant differences. For all analyses, a P-value of < 0.05 was considered statistically significant. All analyses were performed using Statistical Package for the Social Sciences software .All data were expressed as mean ± SD, median (IQR) or number (proportion) as appropriate. Missing data were managed either by the deletion of the case or variable. Categorical variables were analyzed using Pearson Of the total 400 pediatric patients, whose electronic medical records were reviewed, 164 were excluded. Of the 236 patients included in the final analyses, 78 patients were assigned to the VSD group, 74 to the TOF group and 84 to the control group. The process of patient selection and classification is described in Fig. 2) compared to controls  (Table P = 0.060) because of low basal Ea, which was matched with decreased Ees. After surgical correction, EDVI (− 31%) notably reduced compared to the reduction in ESVI (− 20%); thus, SVI was reduced. Post-operative ESP was not different from pre-operative ESP; therefore, Ea markedly increased , coinciding with a rise in VAC  despite an increase in Ees , on the left-shifted PV loop  compared with controls  and patients with VSD . Ea (3.70 ± 2.03 mmHg/ml/m2) also elevated significantly compared with the other groups . As a result, the represented VAC was slightly lower than that of controls . Contrary to patients with VSD, Ea and Ees reduced after surgery . Post-operative PV loops were slightly shifted to the right .In patients with TOF, pre-operative EDVI, ESVI and SVI were significantly lower than those in controls and in patients with VSD Table . Patientmax (>5) and prolonged hospital stay (>7 post-operative days) on univariate analysis; however, it was not significant after multivariate adjustment. A post-operative increase in VAC in patients with VSD was independently associated with high VISmax , prolonged duration of mechanical ventilation (>15 h)  and longer post-operative hospital stay  (Table P = 0.045) . In patients with TOF, in contrast, post-operative changes in PV loop-derived variables including VAC were not associated with post-operative outcomes.In patients with VSD, post-operative Ees indicating ventricular contractility was significantly associated with high VISIn this study, we investigated the characteristics of the P–V relationship estimated non-invasively from echocardiographic measurements before and after surgery for VSD and TOF with different loading conditions.VSD patients represented low-basal Ea and Ees and post-operative Ea increased in disproportion to the change of Ees. As a result, relationship between ventricular contractility and loading was uncoupled on left-shifted P–V loops immediately after surgery. Accordingly, VAC in children with VSD was elevated by abrupt changes in loading, which was associated with worse post-operative outcomes. Meanwhile, TOF patients characterized by high-basal Ea and Ees, and post-operative VAC were still maintained and not related to worse outcomes.Basal interaction between ventricular contractility and loading are matched within a narrow range to optimize cardiac energetic efficiency . In our After surgical correction for VSD, the P–V relationship could be changed abruptly. Left-to-right shunt is disappeared, and volume overload is relieved leading to an instant reduction in EDVI. However, ESVI slightly decreases or remains stationary following the block of the shunt because the impaired ventricle cannot readily restore the systolic function . RegardiOn the contrary, TOF is characterized by significantly decreased EDVI and ESVI , 20. AltAfter total correction of TOF, there were no significant differences in left ventricular volumes, and VAC was also maintained on the similar P–V loop with decreases in Ees coinciding with reduced Ea. We found that the change in VAC could not predict post-operative outcomes after the repair of TOF. Because pulmonary stenosis burdens the right ventricle rather than the left ventricle, right ventricular dysfunction has generally been targeted for management after surgery for TOF , 22. CliIn this study, Ees was obtained on the end-systolic P–V relationship using a simple equation: Ees = ESP/ESVI , which rmax of 3 and hospital stay of 6 and 7 days, given the small size of the population. Although we adjusted for confounding factors that affected post-operative outcomes, further study in larger population is required to clarify the prognostic impact of VAC on the clinical outcomes and to discriminate the cut-off value with narrow CIs. Second, this simple method is to assume that the volume intercept of the P–V curve (V0) is zero [0, especially in VSD patients who have increased ESVI. It has been reported that values of area-axis intercept are not significantly different from healthy controls, using pressure–area analysis constructed by ventricular area measurement [There are several limitations to this study. First, this single-center study was performed as a retrospective analysis, reviewing routine pre- and post-operative evaluations. Therefore, these results should be interpreted with caution because the timing of the echocardiographic evaluation could not be rigorously controlled. Moreover, post-operative outcomes were relatively favorable, such as median VIS is zero . Therefosurement . Howeversurement . InstantPreoperative variables derived from P–V loops can reflect baseline characteristics of ventricular performance-integrated loading condition, according to volume loading status of CHDs. In the VSD and TOF groups, VAC was favorably maintained, suggesting that ventricular contractility may be matched with loading abnormalities to preserve systemic outflow. However, abrupt post-operative changes of loading on the left ventricle may induce contractility-load decoupling. Especially in patients with VSD, an impaired ventricular function is unmasked by the disproportionate change in loading resulting in an increased VAC that is associated with worse post-operative outcomes. Therefore, our results suggest that non-invasive and simple estimation of VAC by P–V analysis helps in determining the appropriate target to optimize treatment after surgical correction for CHDs.Supplementary file1 (DOCX 42 kb)Below is the link to the electronic supplementary material.


PH) have disproportionate right ventricle (RV) dysfunction, but the correlates and clinical implications of RV dysfunction in Group 3 PH are not well defined.Patients with pulmonary hypertension caused by chronic lung disease  and +dP/dtmax/instantaneous pressure. Tau and RV diastolic stiffness characterized RV diastolic function. Multivariate linear regression was used to define correlates of RVFAC. Kaplan‐Meier and Cox proportional hazards analyses were used to examine freedom from heart failure hospitalization and death. Positive correlates of RVFAC on univariate analysis were pulmonary arterial compliance, cardiac index, and left ventricular diastolic dimension. Conversely, male sex, N‐terminal pro‐brain natriuretic peptide, heart rate, right atrial enlargement, mean pulmonary arterial pressure, and pulmonary vascular resistance were negative correlates. Male sex was the strongest predictor of lower RVFAC, after adjusting for pulmonary vascular resistance and pulmonary arterial compliance. When comparing sexes, males had lower RVFAC  both overall and for any given mean pulmonary arterial pressure and pulmonary vascular resistance value. Males exhibited a reduction in +dP/dtmax/instantaneous pressure as pulmonary vascular resistance increased, whereas females did not. There were no sex differences in RV diastolic function. RV dysfunction (RVFAC <28%) was associated with increased risk of heart failure hospitalization or death .We performed a cohort study of 147 Group 3 RV dysfunction in Group 3 PH, even after adjusting for RV afterload. RV dysfunction (RVFAC <28%) identifies Group 3 PH patients at risk for poor outcomes.Male sex is associated with  In our pulmonary hypertension caused by chronic lung disease cohort, male sex is independently associated with right ventricular dysfunction even after correcting for pulmonary vascular disease severity.Right ventricular dysfunction is associated with increased risk of heart failure hospitalization or death, highlighting its clinical significance in pulmonary hypertension caused by chronic lung disease.Presence of right ventricular dysfunction identifies a high‐risk phenotype in pulmonary hypertension caused by chronic lung disease, and future therapies that target right ventricular dysfunction may improve outcomes in this vulnerable patient population.Pulmonary hypertension caused by chronic lung disease Group 3 PH) is the second leading cause of PH. PH is thRecently, we showed that Group 3 PH patients have worse right ventricular (RV) systolic function than PAH patients despite having less severe pulmonary vascular disease, as determined by hemodynamic measures.Accordingly, we aimed to (1) describe the clinical correlates of RV dysfunction in Group 3 PH to identify variables that may provide insight to better understand the risk factors for disproportionate RV dysfunction in Group 3 PH, and (2) examine the impact of RV dysfunction on clinical outcomes in Group 3 PH.The data that support the findings of this study are available from the corresponding author upon reasonable request.We studied adult patients (≥18 years of age) with Group 3 PH in the Minnesota Pulmonary Hypertension Repository.Chronic obstructive lung disease: diagnosed by reduced expiratory flow rates  and/or moderate‐to‐severe emphysema on a computerized tomography scan of the chest based on the visual classification system from the Fleischner Society.Interstitial lung disease: diagnosed by reduced total lung capacity <60% and/or evidence of moderate‐to‐severe interstitial fibrosis of lung parenchyma by computerized tomography scan of the chest.Combined pulmonary fibrosis and emphysema: based on computerized tomography scan of the chest and pulmonary function test.2.Obesity‐related lung disease: including obstructive sleep apnea (diagnosed by overnight sleep study) and obesity hypoventilation syndrome. Obesity was defined as body mass index >30 kg/mGroup 3 PH was defined as a mean pulmonary arterial pressure (mPAP) ≥25 mm Hg at rest with a pulmonary capillary wedge pressure of ≤15 mm Hg in patients with 1 or more of the following lung conditions in the absence of other causes to explain PH:We excluded patients with other World Health Organization categories of PH based on clinical evaluation and objective