Atrial fibrillation is frequently seen in patients with dilated cardiomyopathy (DCM), and its presence impacts the function of the heart, with clinical and prognostic consequences. In this prospective single-center study, we aimed to assess the impact of atrial fibrillation on cardiac structure and function, using comprehensive two- and three-dimensional echocardiography. We included 41 patients with DCM and persistent or permanent atrial fibrillation , as well as 47 patients with DCM and in sinus rhythm . Cardiac chambers and mitral and tricuspid valves’ structure and function were assessed via standard two-dimensional, speckle-tracking, and three-dimensional echocardiography (3DE). Patients with DCM and atrial fibrillation had a more impaired left ventricular global longitudinal strain, higher 3DE left atrial volumes, and reduced function compared to patients in sinus rhythm in the presence of similar left ventricle volumes. Mitral annulus configuration was altered in atrial fibrillation DCM patients. Also, right heart volumes were larger, with more severe atrial and ventricular dysfunction, despite similar estimated pulmonary artery pressures and severity of tricuspid regurgitation. Using advanced echocardiography techniques, we demonstrated that atrial fibrillation induces significant remodeling in all heart chambers. Dilated cardiomyopathy (DCM) is defined by the presence of left ventricular (LV) or biventricular dilation and systolic dysfunction in the absence of abnormal loading conditions  or coronary artery disease sufficient to cause global systolic impairment. In some cases, LV dilation can be absent, although overt LV systolic dysfunction is present, which led to the proposal of a new category—hypokinetic non-dilated cardiomyopathy—to avoid diagnostic misinterpretations ,2,3,4. TThus, the scope of the present study was to (1) evaluate the impact of AF on the geometry and function of both left and right heart chambers using two-dimensional speckle tracking echocardiography (2DSTE) and three-dimensional echocardiography (3DE), a (2) compare the results to those found in patients in sinus rhythm (SR) in this specific clinical setting.The present study was a comparative observational study conducted between 1 October 2021 and 1 July 2022 in an in-hospital setting on DCM patients. These patients were referred to our laboratory for clinically indicated transthoracic echocardiography. Inclusion criteria consisted of confirmed DCM diagnosis, as per current guidelines, being aged over 18 years old, and giving consent to be part of the study. Exclusion criteria were the presence of significant coronary artery disease and/or suboptimal echocardiographic window. The initial cohort consisted of 115 patients, of which 27 were excluded . The final cohort comprised 88 DCM patients. Patients were divided into two groups based on the presence of SR or persistent/permanent AF (as defined by current guidelines). All patients underwent comprehensive clinically indicated transthoracic 2DSTE and 3DE. Heart rate, blood pressure, height, weight, and body surface area (BSA) were measured in all subjects immediately before the echocardiographic examination. Evaluation was performed when patients were in a compensated state to diminish as much as possible the load-dependency effect on several echocardiographic parameters. Measurements were averaged from three cardiac cycles, in case of SR, or five cardiac cycles, in the presence of AF.Data were acquired using a commercially available ultrasound system . The analysis was performed offline using EchoPAC version 204 software (GE Vingmed Ultrasound).For LV global longitudinal strain (LVGLS), a 17-segment model was used. After acquiring the three dedicated apical views , at a frame rate > 50 fps, endocardial and epicardial borders were tracked. The region of interest (ROI) was carefully defined as not to include the pericardium and, thus, avoid potential reductions in the measurements. Images were generated automatically and manually edited if deemed necessary. Dedicated software was used . End-diastole was selected as the reference point in time and defined based on the peak of the QRS complex . From LVFor the evaluation of right ventricular (RV) strain, the RV-focused apical four-chamber view was obtained, making sure to display the largest basal RV diameter, avoid RV foreshortening, and keep the LV apex at the center of the scanning sector ,12. The Left atrial (LA) tracing was performed using dedicated four- and two-chamber views, at adequate gain and depth and with proper orientation, to obtain non-foreshortened images and visualize the entire LA throughout the cardiac cycle ,14. TracComplete 2DE and 2DSTE examination was followed by 3DE focused studies using a dedicated probe . Before 3DE acquisition, 2DE images were optimized. To ensure satisfactory spatial resolution, the pyramidal volumes were optimized to encompass the structures of interest. For a higher temporal resolution, multibeat acquisitions were performed at >20 volumes/second (vps). To avoid stitching artifacts, holding of breath, where possible, was performed by the patients, and acquisitions were undertaken at a relatively stable heart rate. The analysis was conducted offline .The acquisition of LV full-volume data sets was realized from an apical approach. Off-axis positions were used where considered necessary. To obtain LV volumes and EF, a semi-automated algorithm was utilized . Firstly, views were correctly aligned. Afterwards, landmarks were set at the level of the base and center of the apex. Selected end-diastolic (ED) and end-systolic (ES) frames were modified, when it was deemed necessary, to ensure proper 3D reconstruction models and waveforms .Due to its peculiar form, multiple trabeculations, and fibers’ orientation, global assessment of the RV is difficult, with multiple limitations of 2DE that are readily overcome via 3DE evaluation. We used the apical four-chamber view, which was modified to include the entire RV, and acquired full volume data sets at >20 vps. To measure the RV cavity volumes, a semi-automated algorithm was applied (4D autoRVQ). After proper alignment, landmark points were established: two were established at the level of the tricuspid valve; one was established at the RV apex in four-chamber view, the RV/LV anterior, and posterior points; and, lastly, one was established at the RV free wall point in the short axis mid-view. The initial contours were modified manually. The 3D model was visualized and checked in all slices .In addition to the strain parameters used to assess LA deformation, 3DE analysis also provides the emptying fraction and an accurate measurement of LA volumes. Care was taken to ensure that complete LA was included. The semi-automated segmentation algorithm used (4D auto LAQ) was initiated by placing one landmark at the mitral valve (MV) at the level of the annulus. The frame was adjusted until the MV was closed. Image position was modified to ensure that the vertical line intersected both the center of the MV and LA roof. Manual editing was performed where circumstances indicated that it was necessary . The samIn this context, we also sought to examine the mitral and tricuspid valves with the use of 3DE to obtain a more accurate anatomical and geometrical valvular assessment . To evaln) or percentage for categorical variables. The normal or skewed distribution of the variables was checked using the Kolmogorov–Smirnov test. To compare data between the two pre-defined groups (AF-group vs. SR-group), we used an unpaired t-test. Significance was defined as a two-tailed probability level of <0.05.Our analysis was conducted using IBM SPSS Statistics version 28.0.1.1. Baseline characteristics and echocardiographic parameters were defined as mean ± standard deviation (SD) for continuous variables and as absolute number (p = 0.01)  .2, indexed LVESV 80 ± 26 vs. 87 ± 52 mL/m2, LVEF 29 ± 8 vs. 27 ± 7% in the SR vs. AF group, p > 0.05 for all). RV dimensions  and functional parameters  had no statistically significant differences between the SR and AF groups. In all patients with at least moderate mitral and/or tricuspid regurgitation, the 2D PISA method was used for quantification of regurgitant lesions. Neither mitral nor tricuspid regurgitant volumes and effective regurgitant orifice areas (EROA) were notably distinct in the two groups . In both groups, the mean-estimated systolic pulmonary artery pressure (sPAP) was similar   .2, indexed 3DE LVESV 82 ± 25 vs. 96 ± 54 mL/m2, 3DE LVEF 31 ± 9 vs. 27 ± 8% in the SR vs. AF group). In the presence of similar LV volumes and EF, LVGLS as an absolute value was significantly lower in the AF group , as were myocardial GWI and GCW , though myocardial GWW and GWE were not (p > 0.05) , LA function was evaluated via the 3DE LA emptying fraction (LA EF), and biplane left atrium global longitudinal strain in the reservoir phase (LASr) significantly reduced  in AF-group compared to patients in SR-group . Unlike in the LV, 3DE RV end-diastolic and end-systolic indexed volumes  were significantly larger , and the 3DE RV ejection fraction (RVEF) was significantly lower , in the AF-group compared to the SR-group  . MoreoveSR-group . SimilarSR-group .Our study demonstrated via the use of advanced transthoracic echocardiographic techniques  that, in DCM patients, the presence of AF has a significant impact on both left and right heart chambers’ geometry and function. The main findings of our study can be summarized as follows: (i) regarding the left heart, compared to patients with DCM and SR, in the presence of similar 3DE LV volumes, 3DE LVEF, and mitral regurgitation severity grading distribution, patients with DCM and AF exhibited (1) more reduced LVGLS evaluated via 2DSTE, (2) higher 3DE LA maximum and minimum volumes, (3) a more impaired LA function evaluated by 3DE LA emptying fraction and biplane LASr, and (4) an altered mitral annulus configuration (3DE); (ii) regarding the right heart, in the presence of similar estimated pulmonary artery pressures and tricuspid regurgitation severity grading distribution, patients with DCM and AF had (1) higher 3DE RV volumes, (2) a more reduced RV function evaluated via 3DE RVEF and RVFWLS, (3) larger RA maximum and minimum volumes, and (4) a more impaired RA function evaluated via 3DE RA emptying fraction and RASr.The patients included in our study had similar baseline characteristics in both the AF and SR groups , although a more severe clinical presentation was encountered in patients with DCM and AF. After evaluating the left heart chambers and MV, we found that in patients with DCM and AF, compared to those in SR, despite similar 3DE LV volumes, 3DE LVEF and similar distribution of mitral regurgitation severity grading exhibited a significant reduction in LVGLS  and myocardial work parameters, such as GWI and GCW. They also displayed increased LA maximum and minimum volumes evaluated via 3DE and reduced LA function evaluated via 3DE left LA emptying fraction (LA EF) and biplane LA global longitudinal strain in the reservoir phase (LASr). In our study, although the presence of AF in DCM patients did not significantly influence the distribution of mitral regurgitation severity grading, it, importantly, modified the configuration of the MV annulus, which was larger. AF was also associated with an increased tethering of the mitral valve (MV). The MV apparatus is an intricate structure, and its optimal functioning mandates a delicate interplay between LV contraction/relaxation, papillary muscles contraction, leaflets, and annular motion. In DCM, functional mitral regurgitation (FMR) occurs due to an imbalance between tethering forces, which are increased , and closing forces  in the presence of a structurally normal valve. This imbalance is influenced by the dynamics and dimensions of the mitral annulus (MA) ,19. The The fact that AF, as a frequent arrhythmia that often complicates disease course in DCM patients, negatively impacts all heart chambers’ function and geometry in this setting has many implications. In a bicentric study of DCM patients, LVGLS emerged as an independent predictor of adverse outcomes, which exceeded LVEF in optimally treated patients . VariousRegarding the right heart chambers and tricuspid valve, in patients with DCM and AF, compared to patients in SR, although no statistically significant differences in estimated systolic pulmonary artery pressure and tricuspid regurgitation severity grading distribution were noticed between groups, 3DE RV volumes were higher, and RV function evaluated via both 3DE RVEF and RVFWLS was notably reduced. The traditional M-mode and 2DE parameters used in quantifying RV dimensions and function, which were similar between groups, are much less accurate than 3DE. The 3DE RA maximum and minimum volumes were larger, and RA function was also more impaired in AF-DCM patients. The tricuspid valve (TV) in the setting of DCM is mainly, but not exclusively, affected because of secondary pulmonary hypertension, progressive RV dysfunction, and dilation. These changes led, on one hand, to annular dilation mainly in the anterolateral direction due to eccentric forces applied by the RV free wall, and on the other hand to leaflet tethering in the context of papillary muscles displacement. Ventricular functional tricuspid regurgitation (TR) develops as the TV becomes more planar, with reduced excursion, reduced leaflet coaptation, and an increase in tenting volume ,28,29. AAlthough AF is a proven predictor of outcome, to our knowledge, no extensive studies regarding the exact impact on cardiac remodeling and function in DCM of the use of advanced echocardiographic techniques were previously conducted. Our findings might explain more precisely why AF is associated with an impaired prognosis in DCM patients and support the need to follow an extensive echocardiographic multiparametric approach both at baseline and during follow-up when examining DCM patients. After showing the ways that AF impacts the geometry and function of all heart chambers, through our results, we emphasize that, in clinical practice, more intense efforts should be performed to maintain SR in DCM patients. DCM-AF patients should be proposed for AF conversion  or even catheter ablation whenever indicated and considered suitable. Besides the benefits of expanding functional capacity , restoring SR from AF might increase survival in DCM patients.Some limitations can be pointed out. This was a study developed in a single center using a relatively reduced sample of patients. Most subjects included were male, and we cannot ignore the possibility of observing different findings in female patients. Besides exclusion of coronary artery disease, we did not focus on DCM etiology and did not consider the possibility of tachycardia-induced cardiomyopathy, and as such, we were unable to make etiology-based correlations.DCM patients with AF showed a more impaired LVGLS evaluated via 2DSTE, higher 3DE LA volumes, and reduced LA function evaluated via 3DE and biplane LASr compared to patients in SR in the presence of similar 3DE LV volumes, 3DE LVEF, and distribution of mitral regurgitation severity grading. Mitral annulus configuration was altered in AF-DCM patients. The 3DE RV volumes were larger and RV function assessed via 3DE RVEF and RVFWLS was more reduced, as were RA volumes and function in AF patients, despite similar estimated pulmonary artery pressures and distribution of tricuspid regurgitation severity grading.


