Postoperative SpO2 values, measured at room temperature also increased significantly . There was a significant improvement after surgery in RV systolic functions, represented by global longitudinal strain (GLS)  and systolic global longitudinal strain rate (GLSRs) . No significant differences in terms of RV diastolic function parameters were detected, including the RV early diastolic global longitudinal strain rate (GLSRe)  and RV late diastolic global longitudinal strain rate (GLSRa) . Conclusion: This study was performed with an advanced technique capable of tissue level examination. The findings demonstrated significant improvement in both chronic hypoxia and RV systolic myocardial functions, measured at the tissue level after nasal surgery.Objective: One of the most common causes of upper airway obstruction in adults is nasal septum deviation (NSD). The chronic hypoxia caused by this obstruction gradually leads to increased pulmonary vascular resistance, pulmonary hypertension (PHT), and right ventricular (RV) failure. The purpose of this study was to determine changes in RV myocardial functions at the tissue level before, and after surgery in patients with NSD. Subjects and Methods: Fifty-eight patients with symptoms of nasal obstruction and snoring were included in this observational study. Preoperative and postoperative third-month peripheral arterial oxygen saturation (SpO2), and RV systolic and diastolic functions measured by pulmonary artery systolic pressure (PASP), tissue Doppler parameters, and speckle tracking echocardiography (STE) were studied in these patients. Results: We observed a very significant decrease in PASP in the postoperative period (32.54 ± 5.24 mmHg vs. 24.22 ± 4.55 mmHg,  The nose constitutes the main conduit of the upper respiratory tract and is responsible for approximately half of airway resistance. Nasal septum deviation (NSD), is a frequent cause of nasal obstruction in adult patients. Other causes of upper airway obstruction include adenoid vegetation, tonsillar hypertrophy, nasal polyps, and nasal valve pathologies ,4,5,6,7.The main diagnostic procedure in the evaluation of the effect of this obstruction on RV functions, is the transthorasic echocardiography. The effects of upper airway tract obstruction on the right ventricle have been evaluated using various echocardiographic methods ,9,10,11.The recently developed two-dimensional (2D) strain–strain rate or speckle tracking echocardiography (STE) is a new, non-invasive, reproducible, objective and minimally operator-dependent method, which measures myocardial functions at the tissue level . The strThis study, evaluated the RV functions in patients with NSD-related nasal obstruction before and after the corrective surgery, using conventional and STE parameters.To the best of our knowledge, this was the first study using this method to evaluate patients who underwent surgery due to NSD in terms of RV function in the postoperative period.The study commenced post-approval, from the Erzurum Regional Training and Research Hospital Clinical Research Ethics Committee . All procedures involving human participants were performed in accordance with the ethical standards of the institutional and/or national research committee and were in line with the Helsinki Declaration, and its later amendments or comparable ethical standards. The study was conducted between, June 2016 and May 2017 at the Cardiology and Otorhinolaryngology departments of Kayseri Education and Research Hospital .Fifty-eight patients scheduled for septoplasty due to nasal obstruction and snoring were included in this observational study. All patients were informed about the study and they gave written their consent to participate. Anterior rhinoscopic and transnasal endoscopic examinations of all patients were assessed by an otorhinolaryngologist. Patients with marked NSD, with or without inferior concha hypertrophy were selected. All patients underwent echocardiographic evaluation before, and three months after surgery. Patients with a history of cardiovascular disease, diabetes mellitus, hypertension, sleep apnea, chronic obstructive pulmonary disease, smoking or other conditions that might cause RV dysfunction or pulmonary hypertension were excluded from the study. Other exclusions, comprised of patients with a history of long-term drug use for chronic diseases and upper airway tract obstructions other than NSD or inferior concha hypertrophy .2).The peripheral oxygen saturation (SpO2), heart rate, diastolic blood pressure (DBP) and systolic blood pressure (SBP) of all patients, were measured using a pulse oximeter in the same room before, and three months after surgery. Body weight and height were also recorded. Body mass index (BMI) was calculated as weight in kilograms divided by the square of height in meters  scale. Patients with NOSE scores of 75–100 were included in the study ,17.All patients were operated on by the same surgeon, under general anesthesia. A standard septoplasty technique was applied in all cases. Each nasal cavity was packed with a piece of gauze pack, containing adrenaline dissolved in saline at a concentration of 1:200,000. The gauze