tests. Patients were excluded if they had idiopathic PAH, heritable PAH, drug‐induced PAH, or PAH associated with connective disease, liver disease, congenital heart disease, or HIV infection. Chronic pulmonary thromboembolic disease was excluded based on the findings on ventilation perfusion (V/Q) scan (high or intermediate probability), contrast‐enhanced chest computerized tomography, or pulmonary angiography if necessary. Patients with pulmonary venous hypertension, defined as mPAP ≥25 mm Hg at rest with a pulmonary capillary wedge pressure of >15 mm Hg, were also excluded.The following baseline variables at the time of referral were analyzed: age, sex, comorbid conditions, World Health Organization functional class, and medication use including PAH‐specific medications . Baseline laboratory tests included serum hemoglobin, serum creatinine, and serum N‐terminal pro‐brain natriuretic peptide. Pulmonary function testing and assessment of exercise capacity by 6‐minute walk test were also recorded. The Charlson Comorbidity IndexEchocardiography was performed using a commercially available Philips system  with a 3.5‐MHz multiphase‐array probe. The baseline echocardiographic variables collected on all available patients included the following: left ventricular ejection fraction, dimensions and mass, presence of left or right atrial (RA) enlargement, RV size and function, and presence of pericardial effusion. RV size was semiquantitatively described as normal size (two thirds or less of the left ventricular size) or as mildly (RV similar size as the left ventricle size), moderately (RV larger than the left ventricle), or severely enlarged (RV much larger than the left ventricle), using visual estimations as previously described.Patients underwent right heart catheterization, as clinically indicated by echocardiogram showing pulmonary hypertension or RV dysfunction or worsening dyspnea, in the University of Minnesota cardiac catheterization laboratory. Hemodynamics were obtained using a 7‐Fr, balloon‐tipped, flow‐directed catheter placed either into the internal jugular vein or the common femoral vein. The following hemodynamic variables were recorded at the end of expiration: RA pressure, RV systolic and end‐diastolic pressures, systolic pulmonary artery pressure, diastolic pulmonary artery pressure, mPAP, and pulmonary capillary wedge pressure. Cardiac output was determined as the mean of 3 measurements with the thermodilution method or indirect Fick method based on total body oxygen consumption, as estimated via the formula of LaFarge and Miettinen.+dp/dtmax, −dp/dtmin, and the instantaneous pressure (IP) at +dp/dtmax were calculated using a custom‐made program on LabView . Values for each variable were calculated as the average of 3 cardiac cycles. RV contractility was estimated using +dp/dtmax/IP to adjust for differences in preload.We quantified RV function by calculating right ventricular fractional area change (RVFAC), S’ velocity, and tricuspid annular plane systolic excursion (TAPSE) using echocardiography.To quantify RV diastolic function, we calculated Tau in the subset of patients who had RV pressure tracings from right heart catheterization using a custom‐made program in LabView, based on the formula described by Weiss et al.All patients were followed at the University of Minnesota PH clinic every 3 to 6 months. Vital statistics were obtained for all patients by chart review and Minnesota Death index. For each death, the date and cause of death was collected. In all patients who were not identified as deceased using the Minnesota Death Index, it was possible to establish vital status by chart review. Heart failure hospitalizations were collected for all patients and independently confirmed by chart review of the encounter by L.R.t tests or Wilcoxon–Mann–Whitney test were used to compare means of 2 groups with continuous variables as appropriate. Chi square or Fisher exact test were performed to compare proportions for categorical variables as appropriate. We used RVFAC to define reduced RV function, to determine the clinical correlates, and to compare clinical outcomes because it is more strongly associated with RV ejection fraction (RVEF) measured using cardiac magnetic resonance imaging (MRI) than TAPSE, especially in patients with severe pulmonary vascular disease.Categorical data were expressed as frequency and proportions, whereas continuous data were presented as mean±SD unless otherwise indicated. Unpaired P value of <0.05 was considered statistically significant.All statistical analyses were performed using Stata software Version 10 and 15  or GraphPad Version 7. A We studied 147 consecutive Group 3 PH patients at the University of Minnesota Pulmonary Hypertension Clinic. The clinical, echocardiographic, and hemodynamic characteristics of the cohort are described in Table +dp/dtmax/IP was 16.0±6.2/s. RV diastolic function was impaired with a mean Tau of 49.1±18.0 ms  . Similarly, when RVFAC was plotted against PVR, males had a significantly lower RVFAC at all PVR . There was no sex difference in RV contractility (+dp/dtmax/IP) between males and females . However, when +dp/dtmax/IP was plotted against PVR, females maintained +dp/dtmax/IP as PVR increased , but in males, +dp/dtmax/IP dropped as PVR increased  , providing evidence of sex‐based divergent responses of RV contractility to increasing afterload.Overall, males had significantly lower RVFAC than females , RV diastolic stiffness , RA pressure , and RV end‐diastolic pressure  between males and females   or by considering lung transplant as a primary end point  yielded similar results.We analyzed how RV dysfunction impacted clinical outcomes in Group 3 PH. When the cohort was divided by median RVFAC (28%), patients with RV dysfunction had similar functional impairments, 6‐minute walk distance, and medical treatment. However, patients with RV dysfunction had higher forced expiratory volume in 1 s on pulmonary function testing and higher serum hemoglobin and N‐terminal pro‐brain natriuretic peptide on laboratory investigation. On echocardiography examination, patients with impaired RV function had more RV and RA dilation and were more likely to have pericardial effusion. Patients with RV dysfunction had more severe pulmonary vascular disease as demonstrated by a higher mPAP and PVR and lower PAC Table . Over a ) Figure . In the +dp/dtmax/IP, a surrogate marker of intrinsic RV contractility,In this study, we defined the correlates of RV function and the impact of RV dysfunction on clinical outcomes in a cohort of Group 3 PH patients. We show that male sex is the strongest predictor of RV systolic dysfunction even after adjusting for RV afterload in Group 3 PH patients. Male patients have lower RVFAC at all mPAP and PVR than female patients. When assessing the response of RV contractility to increasing PVR, males drop Our finding that males have worse RV function than females in patients with Group 3 PH is novel, in that this form of PH has not been studied, but is entirely consistent with prior reports of sex‐based differences in RV function in normal subjects and patients with PAH (Group 1 PAH) and heart failure with preserved ejection fraction (Group 2 PH). In the MESA (Multi‐Ethnic Study of Atherosclerosis) cohort, cardiac MRI examination of 4204 patients revealed that males have a significantly lower RVEF than females, in the absence of pulmonary hypertension.There is strong preclinical and clinical data that demonstrate that sex hormones contribute to the sex differences in RV function. In particular, there is evidence that testosterone plays a maladaptive role in RV pressure overload, while estrogen preserves RV function in PAH models. First, in male pulmonary artery–banded mice, castration results in less pathological RV remodeling and fibrosis, which is prevented by testosterone replacement.P=0.316) and systemic oxygen saturation at rest  were not associated with RVFAC. This was true when we analyzed the association between supplemental oxygen requirement  and systemic oxygen saturation  with RVFAC as a binary variable. Thus, hypoxemia does not appear to mediate RV dysfunction in Group 3 PH; however, we did not have data about nocturnal hypoxemia so we cannot completely rule out a relationship between hypoxemia and RV function.As for why there are disproportionate decreases in RV function in both sexes in Group 3 PH, we evaluated the possibility that this might relate to the chronic hypoxia that characterizes this syndrome. Chronic hypoxemia has been shown to depress ventricular function.Our findings that RV dysfunction increases the risk of heart failure hospitalization and death in Group 3 PH is congruent with the findings that reduced RVEF on cardiac MRI is a univariate predictor of mortality in a Scottish cohort of severe Group 3 PH patients.P<0.05 as significant may have resulted in some false‐positive results. To account for this, we have presented all P values in 3 decimals. Finally, most of the Group 3 patients in our cohort had severe PH and thus, our data reflect referral bias to an academic PH program and is not representative of a population‐based Group 3 PH cohort.Our study has several limitations. This is a single‐center longitudinal observational cohort study. Nearly half of the patients were entered into our registry retrospectively. However, this is one of the largest studies to comprehensively describe RV function in patients with Group 3 PH. In addition, we collected the baseline variables at the time of the original referral to our practice instead of the variables at the time of enrollment in the registry. This approach reduces survival bias. Furthermore, there are no significant differences in clinical characteristics and outcomes between the incident and the prevalent cohort in our registry (data not presented). We did not have raw echocardiogram data on all patients to quantify RV function and some patients did not have quantifiable images. RVFAC has more variability than TAPSE,Prins is funded by NIH K08 HL140100, Archer is supported by Canada Foundation for Innovation (229252 and 33012), NIH RO1 HL113003, a Tier 1 Canada Research Chair in Mitochondrial Dynamics and Translational Medicine (950‐229252), the Queens Cardiopulmonary Unit (QCPU), and a grant from the William J Henderson Foundation. Thenappan is funded by American Heart Association Scientist Development Grant 15SDG25560048.Dr Thenappan received modest consultation fees from Actelion and Gilead. The remaining authors have no disclosures to report.