This Research Topic targeted studies dealing with pathological myocardial remodeling (MR). Therefore, we considered evaluating manuscripts that contribute to the knowledge of the pathophysiology of RM. In addition, we encouraged the submission of manuscripts addressing multitarget approaches to MR therapy. At the end of the review process, four articles were accepted for publication in the journal.Fonsecas and Izar clarified the role of inflammation in post-infarction MR. This is an interesting review that allows us to understand the role of inflammation in disease progression and shows that anti-inflammatory therapies can reduce major cardiovascular outcomes. The authors have assembled a body of evidence that only therapies that act on the NLRP3 inflammasome or interleukin 1 beta have cardiovascular disease benefits. This notion is based on findings that inflammasome (NLRP3) activation, subtypes of lymphocytes, interleukin 6, and some inflammatory biomarkers are associated with greater infarct size and impaired ventricular function after myocardial infarction (MI).In a mini review, Portes et al. examined the role of swimming training on myocardial responsiveness to infarcts of different sizes. The MI was induced by permanent coronary artery occlusion in female Wistar rats. After 4 weeks MI, surviving animals were subjected to swimming training of 60 min/day for 5 days/week for an additional 8 weeks. Working with in vitro papillary muscles derived from the left ventricle, the authors documented significant depression of myocardial inotropism and lusitropism at different calcium concentrations. Exercise training attenuated the deleterious effects of MI, particularly in relation to the maximal positive and negative values of the first temporal derivative and the time to peak tension. In addition, exercise training attenuated the decrease in myocardial responsiveness proportional to the size of MI.Exercise training is one of the most important cardioprotective interventions . The benCarvalho et al. examined the effects of lipid-lowering agents and antiplatelet agents on monocyte subpopulations in patients with acute myocardial infarction (AMI). The study included patients treated with pharmacological thrombolysis in the first 6 h of a ST segment elevation myocardial infarction (STEMI). Before the invasive procedure, patients were randomised to rosuvastatin 20 mg or simvastatin 40 mg plus ezetimibe 10 mg and ticagrelor 90 mg or clopidogrel 75 mg, in addition to routine therapy for AMI. At six-month follow-up, the study showed a higher percentages of classical monocytes  and a lower proportion of nonclassical monocytes  compared with baseline analysis. Furthermore, modulation of the chemokine receptors CCR2, CCR5, and CX3CR1 by different classes of monocytes was altered after infarction, with no apparent effect of pharmacological therapy. Overall, the data from this study demonstrate that the inflammatory phenotype of monocytes in infarcted patients persists even with lipid-lowering and antiplatelet therapy.It is known that cardiovascular risk factors and stage of disease can influence the phenotype of monocyte subpopulations . In a clSilva et al. carried out an experimental study to investigate the structural, functional, and genetic adaptation of cardiac pressure overload induced by pulmonary artery banding (PAB) in rats. An important contribution of the study was to document changes over time in PAB to understand the evolution of ventricular remodeling and to identify transitions from a physiological adaptation process to a state of maladaptation. Male Wistar rats were subjected to a well-documented method of inducing PAB (Finally, cing PAB  and obseIn conclusion, in this Research Topic, manuscripts have been gathered aiming to explore physiological and therapeutic aspects for various causes of adverse cardiac remodeling. We hope that the research topics will reach readers who specialize in fields other than heart disease.


The availability of a human-like chronic heart failure (HF) animal model was critical for affiliating development of novel therapeutic drug treatments. With the close physiology relatedness to humans, the non-human primate (NHP) HF model would be valuable to better understand the pathophysiology and pharmacology of HF. The purpose of this work was to present preliminary cardiac image findings using echocardiography and cardiovascular magnetic resonance (CMR) in a HF-like cynomolgus macaque model.n = 10) and LVEF ≥ 65% with diastolic dysfunction . Another group of ten healthy monkeys was used as the healthy control. All monkeys underwent a CMR study to measure global longitudinal strain (GLS), myocardial extracellular volume (ECV), and late gadolinium enhancement (LGE). In healthy controls and HFpEF group, quantitative perfusion imaging scans at rest and under dobutamine stress were performed and myocardial perfusion reserve (MPR) was subsequently obtained.The NHP diet-induced model developed cardiac phenotypes that exhibited diastolic dysfunction with reduced left ventricular ejection fraction (LVEF) or preserved LVEF. Twenty cynomolgus monkeys with cardiac dysfunction were selected by echocardiography and subsequently separated into two groups, LVEF < 65% , as well as for stress perfusion  and corresponding MPR . After adjusting for age, ECV (p = 0.01) and MPR (p = 0.048) still showed significant differences among the three groups.No LGE was observed in any monkey. Monkeys with HF-like features were significantly older, compared to the healthy control group. There were significant differences among the three groups in ECV (20.79 ± 3.65% in healthy controls; 27.06 ± 3.37% in HFpEF group, and 31.11 ± 4.50% in HFrEFgroup, Our preliminary imaging findings demonstrated cardiac dysfunction, elevated ECV, and/or reduced MPR in this HF-like NHP model. This pilot study laid the foundation for further mechanistic research and the development of a drug testing platform for distinct HF pathophysiology. Heart failure (HF), with either reduced (HFrEF) or preserved ejection fraction (HFpEF), is an increasingly prevalent condition affecting over 64 million people worldwide . TypicalAnimal models have played a significant role in the development of putative treatments. For translational applications, there was a strong need for continuous improvement of clinically relevant large animal models, especially in human-like primates. Although several other large animal models of HF have been reported recently, few of them have been able to achieve satisfaction in replicating the pathophysiological state of human HF . A lack The HF-like model was induced by a high-fat diet. Male monkeys were divided into the HF group and the Healthy group. Both groups were supplied with 100 g of a normal diet for breakfast, and 150 g of fruit for lunch every day. A high-fat diet feeding was arranged at dinner, where the HF group was fed 100 g of a high-fat diet and the control group was provided with 100 g of a normal diet. The two diets have been formulated as follows: (1) High-fat diet: Carbohydrate 58.6 g/100 g; Energy 418 kcal/100 g , Vitamin B12: 47.1 μg/100. Fat: 15% of the diet. (2) Normal diet: Carboydrate 58.3 g/100 g; Energy 363 kcal/100 g , Vitamin B12: 109 μg/100. Fat: 4.8% of the diet. The main component of fat was lard, which was mainly composed of saturated fatty acids and cholesterol. During the diet-induced period, echocardiography screening was conducted and the modeling was considered to be complete when the diagnostic criteria for HFpEF or HFrEF were met. Subsequently, a CMR examination was conducted to further characterize the myocardial tissue in these monkeys.E′/A′ or E/A ratio < 0.8 or >3; (2) septal E′ < 7 (cm/sec); (3) E/E′ ratio > 10. Ejection fraction (EF) < 65% as HF with reduced EF (termed as the HFrEF group). Additionally, 10 normal cynomolgus monkeys on a regular diet were included as the healthy control group. The animal model selection process was illustrated in Twenty monkeys with cardiac dysfunction based on echocardiogram were identified as the HF-like group. These monkeys were further classified into two groups: EF ≥ 65% with diastolic dysfunction as HF with preserved EF (termed as the HFpEF group). Diastolic dysfunction was determined if at least two echocardiography criteria were met: (1) The monkeys were maintained according to guidance of National Institutes of Health Guide for the Care and Use of Laboratory Animals and the Association for Assessment and Accreditation of Laboratory Animal Care. All experimental protocols were reviewed and approved by the Experimental Animal Ethics Committee of KBI.A peripheral blood sample was collected for serum biochemistry and hematocrit measurements prior to an echocardiogram and CMR examination.E wave, the late peak velocity of the A wave, and the E/A ratio were recorded and registered by standard echocardiography. To measure the EF value, conventional M-mode Doppler ultrasound was used to acquire real-time two-dimensional targeted echocardiograms of the left ventricle's minor axis at the papillary muscle level. Tissue Doppler imaging was employed from the apical four-chamber view at the septal side of the mitral annulus. Early (E′) and late (A′) diastolic mitral annulus peak velocities and the ratio of early to late peak velocities (E′/A′) were then obtained.Transthoracic echocardiography was performed using a standard protocol with a diagnostic ultrasound system  . All monThe CMR examinations were performed in a 1.5T scanner  with a body phase-array and spine coils on the scanning table as the signal receivers. All monkeys underwent CMR with the following imaging protocol: (1) cine imaging along 2-, 3-, and 4-chamber views; (2) pre- and post-contrast T1 mapping; and (3) late gadolinium enhancement (LGE) on one mid-short-axis slice. Additionally, both in the HFpEF group and the healthy control group, first-pass perfusion imaging scans at rest and under dobutamine stress were performed to quantitatively evaluate myocardial perfusion and perfusion reserve. The perfusion examination was not carried out in monkeys with HFrEF for safety reasons. For each perfusion imaging, a double-bolus method was adopted: a 0.01 mmol/kg and 0.09 mmol/kg MRI contrast agents were administrated  with a flow rate of 1 ml/s and flushed with 10 ml of saline at the same flow rate. The monkey was held in breath-holding by briefly stopping airflow through the tracheal tube for the initial 15 s of the perfusion scan and then resumed normal breathing. To induce dobutamine stress, dobutamine was titrated at 5 μg/kg/min increments every 3 min until a maximum of 40 μg/kg/min was reached, or until the heart rate (HR) reached at least 25% higher than the resting HR, followed by stress perfusion imaging.For myocardial native T1 measurements, mid ventricular short-axis images were acquired by the modified Look-Locker inversion recovery (MOLLI) 5(3)3 acquisition scheme sequence after local shimming. Post-contrast MOLLI T1-mapping was performed 15–20 min