Diastolic dysfunction is associated with morbidity and mortality in multiple pediatric disease processes. Cardiovascular magnetic resonance (CMR) provides a non-invasive method of studying left ventricular (LV) diastolic dysfunction through the assessment of LV filling curves and left atrial (LA) volume and function. However, there are no normative data for LV filling curves and the standard method is time-intensive. This study aims to compare an alternate, more rapid method of obtaining LV filling curves to standard methodology and report normative CMR diastolic function data for LV filling curves and LA volumes and function. Ninety-six healthy pediatric subjects (14.3 ± 3.4 years) with normal CMR defined by normal biventricular size and systolic function without late gadolinium enhancement were included. LV filling curves were generated by removing basal slices without myocardium present throughout the cardiac cycle and apical slices with poor endocardial delineation (compressed method), then re-generated including every phase of myocardium from apex to base (standard method). Indices of diastolic function included peak filling rate and time to peak filling. Systolic metrics included peak ejection rate and time to peak ejection. Both peak ejection and peak filling rates were indexed to end-diastolic volume. LA maximum, minimum and pre-contraction volumes were calculated using a biplane method. Inter-and intra-observer variability were assessed with intraclass correlation coefficient. Multivariable linear regression was used to assess the effects of body surface area (BSA), gender and age on metrics of diastolic function. BSA had the largest effect on LV filling curves. Normal LV filling data are reported for both compressed and standard methods. The time to perform the compressed method was significantly shorter than the standard method . Both methods had strong to moderate correlation for all metrics. Intra-observer reproducibility was moderate to high for all LV filling and LA metrics except for time to peak ejection and peak filling. We report reference values for LV filling metrics and LA volumes. The compressed method is more rapid and produces similar results to standard methodology, which may facilitate the use of LV filling in clinical CMR reporting.The online version contains supplementary material available at 10.1186/s12968-023-00936-x. Left ventricular (LV) diastolic dysfunction is an important predictor of morbidity and mortality in adult and pediatric heart disease. It is characterized by impaired ventricular relaxation and is associated with increased risk for adverse cardiac outcomes including arrhythmias, myocardial hypertrophy, ventricular fibrosis and ischemia, progression to systolic dysfunction, and sudden cardiac death –4. DiastEchocardiography is commonly used to assess diastolic dysfunction in children, as it is non-invasive, readily available, and a relatively rapid means of doing so. Although there are multiple parameters to evaluate diastolic function by echocardiography, they all have limitations, which makes accurate assessment challenging . CardiovThis study was approved by the Vanderbilt University Medical Center Institutional Review Board. We performed a retrospective review of patients that had a normal CMR as defined by normal biventricular sizes and systolic function without evidence of late gadolinium enhancement. Of these patients, those 21 years old or younger referred for CMR for the following reasons were included: chest pain, exercise intolerance, syncope/pre-syncope, palpitations, abnormal electrocardiogram (ECG), abnormal echocardiogram, and family history of sudden cardiac death or cardiomyopathy. Patients were excluded if they had history of prior cardiac surgery, genetic syndromes, myocarditis or elevated troponin, hemodynamically significant structural heart disease (Qp:Qs > 1.5), exposure to cardiotoxic medications, prior coronavirus disease 2019 (COVID-19) infection, arrhythmia, or other chronic medical conditions. All patients retrospectively enrolled were cleared by their cardiologist. All patients with family history of cardiomyopathy were phenotypically negative, asymptomatic, had normal CMR, and had no abnormalities detected on subsequent evaluations. An additional subset of patients was enrolled prospectively as healthy volunteers to determine normal parametric mapping values. Written, informed consent was obtained for all healthy volunteers. Height and weight were measured prior to the CMR. Heart rates were taken from the heart rate calculated during the short axis stack. Blood pressure was taken prior to CMR for all clinically indicated scans but not in healthy volunteers. An initial pool of 783 patients was evaluated; a total of 96 subjects met inclusion/exclusion criteria. CMR images were obtained between 2013 and 2021.Images were obtained on a 1.5T magnet . Balanced steady-state free precession (bSSFP) imaging was used to obtain retrospectively gated cine images in the apical two chamber, LV outflow tract, apical four chamber, and short axis views. Short axis images were obtained in a stack covering the entire LV from base to apex. Images were 8 mm thick with no gap. Typical scanning parameters were: TR = 36.5 ms, TE = 1.2 ms, flip angle 80°, voxel size 1.5 × 1.5 × 8 mm, 25 phases per cardiac cycle. Breath held images without sedation were obtained in the majority of cases, as is standard protocol in our institution. In our cohort, two patients were performed under anesthesia and two were unable to breath-hold, requiring free breathing with multiple signal averages.max), minimum volume (LAmin), and at pre-atrial contraction (LAbac). The time of LAmax was defined as the last image immediately before mitral valve opening. The time of LAmin was defined as the first image after the closure of the mitral valve. LAbac was determined by visual inspection as the last image before atrial contraction; if this could not be determined based on visual inspection, the LAbac was not measured (N = 7). LA areas excluded the atrial appendage and the pulmonary veins. LA volumes were calculated using the area-length method: volume = (0.848 × area4ch × area2ch)/([length2ch + length4ch]/2) /2) .Passive) and active (LAEFActive) phases. LAEFPassive is defined as the difference between LAmax and LAbac. LAEFActive is the difference in LAbac and LAmin. LAEF was calculated as (LAmax-LAmin)/ LAmax × 100; LAEFPassive as (LAmax-LAbac)/LAmax × 100; and LAEFActive as (LAbac-LAmin)/LAbac × 100 , 1413, 1PFR: maximal increase in LV volume over time, which correlates to the maximal positive slope in the volume curve occurring in early diastole.tPFR: time interval from the end-systole phase to PFR.PER: maximal decrease in LV volume over time, which correlates to the maximal negative slope in the volume curve occurring in systole.tPER: time interval between end-diastolic phase to PER.For both methods, indices of diastolic function, including peak filling rate (PFR), time to peak filling (tPFR), and PFR indexed to end-diastolic volume , and indices of systolic function, including peak ejection rate (PER), time to peak ejection (tPER), and PER indexed to EDV (PER/EDV), were automatically generated by QMass. After generating a LV time-volume curve with instantaneous filling rates plotted over time, LV filling indices were defined as the following Fig. :PFR: maxTo evaluate intra-observer variability, the same reader re-measured LA volumes and LV filling (both compressed and standard) in a subset of 25 subjects. These same 25 subjects were re-contoured by a second reader (JHS) to obtain inter-observer variability. Time to complete LV filling measurement was measured by the second reader to evaluate the length of time it would take to complete the analysis using both the compressed and standard methods.Demographic variables were compared using either a Wilcoxon rank-sum (continuous variables) or a Chi-square or Fisher’s exact test . Inter- and intra-observer variability were assessed using an intraclass correlation coefficient. The following values were used as cutoffs for weak, moderate, and strong correlation respectively: 0.20–0.39, 0.40–0.59, and ≥ 0.60 . Bland–AAnalyses were performed with STATA . Study data were collected and managed using REDCap (Research Electronic Data Capture) electronic data capture tools hosted at Vanderbilt.Of the 96 healthy subjects enrolled, 53 were male. Mean age of all participants was 14.3 ± 3.4 yr range 7–21). The majority of participants self-identified as White . There was moderate correlation for tPER and tPFR . ICC data are summarized in Table max, LAmin, and LAbac. Inter-observer reproducibility was high for LAmax and moderate for LAmin and LAbac  vs 12.5 min IQR , p < 0.001.Multivariable linear regression analysis was used to determine the effects of body surface area (BSA), gender, and age on measures of diastolic function. These results were used to determine how the normative data would be presented for each variable. Of note, age did not have an effect on filling metrics when BSA was included in the models, therefore no normative data are stratified by age. Both BSA and gender had significant effects on PER and PFR; normal values for PER and PFR are therefore categorized by BSA and gender Table . The effPredicted PER = 32.5 + 197(BSA) – 32.4(gender); Root mean squared error (RMSE) = 67.5Predicted PFR = 26.5 + 215(BSA) – 23.0(gender); RMSE = 79.6Where gender is coded as 1 for male and 2 for female. The equations for Z-score calculation are:PER = (PER – (32.5 + 197(BSA) – 32.4(gender))) / 67.5ZPFR. = (PFR – (26.5 + 215(BSA) – 23.0(gender))) / 79.6ZUsing the compressed method, PFR/EDV and PER/EDV were not significantly affected by BSA, gender, or age. PFR/EDV using the standard method was also not affected by BSA, gender, or age, but PER/EDV measured using the standard method demonstrated a small difference by gender (p = 0.02). Therefore, normative data for all of these metrics are stratified by gender Table .Table 7RBecause tPER and tPFR were not significantly affected by BSA, gender or age, normal values are reported without further categorization Table . LA voluPFR correlated strongly with systolic blood pressure, but PFR/EDV did not  reporting normative data for LA function and ventricular filling curves in pediatric patients; (2) reporting an alternative, compressed method for ventricular filling curves that can be performed more quickly than the standard method. Importantly, the filling metrics derived from the compressed method correlate strongly with those from the standard method and are equally reproducible.Several prior studies have reported normal values for biventricular EDV, end-systolic volume (ESV), stroke volume, wall mass and ejection fraction in children –19. The There are no established pediatric reference ranges for LV filling curves of which we are aware. This is also the first report of our compressed method for calculating LV filling, which substantially decreases the analysis time for calculating LV filling. A recently published study by Kikano et al. highlights the association of CMR diastolic indices with arrhythmia in repaired tetralogy of Fallot. Prolonged tPFR and lower PFR/EDV were indicators of future arrhythmia development and associated with higher rates of mortality . AbnormaBoth methods of diastology in this study have similar reproducibility, but our laboratory’s compressed method takes approximately half the time compared to standard methodology. Not surprisingly, the compressed method generates slower absolute filling and ejection rates when compared to the standard method. The most likely explanation for this difference is the relative differences in ventricular volumes that are used for rate calculation. The rate of ventricular filling is a product of ventricular volume and heart rate. Several slices are removed from the base and apex, resulting in a relatively smaller ventricular volume compared to the standard method. Furthermore, standard methodology will often add additional volume at the base during diastole, but not systole, due to the longitudinal motion of the heart. The combination of these two factors results in a disproportionally higher volume removed from the EDV volume measurements compared to ESV. Although there is a difference in the absolute values, it is important to note that the basic shapes of the LV filling curves are similar, which results in the strong ICC between the two methods. Thus, we propose that when used in a consistent manner, our compressed method remains an effective and highly reproducible approach to diastology that is less time intensive than standard methodology.Prior work in adults with various heart diseases demonstrate an association between CMR derived values for PFR, tPFR, PFR/EDV and LAEF and elevated LV end-diastolic pressure , 28–30. This study has several limitations. Most notably, tPFR and tPER reproducibility is average to poor compared to the other indices that were highly reproducible. We hypothesize that the poor reproducibility is a consequence of the inherent limitations in CMR temporal resolution. A small difference in the slope of the curve could move the tPFR or tPER by 1–2 phases, thus resulting in a significant decrease in the correlation. Interpolation of phases may improve the reproducibility. Additionally, it was not possible in this retrospective study to obtain full atrial volumes with volumetry. Best estimations are reported with the area-length method, but there may be significant differences between these estimates and true volumes. Further investigation with a prospective cohort may improve LA volume analysis. Our study was also limited by sample size, though the total sample is similar to prior pediatric reports , 18, 31.In conclusion, we report normative CMR LV filling data for pediatric patients as measured by two different methods. We also report normative data for LA volume and function. Our laboratory’s compressed method of generating LV filling curves is more rapid with similar results to the standard method and may facilitate the measurement of diastolic function in pediatric patients.Additional file 1:Table S1. Spearman Correlation, p-values, and N for CMR correlation with systolic blood pressure, heart rate, and body mass index. Fig. S1. Bland-Altman comparison of compressed and standard methods for calculation of A PFR, B tPFR, and C PFR/EDV. As expected, there is a significant bias for PFR and tPFR; the bias for PFR resolves with calculation of PFR/EDV. Fig. S2. Bland-Altman evaluation of inter-observer variability for A PFR, B tPFR, and C PFR/EDV for compressed method. Fig. S3. Bland-Altman evaluation of inter-observer variability for A PFR, B tPFR, and C PFR/EDV for standard method.