P < 0.05). In multivariate analysis, LHRs and EDVs were independent contributors to SSS. Dipyridamole-induced ischemia and LV dysfunction is common, and dipyridamole stress could be a safe diagnostic tool in evaluation and follow-up in patients with AS.The role of vasodilator myocardial perfusion imaging (MPI) for aortic stenosis (AS) is controversial due to safety and accuracy concerns. In addition, its utility after aortic valve (AV) interventions remains unclear. Patients with AS who underwent thallium-201-gated dipyridamole MPI using a cadmium-zinc-telluride camera were retrospectively reviewed and divided into three groups: mild AS, moderate-to-severe AS, and prior AV interventions. Patients with coronary artery disease with ≥50% stenosis, severe arrhythmia, left ventricular ejection fraction (LVEF) <40%, left bundle branch block or no follow-up were excluded. Relationships between the severity of AS, clinical characteristics, hemodynamic response, serious adverse events (SAE) and MPI parameters were analyzed. None of the 47 patients had SAE, including significant hypotension or LVEF reduction. The moderate-to-severe AS group had higher summed stress scores (SSSs) and depressed LVEF than the mild AS group, however there were no differences after AV interventions. SSS was positively correlated with AV mean pressure gradient, post-stress lung-heart ratio (LHRs), and post-stress end-diastolic volume (EDVs) ( Clinical factors such as older age, male sex, smoking, hypertension, diabetes and hypercholesterolemia are important in the progression of AS4. LV remodeling is attributed to several sequelae: (a) hemodynamic factors including increased LV pressure, reduced coronary perfusion pressure and extravascular compressive forces5; and (b) pathological changes including myocardial fibrosis and decreased density of vessels in myocardial tissue6.AS can result in microcirculatory dysfunction, defined as abnormalities in myocardial blood flow (MBF) despite the presence of normal left ventricular (LV) function and normal coronary arteries5. Unfortunately, because of similar risk factors, concomitant coronary artery disease (CAD) in patients with AS is common, and similar symptoms may impede the proper management in this population7.The natural history of AS begins with a prolonged asymptomatic period. In general, mortality is not significantly increased in patients with asymptomatic AS or in those who receive aortic valve (AV) interventions, whereas the mortality is high after the development of symptoms. The management guidelines for patients with severe AS from the American College of Cardiology/American Heart Association Guidelines recommend that patients with equivocal symptoms should receive modified exercise tests8, and single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), a non-invasive examination of last resort, may play an important role in this strategy, especially for those with high operative risk9. Nevertheless, the role of vasodilator MPI in patients with significant AS is still controversial due to safety concerns and uncertainty over the clinical accuracy. Vasodilator stress decreases systemic blood pressure, which may be unsafe in patients with AS. Given the potential risks, previous guidelines have discouraged stress testing in patients with severe and symptomatic AS, and few studies have investigated the safety of vasodilators stress in these patients14. Several studies on the presentation of AS with regards to MBF and subsequent myocardial flow reserve (MFR) derived from dynamic MPI have been published in recent years, however no definite characteristics have been found on conventional MPI imaging18. In addition, its utility in detecting myocardial ischemia in patients after aortic valve (AV) interventions has not been established15. The purpose of this study was to evaluate the efficacy and safety of dipyridamole stress SPECT MPI in patients with AS and after AV interventions.There is increasing consensus on the management strategy for patients with coexisting transcatheter aortic valve implantation (TAVI) and percutaneous coronary intervention (PCI)Forty-seven patients with AS were included in this study Table . The meaMost of the post-AVR/TAVI group had normal or slightly dilated LV, fair left ventricular ejection fraction (LVEF) (i.e. LVEF ≥50%) and a trans-valvular pressure gradient >20 mmHg before the AV intervention. The severity of AS greatly improved after the intervention [AV mean pressure gradient (PG) = 7.09 ± 4.62]. The time interval between the index MPI and AV intervention ranged from 350 days to more than 30 years.P = 0.009), there was no significant differences in sex, body mass index (BMI), cardiac risk factors, and other comorbidities including end-stage renal disease, chronic obstructive pulmonary disease/asthma, and right bundle branch block.Comparing groups, the patients in the prior AVR/TAVI group were relatively younger. Except for the higher proportion of patients receiving pacemaker implantation in the prior AVR/TAVI group (P < 0.001). The mean LVEF measured in the patients with mild AS showed marginal statistical significance compared with the moderate-to-severe AS and prior AVR/TAVI groups . The AVR/TAVI group had a significantly lower atrial filling (A) velocity than the mild AS group (P = 0.023). However, there were no significant differences in left atrial (LA) and LV dimensions and other diastolic parameters between groups (P > 0.05).The echocardiographic variables are summarized in Table P = 0.007), but similar result between the moderate-to-severe AS and prior AVR/TAVI groups. There were no significant differences in summed rest score (SRS), summed difference score (SDS), post-stress or resting lung-heart ratio (LHRs or LHRr) or stress-induced increased LVEF (ΔLVEF = post-stress LVEF- resting LVEF) among the groups.The MPI parameters are summarized in Table Overall and subgroup analysis were performed to evaluate the contributors to SSS Table . IncreasP = 0.014), and marginal significance of higher AV PG in multivariate analysis (P = 0.052) (see Supplementary Table P = 0.022) . Bland-Altman plot showed fair agreement but a regression line with a positive slope, indicating systemic bias existed , and higher prevalence of small hearts (ESVs < 20 ml) in mild AS group.There was some difference in LVEF as measured by UCG and SPECT Table   were recorded 4. Furthermore, in whom post-AVR, the increase in hyperemic MBF and MFR was directly related to the increase in AV area20. Burwash et al. found that low-flow, low-gradient AS was characterized by higher resting MBF and reduced MFR, which were related to the severity of AS6. Carpeggiani et al. also found depressed MBF and MFR in severe AS patients, yet they were independent of LVH and AV PG15. No improvement of myocardial perfusion was noted despite the decrease in LV mass after interventions. We also noted similar phenomenon.Dipyridamole induced perfusion defects was not uncommon in our overall AS cohort, although mostly mild, and SSS was positively correlated with degree of AS. An increasing number of studies have investigated MBF and MFR obtained from dynamic imaging protocols in recent years. Rajappen 22.In the current study, we demonstrate that increased LHRs and LV volumes contributed to dipyridamole-induced perfusion abnormalities. LV size reflects the LV remodeling process. An increased lung to heart ratio (LHR) on stress MPI is a predictor of adverse cardiac events and identifies people with extensive CAD. It has been demonstrated to reflect stress-induced LV dysfunction in previous studiesUCG, P > 0.05). Diastolic dysfunction starts before systolic dysfunction in patients with aortic valve disease24. In our study, most patients with native valves were in the earlier stages of AS, although with preserved LVEF, diastolic dysfunction are rather common.The peak velocities of transmitral flow at early filling (E) to A (E/A ratio) reversal was noted in majority of patients with native valves, but not significantly correlated to the presence of LVH or systolic dysfunction  in mild AS group.Quantification of LVEF and LV volumes using gated SPECT was a reliable complementary tool36. These might be explained by LVEF differences between two methods.LVEF by 2-dimensional echocardiography with modified Simpson’s biplane measurement were not routinely performed. LVEF and volumetric data derived by M-mode echocardiography are less accurate because by M-mode echocardiography has limitations, including 1) the mathematic and geometric assumptions used to derive the volumes from which the ejection fraction is calculated, and 2) the lack of applicability to asynergic ventricles5, the role of vasodilator stress agents in these patients is controversial. In the current study, none of the AS patients experienced severe adverse events with unstable hemodynamics, which is similar to prior studies38. Scarsini et al. revealed substantial agreement between stress MPI and fractional flow reserve (FFR) and high negative predictive value (NPV) in identifying coronary lesions39. Our findings agreed that vasodilator stress can be a valuable tool to evaluate dipyridamole-induced ischemia in patients with AS and guide the treatment strategy.Although the American College of Cardiology/American Heart Association Guidelines recommend that patients with AS having equivocal symptoms should receive modified exercise testsThis study was a retrospective study with a relatively small number of patients conducted at a single tertiary medical center, and therefore referral bias exists. The majority of patients had mild and moderate AS. We excluded patients with known significant CAD and impaired LV systolic function, thus the severity of ischemia and dipyridamole related adverse effects could be less severe than previous reports. Due to the retrospective nature, not all patients had coronary angiography within 6 months, and LVEF by two-dimensional echocardiography with modified Simpson’s biplane measurement were not routinely performed. Besides the small sample size, the interval between AV intervention and MPI was heterogeneous.Further studies are merit to investigate the use of dipyridamole MPI in patients with severe AS, pre and post AV intervention, with a larger population and longer follow-up.UCG <40%, or loss of follow-up after MPI were excluded. To reduce the interference to ECG-gated SPECT imaging analysis, those with left bundle branch block (LBBB) or frequent arrhythmia, which meant frequent atrial or ventricular premature contractions (APCs or VPCs) or atrial fibrillation (Af) were also kept out of the study. The demographic data included age, sex, cardiac risk factors , and other comorbidities . Based on the AV mean PG and AV peak velocity (Vmax) recorded on UCG in the last 6 months, the population was divided into three groups: (1) mild AS (AV Vmax < 300 cm/s or AV mean PG < 20 mmHg), (2) moderate-to-severe AS (AV Vmax ≥ 300 cm/s or AV mean PG ≥ 20 mmHg), and (3) with prior AVR or TAVI. The clinical characteristics, safety of dipyridamole stress and MPI parameters were compared between the groups.This study was approved by the Institutional Review Board of Far Eastern Memorial Hospital (107167-E). The need for written informed consent was waived due to the retrospective nature of the study. All procedures and methods were performed in accordance with the updated guidelines and regulations. We retrospectively analyzed data from the database of a medical center in Taiwan. We reviewed all patients who underwent ECG-gated dipyridamole MPI using a cadmium-zinc-telluride camera between 2015 and 2016, and those with valvular AS diagnosed by UCG and preserved LV function within 6 months were included. The inclusion algorithm of the study population is shown in Fig. Resting echocardiography was performed by experienced cardiologists. M-mode and two-dimensional Doppler imaging data were collected. LA and LV dimensions and related indexes were measured. Diastolic parameters including E and A waves, derived E/A ratio, deceleration time (DT) at early filling and tricuspid regurgitation pressure gradient (TRPG) were recorded.42. Images