after the administration of Gd-DTPA, using a MOLLI 4(1)3(1)2 acquisition scheme sequence on the same short-axis location. This study has adjusted the parameters of the T1 mapping sequence to adapt to a relatively high heart rate in monkeys (∼150 beats per min), by increasing the number of recovery heartbeats between two groups of T1-weighted data acquisitions. The LGE scan was performed approximately 15 min after the injection of the contrast agent, followed by the rest of the perfusion imaging. All imaging parameters are shown in Myocardial global longitudinal strains (GLS) were calculated using a commercial Medis software , using 2-, 3-, and 4-chamber cine images. Myocardial extracellular volume (ECV) of the mid slice was calculated from the pre- and post-contrast T1 values with the hematocrit obtained from the serum . A custop-value of less than 0.05 indicates statistical significance. Statistical analysis was performed using SPSS  and MedCalc .The data was presented as the mean ± SD. Comparisons of CMR parameters and echocardiographic parameters among the three groups were performed using one-way ANOVA. Correlations among ECV, MPR, GLS, and LVEF were performed with a linear regression. An analysis of covariance and partial correlation was used for the age adjustment. In addition, the diagnostic efficacy of ECV for different groups of monkeys was assessed by a nonparametric receiver operating characteristic (ROC) curve. The cutoff values were determined based on the Youden index, and the areas under the curves (AUCs) were obtained. A p = 0.01 for HbA1c%; 6.91 ± 4.81 vs. 3.84 ± 2.32 for CHO, p = 0.04; 4.54 ± 1.80 vs. 2.54 ± 1.90 for LDL p = 0.01). A HbA1c (%) level greater than 4.5% was considered as diabetes in monkeys , stress perfusion , and MPR . It was noteworthy that the age-adjusted ECV values were still statistically significant between the HFpEF and HFrEF groups, although they were no longer significantly different from the ECV of the healthy control group. The ECV correlated negatively with myocardial GLS , LVEF , E’/A’ , E’ , and E/A . After the adjustment for age, the myocardial global ECV was only found to be negatively correlated with LVEF . There was no LGE observed in any monkeys. The ECV exhibited apparent distinctions not only between the HF-like group and the healthy group , but also between the HFrEF group and the HFpEF group  (= 0.005) . Figure In this study, the utilization of a high-fat diet to induce lipid metabolism disorder was employed to create a chronic HF-like NHP model. Our preliminary imaging findings showed HF-like features in the cardiac structure, function, and tissue characterization in these monkeys with both preserved and reduced EF. Diastolic dysfunction was clearly demonstrated by echocardiography, whereas the diffuse fibrosis (ECV) and perfusion determined by CMR exhibited similar abnormalities demonstrated in human patients with HF. The outcome of this research indicates that hyperlipidemia induced metabolic disorder could be a viable means for creating a HF-like NHP model. The use of the non-invasive CMR approach allows a reliable and sensitive assessment of myocardial tissue composition and perfusion. The current study thus may lay a solid foundation for building a HF-like NHP model for novel drug development and mechanism research in the future.The most prevalent large animal HF models were dogs, pigs, sheep, cows, and NHPs –18. SeveHigh-fat diet NHP models have been reported previously, in which increased oxygen consumption and/or cardiac contractile dysfunction was observed, along with increased expression of proinflammatory cytokines and altered phosphorylation of intracellular signaling proteins in myocardial tissue , 23. TheE/E′ and E/A in various animal studies. The normal ranges for these parameters differ among animal species, with E/E′ typically ranging from 10 to 16 and E/A ranging from 1 to 2.5 . There were conflicting reports about how age affects myocardial ECV , 36. ThiMyocardial perfusion abnormality was highly prevalent in patients with HFpEF and was an independent factor of prognosis –41. Our There were several limitations in the present study. First, we have not conducted a comprehensive measurement of serum biomarkers, including BNP and NT-proBNP, as there was no suitable test kit for the monkey . This isIn this preliminary imaging study, a HF-like NHP model recapitulates major cardiac features of myocardial function, tissue characterization, and perfusion in human patients with preserved and reduced EF. While this HF-like NHP model needs more comprehensive assessments, the current image results will certainly serve as a stepping stone for further mechanistic research and the development of a drug testing platform for distinct HF pathophysiologies.


The effects of particle fineness and content of GDMR  on the physical properties of cement and the mechanical properties of mortar were studied. After that, the leachability of heavy metal ions was tested, and the hydration products of GDMR cement were analyzed using XRD and SEM. The results show that the addition of GDMR can regulate the fluidity and water requirement for the normal consistency of cement, delay the hydration process of cement, increase the initial setting and final setting time of cement, and reduce the strength of cement mortar, especially the strength of early age mortar. As the fineness of GDMR increases, the reduction of bending strength and compressive strength decreases, and the activity index increases. The content of GDMR has a significant effect on short-term strength. With the increase in GDMR content, the strength reduction degree becomes higher and the activity index decreases. When the content of GDMR was 30%, the 3D compressive strength and bending strength decreased by 33.1% and 29%. When the content of GDMR in cement is less than 20%, the maximum limit of leachable heavy metal content in cement clinker can be met.The desulfurized electrolytic manganese residue (DMR) was prepared by calcination and desulfurization of industrial waste electrolytic manganese residue, and the original DMR was ground to prepare DMR fine powder (GDMR) with specific surface areas of 383 m With the continuous development of the construction industry, the demand for cementitious materials is increasing day by day, and the annual output of cement in China in 2022 was about 2.118 billion tons ,4,5. PatManganese is an important basic material in the national economy and one of the important strategic resources of the country. As a typical hydrometallurgical industry, the electrolytic manganese production industry has developed rapidly, but it has also produced serious harm to the environment. According to statistics, every ton of manganese produced will produce 8–12 tons of electrolytic manganese residue ,11,12,132, some scholars use it as sulfur source, calcium source, and silicon source to prepare the cement [−2 cm/s. Li et al. [2+ and Cd2+. Li et al. [2 and activated potash feldspar to prepare autoclaved sintering-free brick, and its 1 day compressive strength reached 23.5 MPa, and the manganese ion leaching concentration was less than 0.02 mg·L−1. Some scholars have mixed electrolytic manganese slag with other minerals to prepare roadbed materials, and obtained good environmental protection and mechanical properties [To effectively utilize electrolytic manganese slag, many scholars have performed much in-depth research on it. Lan et al.  preparede cement . He et ae cement  used elee cement  used elee cement  studied e cement  preparedi et al.  preparedi et al.  mixed eloperties . Zhang eoperties  preparedAlthough a great deal of studies have been performed on electrolytic manganese slag so far, it seems that the problem of a large accumulation of electrolytic manganese slag has not been effectively solved due to poor technical feasibility, high treatment cost, or limited consumption of electrolytic manganese slag. Therefore, to eliminate the environmental pollution caused by electrolytic manganese slag at a low cost, technology is much needed to treat electrolytic manganese slag. To dispose of electrolytic manganese slag and reduce its impact on the environment, Ningxia Tianyuan Manganese Industry Co., Ltd. . improved the process and treated the filtered acid slag produced by manganese ore with sulfuric acid in the process of producing electrolytic manganese metal, and prepared desulfurized electrolytic manganese slag after calcination and desulfurization treatments. Compared with electrolytic manganese slag, desulfurized manganese slag does not contain ammonia nitrogen, and the leaching toxicity of heavy metals and gypsum content are greatly reduced, which provides the possibility for the wide application of desulfurized manganese slag. Wang et al.  analyzedBased on this, this paper takes the desulfurized manganese slag–cement as the research object. By mixing different fineness and different content of GDMR, the effects of particle fineness and content of GDMR on the water requirement for normal consistency, fluidity, setting time, and mechanical properties of cement are compared and analyzed, and the leaching toxicity of heavy metals is detected. At the same time, XRD and SEM are used to analyze the strength mechanism of DMR cement, revealing the influence of the fineness and content of GDMR on the performance of cement.P.O 42.5 Ordinary Portland Cement (OPC) and P.II 42.5 Portland Cement (PPC) are selected as the cements and their physical properties are shown in The sand used in the test is Chinese ISO standard sand according to GB/T 17671-1999 “Test Method for Strength of Cement Mortar (ISO Method)”.2/kg, 428 m2/kg, and 629 m2/kg; the sieve residues at 45 μm were 16.5%, 15.8%, and 2.3%, respectively. They were made by drying in a 105 °C air-blast drying oven and grinding with an SM-500 laboratory standard small mill for 50 min, 70 min, and 90 min. The desulfurized electrolytic manganese residue (DMR) used in this test was provided by Ningxia Tian yuan Manganese Industry Group Co., Ltd. When sampling from the yard, the outer layer was removed by 150 mm~200 mm, and the same amount of samples was taken from more than 20 different parts, of about 20 kg, which were mixed and reduced to about 5 kg by the quartering method. The specific surface areas of the DMR samples were 383 m2, Al2O3, Fe2O3, CaO, etc., which are similar to those of common silicate materials. They are mainly clay minerals and the content of silicon and aluminum components is high, accounting for 54% at the highest. 