HFNC showed significant improvements in right ventricular morphology and function, and a reduction in sPAP. However, there were no significant changes in the left heart measurements with HFNC application. Conversely, COT did not lead to any modifications in echocardiographic measurements. In both groups, oxygenation significantly improved from baseline to T10 . In conclusion, these data suggest an improvement of oxygenation with both treatments; however, only HFNC was able to improve the right ventricular morphology and function after 10 days from the beginning of treatment in a small cohort of patients with acute-on-chronic respiratory failure with PH.High-flow nasal cannula (HFNC) has several benefits in patients affected by different forms of acute respiratory failure, based on its own mechanisms. We postulated that HFNC may have some advantages over conventional oxygen therapy (COT) on the heart function in patients with acute-on-chronic respiratory failure with concomitant pulmonary hypertension (PH). We therefore designed this retrospective observational study to assess if HFNC improves the right and left ventricle functions and morphologies, arterial blood gases (ABGs), and patients’ dyspnea, compared to COT. We enrolled 17 hospitalized patients receiving HFNC, matched with 17 patients receiving COT. Echocardiographic evaluation was performed at the time of admission (baseline) and 10 days after (T Pulmonary hypertension (PH) is a condition characterized by a mean pulmonary arterial pressure (mPAP) greater than 20 mmHg . The priTreatment of PH includes calcium channel blockers, prostacyclin analogues, endothelin 1 (ET-1) receptor antagonists, phosphodiesterase-5 inhibitors, and supportive therapy with diuretics, oral anticoagulants, and especially in group 3 PH, conventional oxygen therapy (COT) . Several2), which can be set between 21% and 100%  (IQR) based on their normal distribution. Categorical data were expressed as counts and percentages. For comparisons between groups, we employed the paired 10 to baseline for all recorded parameters and compared them between treatments. Mean differences with corresponding 95% confidence intervals were calculated to evaluate the treatment effects.In both the HFNC and COT cohorts of patients, we computed the differences from TTo assess relationships between variables, we used the Pearson correlation coefficient (r) and performed linear regression analysis.p-value < 0.05 for all tests. All statistical analyses were conducted using Prism version 9.4.0 .Statistical significance was set at a We collected data from 34 adult patients, with 17 receiving HFNC and 17 receiving COT, from September 2019 to September 2020. The enrollment flowchart is reported in p = 0.999).Patients’ characteristics are shown in Data from TTE are presented in 10. HFNC exhibited its most substantial effect in reducing sPAP, improving right ventricle contraction (measured by TAPSE and TAPSE/sPAP), and slightly reducing preload (measured by IVC and RAA) when compared to COT.2/FiO2) significantly increased from 155 ± 47 to 204 ± 61 (p < 0.001). On the contrary, pH , PaCO2 , and HCO3−  did not change from baseline to T10.In the HFNC cohort, oxygenation . In addition, no significant modifications were detected with respect to pH , PaCO2 , and HCO3− .In the COT group, we also recorded a significant improvement of PaOp < 0.001 for both comparisons).Dyspnea was reported as reduced from 7  to 4  in the HFNC group and from 7  to 5  in the COT group , pH , PaCO2 , HCO3− , and VAS .At T2/FiO2 . Conversely, no other statistically significant correlations were detected between PaO2/FiO2 change and variations in RAA , IVC diameter , TAPSE , TAPSE/sPAP , IVST , RVOT , LAVI , LVEF , and aortic root dimensions .In the HFNC group, only an sPAP decrease was found to be inversely correlated with PaO2/FiO2 changes and variations in RAA , IVC diameter , sPAP , TAPSE , TAPSE/sPAP , IVST , RVOT , LAVI , LVEF , and aortic root dimensions .In the COT cohort of patients, no correlations were found between PaO10, although only HFNC reduces sPAP and right ventricle function.This study demonstrates that, in patients with acute-on-chronic respiratory failure and concomitant PH, both HFNC and COT improve oxygenation at TSeveral studies have reported that HFNC therapy improves oxygenation and reduces dyspnea in patients with hypoxemia of different origins and severity. However, few studies have explored the hemodynamic effects of HFNC and how the cardiopulmonary interactions may be influenced by the small changes in intrathoracic pressure caused by the flow delivered, as well as by the positive end-expiratory pressure effects generated, particularly in decompensated chronic pulmonary hypertension.2), and the administration of heated and humidified air –oxygen admixture. Indeed, chronic lung diseases are characterized by abnormalities of both the ventilation–perfusion ratio and lung diffusion capacity, resulting in gas exchange impairment [2O [We believe that the observed reduction in dyspnea and hemodynamic effects are mainly due to an improvement in the ventilation-perfusion ratio and lung diffusion capacity , improvement in gas exchange , which typically have a restrictive impairment characterized by a decrease in forced vital capacity, total lung capacity, and diffusing lung capacity for carbon monoxide, as well as a decreased exercise capacity. The reduction in lung compliance causes an increase in respiratory rate as a compensatory mechanism, while hypercapnia occurs only in the late phase of such diseases . Within 2, as well as subjective comfort using the HFNC device. Moreover, these patients did not undergo instrumental exams that could specifically prove an improvement in the right ventricle function and a reduction in PH.We wondered if there were some beneficial effects of HFNC on dysfunctional right heart in patients with acute-on-chronic respiratory failure and PH. The available evidence is still not conclusive. In a study of 10 patients with heart failure and New York Heart Association (NYHA) class III, Roca et al. demonstrated that after a 60 min trial with HFNC, there was a reduction in the inspiratory collapse of the IVC and right ventricular preload, while sPAP did not change . In our To the best of our knowledge this is the first study that showed that HFNC therapy in patients with chronic lung diseases and concomitant PH can induce a greater improvement of right ventricle preload and function, compared to COT.Our study has limitations. First, the small sample size and the single-center design may limit the generalizability of our findings. Second, we performed TEE but not a lung volume or airway pressure assessment . As a reIn conclusion, HFNC ameliorates the right ventricle preload and function and sPAP in patients with acute-on-chronic respiratory failure and concomitant PH.Although these are promising data, we cannot provide any definitive conclusion; further studies are therefore required to better understand the underlying mechanisms in this population of patients.