were reconstructed with a maximum likelihood expectation maximization-based iterative algorithm  using a Butterworth filter 44.All patients were stable at the time of stress imaging, and they all received dipyridamole infusion over 4 minutes at a dose of 0.56 mg/kg. A dose of 2 mCi (74 MBq) thallium-201 was then injected at the 7th minute. The injected dose was 2.5 mCi (92.5 MBq) if the patient weighed more than 90 kg, and 3.0 mCi (111MBq) if they weighed more than 100 kg. At the 10th minute, routine 75–125 mg of aminophylline was injected intravenously for dipyridamole-induced adverse effects. Imaging began within 5 minutes after the aminophylline injection and was repeated 4 hours later. ECG, oxygen saturation and blood pressure were continuously monitored during the stress test. The development of any arrhythmia, ST segment changes, significant blood pressure (BP) changes or symptoms were recorded. ECG-gated SPECT MPI was performed in the supine position using a cadmium-zinc-telluride gamma camera  which was equipped with 19 pinhole collimators and 19 solid-state cadmium-zinc-telluride detectors along a 180-degree arc. Each detector was 8 × 8 cm in size, and projections were obtained using a 32 × 32 matrix (2.46 × 2.46 mm in size). The energy window was set as default for thallium-201: asymmetrically (−14% to +23%) at 70 keV, and symmetrically (−9% to +9%) at 167 keV. ECG-gating was also implemented using a built-in systemSPECT quantitative perfusion and quantitative gated SPECT (QPS/QGS) software  was used to analyze the gated images. Perfusion defects were read using a 17-segment model; segmental uptake was assessed using a 5-point scoring system . SSS, SRS and SDS were derived. In addition, LHR, LVEF, volumetric and right ventricular (RV) uptake data were also calculated.Aminophylline injection was given in routine to resolve the side effect or to prevent late onset adverse effect during scanning. The safety of dipyridamole stress was assessed according to hemodynamic response, significant changes in ECG, stress-induced attacks of asthma or chronic obstructive pulmonary disease, and any adverse events recorded during the stress and rest tests. A significant hemodynamic response was defined as hypotension (BP <90 mmHg) and a drop in systolic blood pressure >40 mmHg after stress. Dipyridamole-induced arrhythmia and ST-T changes such as premature contraction, atrioventricular block, ST depression and T wave inversion were recorded. Chest pain and chest tightness were classified as chest discomfort. Dizziness, head fullness, headache or heavy headiness were classified as head discomfort. Other categories of side effects included abdominal discomfort, dyspnea, body soreness and hot flushes.P < 0.05 in univariate analysis. For parameters in collinearity, we chose one representative factor to undergo multivariate analysis. A P value < 0.05 was considered to be statistically significant. To assess relationships between AS severity and perfusion defects, the parameter AV mean PG was further separated by cutoff points of 20 mmHg. In addition, SSS data were also classified as being normal (SSS < 4) and abnormal (SSS ≥4), and logistic regression was used to analyze the contributors. Bland-Altman plot was further performed to compare the difference between LVEFr and LVEFUCG. SPSS 22  was used for the statistical analysis.Continuous variables are reported as mean ± standard deviation and categorical data as percentages, apart from post-AVR/TAVI time which is presented as median (range). Differences in continuous variables among groups were compared using analysis of variance (ANOVA) or the Kruskal-Wallis test, based on normal or non-normal data. The chi-square test was used for categorical data. Power transformation was performed to transform non-normal variables into normal variables. To determine the contributions of SSS, SRS and SDS, linear correlation and the logistic regression analyses focusing on SSS were performed. Besides the impact of AV severity, multivariate regression analysis was carried out to adjust for other covariates, using variables with Dipyridamole stress is clinically feasible with a reasonable degree of safety in patients with mild and moderate AS. Dipyridamole-induced perfusion abnormalities in patients with AS are not uncommon, but are mostly mild and in correlated to the AS severity. Valvular AS may be a potential cause of microvascular dysfunction. A normal MPI in a patient with documented AS could help clinicians to exclude the presence of obstructive CAD.Dipyridamole stress MPI could be safe in patients with mild and moderate AS. Normal MPI results can be helpful to exclude the possibility of CAD.Supplementary Information


The complex anatomy and physiology of the right ventricle (RV) is a major limitation of visual echocardiographic gradation of RV systolic function (RVF). The aim of this study was to compare visual assessment  of RVF with gold standard magnetic resonance imaging (MRI)-derived right ventricular ejection fraction (RVEF). Medical professionals from a range of clinical settings and with varying degrees of echocardiography experience were recruited via an online ultrasound teaching platform. In an anonymized web-based test, participants graded RVF in 10 patients with varying degrees of RVF via “eyeballing” of an RV-focused four-chamber view. Two skills were evaluated: (1) ability to differentiate between normal and reduced RVF; and (2) ability to determine the correct degree of RV systolic dysfunction. A total of 868 participants from 99 countries were included. For detection of reduced RVF (MRI-RVEF < 50%), sensitivity was 97.1%, 96,8%, 96.5%, and 95.8% and specificity was 55.7%, 52.8%, 54.6%, and 42.5% for the expert, advanced, intermediate, and beginner groups, respectively. For determination of the correct degree of RV dysfunction, even experienced examiners assigned a diagnosis that was discordant with MRI in > 40% of cases. In the present cohort, “eyeballing” was associated with excellent sensitivity but poor specificity in terms of differentiation between normal and abnormal RVF. Even among experts, classification of the degree of RV dysfunction was imprecise. In accordance with current guidelines, the present data suggest that “eyeballing” should be combined with evaluation of other echocardiographic parameters of RVF. Evaluation of right ventricular function (RVF) is an essential component of echocardiographic evaluation. While the geometry of the left ventricle allows precise evaluation of ejection fraction via visual assessment  , 2, deteCurrent guidelines for echocardiographic chamber quantification recommend that RVF should be evaluated by both visual assessment and measurement of at least one additional RVF parameter, such as tricuspid annular plane systolic excursion (TAPSE), tissue Doppler imaging of the basal free lateral wall of the RV (S’), or fractional area change (FAC) , 4. ThesPrevious studies have investigated the reliability of RVF assessment using “eyeballing” alone. However, the results have been inconsistent. While two studies suggested that “eyeballing” alone is insufficient in terms of determining the degree of RVF , 8, a reIn recent years, rapid developments in ultrasound technology and the increasingly widespread availability of wireless handheld devices have rendered RV imaging possibilities beyond the context of highly specialized cardiology centers. In the non-cardiology setting, emergency cardiac ultrasound protocols include a quick visual assessment of right and left ventricular function. Since further dissemination of emergency cardiac ultrasound is anticipated, in the foreseeable future RVF will be assessed by more, and inevitably less experienced, examiners. Evaluation of the accuracy of “eyeballing” is therefore crucial in terms of patient safety.The aims of the present study were twofold. First, to evaluate the ability to differentiate between normal and reduced RVF by “eyeballing”. Second, to assess how visual gradation into class of dysfunction compares to the gold standard CMR-derived right ventricular ejection fraction (RVEF).https://www.123sonography.com). All participants completed an online questionnaire and a web-based test. The study was open for participation between April 1 and July 31, 2017. The study was approved by the ethics committee of the University of Vienna (EK #1288/2016). The study protocol conformed to the ethical guidelines of the Declaration of Helsinki.Participants were recruited via the network of the English-language based online ultrasound teaching platform 123 sonography . To establish study groups, the participants were asked to specify their level of echocardiography experience: beginner, intermediate, advanced, or expert.The RV focused apical four-chamber view video loop of 10 real patients was presented online to the study participants. The participants were instructed to grade each RV solely by “eyeballing” according to a four-grade scale .The ten patients were selected retrospectively from the echocardiography database of the University Hospital of Vienna. Inclusion criteria were good echocardiographic image quality and a CMR within three months of the echocardiographic examination. Selected patients represented the entire RVF spectrum from normal to severely reduced systolic function. The clinical, CMR, and echocardiographic characteristics of all 10 patients are summarized in Table Standard transthoracic echocardiograms  were obtained from all 10 patients using echocardiography systems equipped with 3.5 MHz transducers . Echocardiography was performed in accordance with the recommendations of the American Society of Echocardiography and the European Association of Cardiovascular Imaging . From thAll cardiac CMR examinations were performed by using a 1.5-T imager  with standard protocols. Steady-state images were used for cine imaging . A transaxial stack of images was used for volumetric assessment of RVs. Trabeculations, papillary muscles, and the right ventricular outflow tract were included as part of the RV volume as previously suggested . RV dysfAll patients had undergone both CMR and an echocardiographic examination within a mean period of 12 ± 22 days. According to CMR, five (50%) patients had normal RVEF (RVEF > 50%), one (10%) patient had mildly reduced RVEF (RVEF: 40–50%), three (30%) patients had moderately reduced RVEF (RVEF: 30–40%), and one (10%) patient had severely reduced RVEF (RVEF < 30%). Median RVEF was 52% (range 21–74%). Detailed information on CMR assessment is presented in Table χ2 test or Fisher’s exact test, as appropriate. A p-value of < 0.05 was considered statistically significant. All statistical analyses were performed using SPSS Version 24 .Categorical data are presented as absolute numbers and percentages. Inter-group comparisons of descriptive data were performed using the First, the ability to detect a decrease in RVF (CMR-RVEF < 50%) via “eyeballing” alone was evaluated. Sensitivity, specificity, negative predictive value, positive predictive value, area under the curve (AUC), and accuracy were calculated.Apart from correct classification into normal or decreased function, consensus between a large group of examiners in terms of the degree of dysfunction is necessary to enable uniform nomenclature and reliable follow-up examinations. Therefore, a scoring was performed for concordance between visual assessment of the degree of RV systolic dysfunction and the CMR gold standard . For instance, if CMR-RVEF was normal with 55%, and the participant graded the RV as mildly reduced, a score of 1 point was attributed. For each participant, the total score for the evaluation of all 10 patients was calculated. The lower the score, the better the agreement between the participant and the CMR diagnosis.We compared two different systems of classification. A three-grade scale  and a four-grade scale . For the three-grade scale the participants’ ratings for mildly and moderately reduced RVF were counted as one combined category (reduced RVF).A total of 868 participants completed both the questionnaire and the web-based test. Eighty-one percent of the cohort