2 (PDF#00-046-1045), Ca6(SiO4)(Si3O10) (PDF#00-046-1479), and CaSO4·2H2O (PDF#97-001-5982) are sharp, indicating that they have high crystallinity and large grains. At the same time, the intensity of diffraction peaks of the quartz phase and the gypsum phase in DMR gradually weakened, which indicated that at this calcination temperature, quartz gradually became amorphous and melted with other metal elements to change into glassy silicate, while gypsum decomposed into CaO, and the main diffraction peak of low-temperature cristobalite appeared at 21°, which indicated that some quartz recrystallized into cristobalite. In order to clarify the microstructure of DMR, scanning electron microscopy was used to analyze the microstructure of DMR. The chemical composition of DMR is shown in cement/MDMR), and the cement mortar was prepared according to 450 g cementitious material, 1350 g standard sand, and 225 g water. The cuboid specimens of 40 mm × 40 mm × 160 mm were prepared from cement mortar to test the bending strength and compressive strength. After molding and demolding, the specimen was cured at a temperature of (20 ± 1) °C and humidity of no less than 90% and then taken out after 28 days. The GDMR mortar was produced by mixing different mass ratios of DMR fine powder to cement . When the test needle sinks to a distance of 4 mm ± 1 mm from the bottom plate, the cement reaches the initial setting state. When the test needle sinks 0.5 mm into the paste, that is, when the annular attachment cannot leave traces on the test piece, the cement reaches the final setting state. By testing the penetration of cement slurries with different water contents, the amount of water required to be added to the cement standard consistency slurry is determined, and the water requirements for normal consistency were tested in accordance with the provisions of GB/T 1346 “Standard test method for water requirement of normal consistency, setting time and soundness of the cement”.The fluidity is determined by a cement sand fluidity tester  (referred to as a jumping table). The fluidity shall be tested according to GB/T 2419 “Method for determination of fluidity of cement mortar”.The cuboid specimens of 40 mm × 40 mm × 160 mm were prepared from cement mortar to test the bending strength and compressive strength. The compressive strength and bending strength of mortar specimens at different ages were measured. The loading rate of compressive strength is 2400 N/s, and the loading rate of bending strength is 50 N/s. The compressive strength and bending strength of cement mortar were tested according to GB/T 17671-2021 “Test Method for Strength of Cement Mortar”.2/kg) according to Mcement/MDMR. According to the limit value of heavy metal content in cement clinker leaching solution in GB/T 30760-2014, the dried test block was broken, ground using a ball mill, screened by a square hole screen, and the particles with a particle size of 0.125 mm~0.25 mm were collected as samples to be tested. According to GB/T 30810 “Determination Method of Leachable Heavy Metals in Cement Mortar”, the leachability of heavy metal ions in GDMR was determined.Cement mortar was prepared by mixing cement and GDMR fine powder . When the sample reached the age to be measured, the sample was crushed and placed in ethanol to stop hydration. Then, a small amount of powder sample was prepared by grinding and sieving and dried to constant weight in a vacuum oven. The scanning parameters used in the test are as follows: the diffraction anode target is Cu target, the acceleration voltage is 40 kV, the current is 40 mA, the scanning speed is 8°/min, and the diffraction angle is 5~80°.The microscopic morphology was observed using a Quanta 250 FEG environmental scanning electron microscope , Tokyo, Japan.). The resolution of secondary electrons in a low vacuum and environmental vacuum mode was less than 1.4 nm, and the resolution of the energy spectrum was 127 eV.(1)GDMR fineness has little effect on the water requirement for normal consistency of cement, but has a great effect on fluidity a. With t(2)As the content of GDMR increases gradually, the water requirement for normal consistency of cement does not change, showing a slow downward trend, and having little influence on fluidity b.(3)The influence of the GDMR on water requirement for normal consistency and fluidity of OPC and PPC cement is just the opposite. For PPC, GDMR can improve its fluidity and reduce its water requirement for normal consistency. However, for OPC, GDMR will reduce its fluidity and increase its water requirement for normal consistency. The fluidity and water requirement for normal consistency of two kinds of cement mixed with GDMR are basically the same, which shows that GDMR can regulate the fluidity and the water requirement for normal consistency of cement.Water demand is an important comprehensive reference index for the application of GDMR as cement and concrete admixture in practical engineering. The water requirement of GDMR cement paste refers to the water requirement when the cement paste reaches a specific plastic state after adding water, which is expressed by the percentage of the ratio of the weight of mixing water to the weight of cement and becomes the water requirement for normal consistency of cement. The smaller the water requirement for normal consistency of GDMR cement, the higher the engineering utilization value of GDMR. The water requirement of GDMR cement mortar is usually expressed by the fluidity of standard mortar, which reflects the plasticity of cement mortar. The fluidity of mortar is related to the water requirement for normal consistency of cement but the relationship between them is not completely consistent. (1)With the increase in GDMR specific surface area, the initial setting time and final setting time of cement are prolonged gradually. Compared with the final setting time, GDMR fineness has a more significant influence on the initial setting time of cement. Moreover, with the increase in GDMR fineness, the trend of the increasing cement setting time ratio decreases.(2)With the increase in GDMR content, the initial setting time and final setting time of cement are prolonged gradually, and the setting time ratio is also increased gradually. When the content of DMR is more than 20%, the setting time of cement is prolonged significantly. Compared with the final setting time, the influence of GDMR content on the initial setting time of cement is more significant.(3)The GDMR can prolong the setting time of the two kinds of cement significantly. Compared with the final setting time, the influence of GDMR on the initial setting time of the two kinds of cement is more significant.As GDMR is a weak pozzolanic material, the content of cement in the cementing material will be reduced when it is partially replaced by cement, while the reaction of the volcanic ash material generally occurs in the middle and late hydration period. Therefore, the setting time of the paste mixed with GDMR is longer than that of the pure cement.(1)Fineness and strength activity indexSiliceous or aluminosiliceous materials have no or only weak cementitious properties, but they will combine with CaO to form hydraulic solids in the presence of water, which is called the pozzolanic property. GDMR is a kind of inactive admixture with weak pozzolanic properties, so the pozzolanic property can be characterized by the strength activity index. The strength activity index is the ratio of the compressive strength of test mortar to the compressive strength of contrast mortar. It can be analyzed from (2)Content and Strength Activity IndexThe test results of the strength activity index of GDMR cement mortar with different dosages (0%~30%) are shown in (1)As can be seen from (2)2 generated by cement hydration decreases, and the excitation effect on GDMR is relatively weakened, resulting in a decrease in strength [As can be seen from strength .(3)As can be seen from (1)Comparing the bending strength of cement mortar at different ages, it can be seen that the bending strength of cement mortar at younger age increases with the increasing fineness of GDMR, while the bending strength at later ages decreases.(2)The bending strength of cement mortar decreased by 4.3%, 16%, and 29% at 3 days; 2.5%, 12.5%, and 21.3% at 7 days; 4.5%, 10.1%, and 9% at 28 days; and 1.1%, 1.1%, and 8.7% at 90 days with the increase in the content of DMR. It can be seen that the content of GDMR has a similar influence on bending strength and compressive strength, and both have a greater influence on early-age strength. When the content of GDMR is less than 20%, its 90-day bending strength is basically the same as that of OPC and PPC.(3)The effect of GDMR on the bending strength of PPC at different ages is almost the same.Therefore, when the content of GDMR in PPC is less than 20%, the content of leachable heavy metals in cement meets the limit requirements of relevant national standards, but it is still necessary to pay attention to the impact of chromium, copper, nickel, and manganese dissolution on the environment.SEM and XRD analysis results of hydration products of GDMR cement paste at 1 d, 3 d, and 7 d ages are shown in It can be seen from 2 to produce calcium silicate hydrate (C-S-H) gel over time, which leads to the reduction in Ca(OH)2 content. Compared with curing for 3 d, the intensity of tricalcium silicate and Ca(OH)2 diffraction peaks decreased slightly at a curing age of 7 days, indicating that there was more hydration of cement clinker at this time. The pozzolanic activity of GDMR mainly occurs in the later stage of hydration. It can be seen that the dilution of GDMR reduces the content of cement clinker in the composite cementitious material, thus delaying the early hydration process of the composite cementitious material [As can be seen from material . Therefo(1)GDMR can adjust the fluidity of cement and the water requirement for normal consistency. When using GDMR–cement to prepare concrete, the regulation of mineral admixture GDMR and superplasticizer on concrete workability should be fully considered in the design of concrete mix proportion. The unit water consumption and water–cement ratio should be determined according to compressive strength, and appropriate modifications should be made to give consideration to durability.(2)When the content of GDMR in cement is less than 20%, the leachable heavy metal content in cement is lower than the maximum limit value of leachable heavy metal content in clinker, but attention should be paid to the environmental impact of chromium, copper, nickel, and manganese dissolution.(3)With the increase in the specific surface area of GDMR, the initial setting time and final setting time of cement are extended by 12 min and 15 min, respectively. The cement set time ratio increased by 0.06.(4)The addition of GDMR will delay the hydration process of cement, thus reducing the strength of cement mortar, especially at early ages. When the dosage is 20%, the compressive strength of 3 d and 7 d cement decreases by 16% and 17.1%, respectively. The greater the fineness of GDMR, the smaller the reduction degree of flexural strength and compressive strength, and the higher the activity index. However, the fineness should not be too large, when it is too fine it will increase the production cost and will have an adverse effect on the cement fluidity. At the same time, the content of desulfurization manganese slag should be controlled within 20%.