Heart failure (HF) is a major health problem and early diagnosis is important. Atherosclerosis is the main cause of HF and carotid intima-media thickness (IMT) is a recognized early measure of atherosclerosis. This study aimed to investigate whether increased carotid IMT is associated with changes in cardiac structure and function in middle-aged participants of the UK Biobank Study without overt cardiovascular disease.P < 0.05).Participants of the UK Biobank who underwent CMR and carotid ultrasound examinations were included in this study. Patients with heart failure, angina, atrial fibrillation, and history of myocardial infarction or stroke were excluded. We used multivariable linear regression models adjusted for age, sex, physical activity, body mass index, body surface area, hypertension, diabetes, smoking, ethnicity, socioeconomic status, alcohol intake, and laboratory parameters. In total, 4301 individuals  were included. Multivariable linear regression analyses showed that increasing quartiles of IMT was associated with increased left and right ventricular (LV and RV) and left atrial volumes and greater LV mass. Moreover, increased IMT was related to lower LV end-systolic circumferential strain, torsion, and both left and right atrial ejection fractions (all Increased IMT showed an independent association over traditional risk factors with enlargement of all four cardiac chambers, decreased function in both atria, greater LV mass, and subclinical LV dysfunction. There may be additional risk stratification that can be derived from the IMT to identify those most likely to have early cardiac structural/functional changes.  Therefore other CV biomarkers might be important for the early detection of HF.Since heart failure (HF) is associated with high morbidity, mortality, and health-care costs, timely diagnosis of subclinical cardiac dysfunction is an important aspect of cardiovascular (CV) preventive strategies. Myocardial strain has been shown to be a reliable marker of systolic dysfunction, especially in the early stages, when ejection fraction (EF) is not able to depict subtle alterations in cardiac function.2 Carotid intima-media thickness (IMT) is a well-established subclinical marker of early atherosclerosis.3 Even if its use is not recommended for risk stratification in clinical guidelines, previous studies have shown that IMT is associated with future CV events such as myocardial infarction, angina, coronary intervention, stroke, or transient ischaemic attack.4–7 Due to its simplicity and excellent correlation with histology, it is widely used in everyday clinical practice.8 In a recent study of 1161 participants, increased carotid IMT was associated with impaired left ventricular (LV) and left atrial (LA) strain parameters, as assessed by 2-dimensional speckle-tracking echocardiography.9 Due to its superior spatial resolution, CMR is considered as the gold standard for the evaluation of LV structural and functional parameters.10 Moreover, it allows the precise assessment of the right ventricle (RV) and the atria.11Atherosclerosis and its sequelae are one of the main causes of HF in the developing world.We aimed to study the association between carotid IMT and cardiac structural and functional parameters as assessed by CMR. Moreover, we aimed to investigate the association of IMT with subclinical LV dysfunction in a large UK cohort of participants without clinically manifested CV disease.12 In total, 100 000 participants are being recalled to undergo comprehensive imaging of the brain, heart, whole body, carotid artery, bone, and joints. Imaging of the heart is performed by CMR and carotid IMT was assessed by carotid ultrasound.14 CMR examinations of 5065 consecutive participants have already been manually contoured and analysed. These participants formed the recruitment cohort for our analysis. Exclusion criteria of the current study were poor image quality, HF, angina, prior myocardial infarction, and stroke based on the criteria described previously.14The UK Biobank is a prospective cohort study that collected questionnaire data, physical measurements, and biological samples from half a million 40–69 year-old individuals in the United Kingdom.This study was covered by the ethical approval for UK Biobank studies from the National Health Service (NHS) National Research Ethics Service on 17th June 2011 (Ref 11/NW/0382), extended 10th May 2016 (Ref 16/NW/0274), and extended on 18 June 2021 (Ref 21/NW/0157) with written informed consent by all UK Biobank participants.https://www.ukbiobank.ac.uk/data-showcase/).Covariates were determined from patient interviews or touchscreen questionnaires. These included age, sex, ethnicity, Townsend deprivation index (a socio-economic measure based on area of residence), weight and height, and comorbidities. Moreover, lifestyle factors such as physical activity  score), alcohol intake frequency , and smoking status (never smoker and previous or current smoker) were also ascertained. The following serum biochemistry measures from blood collected at the baseline visit were considered as potential mediators: total cholesterol, lipoprotein A, apolipoprotein A and B, triglyceride, glycated haemoglobin, urate, and C-reactive protein. Detailed questions of the UK Biobank questionnaires can be found in UK Biobank Data Showcase  at two pre-defined angles for each carotid giving a total of four carotid IMT values: right 150°, right 120°, left 210°, and left 240°. A mean, maximum, and minimum of the carotid IMT tracking was recorded for each carotid for each angle of acquisition. The average of the four mean measures was calculated and incorporated into our analysis. The detailed protocol has previously been published.16 Briefly, all examinations was performed on a 1.5 Tesla scanner . For cardiac function, long-axis cines and a complete short-axis stack of balanced steady-state free precession (bSSFP) cines were acquired covering the LV and RV.The UK Biobank CMR protocol has been described in detail previously.16Analysis of the LV, RV, LA, and right atrium (RA) for all CMR examinations were performed across two core laboratories in London and Oxford according to pre-approved standard operating procedures using dedicated post-processing software . LV papillary muscles were included in the LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV). For the measurement of RV parameters, manual tracing of the end-diastolic and end-systolic endocardial borders was carried out in the short-axis view. Thin-walled structures with no trabeculation were excluded and volumes below the pulmonary valves were included as part of the RV. LA and RA end-diastolic volumes (EDV) and end-systolic volumes (ESV), stroke volumes (SV), and EF were calculated based on the manually traced endocardial atrial contours in a four-chamber view. Detailed descriptions of analysis methodology, including exemplar contours and intra- and inter-observer variability, have been previously described.17 A grid was aligned automatically to the myocardial tagging planes at end-diastole. End-systole was determined visually, and tags were manually adjusted at key phases during the cardiac cycle including the end-systolic and last frame. Global circumferential strain (GCS) was calculated from the motion of the intersected tag lines at basal, mid, and apical levels. Torsion, the wringing motion induced by the contracting myofibers in the LV wall during systole has been shown to be a sensitive marker of myocardial dysfunction.18 Torsion was calculated from the basal and apical strain measures, as previously described.19 In those cases when a basal or apical slice was missing or not analyzable, torsion was calculated between the mid-ventricular and the other available slice.Semi-automated analysis of tagged cine images was performed with CIM software .21 Statistical analysis was performed using R (version 4.0.3) Statistical Software.22Summary statistics for independent variables were calculated as means and standard deviation (SD) for continuous variables. Categorical variables were expressed as frequencies and percentages. Carotid IMT was handled as a categorical variable using quartiles. To assess the relationship between carotid IMT and cardiac anatomy and function, the various CMR parameters were analysed using unadjusted and multivariable linear regression analyses. In order to test the mediating effects of the potential confounders and mediators, we built two sets of models: Model 1: Adjustment was made for age, sex, physical activity, body mass index (BMI), body surface area (BSA), hypertension, diabetes, smoking, non-European ethnicity, Townsend deprivation index, alcohol intake frequency, total cholesterol; Model 2: Adjustment was made for Model 1 + lipoprotein A, apolipoprotein A and B, triglyceride, glycated haemoglobin, urate, and C-reactive protein. Definitions for these covariates were previously described.Figure S1. After exclusion, 4301 participants were included in our analysis. Mean age was 61.6 ± 7.5 years and 1976 (45.9%) were male. The average of the mean carotid IMT was 673.6 ± 123.7 micrometer. Participants were grouped into four carotid IMT categories using quartiles: quartile 1 (<584 micrometer), quartile 2 (584–652 micrometer), quartile 3 (653–746 micrometer), and quartile 4 (>746 micrometer). Almost all CV risk factors were positively associated with gradually increasing carotid IMT. Clinical characteristics of the study population by IMT quartiles are reported in Table 1.A number of exclusions is listed in P < 0.001). While left ventricular ejection fraction (LVEF) values did not differ among the carotid IMT quartiles, significant worsening in the end-systolic circumferential strain at the basal, mid, and apical levels of the heart were observed together with significantly increasing torsion . The distribution of the above-mentioned LV parameters by IMT quartiles can be seen in Figure 1. In fully adjusted linear regression models, compared to the reference quartile 1 of IMT, all higher carotid IMT quartiles were associated with bigger LVEDV and LVM values, and IMT quartile 4 was independently associated with higher LVESV, LVSV, end-systolic circumferential LV strain, and torsion values. There was no association with LVEF in any higher carotid IMT quartiles. Results of the uni- and multivariable analyses can be seen in Table 2.Significantly increasing LVEDV, LVESV, left ventricular stroke volume (LVSV), and left ventricular mass (LVM) values were measured by quartiles reflecting increasing carotid IMT , right ventricular end-systolic volume (RVESV) , maximal LA , and RA  volumes, as compared to quartile 1. Regarding functional parameters, while there were no differences among the groups in right ventricular ejection fraction (RVEF), gradually decreasing LA EF and RA EF values were measured parallel with higher carotid IMT (both P < 0.001). The distribution of significantly increasing RV and atrial structural and functional parameters can be seen in Figure 2. After adjustment for all CV risk factors and pertinent laboratory parameters, association with RVEDV, maximal LA volume, and reduced atrial function remained significant. Results of the uni- and multivariable analyses can be seen in Table 3.Those having the highest IMT values had significantly higher right ventricular end-diastolic volume (RVEDV) (158.9 ± 37.7 vs. 146.8 ± 34.6 mL, To our knowledge, this is the largest study to investigate the association between carotid IMT measured by ultrasound and cardiac structural and functional parameters depicted by gold standard CMR in a largely middle-aged population without known overt CV disease. Our results suggest that higher carotid IMT is associated with subclinical dysfunction and changes in cardiac structure.23 In the Atherosclerosis Risk in Communities Study of 13 590 participants without baseline HF, carotid IMT was identified as an independent risk factor for HF development beyond risks explained by major CV risk factors and coronary heart disease.24 These results suggest that carotid IMT and HF might be associated with mechanisms other than myocardial ischaemia or infarction. Therefore, assessment of early alterations in the cardiac structure and function may be important in order to recognize the early stages of HF. However, literature data regarding the association between carotid IMT and subclinical LV dysfunction are limited. Echocardiography studies have found that higher carotid IMT is associated with impaired LV and LA strain independent of traditional CV risk factors, pertinent laboratory, and echocardiographic parameters.25Previous studies reported an association between carotid IMT and incident HF. In a study of 4691 individuals without