was removed 15 min after the start of surgery. The cartilaginous and bony nasal septum was exposed from both sides by the elevation of mucoperichondrial and mucoperiosteal flaps. Deviated structures were then removed . SufficiEchocardiographic measurements of all patients were performed using a 2.5 MHz probe and GE Vingmed Vivid 7 echocardiography device , under electrocardiography (ECG) monitoring, with patients in the left lateral decubitus position, as recommended by the American Society of Echocardiography guidelines . All meaRV images were taken from apical four chamber images. Three consecutive cycles in deep inspiration were recorded. The images with the best visible RV endocardial margins were then selected. Recorded images were transferred to the workstation  for offline analysis. The frame rate was 50–90 frames/s. The automated function imaging (AFI) protocol was applied for strain and strain rate analyses. A mean six to seven points were selected starting from the basal septum. After shifting to the cardiac cycle dynamic mode of the selected image, the parts of the selected points out of the pericardium were corrected manually. The consistency of the selected image with aortic valve closure time, and end of the electrocardiographic T wave was then checked. Global longitudinal systolic strain (GLS), global longitudinal systolic strain rate (GLSRs), global longitudinal early diastolic strain rate (GLSRe) and the global longitudinal late diastolic strain rate (GLSRa) values, were measured from each image ,21 Figu.t test, was used to compare parametric variables between pre- and postoperative third month measurements. SPSS 19.0 statistical analysis software  was used to evaluate and test variables. p values < 0.05 were considered significant.Continuous variables were presented as mean ± standard deviation, and categorical variables as percentages. The Kolmogorov-Smirnov test was used for analysis of distribution of variables. All continuous variables exhibited normal distribution. The paired samples p < 0.01). Preoperative and postoperative third month echocardiographic and oxygen saturation data, are shown in p = 0.001) was observed. A significant increase was also determined in postoperative SpO2 values, measured at room temperature  (p = 0.013) and GLSRs . We observed no significant difference, in terms of RV diastolic function parameters including RV GLSRe  and RV GLSRa  (Patients’ demographic data are shown in = 0.001) . Tissue  = 0.76) .NSD and concha hypertrophy, are frequent causes of nasal obstruction in patients who snore. Other causes of upper airway obstruction include adenoid vegetation, tonsillar hypertrophy, nasal polyps, allergic rhinitis, and nasal valve pathologies. Several studies have examined the adverse effects of NSD on the heart ,2. RecenChronic hypoxia due to obstruction in the upper respiratory tract, such as NSD, induces pulmonary vasoconstriction and leads to increased pulmonary capillary pressure. This increase in pulmonary capillary pressure can result in PHT and RV failure ,22. PHT Many parameters, such as PASP, tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), RV index of myocardial performance (RIMP), and right isovolumic myocardial acceleration (IVA) can be used to evaluate RV systolic functions. However, these parameters are volumetric load—and angle-dependent . In routThe evaluation of RV functions is challenging because of the complex structure in patients with mild PHT. The principal method for determining global or segmental RV functions is tissue Doppler imaging. However, this also poses several disadvantages, including active and passive tracking effects of the adjacent myocardial tissues and angle dependence. STE is a tissue Doppler-based technique capable of measuring both systolic and diastolic functions without angle and with minimal operator dependence. It has been described as a more suitable echocardiographic method for the assessment of RV functions ,28. RV lThe automated function imaging (AFI) protocol was originally designed for LV strain analysis. However, an assessment of global and regional strain values using AFI has been shown to be superior to 2D strain and more sensitive to RV pressure loadings . This stStudy limitations: STE-based imaging necessitates better image quality and clear definition of endocardial borders. This study excluded patients with poor image quality. Acoustic rhinometry measurements could have also provide more objective results, but this was not possible citing technical reasons.Our study’s findings indicated significant improvement after surgery in both chronic hypoxia, and RV systolic myocardial functions measured at the tissue level in patients with marked NSD.Nasal obstruction has subclinical effects on the right ventricle, which is a cause of significant health problems. Therefore, patients who need septoplasty operations should be informed about the procedure’s positive effects on the cardiac system. Clinicians should be aware that correction of NSD has the potential to improve the RV systolic function and should consider early septoplasty to avoid the development of RV systolic dysfunction and heart failure.