Early recognition and appropriate treatment has shown to decrease morbidity and mortality in patients with undifferentiated shock. There are many ultrasound protocols in shock; each protocol combines core ultrasound elements such as IVC and cardiac assessment which includes detection of cardiac tamponade, left ventricular function and right ventricular strain.Valvular assessment is absent in majority of ultasound protocols, while lung ultrasound is included in some of them.In this study we investigated which parameters used in Echo – US protocol help differentiate shock types.This cross sectional study was conducted on 150 patients with shock .Sensitivity and specificity of different parameters used in the Echo-US protocol were analyzed to detect which parameters can diffentiate shock types.p < 0.0001) and (Z = 5.079 p < 0.0001) respectively. Left ventricular systolic function, presence of pneumonia, pneumothorax or valve vegetations were of great value in differentiating shock types, while CUST, FAST, TAPSE and RV diameter were not useful in differentiating shock types.Velocity time integral of Aorta and IVC maximum diameter were good discriminators for distributive shock, with area under the ROC curve (AUC) = 0.8885 (95% CI 0.8144 to 0.9406) and 0.7728 (95% CI 0.6832 to 0.8473) (Z = 10.256 Ultrasound and echocardiography are powerful tools that can be used to identify shock etiology when the clinical picture overlaps. Shock is a circulatory failure that results in inadequate oxygen delivery to tissues . This inThe aim of this study is to investigate which echocardiography and ultrasound parameters help to differentiate various types of shock.This cross sectional study was performed prospectively at the Emergency Department of Alexandria Main University Hospital—a tertiary care center in the North of Egypt- between December 2018 and December 2020.The study was conducted on a convenience sample of 150 patients with shock admitted during the clinical shifts of the study conductor (36 h per week). All patients with shock who met the inclusion criteria of this study were enrolled, including obese patients or patients with hyper inflated chest with no selection bias. Shock was defined as SBP < 90 mmHg or shock index ≥ 1 with evidence of tissue hypo perfusion indicated by presence of delayed capillary refill time, altered mental state, low urine output, mottled skin and/or elevated lactate level . ExclusiAll ultrasound examinations were carried out by the first author, who is Point of Care Ultrasound (POCUS) & Egyptian Medical Society of Echocardiography certified with 5 years’ experience in emergency ultrasound. The study was approved by Alexandria University Ethical Committee (Reference number 0201184). Informed consent was taken from all participants or their next of kin.Echocardiography was done using Vivid e-machine  with 2.8–4 MHz phased array probe in long, short axis parasternal view, RV inflow and outflow tract, apical three, four or five chamber view. Different alternatives were used as some views could not be visualized in all patients. Ultrasound was performed by the study conductor parallel to initial assessment and resuscitation of patients which were done by treating physicians without interruption or delay of patient care. Examination was initiated with echocardiography to assess left ventricular outflow tract velocity time integral (LVOT VTI), IVC maximum diameter, collapsibility or distensibility index, which was conducted before any fluid were administered. For accurate measurement of LVOT VTI, the pulsed wave marker was placed directly in line with LVOT blood flow and the pulsed wave sampling gate was placed at LVOT above the Aortic valve . IVC colHypovolemic/ distributive shock:Classification of shock types was made based on the following:Cardiogenic shock:Both types of shock were identified by presence of: hyper dynamic heart, small collapsible IVC, normal RV diameter and function while, the presence of high LVOT VTI, empyema, pneumonia or infective endocarditis helped to distinguish distributive from hypovolemic shock.Obstructive shock:In this type of shock there was reduced LV function, valvular lesion, low VTI, large non- collapsible IVC and diffuse B- lines throughout the lung.Mixed distributive- cardiogenic shock:Diagnosis was made when signs of pneumothorax, cardiac tamponade or acute massive pulmonary embolism were found.Mixed distributive -obstructive:This was suggested when discordant findings were detected in patients with distributive shock (low VTI and reduced LV systolic function).Completing the scan revealed high VTI or ultrasound findings of pneumonia which raised the concern of an underlying septic focus.Patients received all required diagnostic and therapeutic interventions by the treating emergency physicians without delay and were followed to document their final diagnosis. Ultrasound protocol findings were correlated to reach an initial impression about shock type but not final diagnosis. A second physician established the final diagnosis, other than the emergency physician, to whom the patient was transferred to Intensive Care unit, Cardiology Department, Internal Medicine Unit or Surgical Unit. Final diagnosis was made according to reference standard for each shock type as: echocardiography performed by cardiologist for massive pulmonary embolism, cardiac tamponade and cardiogenic shock, laboratory investigations and radiological imaging including CT chest, ultrasound abdomen, CT abdomen and pelvis, interpreted by certified radiologist for septic shock. Treating physicians were not blind to ultrasound exam findings where ultrasound protocol identified life threatening conditions (39.3%) of cases such as: cardiac tamponade, mechanical complication of acute myocardial infarction, pulmonary embolism and mixed shock etiology, which would otherwise have been missed.Sensitivity and specificity of different parameters used in the Echo-US protocol were analyzed to detect which parameters can differentiate shock types., s formula for sensitivity and specificity of diagnostic health studies. To consider and anticipate drop rate of 10%, the sample size was increased to include150 patients with shock.Data were collected and entered to the computer using SPSS program  for statistical analysis (version 21) . Data weWe recruited 140 patients including 71 males (50.7%) and 69 female (49.3%) as in Table Some ultrasound and echo parameters were not feasible in all patients as shown in Tables Obstructive shock was caused by massive pulmonary embolism (PE) in 75% of cases while, 25% had cardiac tamponade. RVOT diameter > 3 cm and TAPSE < 17 mm were 100% sensitive for cases of acute massive pulmonary embolism, but with low specificity 26.13% (95% CI 18.25% to 35.32%) and 63.30% (95% CI 53.53% to 72.33%) respectively.Although tricuspid infective endocarditis had low sensitivity for distributive shock (3.06%), it helped to identify the source of sepsis as demonstrated in Figs. Ultrasound findings of pneumonia were present in distributive or mixed shock types with sensitivity between 33.67% and 80%. FAST exam could not be used to differentiate shock types as it was positive in all types of shock such as ascites, intraabdominal hemorrhage or from perforated viscus with senstivity ranging from 22.45% to 71.43%.Comparison between area under the ROC curve of IVC maximal diameter (cm) and IVC collapsibility index (%) as discriminators of hypovolemic or distributive shock showed that both were good discriminators of these types of shock as compared to other shock types with area under ROC curve (AUC) = 0.8207 (95% CI 0.7025 to 0.9065) and 0.7622 (95% CI 0.6371 to 0.8612) respectively  and (Z = 5.079 p < 0.0001) respectively versus IVC maximum diameter (cm) as discriminators for distributive shock demonstrated that both were good discriminators for distributive shock with area under the ROC curve (AUC) = 0.8885 (95% CI 0.8144 to 0.9406) and 0.7728 (95% CI 0.6832 to 0.8473)  = 0.8207. Atkinson et al. found that IVC maximum diameter < 2 cm with collapsibility index > 40–50% indicates hypovolemic or distributive shock . The AmeIn this study IVCCI > 25.5% had a sensitivity of 84.78%, specificity of 68.75%, PPV 88.6% and NPV62.2%, while Mok et al.  showed tBlanco et al.  showed tIt is essential to look for evidence of pericardial effusion in the context of critically ill patients, but it is more important to look for presence of tamponade as pericardial effusion not causing tamponade, can be present in any shock type. In this study, pericardial effusion was present in 17 patients (12.14%) but tamponade was merely present in 3 cases. This was similar to results of study carried out by Zou et al.  in whichLow specificity for RVOT diameter > 3 cm and TAPSE < 17 mm for diagnosis of acute pulmonary embolism in this study correlated with the study done by Zou et al.  in whichCompression using ultrasound test (CUST) was used for detection of deep vein thrombosis in lower limbs. CUST was negative in all cases of acute pulmonary embolism but, it was positive in patients with hypovolemic, cardiogenic and distributive shock in which advanced age, malignancy or prolonged immobilization were the underlying risk factors. This correlates with a study carried out by Atkinson et al.  who founThe sensitivity of ultrasound findings of pneumonia for detection of distributive, mixed distributive-cardiogenic and mixed distributive-obstructive were 33.67%, 71.43% and 80% respectively. The highest positive predictive value of pneumonia was for distributive shock 70.21% (95% CI 58.60%—79.70%). Pneumonia had similar specificity in all shock subtypes. This could be attributed to 70% of the studied cases had distributive shock, thus when calculating specificity for distributive shock true negative cases constituted about 20% of studied cases versus approximately 63% in other shock types. This agrees with study done by Vaidya et al.  in whichAlthough FAST exam was positive nearly in all types of shock, this provides a clue to septic focus as some cases had perforated abdominal organ or intra- abdominal abscesses that when integrated with other US findings, the diagnosis of septic shock was concluded. Trauma patients were excluded from this study but, three cases with hypovolemic shock had positive FAST exam. One patient had intra-abdominal hemorrhage due to ruptured aneurysm of celiac and renal arteries in a known case of fibromyodysplesia and the other two cases had rupture abdominal aortic aneurysm.Severe left side valvular disease was one of the causes of cardiogenic shock in this study. These valvular lesions were either a complication of acute myocardial infarction or acute decompensation in setting of underlying severe chronic LV systolic dysfunction. The presence of tricuspid infective endocarditis, despite having low senstivity for detection of distributive shock 3.06%, its specificity was 100%. Moreover, it contributed to the early detection of the septic focus especially for those at high risk for infective endocarditis Figs. .More comprehensive echocardiography was needed to diagnose all cases of cardiogenic shock as RUSH exam had a high positive likelihood ratio of 22.29 but only a moderate likelihood ratio of 0.17, so it is not a perfect test to rule out cardiogenic shock.In this study, we highlighted that specific parameters used in Echo-US protocol helps in differentiating shock types such as lung ultrasound, LV systolic function, valve assessment, presence of tamponade, IVC maximal diameter and LVOT VTI.Further studies are needed to identify if implementation of Echo- US protocol could be translated into survival benefit. This study was performed by single operator which might affect generalization of results. We cannot comment on inter- rater reliability of parameters used in the protocol. Combining these individual ultrasound and echo findings together and development of scoring system to reach final conclusion about shock etiology could be a direction for future research.Ultrasound and echocardiography are powerful tools that can be used to identify shock etiology when the clinical picture overlaps. The following exam components should be done when assessing patients with shock: LV systolic function; presence of tamponade, valve assessment, LVOT VTI, IVC and lung US, which help to detect the underlying shock etiology. Other less important parameters which did not differentiate shock type were FAST scan, CUST test TAPSE and RV diameter.