known myocardial infarction or stroke, high carotid IMT and C-reactive protein levels proved to be independent risk factors of future HF requiring hospitalization.10 Torsion of the left ventricle around its long axis is induced by the contracting fibres of the LV wall.26 Because of its direct relation with the orientation of the myofibers, it gives valuable information about the subclinical abnormalities in heart function.27 LV torsion is essential for proper myocardial function and it is directly related to the circumferential-longitudinal shear angle.27 In the Multi-Ethnic Study of Atherosclerosis including 500 participants with tagged CMR and carotid ultrasound greater IMT was linked with impaired midwall systolic circumferential strain.25 Our results are consistent with these findings and beyond midwall strain, participants with the greatest IMT values had significantly lower systolic circumferential strain at the basal and apical levels of the heart even in the fully adjusted model. Our study aimed to examine the atrial alterations, as well. Higher carotid IMT was associated with significantly higher maximal LA volume and lower LA and RA EFs. These changes in atrial structure and function reflect LV dysfunction.Myocardial deformation imaging can detect contractile dysfunction at an early stage in the majority of cardiac diseases. Circumferential myocardial strain represents the myocardial fibre shortening along the circular perimeter.29 Moreover, chronic inflammation in patients with higher carotid IMT might cause changes in cardiac mechanics.Several mechanisms might account for these associations. One explanation can be that subclinical atherosclerosis might cause damage to the myocardial tissue. Carotid IMT has been shown to be positively associated with coronary artery calcium score and incident coronary heart disease. Coronary atherosclerosis can lead to reduced blood flow to the heart muscles, which can result in abnormal CMR parameters. Atherosclerosis not only affects the large coronary arteries but also impacts the microvasculature within the heart muscle. Chronic exposure to atherosclerosis-related risk factors can also lead to cardiac structural and functional alterations. Prior studies have reported an association between higher carotid IMT, impaired LA function, and epicardial fat accumulation.The findings of this comprehensive study may suggest the importance of early detection of cardiac remodelling in a reversible phase before the reduction of ventricular EFs. Our results suggest that patients with higher carotid IMT may guide early therapeutic intervention and close follow-up in order to prevent HF occurrence. Further study in this area may help to guide future preventative strategies.This study has several limitations. First, the effect of asymptomatic coronary artery disease on our findings cannot be excluded. Second, even though we adjusted for potential clinical and laboratory confounders and mediators in the multivariable analyses, unmeasured factors might play a role in the observed associations. Finally, due to its cross-sectional fashion, the cause-effect relationship between the examined associations cannot be confirmed.This study reports a comprehensive assessment of the association between carotid IMT and cardiac structure and function in all four chambers as depicted by CMR in the middle-aged population without known overt CV disease. Higher carotid IMT values were linked with LV, RV, LA, and RA enlargement, greater LVM, reduced atrial function, and subclinical LV dysfunction. Since these atherosclerosis-related changes in cardiac structure and function appear much earlier than previously anticipated, our results may facilitate improved preventive actions for the prognostic assessment of higher IMT even in asymptomatic patients.qyad010_Supplementary_DataClick here for additional data file.


Editorial on the Research TopicTransitional circulationThe transition to extrauterine life represents one of the most challenging and vulnerable processes for the human body, thereby placing the newly born at risk of cardiopulmonary maladaptation. Identifying the etiology of disruption in the cardiocirculatory transition is difficult and often multifactorial. The collection of articles in this edition primarily focuses on the complexity of the transition, relevant physiological concepts and the value of enhanced neonatal cardiovascular monitoring. Failure of fetal-to-neonatal cardiopulmonary transition at birth can occur at multiple levels, commencing with an inability to aerate the lung. Although this is the primary stimulus for the decrease in pulmonary vascular resistance (PVR) at birth, if this fails or in instances of severe lung hypoplasia, both pulmonary blood flow and left ventricular preload decrease. Comprehensive knowledge of cardiopulmonary physiology and the unique intrinsic responses of the immature myocardium to preload (Frank-Starling law), afterload (stress-velocity relationship) and heart rate (force-frequency relationship) are essential to understanding normal vs. abnormal postnatal adaptation.right heart, abnormal transition), closure of the patent ductus arteriosus (DA) may lead to right ventricular dysfunction due to systolic wall stress and increased myocardial oxygen demand and pulmonary hypoperfusion. The consequences of abnormal transition to the left heart include poor left ventricular (LV) filling and low LV output which, despite normal LV systolic performance, reduces the flow of oxygenated blood into the systemic circulation. Persistent hypoxemia can lead to the redistribution of cardiac output, which decreases further the perfusion of some organs and thereby accelerates acidosis and cyanosis. In certain disease states, abnormal transition is associated with persistence of the fetal shunts. On the one hand, sustained right-to-left shunting at the DA and FO may lead to worsening of the hypoxemia. On the contrary, when PVR falls rapidly in extremely preterm babies progressive left-to-right DA shunting may lead to hypotension, pulmonary hemorrhage and intraventricular hemorrhage.The fetal vascular shunts  may play a differential role according to the underlying physiology. In patients with acute pulmonary hypertension and elevated right ventricular afterload  of current trends of hemodynamic evaluation in NICU during the transitional period in extremely low gestational age neonates (ELGANs). The newer modalities of cardiovascular monitoring such as targeted neonatal echocardiography (TnECHO), prefrontal cerebral near-infrared spectroscopy (NIRS) and cerebral saturation (CrSO2) were tested against the conventional methods of systolic and diastolic arterial blood pressure monitoring obtained by oscillometry. Simultaneous multimodal monitoring with TnECHO, NIRS, and CrSO2 may provide an enhanced understanding of the relationship between cerebral oxygenation and systemic blood flow during transition among vulnerable population of ELGANs. Of note, TnECHO enables bedside assessment of systemic and pulmonary blood flow, cardiac function and the presence and direction of the fetal vascular shunts  infants during the transitional period . While these data highlight the differences between populations, the application of echocardiography and a comprehensive integrated multimodal approach for assessing the cardiovascular system has many limitations. First, a metareview of the literature related to characterization of the neonatal transition reveals that there are major gaps in normative echocardiography data; specifically, differences in timing of evaluation, training, and imaging techniques limit the ability to generate reliable conclusions . Second, longitudinal normative data in preterm babies during the early transitional period are lacking. There is almost no normative data in preterm infants born less than 24 weeks gestation. Third, differences in adaptive patterns according to sex, race or ethnicity are lacking. There is an urgent need to establish standardized echocardiography measurement techniques, protocols and training to advance our ability to recognize and intervene in the care of a baby with an abnormal transition. In addition, a high degree of methodological rigor in both image acquisition and measurement analyses are essential pre-requisites to enhance the generalizability and the validity of future research studies. The use of centralized system for echo review and analysis (CORE labs) for multicenter studies to (i) oversee echocardiography training, (ii) ensure quality assurance, and (iii) conduct all echocardiography analysis to ensure measurement consistency may further enhance the quality of all neonatal echocardiography research.Characterization of the transition in at-risk populations has received little scientific attention. In the study by


Research on dairy consumption in China is lacking, however, some evidence has demonstrated significant changes in recent years, with a reported increase in the overall consumption of dairy products. To fully understand these changes, a systematic review was conducted to examine reported dairy intakes and differences between dairy consumption in different population groups in China. Methods: Web of Science, Embase, and PubMed databases were searched for studies published from January 2000 to September 2022. The China National Knowledge Infrastructure (CNKI) was used to retrieve papers available in Chinese. Papers reporting dietary intakes of dairy consumption across age, sex, and geographical location sub-groups were considered for inclusion in this review. In addition, this review includes the consumption of different types of dairy foods and changes in dairy intake over time. Results: Forty-seven papers were included in the present study. Twelve papers examined dairy consumption across age groups, showing that middle-aged adults tend to consume less dairy than other age groups. Studies comparing across location-specific cohorts reported dairy intakes among urban populations were higher than rural, as well as being higher than the national average. Coastal, Northern and Eastern residents consumed more dairy products than those living in other regions of China, and people in larger cities had higher reported intakes than smaller cities. Milk was the primary dairy product reportedly consumed by Chinese population, followed by yogurt. Concerning sex, evidence showed that females generally reported a greater daily dairy intake than males. Conclusions: This review shows that, in China, several different population groups displayed significant differences in the amount and type of dairy consumed. When considering the incorporation of dairy products into healthy eating guidelines or positioning specific dairy products on the market, it is important to consider the differences and variations in consumption patterns within population groups. Dairy foods such as milk, cheese and yogurt are recognized as important sources of beneficial nutrients, including vitamins D, B5  and B12 Recommendations concerning dairy consumption are given in many national nutrition and healthy eating guidelines –27. In IDietary patterns in China are known to differ quite significantly from those reported in other global regions including Europe and the US –35. TradIn recent decades, the dairy industry in China has grown steadily, prompted by economic factors including the growth in household income, consumer preferences and the provision of financial support from the government . HoweverThe purpose of this paper was to systematically review existing literature reporting dairy consumption among the Chinese population, living in mainland China. The objectives of the study were to summarise the available literature providing information on dairy intakes in the Chinese population, to examine the differences in the consumption of dairy across different population sub-groups and to further identify the factors which contribute to the differences in consumption.The present systematic review was carried out following the updated Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA 2020) guidelines . The proWithin this review, the term ‘dairy product’ is defined as milk, yogurt, milk powder, cheese, butter, cream or ice cream. The search strategy of this review followed the PICO framework, focusing on the differences in dairy consumption among different ages, geographic location sub-groups, sex groups among Chinese adults in mainland China, as well as the difference in consumption of the different types of dairy products and the overall changes in dairy consumption over time. The following search terms were used: Dairy OR Milk OR Cheese OR Yogurt OR Yoghurt OR Yoghourt OR Butter OR Cream OR Milk powder OR Food AND