DSTI) in detecting left ventricular systolic function in patients with dilated cardiomyopathy (DCM).To explore the value of three‐dimensional speckle‐tracking imaging (3DCM patients were enrolled in this study. Left ventricular end‐systolic volume (LVESV), left ventricular end‐diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF) were measured using the 3DSTI, two‐dimensional echocardiography (2DE), and magnetic resonance imaging (MRI). Left ventricular end‐diastolic mass (EDmass) and left ventricular end‐diastolic mass index (LVEDmass I) were also detected by 3DSTI and MRI. The differences in these measurements were analyzed and compared.Totally 31 LVESV, LVEDV, and LVEF showed significantly positive correlations among 2DE group, 3DSTI group, and MRI group. The LVEF value showed significant difference among these three groups , whereas LVEDV and LVESV values were not significantly different . Inter‐group comparison showed the mean of LVEF was significantly lower in MRI group than in 2DE group (P = 0.031), whereas there was no significant difference between 2DE group and 3DSTI group and between 3DSTI group and MRI group . The EDmass and EDmassI detected by 3DSTI and MRI were (143.2 ± 40.2) g vs (190.0 ± 58.3) g and (83.2 ± 21.1) g/m2 vs (110.1 ± 29.7) g/m2 .The values of LVEF value detected by 3DSTI is closer to that detected by MRI in DCM patients.The  These patients were in New York Heart Association (NYHA) class III–IV.2.2The equipment used in this study included: a) the Vivid E9 Ultrasound System , which used the M3S and V3 probes with frequencies of 1.7–3.4 and 1.7–3.5 MHz, respectively, for 3DSTI and used the M5S probe with frequencies of 2.0–4.5 MHz for 2DE. Cardiac MRI was performed using a 1.5T MR scanner  with a 48‐channel phased array surface coil.2.3Cardiac images were collected and stored by 2DE and 3DSTI, respectively. The images were acquired by the same cardiac sonographer and then the 2DE and 3DSTI images were analyzed independently by two other cardiac sonographers respectively. Each image was analyzed twice by the same cardiac sonographer at different times, and the average value of the two values is used for statistical analysis.2.3.1Left ventricular end‐systolic volume (LVESV), left ventricular end‐diastolic volume (LVEDV), and LVEF were measured using the biplane Simpson's method in the apical two‐ and four‐chamber views.2.3.2The M3S probe was placed at the apex and near the sternum to collect the 2D ultrasound images in four‐chamber, two‐chamber, left ventricular long‐axis, mitral valve level, papillary muscle level, and apical left ventricular short‐axis views. The V3 probe was placed at the apex to collect images in the apical four‐chamber, two‐chamber, and left ventricular long‐axis views, followed by collection of four consecutive cycles of cone images when patients were holding their breath to form the left ventricular full volumetric 3D images. The images were processed and stored by using the GE EchoPac software. The full volumetric images during the systolic and diastolic periods in the four‐chamber, two‐chamber, and left ventricular long‐axis views were collected to determine the endpoints of the connection line between apex and mitral annulus. The software automatically generated the left ventricular endocardial and the epicardial boundaries, which could be manually adjusted. Subsequently, the software automatically generated LVESV, LVEDV, LVEF, and left ventricular end‐diastolic mass (EDmass). Then, the left ventricular end‐diastolic mass index (LV EDmass I) was calculated based on the body height and body weight.2.3.3The images at transverse, coronal, and sagittal positions and in the standard two‐ and four‐chamber views were collected; with these images as scout images, the cine images in short‐axis, two‐chamber, and four‐chamber views were acquired. A fast gradient echo pulse sequence was used to scan from the base of the heart to the apex sequentially, and the results were collected 6–8 times. The scanning parameters were as follows: time of repetition (TR), 39.75 ms; time of echo (TE), 1.11 ms; layer thickness, 8 mm; interlayer spacing, 0 mm; field of vision (FOV), 340 × 276 mm; deflection angle, 80°; and bandwidth, 930 Hz. After the scanning was completed, the original images were input into the postprocessing workstation, and the