Left ventricular (LV) myocardial strain is a direct measure of myocardial deformation and an excellent method for assessment of systolic LV function. This measure overcomes some of the inherent limitations of the conventional LV ejection fraction (EF). Strain is reported as percentage lengthening and shortening, where systolic shortening results in negative and lengthening in positive strains.Strain imaging allows assessment of global LV function as reflected by global longitudinal (GLS) and global circumferential strain (GCS). GLS is widely used and has important clinical and prognostic implications in a number of cardiovascular diseases including hypertension, stroke, aortic stenosis and coronary artery disease, or in patients undergoing chemotherapy for cancer.Strain imaging also allows assessment of regional LV dysfunction/ischemia when segmental strain is impaired  or show other pathological patterns such early systolic lengthening or post-systolic shortening of both left and right ventricular (RV) myocardium.18In a recent article published in the journal (PJMS), Jun Ye et al.In a study of 323 patients who underwent CMR one week after STEMI, Gavara et al.20Hence, although CMR-FT seems to be a promising technique for assessing global and segmental myocardial strain both in patients with STEMI and cardiomyopathies, further well-designed and prospective research studies in different clinical settings with sufficient power that include both CMR-FT (2D and 3D) and STE, are needed to validate strain values measured from CMR-FT images so the exact role of CMR-FT beyond routinely used CMR indexes are documented - before the data can be used in the clinical decision-making process.SS wrote the first draft of the article which was revised by EE and THL.All authors approved the final submission.


Insulin resistance is an overlapping risk factor for both heart and breast cancer, while its interaction with cardiotoxicity in breast cancer (BC) patients is not clear. This study investigated the impact of insulin resistance on cardiac remodeling in patients with human epidermal growth factor receptor 2 (HER2)-positive BC during and after trastuzumab therapy in real-world clinical practice.HER2-positive BC patients who received trastuzumab treatment between December 2012 and December 2017 were reviewed and 441 patients with baseline metabolic indices and serial echocardiographic measurements  after trastuzumab therapy initiation were included. Repeated measurement analysis of variance was used to evaluate temporal trends in multiparameter echocardiography. Linear mixed model was applied to further evaluate the role of insulin resistance in forementioned changes. Correlation of homeostasis model assessment-estimated insulin resistance (HOMA-IR) and triglyceride-glucose index (TyG) levels to changes in echocardiography parameters was explored.P < 0.01). Noteworthy, a partial reversibility of cardiac remodeling was observed with treatment cessation. Additionally, HOMA-IR level positively correlated to changes in LA diameter from baseline to 12 months . No significant association  was detected between HOMA-IR or TyG level and dynamic left ventricular parameter evaluation. Multivariate linear regression analysis demonstrated that higher HOMA-IR level was an independent determinant for LA enlargement in BC patients during anti-HER2 targeted therapy course after adjusting for confounding risk factors (P = 0.006).Of 441 patients (mean age 54 ± 10 [SD] years), 61.8% received anthracycline-based chemotherapy, 33.5% received left-sided radiotherapy, 46% received endocrine therapy. No symptomatic cardiac dysfunction was observed over the therapy course. A total of 19 (4.3%) participants experienced asymptomatic cancer therapy-related cardiac dysfunction (CTRCD), and the peak onset time was 12 months after the initiation of trastuzumab. Albeit relatively low CTRCD incidence, cardiac geometry remodeling, especially left atrial (LA) dilation over therapy was notable and was more severe in high HOMA-IR and TyG level groups  in HER2-positive BC patients that received standard trastuzumab therapy, indicating that insulin resistance could be a supplementation to baseline cardiovascular risk stratification proforma for HER2-targeted antitumor therapies.The online version contains supplementary material available at 10.1186/s12885-023-11102-y. HFA-ICOS elaborated several risk factors for HER2-targeted cancer therapies, while scarce studies explored novel biomarker for subclinical cardiotoxicity in cardio-oncology.We presented a real-world study where insulin resistance, an overlapping risk factor of cardiac remodeling and breast cancer mortality, was associated with left atrial dilation in HER2-positive breast cancer patients receiving standard trastuzumab therapy.We first demonstrated the causal relation between the prediabetic state and cardiac remodeling in HER2-positive breast cancer patients and supposed insulin resistance as a novel risk factor for subclinical cardiotoxicity of trastuzumab treatment.This article provided novel insights into the crosstalk between metabolism, oncology and cardiology, setting the way forward for the cardio-oncology towards multidisciplinary cooperation.Breast cancer (BC) is the most common malignancy in women all over the world, among which human epidermal growth factor receptor 2-positive (HER2+) BC accounts for 20-30% patients . AdvanceThe Heart Failure Association (HFA) of the European Society of Cardiology together with the International Cardio-Oncology Society (ICOS) proposed charts for baseline cardiovascular (CV) risk stratification of several anticancer therapies . AccordiInsulin resistance (IR), defined as the uncoordinated glucose-lowering response for target tissues at a normal plasma insulin level, plays a key role in the etiology and pathogenesis of MeS , 14. HomIn terms of oncology, IR was reported to be associated with higher BC incidence and all-cause mortality –25. In pAs a hazard for both heart and breast cancer, the impact of IR on cardiotoxicity in HER2-positive BC patients has not been fully explored. Here, we investigated the association between insulin resistance and cardiac remodeling in HER2-positive BC survivors with serial echocardiography measurements during and after trastuzumab therapy in real-world clinical practice.BC patients who received surgery at General Surgery Department, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine between December 2012 and December 2017 were retrospectively reviewed. A total of 1133 patients were HER2-positive and received adjuvant trastuzumab therapy (TT). All participants were East Asian. Trastuzumab was intravenously administered with an initial dose of 8 mg/kg followed by a maintenance dose of 6 mg/kg every 3 weeks for 12 months. The main exclusion criteria included: (1) hereditary breast cancer, (2) less than 1 year of TT course, (3) previous exposure to trastuzumab or other anti-HER2 agents, (4) history of other malignancy, (5) absence of baseline metabolic indices or serial echocardiography measurements . Eventually, 441 participants were enrolled for final analysis . The adjuvant therapy scheme for each patient was decided by a multidisciplinary team consisting of breast surgeons, medical oncologists, radiation oncologists, pathologists and specialized breast nurses.Histopathological evaluation of tumor histological subtype, grade and lymphovascular invasion was conducted by professional pathologists at the Department of Pathology of Ruijin Hospital in accordance with the World Health Organization classification . Estroge2 (kilograms per square meter). Body surface area (BSA) was calculated using the formula: BSA = 0.0061 × height + 0.0128 × weight − 0.1529.The blood samples were collected in a quiet, air-conditioned room after overnight fasting and after at least 20 min supine rest. Metabolic indices including fasting plasma glucose (FPG), insulin (FINS), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein cholesterol (HDLC), triglycerides (TG) were assessed . HOMA-IR was calculated according to the formula: HOMA-IR = FINS (µU/L) × FPG (mmol/L) / 22.5. TyG was calculated using the formula: TyG = LN [TG (mg/dl) × FPG (mg/dl)] / 2. Body mass index (BMI) was calculated using the formula of weight/heightTransthoracic echocardiography was performed before and 6, 12, 18 months after the initiation of TT, via a commercially available system  with a 1.9-3.8-MHz phased-array transducer. Two dimensional (2D), pulsed-Doppler imaging was performed from standard parasternal and apical transducer positions with 2D frame rates of 60 to 100 frames/s. All data were stored digitally, and offline data analysis was performed  at the termination of the study by two cardiologists blinded to the study members.3 - LVEDD3 + 0.6. LVEDV, LVESV and LV mass were indexed by BSA calculated at each study time point.Left ventricular dimensions and wall thickness including left ventricular end-systolic diameter (LVESD), end-diastolic diameter (LVEDD), interventricular septal wall thickness (IVST) and LV posterior wall thickness (LVPWT), in diastole (d), were made in the parasternal long axis with the M-mode cursor positioned just beyond the mitral leaflet tips, perpendicular to the long axis of the ventricle. Maximal left atrial diameter (LAD) was also observed in the parasternal long axis. Left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) were measured from the apical four chamber view and calculated by Simpson’s biplane method. The LVEF was determined as the difference between LVEDV and LVESV, relative to the LVEDV. All parameters were measured twice, and the average value was recorded. Relative wall thickness (RWT) was determined by the formula: RWT = (IVST + LVPWT) / LVEDD. LV mass was estimated by the formula: LV mass = 0.8 × 1.04 × (LVEDD + IVST + LVPWT)P < 0.05 was considered statistically significant. All authors had full access to the data in the study and took responsibility for the integrity of data and accuracy of data analysis.Continuous variables were expressed as the mean and standard deviation (SD) if data were normally distributed or the median with interquartile ranges (IQR) if not. Normal distribution was evaluated with Kolmogorov-Smirnov test. Between-group differences (3 groups) were compared by one-way analysis of variance (ANOVA) if data were normally distributed or Kruskal-Wallis test if not, followed by post hoc Bonferroni test. Categorical data were summarized as proportions and frequencies and analyzed by Chi-square or Fisher’s exact test. Repeated measurement analysis of variance was used to evaluate temporal trends in multiparameter echocardiography. Linear mixed model was conducted to evaluate the impact of IR in forementioned changes. Correlation between IR and changes in echocardiography parameters was determined by Spearman’s correlation test. HOMA-IR was defined as a log-transformed continuous variable in linear regression model analysis and an ordinal variable divided by its tertiles with the lowest tertile as reference to evaluate its value. Multivariable linear regression analysis was implemented to interrogate the independent diagnostic value of HOMA-IR for LAAR. Coefficients were presented after adjusting for age, BMI, hypertension, previous CVD and whether or not receiving anthracycline-based chemotherapy, left-sided radiotherapy, endocrine therapy. All statistical analyses were performed with the SPSS 25.0 for Windows . A 2-tailed r = 0.560, P < 0.001)  and TyG (4.57 [4.42–4.75]) was higher than the normal range according to previous reports , 30. The01) Fig. 31]..r = 0.56Transthoracic echocardiography examinations before and 6,12,18 months after the initiation of 1-year course of TT were conducted according to the position statement . At baseP = 0.014), LV dilation  and LVEF decline (P = 0.080) from baseline to 12 months, while the situation was partly reversed 6 months after the cessation of TT . Likewise, a similar trend was observed between different groups of TyG at 12 months   was detected between HOMA-IR or TyG level and dynamic LV diameter and volume parameter