Intake OR Consumption OR Market OR Diet OR Dietary AND China OR Chinese OR Asian. The search was limited to studies carried out in human adults (≥ 18 years), written in English or Chinese languages. A manual search of references from included studies was also conducted. We used Google Scholar to retrieve papers where applicable. The China National Knowledge Infrastructure (CNKI) was also used to retrieve papers when the full-text papers were only available in Chinese. Two authors (S.Y. and N.B.) independently performed the literature search in Web of Science, Embase, and PubMed databases for papers published between January, 2000 and October, 2021. To ensure a focus on the most recent research regarding dairy consumption status, papers published before the year 2000 were not searched. An updated search of all the datasets was completed by one researcher (S.Y.) on 06 September 2022.Published papers examining dairy intake by considering mean intake, median intake, frequency of consumption, and/or percentage of Chinese adult consumers living in mainland China were included. Study designs that were considered in this review included but not limited to dietary intake assessment study, intervention study but reporting dairy intake of control group at baseline, and consumer behaviour papers that reported findings of dairy intakes. Papers reporting the findings related to comparison of dairy consumption across age, sex, and geographical location sub-groups, different types of dairy products, and different years were included in the analysis in the present review. Papers were excluded if the original study was conducted in Chinese group living in other countries except for China. Papers were excluded if there were only children and/or teenagers involved in the study. Papers that assessed intake of human milk only were excluded. Papers reporting intakes of dairy food groups but including irrelevant food such as egg were excluded. Papers, involving intervention studies but did not report dairy intake data of participants in general good health in control group at the baseline, were excluded. For papers that reported data for those aged < 18 and ≥ 18 years, only data from those over 18 years were considered in the analysis of this review where applicable. Two authors (S.Y. and N.B.) independently screened papers for eligibility firstly based on titles, then abstracts and finally full texts based on the predefined inclusion and exclusion criteria. In the case of disagreement, a third researcher (E.R.G.) was involved, and consensus on inclusion or exclusion was reached after discussion.Papers included in the present review reported dairy consumption in varies ways. The following information were extracted by one author (S.Y.) firstly from the all the papers reporting dairy intakes: study characteristics ; population demographic characteristics ; type of reported dairy food . For the studies using data from national survey  without specifying study location, the survey location information was searched and taken from the survey website  or preseTo assess risk of bias, the quality of the studies included in this review was examined. S.Y. performed the quality assessment. Given the various of study methods in those studies, the Critical Appraisal Skills Programme (CASP) checklist for Cohort Studies  was applA total of 10,685 papers were searched from three databases after removing duplicates. Studies identified were screened based on titles and abstracts, and finally full texts of 375 papers including the 54 papers which were identified from the reference lists were assessed according to the inclusion and exclusion criteria. Ultimately, 47 papers were included in the present study. Full details of the search are outlined in Fig. Full characteristics of the papers and CASP scores from quality assessment are shown in Table Of the 47 studies included in the final review, 12 reported dairy consumption across different age groups , 79, 89 Of the three studies that compared dairy consumption in population groups aged under and over 60 years, two of these studies showed that people aged over 60 years reported consuming higher amounts , while hP < 0.001 and P < 0.05 separately), with average intakes in these two age groups of 39.57 and 28.49 g/d, respectively. Similarly, Huang et al. [P > 0.05). Similarly, results from the survey of Bai et al. [P > 0.05).Focusing on people aged over 50 years, dairy consumption was reported in four studies. Xu et al.  reportedg et al.  comparedg et al.  assessedi et al. , conducti et al.  analysedOf the 13 studies reporting on dairy consumption across location-specific cohorts comparing people living in different cities or provinces, two papers focused on dairy consumption in individual cities , 45, andNine of the 11 papers examined dairy consumption between urban and rural areas, and reported higher intakes of dairy products in urban populations compared to those living in rural areas , 72, 79.P < 0.0001) [P < 0.05) [Wang et al. examined differences in reported dairy intakes from urban and rural areas from 1989 to 2011 using data from CHNS. The authors reported that urban residents had a significantly higher consumption than people living in rural areas across these years ( 0.0001) . Most re 0.0001) . In addi < 0.05) .Of the papers that examining dairy consumption in other geographical location groups, Li et al.  comparedTable At the national level, papers that studied the survey data in different years from 1989 to 2011 reported higher dairy intakes among females, with significant differences found by Wang et al.  and TianMirroring the findings from these national studies, Zong et al.  examinedP < 0.001) and more dairy in general compared to females [Four of the 16 papers examining differences in reported dairy intake across sex groups found that, for those who consumed dairy products, males had higher dairy intake compared to females with only one study reported significant difference , 84, 92.Differences in the consumption of the different types of dairy products were reported in six papers , 95, 96 All six papers showed that participants had highest intake of milk among these types of dairy products in China. Fuller et al. , examiniP < 0.001) [Seven papers report analysis of dairy consumption over time at a national level using data from CHNS , 63, 65,< 0.001)  reported< 0.001) . It also< 0.001) .In addition, researchers examined the changes of eating habits in elderly residents during COVID-19 lockdown in March 2020 in Wuhan city in China, finding that dairy consumption was reduced during this period . SpecifiBased on published literature between 2000 and 2022, which reported the consumption of total or individual dairy foods in China, some consumption patterns of dairy can be observed. Our review found noteworthy differences in dairy consumption across population groups of age, geographic location and sex, as well as differences by type of dairy. Specifically, milk and yogurt were reported to be the main dairy foods consumed in China with milk powder playing an important role in the intake of dairy in older adults. In terms of sex-related differences in dairy consumption, evidence showed that females had higher intakes than males. Clear patterns of dairy emerged across different geographical locations. The intake of dairy products among the urban population was higher than rural areas and also greater than the national average. Furthermore, coastal citizens and those in northern and eastern regions consumed more dairy products than others. Meanwhile, residents in larger cities had higher intakes than smaller cities or rural area. To the best of our knowledge, this is the first systematic review to summarise reported dairy intakes to determine factors that influence the consumption of dairy in different groups in China.When examining dairy intake in the studies, both total dairy and also the following individual dairy foods were considered: milk, yogurt, ice cream, milk powder, butter. Much of the reporting considered total dairy and did not break down reported intakes into these individual dairy foods. From studies included in this review, milk, yogurt and milk powder were the main dairy foods reported among Chinese adults. In contrast, consumption of butter and cheese were particularly low, albeit data on these dairy products is limited. It is important to note that comparisons of reported intake of total and specific dairy products across studies are often challenging due to the manner in which dairy can be grouped and/or reported in many studies. For example, in a previous study in Poland, the main reported dairy foods were ‘Milk’, ‘Cheese and cottage cheese’, and ‘Yoghurt and milk drinks’ . SimilarIn terms of the individual dairy foods consumed, this review showed that milk was the largest contributor to dairy consumption in China, similar to other countries such as Australia  and SpaiThis review identified 16 papers that reported differences in dairy intakes across sex groups. Most of the available evidence showed the females had higher intakes of dairy foods than males, although not all the studies reported or conducted statistical analysis. The association between gender and dairy consumption was also observed in other recent studies examining dietary intakes in Europe , 105. OnAssociations between different regions and dairy consumption in China are considered in this present review. Based on the available papers’ comparisons across different location sub-groups including urban v rural, north south east and west, costal vs. inland, and size of city were examined. One of the main findings was that people living in urban areas had a significantly higher consumption of dairy than those living in rural areas, and this gap appears to have existed for a long time period. For example, data from a national survey in 2002 reported that the mean dairy intakes among urban residents were 65.8 g/d, whereas the amount in rural was only 11.4 g/d . More reKnowledge of these differences in the amount (and type) of dairy products consumed across regions, sex and age groups are of importance, as it is known that the type, and amount of dairy products consumed, can have different effects on human health , 110. DaWhilst this review comprehensively examined the available literature, due to the complexities in reporting discussed previously, and the limited number of papers for the question being considered, the findings reported here are limited and merit further investigation. This review only presented the findings from existing comparison within the studies, therefore no analysis was conducted to compare across the studies. And there might be some published studies not identified for inclusion in this review due to the search terms used in our search. Furthermore, although limited to papers published since 2000, many of the studies use older datasets, and it is likely that dairy intakes have changed considerably and work on more recently collected data is needed. Therefore, there is a need for a detailed analysis of more recent intake data, to determine if the trends reported here are a true reflection of the current status. In addition, in this present review, we only focused on the influence of key factors - age, gender and regions which were most frequently studied and reported in published studies to investigate the difference in dairy consumption in the population group. Many other factors could be examine in future reviews.Regardless of these limitations, this review demonstrates clear differences in consumption of different types of dairy products, and in population groups . When considering incorporation of dairy consumption into healthy guidelines, it is important to note these differences, and adapt recommendations and promotions accordingly. Furthermore, more detail on how dairy is specifically consumed within the diet is needed, which would support further development of nutrition recommendations through modelling scenarios for differing population groups.This review has shown deviations in dairy intake across different population groups in China, including age, sex, and geographic location as well as across the different types of dairy products. The main findings of this review demonstrate that middle-aged adults tend to consume less dairy than other age groups, females in generally had higher intakes of dairy foods than males, and that milk and yogurt and milk powder are the main types of dairy products consumed in China. Whilst this review highlighted some novel and interesting findings, it also highlights a detailed lack of understanding of the use of dairy within the diet, and differences in the dairy consumption among different population groups.