epicardium and endocardium regions were delineated from the base of the heart to the apex by manual sketching, and the results were adjusted by manual and semiautomatic calibration. The software automatically calculated LVESV, LVEDV, LVEF, and EDmass. Then, the LV EDmass I was calculated based on the body height and body weight.2.4x ± s). One‐way ANOVA was used to analyze the data differences among these three groups, and Student‐Newman‐Keuls test was used to compare the data between two groups. The comparisons between two groups were based on t test. Correlation analysis was based using Pearson correlation analysis; P < 0.05 was considered significantly different.Data were expressed as mean ± standard deviations , whereas there was no significant difference between 2DE group and 3DSTI group and between 3DSTI group and MRI group . The means of LVESV and LVEDV showed no significant difference among three groups .The values of LVESV, LVEDV, and LVEF detected by the three methods were positively correlated with each other (3.22 vs (110.1 ± 29.7) g/m2, decreased by 24.6% and 24.4% . Therefore, the left ventricular diastolic myocardial mass measured by 3DSTI was underestimated compared with that measured by MRI.The EDmass and EDmassI detected by 3DSTI and MRI were (143.2 ± 40.2) g vs (190.0 ± 58.3) g and (83.2 ± 21.1) g/m4Left ventricular ejection fraction is the most valuable indicator that reflects the degree of left ventricular systolic dysfunction and predicts the prognosis of patients with chronic congestive heart failure (CHF). LVEF is calculated as the difference between LVEDV and baseline LVEDV, divided by baseline LVEDV. Accurate measurement of LVESV and LVEDV ensures a true LVEF.The modified Simpson method is the most commonly used method for detecting LVEF in clinical settings. It estimates LVESV and LVEDV by measuring intracardiac area. Its accuracy is based on the uniformity and coordination of the left ventricular wall motion, and there is no abnormal segmental wall motion. In theory, the LVESD and LVEDV yielded by 3DSTI are based on the change in left ventricular volume and thus are more accurate than the LVESV and LVEDV values estimated by 2DE, especially when the left ventricular wall motion is uncoordinated or segmental.P > 0.05), the values of LVEF, calculated by LVESV and LVEDV, showed significant difference among these three groups (P < 0.05). The LVEF values showed a decreasing trend in 2DE, 3DSTI, and MRI groups. Although the LEVF value in 3DSTI group was not significantly different from those in 2DE group and MRI group , it was significantly different between MRI group and 2DE group (P < 0.05). In DCM patients, the value of LVEF obtained by 3DSTI was closer to that obtained by MRI than that obtained by 2DE. Of course, only 31 cases of DCM patients were included in this study, which may be the reason why there was no statistical difference in LVEF measurement between 3DSTI group and 2DE group.As shown in our current study, there were significant positive correlations among the values of LVESV and LVEDV obtained by 2DE, 3DSTI, and MRI and then the LVEF value, suggesting the data obtained by these three methods are quite similar. Currently, the MRI is regarded as the gold standard for detecting left ventricular systolic function. Therefore, the values of LVESV, LVEDV, and LVEF obtained by both 2DE and 3DSTI can, at a certain degree, reflect the real left ventricular systolic function. Although there was no significant difference in the values of LVESV and LVEDV among these three groups , suggesting that the results of left ventricular end‐diastolic myocardial mass measured by 3DSTI were remarkably underestimated when compared with those in MRI.For CHF patients, the left ventricular myocardial mass reflects the degree of left ventricular remodeling and is an indirect indicator of left ventricular dysfunction. In our current study, the mean values of EDmass and EDmassI in 3DSTI group were 24.6% and 24.4% lower than those measured by MRI (In conclusion, LVEF is the most commonly used parameter for evaluating left ventricular systolic function. In DCM patients, LVEF value measured by 3DSTI is closer to that detected by MRI. It indicated that, as a more convenient and affordable technique on LVEF detection, 3DSTI is more feasible in clinical application than MRI.