evaluation (Table S4).As HER2-positive BC patients experienced the severest cardiac remodeling at 12 months after the initiation of TT, correlation between HOMA-IR and echocardiographic parameters changes at 12 months was further investigated. And it turned out that Log-transformed HOMA-IR level positively correlated to changes in LA diameter from baseline to 12 months (03) Fig. . No sign12m . Compared with the low tertile, high tertiles of HOMA-IR corresponded to 0.87-mm and 1.13-mm increases in LAD. In model 2, we further included whether or not receiving anthracycline-based chemotherapy, left-sided radiotherapy, endocrine therapy to rule out the impact of different treatment regimens . In summary, higher HOMA-IR level was an independent determinant for LA enlargement. In a word, insulin resistance played a role in suboptimal cardiovascular health in BC patients during TT course.Finally, multivariate linear regression was performed to interrogate the association between IR and LA dilation Table . In modeThe major finding of the current study was that relatively low CTRCD incidence but significant cardiac remodeling, especially LA enlargement, existed in HER2-positive BC patients receiving standard anti-tumor therapy. And insulin resistance was an independent determinant for LA enlargement that reflected subclinical cardiotoxicity.Monitoring of cardiac function is of critical importance for CTRCD surveillance and prevention in BC patients. Echocardiography is recommended as the first-line modality for the assessment of cardiac function in patients with cancer . Serial In our study in the non-clinical trial setting, the rate of asymptomatic CTRCD was low probably due to overall low HFA-ICOS baseline CV risk scores. Nonetheless, LAAR trend observed over TT course should not be overlooked for that it might be the herald of late cardiac complications. In line with our study, Flora et al. observed that HER2-positive BC patients suffered from significant decline in LA ejection fraction and increase in LA minimum volume during and after TT via a small prospective 2-center longitudinal study . Lisi et12m, P < 0.05). After adjusting for confounding clinical variables, including well-recognized risk factors for HER2-targeted cancer therapies proposed by HFA-ICOS, IR was independently associated with LA enlargement in HER2-positive BC patients. Furthermore, 61.8% received anthracycline-based chemotherapy and 33.6% underwent left-sided radiotherapy in our cohort. Anthracycline application moderately modified the association of HOMA-IR with changes in LAD at 12months, suggesting that the combination of anthracycline and trastuzumab exacerbated the risk of LAAR as well. Nonetheless, forementioned effect was not present in patients coincided with left-sided radiotherapy.HFA-ICOS had elaborated several risk factors for HER2-targeted cancer therapies, while scarce studies explored novel biomarkers for subclinical cardiotoxicity in cardio-oncology. IR was reported to be associated with adverse cardiac remodeling and poor prognosis of BC as well. As reported by prior studies, higher level of HOMA-IR was accompanied by lower LAS and higher LASI in general population , 40. IR The underline mechanism may be the sophisticated interaction between IR, myocardial dysfunction, BC biology and HER2 signaling. First, IR related with numerous adverse effects in the heart including perturbation in myocardial energy metabolism, mitochondrial dysfunction, endoplasmic reticulum stress, calcium homeostasis imbalance and immune response incoordination. These pathological changes fired the susceptibility of myocardial damage in that HER2 inhibition also increased ROS production, induced mitochondrial function deterioration and diminished cardioprotective effects of neuregulin 1. SecondlThe primary prevention of CV toxicity emphasizes lifestyle optimization and early intervention of CV risk factors, namely giving propriety to cardiometabolic health management. In our study, we first demonstrated the causative relation between this prediabetic state and cardiac remodeling in HER2-positive BC patients and supposed IR as another novel risk factor for asymptomatic CTRCD. Moreover, we provided a novel insight into the crosstalk between metabolism, oncology and cardiology, setting the way forward for the cardio-oncology towards multidisciplinary cooperation.We appreciate limitations in our study. First, this was a retrospective study based on prospectively collected data. Second, the evaluation of LA and LV remodeling was limited to echocardiography parameters. Cardiac magnetic resonance would provide more information. Further prospective studies are warranted to comprehensively assess the impact of IR on the composite endpoint integrating cardiology and oncology.In conclusion, this study revealed that insulin resistance was associated with LA dilation in HER2-positive BC patients receiving 1-year of TT in real-world clinical practice, which could be recognized as a sensitive indicator for asymptomatic CTRCD. We appeal for the cardiometabolic health management in BC patients since appropriate intervention of IR would promote a win-win outcome for both heart and breast cancer.Below is the link to the electronic supplementary material.Supplementary Material 1


Acute respiratory distress syndrome is characterized by non-cardiogenic pulmonary edema, decreased pulmonary compliance, and abnormalities in gas exchange, especially hypoxemia. Patients with acute respiratory distress syndrome (ARDS) who receive support with venovenous (V-V) extracorporeal membrane oxygenation (ECMO) usually have severe lung disease. Many patients with ARDS have associated pulmonary vascular injury which can result in elevated pulmonary vascular resistance and right heart dysfunction. Since V-V ECMO relies upon preserved cardiac function, right heart failure has important implications for patient evaluation, management, and outcomes. Worsening right heart function complicates ARDS and disease processes. Given the increasing use of ECMO to support patients with ARDS, an understanding of right ventricular-ECMO and cardiopulmonary interactions is essential for the clinician. A narrative review of the manifestations of right heart dysfunction, as well as diagnosis and management strategies for the patient with ARDS on ECMO, is provided. Acute respiratory distress syndrome (ARDS) is marked by non-cardiogenic alveolar edema, diminished pulmonary compliance, derangements in gas exchange, and abnormalities in the pulmonary vasculature . PulmonaThe normal pulmonary vascular bed is characterized by low resistance which is lowest at functional residual capacity (FRC) and increases as lung volumes deviate from FRC . ConsequThe vascular manifestations of lung disease have important effects on cardiac function. The relationship between ARDS and cardiac dysfunction has been well documented –11. The Given the increasing use of ECMO to support patients with ARDS, an understanding of right ventricular-ECMO and cardiopulmonary interactions is essential for the clinician. This review seeks to provide a broad overview of RV physiology and the role of the right ventricle in V-V ECMO. A narrative review of the manifestations of right heart dysfunction, as well as diagnosis and management strategies for the patient with ARDS on ECMO, is provided.Historically, the RV has been viewed as the lesser of the two ventricles with the less essential role of sending blood to the lungs while the LV perfuses the entire body . This peThe RV has a complex structure determined by a unique myofiber arrangement and interactions with the LV , 18. TheThe physiology of RV contraction also cannot be isolated from the pulmonary vasculature. In the healthy state, the RV ejects into a low-resistance, highly compliant pulmonary vascular system. Accordingly, when compared to the LV, the RV exhibits a shorter isovolumetric contraction time, earlier ejection, and lower peak systolic ventricular pressure. Additionally, the phenomenon of a hangout interval—continued ventriculoarterial ejection extending beyond cessation of ventricular contraction—occurs exclusively within the right heart . This php = 0.003, I2 = 0%) and overall mortality . These data were supported by another study of 752 patients with ARDS in which a PaO2/FiO2 ratio < 150 mmHg and a PaCO2 ≥ 48 were found to be independent factors associated with ACP  and biventricular failure (13%) in these patients. Interestingly, there was an increase in the proportion of patients with RV dysfunction following cannulation. In addition to BMI and PO2, RV dilatation was a significant predictor of mortality. Another study evaluating 121 patients with pre-ECMO hyperlactatemia showed that RV dilation before ECMO support was an independent risk factor for death   . Highlig= 0.001) .Adult patients with ARDS who receive V-V ECMO support have significant rates of RV dysfunction. In 46 adults supported with V-V ECMO for ARDS, 60% of the patients had RV hypertrophy (RVH) at cannulation . Furtherp = 0.038). Systematic detailed studies of RV dysfunction in children with ARDS supported with ECMO are lacking but case series have reported ACP in pediatric patients with acute respiratory failure on V-V ECMO  . In thisV-V ECMO .In addition to RVH and RV dilation, ARDS patients may demonstrate pulmonary hypertension. In 74 patients with ARDS supported with V-V ECMO, the pre-ECMO echocardiogram was normal in only 34% of patients while 43% had isolated pulmonary hypertension (PH) and 23% had PH with RV dilation . AdditiotV) and respiratory rates. When appropriately targeted to maintain the lungs at or near FRC, these strategies can help decrease PVR and promote normal RV function (2), V-V ECMO may result in a decrease in PVR through reversal of hypoxic vasoconstriction .In patients with ARDS, ECMO can correct abnormalities in ventilation and oxygenation with an immediate decline in pulmonary artery pressure and increase in cardiac contractility . In one Noninvasive measurement of cardiac function has similarly demonstrated that cardiac function generally improves following initiation of ECMO. One multicenter study of 675 patients with ARDS related to SARS-CoV-2 infection utilized echocardiography to evaluate function and found that while LV dysfunction was global, RV dysfunction appeared to be related to alterations in RV afterload from mechanical ventilation, hypercapnia and pulmonary emboli . Another2 while also reducing the volume load of the RV and is often considered when patients appear inadequately supported by V-V ECMO  ECMO and the hybrid cannulation strategy of venovenoarterial (V-VA) ECMO directly decrease preload to the right heart and provide direct cardiac support . The V-AV-V ECMO . In one Echocardiography is the most widely employed modality for monitoring cardiac function , 40. In Similar to the challenges affecting assessment of RV volume, deriving objective measures of RV function has been difficult. Measures such as ejection fraction (EF), shortening fraction (SF), and fractional area change (FAC) rely upon assumptions of uniform contraction and optimal imaging planes, these metrics are susceptible to the same limitations as 2D volumetric analysis . InteresdP/dT. Both TAPSE and RV-S' are measures of longitudinal RV contraction that can be obtained with relative ease. Both only measure longitudinal contractility and are limited by their high dependence on obtaining an optimal and appropriate image (dP/dT uses the tricuspid regurgitant jet velocity to assess the change in RV pressure (dP) over time (dT) , and te image . MPI is te image , while dime (dT) . Both MPaccuracy .Broader implementation of 3D echocardiography may improve the accuracy of quantitative measures of RV function. While 3D echocardiography technology has been widely adopted in many technologically advanced nations, implementation of 3D echocardiography protocols for RV function has been limited by the time-consuming and user-dependent nature of most software programs. The development of new machine learning-based programs may allow for broader clinical adoption .Ees) and pulmonary