Ex situ heart perfusion (ESHP) has been developed to decrease cold ischemia time and allow metabolic assessment of donor hearts prior to transplantation. Current clinical ESHP systems preserve the heart in an unloaded condition and only evaluate the cardiac metabolic profile. In this pilot study we performed echocardiographic functional assessment using two alternative systems for left ventricular (LV) loading: pump supported afterload working mode (SAM) and passive afterload working modes (PAM). Six hearts were procured from male Yorkshire pigs. During cold ischemia, hearts were mounted on our custom made ESHP circuit and a 3D-printed enclosure for the performance of echocardiography with a standard TEE probe. Following perfusion with Langherdorf mode of the unloaded heart, the system was switched into different working modes to allow LV loading and functional assessment: pump supported (SAM) and passive (PAM). Echocardiographic assessment of left ventricular function in the donor hearts was performed in vivo and at 1 h of ESHP with SAM, after 4.5 h with PAM and after 5.5 h with SAM. We obtained good quality epicardial echocardiographic images at all time points allowing a comprehensive LV systolic assessment. All indices showed a decrease in LV systolic function throughout the trial with the biggest drop after heart harvesting. We demonstrated the feasibility of echocardiographic functional assessment during ESHP and two different working modes. The expected LV systolic dysfunction consisted of a reduction in EF, FAC, FS, and strain throughout the experiment with the most significant decrease after harvesting. Heart failure (HF) is one of the leading causes of death worldwide . AccordiOver the last two decades, the number of suitable donor hearts has plateaued while the demand for organs continues to increase . This haEx situ heart perfusion (ESHP) has been introduced as a technique with the potential to improve heart transplant outcomes by reducing cold ischemic time and supporting aerobic metabolism, thereby allowing better and longer allograft preservation between retrieval and implant , 8. The Heart function is determined by a complex interaction between preload, afterload, heart rate and the inotropic state of the myocardium. Our group has developed and validated a novel modular ESHP system to allow functional donor heart evaluation with biventricular loading (working mode) –15. ThisLV functional assessment has been traditionally achieved experimentally using transduction catheters to obtain pressure-volume loops, allowing quantification of ventricular elastance during LV loading on ESHP . The preUp until now, the validity of using SAM to assess the cardiac function is controversial as the retrograde aortic flow is not physiological and uncontrollable rises in systolic pressure may impact heart function. By allowing a more physiological perfusion of LV, PAM has been proposed as an alternative to SAM that strives to improve the physiological appropriateness of LV afterload during ESHP , 15. A sThis pilot study was conducted on six male Yorkshire pigs . The experimental protocol was approved by our institutional animal care committee and followed the ARRIVE guidelines . Animals2 and invasive arterial pressure. After a median sternotomy and pericardiotomy, the heart and great vessels were exposed. An umbilical tape was placed around the inferior vena cava and a pressure-volume conductance catheter  was inserted into the left ventricular apex. Systemic anticoagulation was achieved with an intravenous injection of heparin .Animals were acclimatized for at least 7 days. The night before experiments, they were fasted. In all animals, premedication was provided with an intramuscular injection of midazolam (0.3 mg/kg), ketamine (20 mg/kg), and atropine (0.04 mg/kg). Anesthesia was induced using inhalational isoflurane  and maintained on the same concentration through an oral endotracheal tube and mechanical ventilation was established with a tidal volume of 6–8 ml/kg. An arterial line was inserted through the right common carotid artery and a central venous line was introduced into the left jugular vein. A pulmonary artery catheter was inserted via the right jugular vein and directed into position beyond the pulmonary artery bifurcation. Standard monitoring consisted of: EKG, pulse oximetry, end tidal COFollowing in vivo baseline echocardiographic evaluation, a purse-string suture was placed in the ascending aorta to allow placement of a cardioplegia cannula. An 18F venous cannula was inserted into the inferior vena cava (IVC) via the right atrium for collection of approximately 1.5 L of whole blood into an auto-transfusion system  to isolate the red blood cells (RBC). Simultaneously, the aorta was cross-clamped, and donor hearts arrested with 1 L of histidine-ketoglutarate-tryptophan (HTK) solution at 4 °C. The donor heart was weighed, excised, and placed in ice-cold HTK for one hour while being cannulated for the ESHP circuit.The donor heart was then connected to the ESHP system cannulas that were suspended in a 3D-printed custom-made holder. The circuit composed a reservoir , an oxygenator  and two centrifugal pumps  working in parallel to selectively load the LV and right ventricle (RV), as described above. A heat exchanger  maintained a stabile temperature of 37 °C.The system was primed with 2000 mL of whole autologous blood from the donor and normal saline to achieve a hematocrit > 25%. Methylprednisolone (500 mg), heparin , cefazolin (1 g), and magnesium (2 g) were also added to the priming. Calcium chloride 10%, sodium bicarbonate 8.4% and dextrose 50% were added to correct calcium (1.1–1.3 mmol/L), glucose (5–10 mmol/L), and bicarbonate (24–30 mmol/L) concentrations, respectively.During LM, oxygenated perfusate is pumped retrograde by a centrifugal pump into the aorta at a constant pressure of 50 mmHg that results in aortic valve closure and perfusate flow into the coronary vessels. The perfusate drains into the coronary sinus and through the right ventricle it is ejected back to the reservoir via a cannula into the pulmonary artery . In thisThe working mode allows for LV loading and functional assessment. During diastole, SAM enables both antegrade flow to the left atrium and retrograde flow into the aorta. The retrograde flow is provided by a pump allowing coronary perfusion. In systole, the same retrograde flow acts as aortic resistance. However, the LV must overcome the aortic backpressure which can cause an uncontrolled rise in aortic systolic and diastolic pressure. PAM is an alternative to SAM that may simulate systemic vascular resistance more closely by connecting the ascending aorta to a Windkessel-based afterload module. In an electrical system, the Windkessel module comprises a circuit containing lumped elements of resistance, capacitance, and inductance. Here, the governing equations of an electric circuit are applied to a fluid system, where fluid pressure, fluid volume and volumetric flow rate directly parallel voltage, electrical charge, and electrical current, respectively . A physi2 based on donor weight. The right atrium was loaded with an inflow such that the sum of the inflow and coronary flow corresponded to a cardiac index of 1.8 L/min/m2 based on donor weight. The centrifugal pump and left atrial resistance were adjusted such that diastolic pressure was maintained between 25 and 30 mmHg. Systolic aortic pressure was not controlled. A Windkessel module was added on the aortic line in order to regulate systolic and diastolic aortic pressure. The evaluation process was performed with a standardized systemic resistance of 2 mmHg/cm3 and a standardized arterial compliance of 2 cm3/mmHg. The LV was assessed in SAM at 1 h (indicated as SAM1), then switched to LM. After 4.5 hours was assessed in PAM and after 1 h of LM (5.5 h of perfusion) the hearts were switched back into SAM2 to perform the final functional assessment. Figure In this experiment, the donor heart was mounted on the ESHP system following 1 h of cold storage. Anterograde flow through the LA was commenced for de-airing of the left cardiac chambers. Once completed, all hearts were first perfused in LM. Over the course of 30 min, hearts were rewarmed to 37 °C. Hearts that fibrillated were defibrillated as required. Perfusion was kept steady at these settings for another 30 min. The metabolic assessment of the donor heart was performed hourly in LM. For the functional assessment, the hearts were transitioned to SAM as described previously and the LA loaded with an inflow corresponding to a cardiac index of 1.8 L/min/m2, pCO2, and oxygen saturation (SpO2) were measured using a blood gas analyzer . Myocardial lactate metabolism was determined as follows:Continuous infusions of dobutamine (0.05 mcg/min), nitroglycerin (1 mcg/kg/min), and insulin (5 units/h) were maintained throughout the experiment. Fraction of inspired oxygen (FiO2) and gas flow through the oxygenator were titrated to maintain a pH between 7.35 and 7.45, a pO2 between 100 and 300 mmHg, and a pCO2 between 35 and 45 mmHg. Arterial and venous samples were collected at baseline and hourly during ESHP. Electrolyte, lactate and hemoglobin concentrations, pH, pOMyocardial Lactate Metabolism [mmol/L] = Pulmonary Artery Lactate [mmol/L] − Aortic Lactate [mmol/L]A positive result indicates production, whereas a negative result indicates extraction. All metabolic parameters were assessed with hearts perfused in LM. The heart was weighed at the beginning and at the end of the perfusion.A standard TEE probe (TEV5Ms Transducer) and echocardiography system  were used to perform a comprehensive epicardial echocardiographic examination. In order to allow for an optimal interface between the donor heart and the probes, a custom-made 3D-printed spacer was applied at the tip of the transducer, filled with gel. The probe was covered by a disposable sterile sheath. Figure We reported the trend in measured parameters at the different time points using the mean and standard deviation. All statistical analyses and graphics were generated using MATLAB .In all six pigs included in the study, we successfully completed all assessments and successfully loaded the ventricles transitioning from unloaded non-working (LM) perfusion mode to two different working modes by loading the left and the right atrium. At all timepoints, we were able to obtain good quality epicardial echocardiographic images that allowed a complete systolic assessment of LV Fig. . OverallThe LVEF was 56.71% ± 7.86, 37.28% ± 14.56, 31.44% ± 6.90, and 20.76% ± 5.23 at baseline, SAM1, PAM, and SAM2, respectively. The LVFAC was 57.64% ± 5.16, 42.19% ± 18.38, 14.78% ± 4.73, and 17.66% ± 6.44 at baseline, SAM1, PAM and SAM2, respectively. The LVFS was 31.98% ± 2.57, 17.97% ± 4.29, 12.99% ± 5.38 and 13.37% ± 5.34 at baseline, SAM1, PAM and SAM2, respectively.GLS was − 12.26% ± 2.50, − 4.72% ± 2.81, − 4.71% ± 2.07, − 3.08% ± 1.60 at baseline, SAM1, PAM, and SAM2, respectively. The GCS was − 24.50% ± 5.57, − 14.75% ± 7.32, − 8.67% ± 4.51, − 7.75% ± 3.20 at baseline, SAM1, PAM, and SAM2, respectively. The RAD was − 21.75% ± 2.50, − 5.25% ± 4.78, − 3.00% ± 7.00, − 5.00% ± 3.83 at baseline, SAM1, PAM and SAM2, respectively.2, pH remained relatively stable during this time period , metabolic