were between 30 and 60 years of age. A total of 40% were cardiologists; 22% were sonographers; and 20% were internists. Employment settings comprised the following: university hospitals, 29%; non-tertiary hospitals, 47%; and private practice, 21%. The number of participants in each of the four study groups was as follows: 17%, beginners; 47%, intermediate; 29%, advanced; and 7%, expert. The participants were based in 99 different countries, including the following: the United States of America, 11%; Germany, 8%; and Austria, 6%. The demographic and professional characteristics of the participants are shown in Table Correct detection of reduced RVF (CMR-derived RVEF < 50%) was analyzed for each of the four study groups. Sensitivity was 95.8%, 96.5%, 96,8%, and 97.1% for the beginner, intermediate, advanced, and expert groups, respectively. Specificity in these four groups was 42.5%, 54.6%, 52.8%, and 55.7%, respectively. Better concordance was found for the intermediate, advanced, and expert groups than for beginners Table . When beCorrect identification of reduced RVF was compared between “eyeballing” and echocardiographic parameters. While the study participants differentiated correctly in 74% of cases by “eyeballing”, correct differentiation was found for TAPSE in all 10 patients, GLS-RV in nine patients, FAC in eight patients, and S’ in seven patients Fig. .Fig. 3CoTwo different systems of systolic function gradation were compared. For the four-grade system, 8% of the participants scored ≤ 2 points, indicating very good concordance with CMR, and 54% of the participants scored ≥ 6 points, indicating poor concordance with CMR. In the three-grade system, 23% of the participants scored ≤ 2 points, and 14% of the participants scored ≥ 6 points (Fig. Further analysis was then performed for the three-grade system. Participants from the expert, advanced, and intermediate groups assigned a diagnosis that was concordant with CMR in 56%, 56%, and 57% of cases, respectively. Participants from these groups assigned a level that was one grade different to CMR in 43%, 43%, and 42% of cases, respectively, and two grades different to CMR in 0.2%, 1%, and 1% of cases, respectively. Participants from the beginners group were concordant with CMR in 48% of cases, and assigned a level that was one grade different to CMR in 48% of cases, and two grades different to CMR in 4% of cases (Fig. The present investigation of “eyeballing” alone for the evaluation of RVF showed that, while sensitivity for the detection of reduced RVF was excellent in all expertise levels, including beginners, specificity was poor. In addition, determination of the degree of RV systolic dysfunction was imprecise.To our knowledge, the present study is the first to utilize the potential of the internet in order to investigate this issue in an international context. A major strength of the analyses was the large study cohort, which represented a broad range of echocardiography expertise and clinical settings.Evaluation of the ability to detect reduced RVF revealed excellent sensitivity and negative predictive value in all four study groups. The more experienced the examiner, the better were sensitivity, specificity, and accuracy. Differences between the groups were marginal, though. Even beginners identified reduced RVF in most cases. This is reassuring, since reduced RVF is a crucial finding that must prompt further diagnostic workup. For instance, reduced RVF impacts the management of pulmonary embolism. In these patients, echocardiography is frequently performed by inexperienced non-cardiologists, and occasionally with the use of wireless handheld devices, for example, in the emergency medicine setting. In these cases, measurement of more sophisticated RVF parameters is precluded. The present data indicate that echocardiography is a very useful tool, also for non-cardiologists in non-tertiary settings. Thus, in view of the ever decreasing cost and increased availability of ultrasound machines, this suggests that basic medical education should involve expanded training in basic echocardiography.Specificity was very poor in all four study groups, with the highest specificity being found among experts and the lowest among beginners. The low specificity observed in the present analyses may have been attributable to the fear of overlooking patients with reduced RVF.Analyses were also performed to determine the degree to which reduced RVF could be detected using more sophisticated echocardiography parameters. TAPSE reliably distinguished between normal and reduced RVF in all 10 patients, while both FAC and GLS-RV were more accurate than “eyeballing” alone. Therefore, comprehensive evaluation of RVF should include a range of parameters to correct for potential visual errors. In cases of diagnostic doubt, the present data suggest that an experienced examiner should re-evaluate the acquired images, and that other imaging modalities, such as CMR, should be considered.Across all four study groups, significant disagreement was apparent, in particular with respect to mildly and moderately reduced RVF. For this reason, accuracy with the three-grade scale was superior. If diagnosis is based solely on visual assessment and 2D echo parameters such as TAPSE, S’, FAC, and GLS-RV, the present authors propose the use of a three-grade system for determination of the degree of RV systolic dysfunction. With 3D echocardiography, an additional parameter has become available in recent years. If a reliable 3D echocardiography dataset is available, RVEF can be calculated, thus allowing further classification into mildly and moderately reduced RVF.When applying the three-grade system, even in the expert group, only half of the examiners classified 80% or more of the patients in accordance with gold standard CMR values. While beginners had slightly lower rates of concordant diagnoses, similar results were found across the expert, advanced, and intermediate groups. These findings suggest that this skill can be learned quickly and is performed on a similar, albeit unsatisfactory, level across all levels of expertise beyond novice status.The present study had limitations. First, participants were recruited from the users of an online teaching platform, which may have introduced a selection bias. This selection bias may have led to the inclusion of professionals with an interest in continued medical education and an open attitude towards new technologies. Level of expertise was self-reported, allowing for false classification both to more and to less advanced levels than accurate. Second, evaluation of RVF was based solely on a RV-focused four-chamber view. In clinical practice, RVF should always be evaluated using several angulations of the RV. However, the one-loop questions enabled a very low threshold for participation and thus a large study cohort. Third, in the real-world setting, assessment of RVF is also dependent on the ability to acquire good images. All video loops in the present study had good image quality. This precludes generalizability of the study. Fourth, as suggested by the literature, CMR-RVEF was used as the gold standard for RVF. Ejection fraction describes volume change during the cardiac cycle. In the RV, a close relationship exists between myocardial contraction, pulmonary pressure, and the pulmonary vasculature, which is not accounted for by RVEF. Future research is necessary to determine whether superior parameters for gold standard RVF measurement are available, which might correlate better with clinical status and outcome. Finally, CMR and echo were not acquired simultaneously. However, the mean time interval between the two examinations was only 12 days, and all patients were in stable clinical condition with no relevant volume shifts having been recorded between the two assessments.To our knowledge, the present study is the first international investigation to demonstrate that “eyeballing” alone differentiates between normal and abnormal RVF with excellent sensitivity but poor specificity, and that accurate classification of the degree of RV systolic dysfunction via “eyeballing” alone is imprecise, even among expert echocardiographers. Better concordance with the gold standard was found for the three advanced groups as compared with beginners. However, overall assessment quality was unsatisfactory. In accordance with current guidelines, the present data suggest that “eyeballing” should be combined with measurement of other parameters of RVF.


The association between global and segmental myocardial strain impairment and fibrosis extent in hypertrophic cardiomyopathy (HCM) is widely verified. The aim of this study was to investigate the contribution of high T2-weighted signal intensity (HighT2) to myocardial deformation in HCM. We prospectively recruited 57 patients with HCM examined by a 3.0 Tesla magnetic resonance scanner with cine, T2-weighted imaging with fat saturation and phase-sensitive inversion recovery. Global and segmental radial, circumferential and longitudinal strains were included for analysis. The extent of HighT2 was negatively correlated with global radial strain  and positively correlated with global circumferential strain  and global longitudinal strain . Radial, circumferential and longitudinal strains were all significantly associated with segment thickness. Regarding circumferential strain, segments at the mid-ventricular level with LGE and HighT2 showed more impairment than segments with only LGE. For longitudinal strain, the influence of HighT2 appeared only at the mid-ventricular level. The HighT2 extent in HCM was observed to contribute to global and segmental strain parameters. At the segmental level, HighT2 indeed affects left ventricular deformation, and follow-up studies are still warranted. Although in the majority of HCM patients global systolic function is usually preserved, the contractility and extensibility of the individual cardiac myocytes are most likely compromised. The thickness and morphology of cardiac tissue affected by HCM decreases myocardial strain2. Researches also suggest that both heterogeneous hypertrophy and fibrosis contribute to left ventricular (LV) myocardial deformation4. Moreover, cardiac magnetic resonance (CMR) with contrast identified that late gadolinium enhancement (LGE) increased the risk of future adverse events6.Hypertrophic cardiomyopathy (HCM) is characterized by heterogeneous left ventricular hypertrophy (LVH) and variability in both clinical presentation and disease course8. Over the past decade, CMR has been used to measure cardiac muscle deformation. The CMR tagging technique was among the first techniques used and soon became validated to assess myocardial strain; in addition, it has good intra-observer agreement9. However, the CMR tagging technique is time consuming and has low-grade spatial resolution. Tissue tracking with conventional cine imaging is well suited to quantify the myocardial global and segmental strain11. Longitudinal strain is computed by using long-axis images, whereas radial and circumferential strains are estimated using short-axis images. Tissue shortening in the circumferential and longitudinal directions is negative, while ventricular wall thickening in the radial plane is positive. Notably, several studies have found a positive correlation between strain parameters measured with STE and CMR tissue tracking13.Myocardial strain, a precise method for quantifying LV function, has been widely used with speckle tracking echocardiography (STE). Global and segmental strain impairments observed in HCM have been verified by STE14 and tachyarrhythmia15, but LGE cannot distinguish between acute and chronic disorders16. The relation between the extent of focal fibrosis and myocardial deformation has been proved by previous research, and the association between the extent of diffuse fibrosis assessed by T1 mapping and strain has been reported17. However, high T2-weighted signal intensity (HighT2) has been shown to increase the risk of sudden death in HCM patients18 and is associated with active tissue injury19. The correlation of HighT2 areas with myocardial