arterial elastance (Ea) with a Ees/Ea ratio of 1.5–2 (The concept of right ventricular-pulmonary artery (RV-PA) uncoupling deserves special attention. Derived from research in the pulmonary hypertension population, RV-PA coupling refers to the dynamic relationship between RV contractility and the afterload against which the RV works . In its of 1.5–2 . In the of 1.5–2 . With thof 1.5–2 .2/FiO2 ratio—was associated with increased mortality risk. In another study of 79 adults supported with V-A ECMO for cardiogenic shock, evaluation of RV-PA uncoupling was superior to other echocardiographic parameters for predicting successful weaned from ECMO  provide direct measurement of pressures relevant to RV function including CVP or RV end-diastolic pressure (RVEDP), RV systolic pressure (RVSP), and pulmonary artery pressure. Furthermore, cardiac output can be derived by thermodilution (assuming a lack of intracardiac shunting). Additionally, a PAC allows for repeated measures and real-time feedback on the effects of various interventions. However, the invasive nature of PACs and the attendant risks have resulted in declining use .Since it does not provide direct cardiac support, the goals of caring for a patient on V-V ECMO should include providing adequate gas exchange and optimizing RV function while limiting factors that will increase RV stress and strain  34, 40,,40, 58. tV was decreased on day #1 of ECMO support to below 3–4 ml/Kg while median PEEP was 12 ± 3 cm H2O  early in the post-cannulation phase of ECMO has been associated with greater survival. In one study of 168 ECMO patients at three separate institutions, 3 cm H2O . The aut2, and in those patients with ACP proning was associated with a decrease in RV dilation and septal dyskinesia. Other studies have shown prone position improved oxygenation in patients with ARDS on ECMO but pulmonary vascular and RV function were not reported  registry of 717 ECMO exposures from 2009 to 2013 in adults with ARDS who received inotropic or vasopressor agents prior to cannulation, 82.4%% received V-V ECMO and 4% required conversion to VA ECMO . PatientIn lieu of altering the ECMO circuit, an alternative option to provide cardiac support while on V-V ECMO includes the addition of an intra-aortic balloon pump (IABP). Although this device operates on the systemic circulation side, the use of IABP has been shown to be helpful in patients with RV or biventricular failure, likely related to the significant ventriculoventricular interactions that affect RV function , 67. Onep = 0.008 and 5.6% vs. 42.9%, p = 0.011).Another approach to managing patients with ARDS and RV dysfunction is the use of a temporary RV assist device (RVAD) placed percutaneously into the pulmonary artery [Protek Duo ] . A singlOverall, the body of evidence supporting specific ECMO or RVAD approaches in the ARDS/RV dysfunction population is limited. There is a great need for randomized studies comparing different cannulation strategies in those with RV dysfunction and evaluating the optimal timing of RV support. One potential approach supplementary support is presented in Right ventricular and pulmonary vascular abnormalities occur commonly in patients with ARDS, especially those with disease severe enough to require V-V ECMO. Severe ARDS can result in elevated PVR thereby increasing RV afterload. This cascade of factors can result in RV dysfunction and subsequent LV dysfunction due to ventricular interdependence. RV dysfunction appears to be associated with worse outcomes in patients with ARDS. V-V ECMO may improve RV afterload by ameliorating hypercarbia and hypoxemia, while permitting protective or ultraprotective ventilation strategies. V-V ECMO usually provides adequate support for the RV but severe dysfunction has been documented despite ECMO support. Thus, care of the patient with ARDS and RV dysfunction on ECMO requires attention to optimizing right ventricular unloading even after cannulation. Careful echocardiographic evaluation should help guide management. Consideration of therapeutic approaches should be broad and include pharmacologic, ventilator, positional, and cannulation/VAD modalities. Further research is needed to elucidate conditions which may exacerbate RV dysfunction and to evaluate therapies which can optimize RV function in the patient requiring ECMO support.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Ventricular arrhythmias, particularly ventricular tachycardia, are ubiquitously linked to 300,000 deaths annually. However, the current interventional procedure—the cardiac ablation—predict only short-term responses to treatment as the heart constantly remodels itself post-arrhythmia. To assist in the design of computational methods which focuses on long-term arrhythmia prediction, this review postulates three interdependent prospectives. The main objective is to propose computational methods for predicting long-term heart response to interventions in ventricular tachycardia Following a general discussion on the importance of devising simulations predicting long-term heart response to interventions, each of the following is discussed: (i) application of “metabolic sink theory” to elucidate the “re-entry” mechanism of ventricular tachycardia; (ii) application of “growth laws” to explain “mechanical load” translation in ventricular tachycardia; (iii) derivation of partial differential equations (PDE) to establish a pipeline to predict long-term clinical outcomes in ventricular tachycardia.  Predicting long-term ablation targets for ventricular tachycardia (hycardia –7. Clinica2.p = 0.016) , ICDs still remain the most effective method to reduce SCD incidence  . The cur= 0.016) .Current ablation procedures use computer simulations that apply a general time-based approach pivoted around the left ventricular ejection fraction (LVEF) to predict arrythmia risk , 7. HoweCurrently, the science focus of most funding agencies is to back innovative research strategies which have scientific rigor and to look out for cost-effective disease interventions. This aligns well with our preposition design of personalized computational models, specifically for the long-lasting ventricular arrhythmia prognosis. These models not only resemble diseased hearts and can simulate mechanistic relationships of cardiac pathologies, but also personalize the interventions specific to the patient's heart condition as previously shown by Trayanova et al., Kroon et al., and Bifulco et al. , 8–10.3.The postulated mechanisms in the pathogenesis of VT include triggered activity, altered automaticity, and re-entry . In this+ ions in cardiomyocytes, forming “metabolic” sinks of current. As mentioned above, O'Rourke's lab created the first cardiac cell model to link: (1) ion fluxes, (2) energy-consuming reactions , and (3) energy production. With respect to hemodynamic homeostasis, they have reported that growth and remodelling, i.e., thickening, and lengthening of cardiac myocytes translates into electrophysiological alterations that could lead to the “re-entry” phenomenon in VT   . The priThe proposition is innovative because it represents a new and substantive departure from the status quo. It utilizes the “metabolic sink theory” to define the re-entry mechanism of ventricular arrhythmogenesis via the development and innovation of cardiac simulation equations. It is driven by the fact that re-entry mechanisms underlying arrhythmogenesis are not comprehensible by direct experimental observation. The reason being the overlapping emission spectra of fluorescent indicators make it hard to record cardiac myocyte ATP/ADP ratio and membrane potential currents simultaneously. Additionally, it provides an understanding of the multifaceted relationship between metabolic and electrophysiological activity. Importantly, the insights gained might improve the selection criteria for ICD candidates and lead to new pharmacological therapies to combat arrhythmia.4.in vivo by enforcing artificial stretches and strains  patients with ICDs, measured using the HeartLogic (Boston Scientific) Index and indicated by an increased third heart sound amplitude, facilitates ventricular ectopy that can trigger VT . Thus, a strains . Severalodelling .Functionally, heart muscles undergo pressure and volume adaptations in terms of growth and remodelling to counter VT. These adjustments allow heart's residual healthy tissue to enable pump blood throughout the body to meet the organ systems’ oxygen perfusion demand. Specifically, heart's blood pressure and volume control system change its geometry to adapt to this new mechanical load by transferring mechanical stress and strain signals to the heart walls. Of note, when ventricles are subjected to increased pressure and/or volume overloading, “growth laws” predict how much would be the compensatory concentric growth  and/or eccentric growth (lengthening of myocytes), respectively. A typical example was Taber's embryonic growth model of heart's alterations in ventricular chambers during foetal growth. Their group acknowledged that pre-natal hyperplasia (increase in cell size) and post-natal hypertrophy (increase in cell number) in response to volume and pressure load respectively was similar to structural changes in human heart . They ar5.As interventional cardiologists face the equivocal challenge of performing the specific interventional procedure for a particular patient, precision medicine paved their way out . PersonaTo construct a 3-dimensional (3D) computer model of an individual patients diseased heart, first LGE-MRI scans are acquired to reconstruct the heart's geometry and fiber/sheet orientation. LGE-MRI scans, in particular—denote a specific variant of cardiac resonance scans that are meant to estimate myocardial regional scar formation and/or fibrosis . Specifiin vitro cell experiments, animal experiments and human studies  “pipeline” for image-based reconstruction of heart geometry and structure is outlined in With the rapid advancement in catheter design and technology  to get accurate information about the patient heart's electrophysiological condition invasively as well as the development of powerful algorithms like coherent mapping, LAT hybrid module and map replay modules from CARTO®3  that provide information critical to accurate VT ablation, these powerful tools can be used to validate our proposed PDE models , 30. In 5.1.Whilst some basic context is provided, this review is not intended to provide coding intricacies or comprehensively discuss mechanistic pathways at the cellular level. For clarity, the intention of this review is to provide three key considerations to assist in devising simulations of long-term heart response to interventions avoiding multiple ablation procedures on patients.6.cardiac ablation—envisage only short-term responses to VT, clinicians have begun to focus on computational methods predicting long-term post arrhythmia responses. To assist in this design, this review postulated the existing gaps in literature. First, the “metabolic sink theory” define the re-entry mechanism of ventricular arrhythmogenesis via development and innovation of cardiac simulation equations. Second, computer-generated simulation models can be haemodynamically translated by applying the “growth laws”—a system of equations that experimentally induce pressure and volume load in vivo by enforcing artificial stretches and strains. Lastly, the derivation of partial differential equations (PDE) “pipeline” for image-based reconstruction of heart geometry and structure will pave way for personalized medicine. The current ventricular tachycardia predictors, particularly in patients who are at high risk of SCD lack specificity. Our proposed mechanistic basis of arrhythmogenesis not only predict long-lasting ventricular tachycardia prognosis, but also has the potential to offer insight into personalized interventions specific to individual patient. Although, we are far-flung from predicting clinical outcomes in ventricular tachycardia (VT), these perspectives can still accelerate the long-term VT prediction quest.While current interventional procedure—the