measurements , and hemodynamic and contractility parameters  . In clinThe evaluation of heart structure and function prior to the cardiac transplantation is therefore auspicable to better identify suitable organs. Previous studies have suggested the advantage of contractility measurements over metabolic parameters during ESHP, but these studies were focused on the use of conductance catheters, which provide a broad range of functional parameters and is the traditional gold-standard when researching myocardial performance , 14, 23.Our study demonstrates the feasibility of a complete non-invasive quantitative echocardiographic assessment of LV systolic function during ESHP by transitioning from LM to two different working modes. It is an important step in facilitating a standardized non-invasive functional assessment of the heart during ESHP to predict the suitability for transplantation. It also provides some quantitative measurements that may establish some references to set a benchmark for future research.This was the first study to use a non-invasive tool such as echocardiography to comprehensively quantify LV systolic performance during ex situ perfusion in two different working modes in a large animal model. Previous studies have assessed LV function during ESHP using conductance catheters and limited their investigations to SAM. Our experimental model closely mimics the clinical scenario of standard ESHP and assessment, ensuring more readily translatable findings.Nevertheless, this work has a few limitations. First, our sample was very small. As such, conclusions regarding the use of echocardiographic assessment of LV performance during SAM and PAM should be considered as hypothesis generating work. Second, the echocardiographic measures in vivo are not entirely comparable to those during ESHP given the different setup and loading conditions. Third, although we tried to provide precise loading and inotropic conditions during the functional assessment, we did not closely control heart rate which may have caused increased variability in some of the parameters evaluated. Fourth, for a comparison between SAM and PAM, the assessment of myocardial function should be done in a closer interval of time and randomizing the technique utilized first. Different degrees of LV dysfunction should also be included. Finally, the RV function, which plays a key role in post-transplant heart failure, was not evaluated due to technical challenges in providing controlled RV afterload during ESHP.We successfully demonstrated the feasibility of echocardiographic comprehensive functional assessment of LV function in an isolated heart during ESHP using two different working modes. The expected LV systolic dysfunction in the context of heart harvesting consisted of a reduction in EF, FAC, FS, and strain throughout the experiment. SAM and the PAM provide different LV loading conditions which is partially demonstrated by the echocardiographic quantification, and therefore may not entirely be fully interchangeable for functional LV assessment. Our work sets the basis for the integration of echocardiographic imaging into an ESHP clinical platform for a non-invasive functional heart assessment.


Heart failure remains a major global burden regarding patients’ morbidity and mortality and health system organization, logistics, and costs. Despite continual advances in pharmacological and resynchronization device therapy, it is currently well accepted that heart transplantation and mechanical circulatory support represent a cornerstone in the management of advanced forms of this disease, with the latter becoming an increasingly accepted treatment modality due to the ongoing shortage of available donor hearts in an ever-increasing pool of patients. Mechanical circulatory support strategies have seen tremendous advances in recent years, especially in terms of pump technology improvements, indication for use, surgical techniques for device implantation, exchange and explantation, and postoperative patient management, but not in the field of treatment of critically ill patients and those undergoing cardiac arrest. This contemporary review aims to summarize the collected knowledge of this topic with an emphasis on complications in patients with left ventricular assist devices, their treatment, and establishing a clear-cut algorithm and the latest recommendations regarding out-of-hospital or emergency department management of cardiac arrest in this patient population. Heart failure (HF) remains a major medical burden, reaching epidemic proportions by affecting up to 50% of the general population with increasing incidence in individuals over 65 years of age ,2. AlthoTraditionally, HF has been divided into distinct phenotypes based on the measurement of left ventricular ejection fraction (LVEF), thus compelling three major groups, namely HF with reduced EF (<40%), mildly reduced EF 41–49%), and preserved EF (>50%) . Regardl–49%, andThe most common causes include ischemic heart disease, dilated cardiomyopathy, arterial hypertension, or end-stage valvular degeneration. There are several factors involved in cardiac remodeling, such as cell death , oxidative stress (increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; decreased antioxidative enzymes), inflammation, fibroblast proliferation, decreased contractility (decreased myosin and troponin phosphorylation) and neurohormonal activation , which may all potentially lead to ventricular dysfunction . As ventThe New York Heart Association (NYHA) classification assesses the patient’s functional capacity and symptoms, progressing from no limitations of physical activity (Class I) to more significant limitations with less and less activity and eventually at rest (Class IV)  12]. . 12]. Taking into account that NYHA Class IV represents a very heterogeneous group of patients, a more specific distinction among advanced HF phenotypes was proposed recently with the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database, which was established in 2008 to facilitate the growth of MCS and improve patient outcomes. Paired with the registry’s first report was a proposal for a new system of classifying patients with advanced HF. Seven clinical profiles were designed to establish an enhanced method for characterizing patients requiring device therapy . These pThe backbone of pharmacological therapy for chronic HF remains a combination of beta-blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) for hypertension, loop diuretics for volume overload, and aldosterone receptor antagonists for reverse myocardial remodeling, as well as SGLT2 inhibitors (dapagliflozin/empagliflozin) and angiotensin-receptor neprilysin inhibitors to reduce the risk of HF hospitalizations or death in patients with preserved or mildly reduced LVEF . ImplantIn patients with acute decompensations, inotropes may reduce congestion, augment cardiac output, and aid peripheral perfusion. In patients who fail to respond to diuretic-based strategies, renal replacement therapy (RRT) should be considered with ultrafiltration as one of the most common approaches .A minority of patients with advanced HF who are unresponsive to the above-mentioned therapy could potentially benefit from surgical therapy. Coronary artery bypass grafting (CABG) should be performed in patients with ischemic cardiomyopathy to reduce anginal symptoms, possibly improve ventricular function, alleviate symptoms of HF, and improve survival . IschemiWhen the patient has advanced HF and is not a candidate for any of the above-mentioned procedures or remains severely symptomatic despite them, more advanced mechanical circulatory support may be required. It is generally divided into short- and long-term MCS, with the former primarily reserved for INTERMACS profiles 1 to 3. Left ventricular assist device (LVAD) technology evolved from the 1st generation pulsatile chambers with volume displacements by external compression via the second generation axial continuous-flow spinning motors mounted on a central shaft to the modern third generation centrifugal continuous-flow hydrodynamic or electromagnetic suspended spinning motors, which are mostly used nowadays . It is wBleeding. The most common adverse effect of continuous-flow MCS is gastrointestinal bleeding due to an abnormal von Willebrand factor degradation and de novo formation of arteriovenous malformations [rmations ,21. Othermations . Regardlrmations . Due to rmations . Infection. Infectious complications are frequently encountered as they represent the second highest event rate and can involve any portion of LVAD—surgical site, driveline , pocket, or the pump itself [p itself . Since tp itself . Three sp itself . Stroke. Not uncommonly observed, a significant neurological event may result in a patient being found unresponsive despite a normally functioning device. The highest risk for any kind of cerebrovascular insult is high fluctuation of antithrombotic therapy ranging from insufficient to excessive [xcessive ,26. EM hxcessive ,26. Endoxcessive . Pump failure. The two most common causes of pump failure are disconnection of the power and failure of the driveline. Therefore, in assessing an unresponsive, mentally altered, or hypotensive patient with an LVAD, it is critically important to ensure that all connections are secure, and an adequate power source is connected. Patients with a current LVAD system typically have two batteries connected to power the device—both should be checked for their status. Controller malfunction, damage, or disconnection can also lead to pump dysfunction/stoppage. Additionally, the driveline is a potentially vulnerable component and subject to wear, damage, or kinking. In these settings, there will often be alarms preceding or accompanying the pump stoppage, but alarms will cease once the batteries are drained [ drained . It is i drained ,21,26. T drained . In the  drained . Systemi drained . Regarding out-of-hospital cardiac arrest, the American Heart Association (AHA) issued its scientific statement regarding CPR in adult and pediatric MCS population . Their a2) in intubated patients correlates with systemic hypoperfusion, low cardiac output, and low venous return [2 is noticed. Pulse oximetry can be unreliable due to the lack of pulsatility; obtain an arterial blood gas early if the peripheral capillary oxygen saturation has a poor waveform [After assisting with ventilation, if necessary, the next step should always be an assessment of flow and perfusion in mentally altered patients with LVAD. This could be achieved clinically via skin color and capillary refill inspection, followed by non-invasive blood pressure measurement using a manual blood pressure (BP) cuff and a Doppler. A manual BP cuff alone is unreliable more than 50% of the time. When using a manual Doppler, pressure measurement is accomplished by attaching a manual BP cuff to the patient’s arm, inflating to at least 120 mm Hg systolic, and slowly deflating while placing a Doppler probe over the radial artery ,31. Earls return ,33. Aftewaveform . The next step after assessing perfusion is assessing the device itself. If LVAD is determined as a destination therapy with a clear do-not-resuscitate notion, the same protocol as for other non-LVAD patients should be applied. If it is placed as a bridge to transplantation/decision/candidacy/recovery, active management is undertaken. The device should be assessed for function by looking and listening for alarms and listening for an LVAD hum over the left chest and left upper abdominal quadrant. The two most often reversible causes of pump failure are a failed connection linking the controller with the pump and inadequate electrical power. Proceed with ensuring secure connections to the controller and ensuring adequate power for the LVAD via an additional power source or external energy source . LVAD patients usually carry a spare controller and additional power source. Failure to identify a repairable cause of device malfunction usually results in unsuccessful outcomes . 