deformation has not been studied before. Thus, the purpose of this study was to investigate the contributions of HighT2 areas to the global and segmental deformation in HCM patients by using CMR tissue tracking.CMR with LGE can identify myocardial fibrosis in HCM. The extent of LGE was associated with sudden deathThe study was approved by the institutional review board of Ren Ji Hospital, and written informed consent were obtained from all subjects. All methods were performed in accordance with the relevant guidelines and local regulations.2 could receive CMR examination.Sixty-four adults with HCM were enrolled from August 2017 to March 2018 at Ren Ji Hospital. The inclusion criteria were as follows: patients with a diagnosis of HCM confirmed by echocardiography or CMR and without systemic disease. Renal function was evaluated by estimated glomerular filtration rate (eGFR) within 3 days prior to the CMR examination. Only patients with eGFR >30 mL/min/1.73 mPatients with hypertension were carefully reviewed his/her medical history and CMR images n = 11). The exclusion criteria were as follows: (1) prior history of significant coronary artery disease (n = 4); (2) previous heart surgery or any interventional therapy (n = 2); or (3) athletic training (n = 1). Ultimately, this prospective study included 57 HCM patients with CMR examinations. Of all the 57 patients, 24 (42%) were taken β-blocker and 14 (24%) were taken Calcium-antagonist for therapy. The clinical characteristics of the patients are summarized in Table 1. The exCMR examinations were performed with a 3.0 Tesla scanner  and a dS Torso coil anterior to the chest. All images were acquired with repeated breath holding and ECG gating. The images obtained included short-axis stacks from base to apex of the left ventricle and long-axis  balanced steady-state free precession (b-SSFP) cine sequences. Short-axis T2-weighted short-time inversion recovery (T2-STIR) and 2D phase-sensitive inversion recovery (PSIR) sequences were matched with the cine images. PSIR images were acquired 10–13 minutes after bolus injection of 0.15 mmol/kg gadolinium-DTPA . The sequences of the technique performed are as follows: (1) b-SSFP cine sequences: repetition time (TR) = 2.8 ms, echo time (TE) = 1.4 ms, slice thickness = 7 mm, slice gap = 3 mm, acquired matrix = 1.2 mm × 1.2 mm, phases per cardiac cycle = 30, field of view (FOV) = 300 mm × 300 mm; (2) T2-STIR sequence: TR = 1714 ms, TE = 75 ms, FOV = 300 mm × 300 mm, acquired matrix = 0.89 mm × 0.89 mm; and (3) PSIR sequence: TR = 6.1 ms, TE = 3 ms, FOV = 300 mm × 300 mm, acquired matrix = 1.6 mm × 1.9 mm.CMR image post-processing was performed with cvi42 . A radiologist with 3 years of experience (RY. S) and a radiologist with 4 years (DAL. A) of experience separately analysed all CMR images and subsequently discussed and settled any uncertainties or discrepancies with a cardiologist with 20 years of experience and 6 years of CMR experience (M. J). Short-axis cine images were imported to the Short 3D module for left ventricular ejection fraction (LVEF) and myocardium mass calculation. Short-axis and 3 long-axis cine images were imported to a Tissue Tracking module for global and segmental strain analysis. The systolic and diastolic parameters of radial, circumferential, and longitudinal strain  were calculated, global and 16 segmental strain parameters were computed. T2-STIR and PSIR sequences were analysed by a tissue characterization module. The extents of HighT2 and LGE are summarized by the percentage of LV mass and the number of involved segments, respectively.Numerical data are presented as the means ± standard deviations. Spearman’s correlation analysis was used to analyse the association of the extents of HighT2 and LGE with strain parameters. One-way analysis of variance with Tukey’s multiple comparisons test or the Kruskal-Wallis analysis with Dunn’s multiple comparisons test was employed for comparisons among segments with and without LGE and/or HighT2. For the gradient of the LV strain from base to apex, a sub-group analysis proceeded separately at the basal, mid-ventricular and apical levels. Linear regression model was used for multivariate analysis of all segments, segments ≥15 mm, and segments <15 mm. All statistical analyses were performed with SPSS  and GraphPad Prism .A total of 57 HCM patients  were included in this study. The 57 patients had predominately septal HCM (n = 41), followed by concentric and diffuse HCM (n = 8), apical HCM (n = 4), mid-cavity HCM (n = 3) and lateral HCM (n = 1). The basic CMR parameters of LV are summarized in Table HighT2 presences were observed in 23(40.4%) patients and LGE presences were observed in 41(71.9%) patients. The Spearman correlations of LV mass and the extents of HighT2 and LGE with global strain parameters determined by tissue tracking are displayed in Table The results of the segmental analysis were divided into four groups according to the presence of LGE/HighT2 in 912 segments from the 57 patients. Most HighT2-positive segments were accompanied by LGE (126 of 178 segments). Neither HighT2 nor LGE was observed in 589 segments. The strain parameters and thickness comparison are summarized in Table The correlations of segment thickness and strain parameters are indicated in Fig. Considering the gradient of the LV strain from base to apex, segments were separately analysed at the basal, mid-ventricular and apical levels. The correlations of the strain parameters and thicknesses at the 3 levels are displayed in Fig. Multivariate linear regression results are shown in Table 20, and a much weaker correlation between the native T1 and LGE was observed21. However, contrast agents are required to measure both LGE and ECV values.Both cellular and extracellular pathological processes are observed in HCM. It is possible to evaluate replacement fibrosis with LGE, the gross macroscopic abnormalities would be reflected by segment thickness, while the cellular and extracellular compartments at the microscopic level could be assessed by ECV and native T1 values. In HCM patients, a strong correlation was reported between the ECV value and extent of LGEet al.22 indicated that focal high signal intensity (SI) areas in T2-weighted CMR are common in patients with HCM and are mostly but not exclusively related to irreversible myocardial injury. Melacini et al.23 performed T2-weighted sequences for edema and late enhancement (LE) sequences. In their study, edema was present in 24/44 (54%) patients, while LE, edema and hypoperfusion presented in corresponding segments. It has been concluded that areas with HighT2 might be suggestive of myocardial oedema as a result of myocardial ischaemic injury, which is representative of a more active disease state in patients with HCM.Interestingly, Abdel-Aty 26 and sudden cardiac death rate compared with patients without HighT218. Cardiac troponin, a biomarker of myocardial injury, has been shown to be correlated not only with HighT2 extent19 but also with GLS in echocardiography studies27. In this context, it has been hypothesized that HighT2 might impact LV strain as well as LGE.Recently, some researchers have investigated whether HCM patients with high T2 show increase in the arrhythmic burden30 and elevated ECV17 impact LV deformation. In our HCM population, patients with weightier LV mass and LGE extent would have more serious impairment of RS, CS and LS. This phenomenon is consistent with previous studies. At the global level, GRS, GCS and GLS were all significantly correlated with HighT2 extent, but it was not sufficient to clarify that HighT2 impairs LV deformation. In addition, the HighT2 extent is correlated with LGE extent and LV mass itself22. Thus, segmental analysis was needed to prove this finding.The effects of both LGEThe strain parameters were significantly correlated with segment thicknesses. However, there is no significant thickness differences between the HighT2 presence with LGE presence and non-presence group. In the two groups with LGE, the HighT2 presence showed a significant difference in CS only at the mid-ventricular level. In the groups without LGE, the HighT2 presence showed a significant difference in LS only at the mid-ventricular level. The statistical differences were both concentrated in mid-ventricular level. HighT2 and LGE presences involved the mid-ventricular levels slightly more than basal and apical levels would be the possible reasons. In the multivariable regression analysis, segment thicknesses were the determinant predictors of strain impairment of all directions. LGE presences were independent predictors of reduction in LS of all segments and segments <15 mm. HighT2s were independent predictors of CS and LS reduction only in segments <15 mm. HighT2 presences, usually considered as edema, were recent pathological changes. The possible reason that the influence of edema to strain would be not as important as thickness especially in thickening segments.31. Myocarditis patients showed reduced RS, CS and LS values compared with those of healthy controls32. T2-STIR was proved to accurately detect acute myocardial infarction and identify the salvage area33.T2-weighted imaging with fat saturation is known as an oedema-sensitive CMR sequence. In the Lake Louise Criteria, HighT2 was one of the diagnostic items of myocardial inflammation19. LGE is detected by CMR in most HCM patients. Furthermore, the presence of LGE was considered to be fibrosis and added to the risk of sudden death. However, LGE could not distinguish recent myocardial infarction from chronic infarction in HCM. RS, CS and LS were all reduced in LGE segments compared with non-LGE segments. HighT2 with LGE in HCM might indicate active tissue injury with elevated cardiac troponin. The minority of segments (52 segments) presented with HighT2 alone. Finally, although the average segment thickness was close to that of negative segments, reduced LS was observed.In HCM, the HighT2 area is mostly localized with LGE in the mid-wall of the myocardium. The mechanism for regional T2-signal enhancement in HCM is still unknown. However, several theories could explain these phenomena. High T2 SI has been related to myocardial tissue oedema, which is due to myocarditis and acute ischaemia and may reflect an atypical distribution of one or both two-pathophysiology statuses. This finding would indicate a potential for high T2 SI to be a biomarker of different extents of disease activity in HCM. In the segmental analyses of our study, a large proportion of HighT2 segments were accompanied by LGE (126/178). This ratio is close to that found in a previous studySeveral limitations of the current study should be mentioned. First, our conclusion needs confirmation within larger prospective multicentre studies, as this was a single-centre cohort setting. Second, although subtle influences of the High T2 to LV strain were observed, the pathology and nature of HighT2 in HCM is not well understood. Third, there are no follow-up data to observe the influence of HighT2 presence on LV deformation. Fourth, the valuation of HighT2 and LGE was completed by two observers, but subjectivity still cannot be avoided. Quantification mapping techniques such as T2 mapping and ECV calculating are still need to be used to verify the conclusion. Finally, no control individuals were involved in the current research because the aim of this study was to explore the relative distribution and prevalence of abnormal T2-weighted image (T2WI) findings among the confirmed HCM patients; we did not aim to identify the high T2WI prevalence relative to normal populations. Notably, high T2WI SI is reported to be rare in normal populations.In this study, the HighT2 extent in HCM was observed to be correlated with global strain parameters. At the segmental level, LGE segments with HighT2 appeared to have lower CS values, and non-LGE segments with HighT2 showed lower LS at the mid-ventricular level. In the multivariable regression analysis, HighT2 were independent predictors of reduction in CS and LS of segments <15 mm. HighT2 indeed affects LV deformation, and follow-up studies are still warranted.