2 as well as low arterial pressure, chest compressions are indicated  should be considered. Paradoxically, hypertension could also cause low flow as afterload increases and LVADs are afterload-dependent. The high-flow alarm could be combined with normal power, thus directing our investigation toward possible sepsis or other distributive shock causes, or with high power, potentially indicating pump thrombosis . A word of caution: the “cardiac output” number on the LVAD screen is a calculation based on the speed and power consumption of the unit and represents true flow only in a state of proper functioning. Any cause of hypotension  will result in elevated screen numbers to alleviate the drop in systemic vascular resistance. Thus, the appropriate clinical examination should lead the EM provider’s management . Another cornerstone in the evaluation of an arresting LVAD patient is transthoracic echocardiography, performed either by an experienced EM provider or a consultant cardiologist. Most important dilemmas should address RV filling (preload) and function, valve competence, degree of LV unloading, and if there are any obstructing thrombi within the pericardial cavity or the device itself ,40. Obtaining an electrocardiography (ECG) strip provides us with additional knowledge about the electrical activity of the heart. Ventricular arrhythmias occur in 22–59% of LVAD patients. Although it is not uncommon for patients to be asymptomatic during ventricular tachycardia or ventricular fibrillation, it is critical to terminate those arrhythmias since the risk of right ventricular failure is high. Interpretation of ECG could be difficult due to electromagnetic interference of the pump that causes high-frequency noise artifacts on 12-lead ECGs. Elimination of noise can be achieved by adjusting filtering parameters . Chest radiographs should be obtained since they provide information on appropriate device placement. A more accurate computer tomography imaging can provide us, in addition to LVAD position itself, data on other pathological events such as the origin of the infection, mediastinal hematomas, pericardial, abdominal wall, and retroperitoneal hemorrhage, inflow and outflow graft and aortic thrombi .Importantly, patients with LVAD should not undergo magnetic resonance imaging due to the highly ferromagnetic component incompatibility . B-type natriuretic peptide (BNP) levels decrease after LVAD implantation due to LV unloading. Acute increases in BNP from the new (post-implantation) baseline may occur during situations of inadequate circulatory support, such as pump failure or tamponade . It should be noted that all patients receive the LVAD coordinator’s contact number at the time of LVAD implantation, and this should remain the early referral connection when being treated by an EM provider. After the above-described primary assessment, simultaneously, local EMS and ACLS protocols are followed while contacting the LVAD coordinator and transferring to the implanting facility. After achieving ROSC, all LVAD patients should be treated in the implanting facility for a higher level of care and definite management. The long-term results of this patient cohort are scarcely reported in the scientific literature. The largest report looked at a recent period of 8 years in the US and identified 93,153 hospitalizations with implanted LVAD. Only 578 patients had experienced cardiac arrest, and 173 patients (33%) among these underwent CPR. In-hospital mortality was 60.8% in patients with cardiac arrest (including do-not-resuscitate LVAD patients) and, interestingly, 74.33% in patients in whom CPR was performed. This resulted in a trend toward fewer CPR performances toward the end of this period. Additionally, age, female sex, peripheral vascular disease, history of CABG, and ventricular tachycardia were independently associated with in-hospital mortality . Regardi2 alone act as a good identifier of patients with (sub)optimal cardiac output; and (III) what kind of identification should patients with LVADs wear on themselves to avoid any uncertainties regarding the presence of an MCS device? Taking into account that no randomized clinical trial could be feasible and ethically justified in this patient population, HF guidelines for the management of out-of-hospital cardiac arrest in patients with an LV assist device will most probably lean on “expert consensus” rather than “evidence-based” data also in the foreseeable future. Certain unclarities persist, such as (I) what are the risks/benefits of chest compressions to patients with an LVAD?; (II) does etCO2 and arterial pressure. After ROSC, initiation of standard post-resuscitation circulation care should be carried out with inotropic support with catecholamines if indicated. All LVAD patients should be transferred to the implanting facility for definite management. When approaching a patient on LVAD with a suspected cardiac arrest, obtain a manual Doppler pulse measurement and plug the device into an external battery source. Auscultation over the chest to listen for a machinery whirring sound should be quickly performed, and CPR should be initiated when clinical signs of hypoperfusion along with decreased arterial pressure are noted. Cardioversion and defibrillation are compatible with LVADs as long as the pads are not placed directly over the pump. The endpoint of resuscitation is clinical signs of improvement with sufficient etCO


Non-invasive assessment of myocardial mechanics using modern imaging techniques became a current topic due to the rapid developments in echocardiography and cardiac magnetic resonance imaging (cMRI) ,6,7,8,9.According to recent guidelines, the characteristics of LV rotational mechanics can be assessed by three-dimensional (3D) speckle-tracking echocardiography (STE) due to their 3D nature . This meSome new theories suggested the possibility that LV also rotates longitudinally during the cardiac cycle. Moreover, abnormalities in patients with complete left bundle branch block (cLBBB) were suggested to be due to a related ventricular dyssynchrony and reduction in systolic and diastolic efficiencies. In a recent two-dimensional 2D) STE study, patients with normal QRS, complete right bundle branch block (cRBBB) and cLBBB were compared to clarify any differences in spatial LV motions. All patients with cLBBB showed significantly a larger clockwise longitudinal rotation than patients with normal QRS or cRBBB. This longitudinal rotation correlated with QRS duration, but was not associated with low LV ejection fraction (EF) or the presence of regional wall abnormalities [D STE stuIn normal circumstances, there is a complex contractility pattern, which can be quantified by STE. The myocardial shortening from LV base to LV apex is determined by global longitudinal strain (GLS), the systolic LV shortening in short-axis views is quantified by global circumferential strain (GCS) and the myocardial thickening from the endocardium to epicardium is measured as global radial strain (GRS). Similar parameters could be measured for the right ventricle (RV) and atria as well ,6,7,8,9.There is inconsistent agreement between 2DSTE- and 3DSTE-derived LV-GLS, when assessed in different clinical scenarios, e.g., in patients with normal LV, reduced LV-EF and cardiac pacing. According to the study of Plasek et al., LV-GLS assessed by 2DSTE and 3DSTE is closely associated, but only on a global level suggesting that LV-GLS comparisons are more representative of global shortening than local displacement. When the effects of RV pacing and decreased LV-EF were investigated, a reduced correlation between 2DSTE- vs. 3DSTE-derived LV-GLS was observed [Strain measurements allow detailed analyses of LV contractility, which can be of particular importance in the assessment of cardiomyopathies. In hypertrophic cardiomyopathy (HCM), LV-GLS is known to be impaired and is associated with an increased risk. In a recent study, the analysis of 2DSTE-derived LV-GLS adjusted to the regional thickness allowed better evaluation of myocardial deformation in HCM, especially in the most hypertrophic LV segments . MoreoveLV noncompaction cardiomyopathy (LVNC) is a relatively new clinical entity characterized by prominent trabecular LV meshwork and deep intertrabecular recesses. When LV noncompaction was diagnosed in pediatric patients by cMRI, LV enlargement and reduced LV systolic function (lower LV strains and LV-EF) were found together with increased RV trabeculations and subclinical impairment of RV myocardial deformation (decreased RV-GRS and RV-GCS with preserved RV-EF) confirming the involvement of the left and right heart in varying degrees . Fabry disease (FD) is an inherited, X-linked, rare, lysosomal storage disease, affecting the heart among other organs. It is also known as alpha-galactosidase-A deficiency leading to the accumulation of sphingolipids in certain organs. In a recent cMRI study, LV-GRS and LV-GLS were found to be reduced in FD patients; moreover, LV-GLS also showed correlations with the FD-specific biomarker globotriaosylsphingosine (LysoGb3) . These fChagas disease (CD) is a tropical vector-borne infection caused by the protozoan parasite Trypanosoma cruzi. Chagas cardiomyopathy (CM) is the leading cause of non-ischemic cardiomyopathy with diffuse myocarditis and focal fibrosis in Latin America. In a recent meta-analysis, different levels of functional derangements in myocardial function across different stages of CD were found. CM patients had a significantly higher LV-GLS compared to patients with the indeterminate form (IF) of CD, while differences between IF patients and healthy controls could not be detected. Segmental strain analyses revealed that patients with the CD-IF form had worse strain values in the basal-inferoseptal and mid-inferoseptal segments compared to healthy controls . Finally, LV and LA myocardial deformation was examined in patients following acute myocardial infarction. The presence of chronic obstructive pulmonary disease was associated with more impaired 2DSTE-derived LV and LA functions, which was independent of age, LV-EF and pulmonary function test parameters .All these findings strengthen previous results confirming the importance of LV rotational and deformation parameters calculated during strain analysis in various pathologies. In addition to the above, the possibility of the significance of disease-specific differences may also arise. However, studying the prognostic impact of these variables is still a task for future investigations in the relevant disorders.