GCS values between TAG, CT-FT, and CMR-FT were similar (p = 0.233). CMR-FT and CT-FT correlated closely for GLS  and GCS , while both of these methods correlated moderately with TAG for GCS . Intraobserver and interobserver agreement was excellent in all techniques. Our findings show that, in elderly patients with severe aortic stenosis (AS), the FT algorithm performs equally well in CMR and cardiac CT datasets for the assessment of GLS and GCS, both in terms of reproducibility and agreement with the gold standard, TAG.In this study, we used a single commercially available software solution to assess global longitudinal (GLS) and global circumferential strain (GCS) using cardiac computed tomography (CT) and cardiac magnetic resonance (CMR) feature tracking (FT). We compared agreement and reproducibility between these two methods and the reference standard, CMR tagging (TAG). Twenty-seven patients with severe aortic stenosis underwent CMR and cardiac CT examinations. FT analysis was performed using Medis suite version 3.0  software. Segment (Medviso) software was used for GCS assessment from tagged images. There was a trend towards the underestimation of GLS by CT-FT when compared to CMR-FT (19.4 ± 5.04 vs. 22.40 ± 5.69, respectively;  Multiple systemic and neuromuscular diseases can affect the cardiovascular system at some point in their course. A wide variety of pathological processes fall under these definitions, some of which have pathognomonic cardiovascular manifestations . HoweverDue to its availability, speckle tracking echocardiography (STE) is the most widely used method for strain assessment. However, the accuracy and feasibility of STE is highly dependent on image quality , warrantIn this study, we used a single commercially available software solution to acquire global strain parameters via computed tomography feature tracking (CT-FT) and CMR-FT in a cohort of patients with severe aortic stenosis (AS). We compared agreement and reproducibility of global longitudinal (GLS) and global circumferential strain (GCS) between both these methods and the reference standard, TAG.Twenty-six patients  with severe AS referred to our institution for transcathether aortic valve replacement (TAVR) were enrolled in this study. Further demographic and clinical data of the study population are listed in Contrast-enhanced, retrospectively electrocardiography (ECG)-gated cardiac scans were performed using a 2 × 128-slice multi-detector computed tomography scanner . The following study protocol was used: tube voltage 100, 120 kV, tube current 320 ref. mAs/rotation, rotation time 280 ms, slice collimation of 128 × 0.6 mm, with a temporal resolution of 75 ms, slice width of 0.75 mm, reconstruction increment of 0.4 mm, and reconstruction kernel B30f. Images were acquired in a cranio-caudal direction, from above the aortic sinuses to below the diaphragm. 3, and 30 phases per cardiac cycle. The complementary spatial modulation of magnetization (CSPAMM) technique was used to acquire tagging images in three short-axis planes  with a temporal resolution of 35 ms, spatial resolution of 1.4 × 1.4 mm, and a slice thickness of 8 mm. CMR acquisitions were made using a 1.5 Tesla magnetic resonance imaging (MRI) scanner . Signals were received using a five-element phased array cardiac coil. A four-lead vector ECG was used for R-wave triggering. A balanced steady-state free precession (bSSFP) sequence with breath hold was acquired in long-axis (LAX) two-, three-, and four-chamber views, as well as a short-axis (SAX) stack. This was used for volumetric and FT analysis. Acquisition parameters used were a repetition time (TR) of 3.3 ms, echo time (TE) of 1.6 ms, flip angle of 60°, acquisition voxel size of 1.8 × 1.7 × 8.0 mmOriginal three-dimensional (3D) datasets were analyzed offline using the commercially available Medis Suite version 3.0  software package to generate two-dimensional (2D) cine loops of three LAX slices , three SAX slices , and a SAX stack with a slice thickness of 0.75 mm and a reconstruction increment of 0.4 mm. Images were generated with temporal resolution of 10 phases per cardiac cycle in 10% increments from early systole (0% cardiac cycle) to end-diastole (90% cardiac cycle). Care was taken to make sure that 2D cardiac CT reconstructions closely matched the anatomical locations of the images used for CMR analysis. End-systolic and end-diastolic cardiac phases were chosen visually. Endocardial and epicardial borders in the SAX stack were outlined manually to calculate the volumetric parameters, which were indexed to body surface area (BSA). Left ventricular mass index (LVMi), left ventricular end-diastolic volume index (LVEDVi), left ventricular end-systolic volume index (LVESVi), left ventricular stroke volume index (LVSVi), and left ventricular ejection fraction (LVEF) were calculated. Global longitudinal strain (GLS) was assessed by averaging the peak systolic strain values of 17 segments extracted from three LAX images, while global circumferential strain (GCS) was acquired from three SAX images using a 16-segment model.bSSFP images were analyzed using Medis Suite version 3.0  software in the same manner as cardiac CT images to determine LVMi, LVEDVi, LVESVi, LVSVi, LVEF, GLS, and GCS. Tagged images were analyzed using commercially available software Segment version 2.2 R6960. Endocardial and epicardial borders were manually outlined at an end-systolic timeframe in three short-axis slices . After applying an automatic propagation algorithm, quality of tracking was visually assessed, and changes were made as needed. GCS was derived using a 16-segment model by averaging the peak systolic values. TAG data of one of the subjects could not be analyzed due to breathing artefacts, therefore 26 patients were used for GCS comparisons. Due to the counter-intuitive increase of strain in more diseased subjects, we chose to report absolute values for easier interpretation. t-test was used to compare differences between cardiac CT and MRI derived volumetric parameters and GLS. One-way ANOVA was used to compare differences in GCS between the three modalities. Pearson’s correlation coefficient and Bland–Altman analysis were used to assess inter-method agreement. Intra- and interobserver variability were assessed using two-way mixed intra-class correlation coefficient (ICC), Bland–Altman analysis, and coefficient of variance (CoV). This was defined as the standard deviation of the differences divided by the mean, in keeping with previous studies [p-values of <0.05 were considered statistically significant.Data analysis was performed using commercially available software . The Shapiro–Wilk test was used to assess the normality of distribution of continuous variables. Unpaired Student’s  studies . Agreeme studies  as follor = 0.913, p < 0.001), LVESVi , LVEF , and LVMi , with good correlation for LVSVi . Results of the Bland–Altman analysis of volumetric measurements are shown in the figures . GCS values were similar between all techniques (p = 0.233). There was good correlation between CMR-FT and CT-FT derived GLS  and GCS , while both of these methods had moderate correlation with TAG for GCS . Bland–Altman analysis revealed similarly wide limits of agreement (LOA) between all techniques in both GLS and GCS . They demonstrated that the results of this method had good correlation with GRS derived from TAG (r = 0.68) and that the method has the ability to discern scarred LV segments [n = 27) to obtain and compare global strain parameters from cardiac CT and transthoracic echocardiography datasets. They found close correlation for GRS (r = 0.97), GCS (r = 0.94), and GLS (r = 0.93) between these modalities [n = 123), Fukui et al. compared FT-derived GLS in a cohort of severe AS patients and found moderate correlation between cardiac CT and transthoracic echocardiography (TTE) (r = 0.62) [In the past decade, multiple methods to assess myocardial strain parameters from cardiac CT datasets have emerged. Most use tissue tracking algorithms originally developed for CMR or echocardiography to track either endocardial or epicardial borders of the left ventricular (LV) in 2D cine loops generated from 3D cardiac CT datasets. As with CMR and echocardiography, these methods allow for the quantification of well-studied global strain parameters, GLS, GCS, and global radial strain (GRS). In 2010, Helle-Valle et al. used a multimodality tissue tracking algorithm, originally developed for analysis of echocardiographic images, to assess GRS in a cohort of ischemic heart disease patients  . r = −0.8) between 3D principal strain and STE-derived GLS in a cohort (n = 35) of severe AS patients [Another method, developed specifically for cardiac CT, allows for the quantification of a cardiac CT-specific 3D principal strain. First, images of neighboring phases are interpolated using a motion coherent algorithm to reduce noise and improve motion coherence. Interpolated images are then analyzed using image and model matching algorithms to create a 3D motion-vector matrix of the LV . Voxels patients . p = 0.065) and GCS . Previous authors have noticed a similar underestimation when comparing cardiac CT-derived strain to STE [As previously noted, in the present study, we used a commercially available feature tracking software to measure GLS and GCS from cardiac CT datasets and compared it to CMR-FT and TAG in a cohort of patients with severe AS. We found a strong correlation between CT-FT and CMR-FT, but CT-FT tended to underestimate both GLS , CT-FT and CMR-FT had similar correlation and LOA for GCS assessment. Additionally, reproducibility analysis revealed similar results for both FT-based techniques. If TAG data are taken as the ground truth, these findings suggest that FT algorithm performs equally well on both CMR and cardiac CT datasets. Additionally, due to its angle independency and high temporal and spatial resolutions, CMR is the gold standard technique for the functional assessment of the heart . HoweverThere is an increasing number of patients who have implanted cardiac devices, and this decreases the feasibility of CMR due to potential artefacts or the inability to condition these devices. Our results imply that cardiac CT datasets are non-inferior to CMR datasets for the assessment of GLS and GCS using the FT algorithm. Furthermore, ours and multiple previous studies have shown potential interchangeability of volumetric measurements between cardiac CT and CMR. With further advancements in technology and an increase in temporal resolution, a cardiac CT might be used as a convenient follow-up tool to previous CMR assessments for both volumetric and strain measurements in patients with implanted cardiac devices. Naturally, there are certain limitations in our study. Firstly, this was a small-scale single-center trial. Secondly, we only had TAG acquisitions for short-axis slices, therefore we could not compare FT-derived GLS to a reference standard imaging technique. However, previous studies suggest that CMR-FT has similar correlation and agreement to TAG for both GCS and GLS . ThirdlyOur findings show that the FT algorithm performs equally well in both CMR and cardiac CT datasets for the assessment of GLS and GCS, both in terms of reproducibility and agreement with the gold standard, TAG. In the clinical routine, cardiac CT might be used as a convenient follow-up tool to previous CMR assessments for both volumetric and strain measurements in patients with implanted cardiac devices.


We read the compilation of Hajjar et al. with interest . CardiogOn the other hand, in a patient with cardiogenic shock, VA-ECMO, which is administered by peripheral cannulation, will increase the left ventricular afterload and increase stress of an already dysfunctional LV. Although this type of application is usually accompanied with introduction of an intra-aortic balloon pump for reducing tension by a degree; unfortunately, this does not change the fact that ECMO increases the afterload.In the light of this information, the benefit of VA-ECMO in cardiogenic shock appears to be a more advanced LV support system or bridge to heart transplantation, as the authors suggest. We believe that instead of VA-ECMO, it would be more appropriate to use devices such as TandemHeart or Impella, in which the left ventricle is vented in patients with a higher likelihood of improvement in the left ventricle, such as post-cardiotomy cardiogenic shock, primary percutaneous transcoronary angioplasty, or myocarditis. We think that learning the ideas of the authors on this subject will add value to their study. p < 0.00001) [We thank Orhan Gokalp et al. for their interest in our article. Acute myocardial infarction (AMI) is the most frequent cause of cardiogenic shock (CS) accounting for about 80% of cases . The mos0.00001) . Further0.00001) .We do not agree with the authors that instead of VA-ECMO, it would be more appropriate to use devices such as TandemHeart or Impella, in which the left ventricle is vented in patients with a higher likelihood of recovery. We strongly believe that ECMO is the most appropriate device for severe cases of CS and that unloading the left ventricle is essential. A device such as IMPELLA might be the best option to decrease afterload and should be inserted concomitantly (ECMELLA). Moreover, as recently published, a standardized team-based approach may improve CS outcomes, increasing significantly 30-day survival from 47 to 76.6% . Prompt


ObjectiveAnorexia nervosa (AN) patients are at an increased risk of developing cardiac complications including bradyarrhythmias, systolic dysfunction, pericardial effusions, and sudden cardiac death. Although previous echocardiographic studies in AN patients have demonstrated a reduction in overall left ventricular (LV) mass, systolic dysfunction, and silent pericardial effusions, little is known about the role of cardiac magnetic resonance imaging (CMR) in assessing this patient population. The objective of this study was to assess cardiac indices and the presence of myocardial fibrosis in AN patients.MethodsBetween 2014 and 2015, a cross-sectional pilot study of 16 female patients who met the Diagnostic and Statistics Manual of Mental Disorders, fifth edition (DSM-5) criteria for AN was conducted at a single tertiary care center. Baseline characteristics including age, weight, food restriction behavior, over-exercise, self-induced vomiting, and laxative abuse were collected in the study population. Electrocardiography, transthoracic echocardiography (TTE), and CMR were performed.Results2 in AN patients as compared to controls. Using CMR, both the mean LVEF of 52 ± 9% and LV mass/BSA of 45 ± 4g/m2 were lower in AN patients as compared to controls. Using CMR, both right ventricular ejection fraction (RVEF) of 50 ± 10% and a right ventricular (RV) mass/BSA of 18 ± 3g/m2 were smaller in AN patients as compared to controls. There was no evidence of late gadolinium enhancement (LGE) in the study population.The mean age was 17 years (range: 13-22 years). There were no conduction abnormalities as the average PR interval was 152 ms (range: 130-190 ms) and QTc was 413 ms (range: 360-450 ms). Using TTE, the left ventricular ejection fraction (LVEF) was 54 ± 4% with a lower LV mass/body surface area (BSA) of 56 ± 7g/mConclusionsYoung patients with AN have lower cardiac mass and volumes with no evidence of myocardial fibrosis. Anorexia nervosa (AN) is a disease characterized by fear of weight gain, caloric restriction, and distorted self-image affecting 0.3% to 1.0% of Canadians -7. As coPrevious echocardiographic studies have demonstrated that AN is associated with a smaller left ventricular (LV) mass, reduced LV cavity volumes, and lower cardiac index (CI); various mechanisms have been described to explain these findings . PreviouCardiac MRI (CMR) is able to overcome some of these limitations with increased spatial resolution. It is also able to non-invasively detect myocardial fibrosis, marked by the presence of late gadolinium enhancement (LGE) . Prior sThe objective of this study was to determine the amount of change in cardiac indices and assess for myocardial fibrosis in AN patients using both TTE and CMR.Study populationA prospective cross-sectional pilot study was performed on 16 adolescent/ young adult female patients diagnosed with severe AN who were followed up as outpatients by the Eating Disorders Service at a single tertiary care center. All patients were between the ages of 12 and 25 years, met the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) diagnostic criteria for AN, and had a weight at diagnosis of less than 80% expected body weight in their convalescence phase. Exclusion criteria included poor renal function (serum creatinine >100 mmol/L), hemodynamic instability, or other contraindications to CMR. The control population included normal values obtained from published literature. The study protocol was reviewed and accepted by the local ethics board (REB number H2013:378).ElectrocardiogramA standard 12-lead electrocardiogram (ECG) was performed for measurement of heart rate, PR interval, and QT interval. The QTc was calculated using Bazett’s formula [EchocardiographyStandard TTE was performed using a Phillips iE33 machine  and a multi-frequency transducer [S8-3 (3-8 MHz) and X5-1 (1-5 MHz) probes]. Parasternal long axis (PLAX) views were used to determine left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), posterior wall thickness (PWT), and interventricular septal thickness (IVS). The right ventricular diameter was measured at the base of the RV apical view. LVEF was calculated using Simpson’s method from the apical four-chamber view -14. LV mCardiac magnetic resonance imagingAll CMR scans were performed using a 1.5 Tesla Siemens Scanner  at a single tertiary care center. Segmented TrueFISP sequences were performed with ECG gating to obtain images representative of the entire cardiac cycle in both long and short axis views. Three- and four-chamber long axis views were used to measure chamber dimensions. Tracing the endocardial and epicardial borders manually on consecutive short axis slices of the LV and RV allowed quantification of the LVEF, LV mass, LV stroke volumes, RVEF, and RV mass. End-diastole and end-systole were determined visually using the slices with the largest and smallest ventricular volumes, respectively. Two blinded observers (KC and DS) analyzed the CMR imagines offline using a CMR analysis software .Statistical analysisp-value <0.05 was considered statistically significant. Statistical analysis was performed using the GraphPad Prism 7 software .Continuous data points were reported as mean ± standard deviation (SD). Comparison between measurements in the AN population and control population  was done by the two-tailed one-sample t-test method. The published normal values to which we compared our patients included pediatric and adult patients who were also stratified by sex allowing us to compare patients to a population with similar age and sex . A p-valStudy populationn = 16) are shown in Table 2, and body surface area (BSA) was 1.6 ± 0.2 m2 for the study population.The baseline characteristics of the study population n = 6 are shoElectrocardiographyThe average heart rate was 65 ± 13 (45-90) bpm, average PR interval 149 ± 19 (120-190) ms, and the average QTc was 413 ± 22 (360-450) ms. There was no evidence of first-degree atrioventricular (AV) block nor a prolonged QTc. Left ventricular geometry and systolic function2 vs. 69 ± 26 g/m2, p < 0.05). Using CMR, AN patients had a statistically significantly lower LVEF, LV mass index, PWT, and CI as compared to controls , of which 10 (15%) had a pericardial effusion [Previous echocardiographic studies have demonstrated a higher prevalence of pericardial effusions in AN patients. Docx et al. prospectively studied 128 female AN patients (9-18 years) demonstrating the presence of pericardial effusion in >20% of patients [effusion . They dieffusion . In our effusion ,8.Hemodynamic remodeling2 versus 2.6 ± 0.6 L/min/m2 in AN [2 was low, similar to those published in the literature using echocardiographic-based assessments of CO [Cardiac output (CO) has previously been assessed by echocardiographic studies in the AN population ,22. Goldm2 in AN -24. To oStructural changesStructural changes including LV dilation, decreased ejection fraction, and specifically, a decrease in overall LV mass have been well documented using echocardiography and in a single CMR study ,6-7,11. Previously, Silvetti et al. demonstrated that a low BMI in AN patients correlated with smaller LV chamber measurements . In thei2) and 28 healthy controls (BMI: 15 ± 1.8 kg/m2) [There has only been a single study to date which utilized CMR in the evaluation of a group of adult patients with AN. In this cross-sectional observational study by Oflaz et al., a total of 68 female patients, aged 22 ± 7 years, were studied including 40 AN patients (BMI: 20 ± 1.6 kg/m8 kg/m2) . As comp8 kg/m2) . Our stuMyocardial fibrosisAN patients are at an risk of increased SCD ,26. AmonLimitationsOur study has several limitations. First, this study has a small sample size. As a pilot study, we sought to evaluate for major structural or functional abnormalities, to compare TTE and CMR findings, and to better quantify RV parameters in AN patients. Without knowing the incidence or degree of abnormality, we could not determine in advance the sample size needed to adequately power the study. We recognize that the assessment of RV mass is limited by variability and conclusions regarding differences in RV mass must be made with caution. With regard to LGE, we were unable to perform T1 mapping which may have uncovered more mild degrees of fibrosis. Also, since many of our patients were substantially weight recovered when studied, we may have failed to detect findings that were present at worse levels of starvation. Specifically, the time period between the diagnosis of AN and TTE/CMR imaging was not constant between each patient. Finally, as we did not have an age-matched population of subjects without cardiac disease, we used adult female published literature normal values as a comparator.Patients with AN are at risk of developing cardiac complications including heart rate and repolarization abnormalities, pericardial changes, hemodynamic changes, and structural changes. As evidenced by CMR, young patients with AN have lower cardiac mass and volumes with no evidence of myocardial fibrosis. Further research is required to evaluate the role of cardiovascular remodeling in AN patients and the potential role of LGE as a marker of increased SCD.