Background: According to the ventricular myocardial band model, the diastolic isovolumetric period is a contraction phenomenon. Our objective was to employ speckle-tracking echocardiography (STE) to analyze myocardial deformation of the left ventricle (LV) and to confirm if it supports the myocardial band model. Methods: This was a prospective observational study in which 90 healthy volunteers were recruited. We evaluated different types of postsystolic shortening (PSS) from an LV longitudinal strain study. Duration of latest deformation (LD) was calculated as the time from the start of the QRS complex of the ECG to the latest longitudinal deformation peak in the 18 segments of the LV. Results: The mean age of our subjects was 50.3 ± 11.1 years. PSS was observed in 48.4% of the 1620 LV segments studied . PSS was more frequent in the basal, medial septal, and apical anteroseptal segments (>50%). LD peaked in the interventricular septum and in the basal segments of the LV. Conclusions: The pattern of PSS and LD revealed by STE suggests there is contraction in the postsystolic phase of the cardiac cycle. The anatomical location of the segments in which this contraction is most frequently observed corresponds to the main path of the ascending component of the myocardial band. This contraction can be attributed to the protodiastolic untwisting of the LV. Left ventricular (LV) function relies on the contraction and relaxation of a complex myocardial fiber architecture organized as a syncytium, which determines changes in the shape and size of the LV ,2.One of the most widespread approaches to describe cardiac function and architecture is Torrent-Guasp’s ventricular myocardial band ,4. AccorVentricular ejection is produced by myocardial contraction of the basal loop and the descending apical segment after stimulation of the endocardial Purkinje fibers ,13, whicAccording to the myocardial band model, the initial diastolic phase that follows ejection is a result of the muscular contraction of the ascending segment of the apexian loop ,16,17, rTwo-dimensional echocardiography allows us to analyze time and space in the complex mechanism of myocardial contraction and deformation in a noninvasive way. We examined segmental myocardial deformation of the LV by speckle-tracking echocardiography (STE), particularly during the initial diastolic isovolumetric period, and assessed its possible correspondence with the active contraction of the ascending segment of the apexian loop suggested by the myocardial band model.This was an observational, prospective study initially including 104 healthy volunteers randomly selected among hospital staff. Inclusion criteria were: age >18 years, absence of cardiovascular disease, and normal physical and electrocardiographic examination results. Exclusion criteria were sports training, pregnancy, and presence of cardiovascular risk factors.The study was approved by the Clinical Research and Ethics Committee of the Hospital. The written informed consent of all the participants was obtained.We employed an ultrasound system  equipped with a 2.5-MHz transducer.Two-dimensional projections of the apical plane  were obtained to calculate longitudinal strain (LS). All images were obtained with a frequency of 50–80 frames/s. The moment of aortic valvular closure was determined in the long axis apical projection. All examinations were transferred to a workstation for computer analysis .To calculate LS, the LV endocardial border was traced manually. Next, a larger second concentric circle was automatically generated near the epicardium to include the entire thickness of the myocardium. The program divided each projection into six equal segments and performed speckle tracking frame by frame, providing automatized tracking confirmation (verified by the operator) and generating strain values, expressed as percentages. LS was used to analyze the occurrence of postsystolic shortening (PSS)  and is dThe duration of latest deformation (LD) was defined as the time from the beginning of the QRS complex in the ECG to the latest longitudinal deformation peak , be it sWe drew the bull’s eye map with the percentages of PSS registered for each of the 18 segments of the LV. The mean of LD times in each segment was used to estimate the segmental deformation sequence.t test as appropriate. A p value < 0.05 was considered statistically significant. Continuous variables are expressed as mean and standard deviation (SD). Strain values between men and women and between regions were compared using a Student’s The intraclass correlation coefficient was used to evaluate intraobserver and interobserver reproducibility of continuous variables for a random sample of 10 cases, with masking and measurements performed at different moments. Graphical representation was analyzed using the Bland–Altman method. Statistical analyses were performed using the IBM SPSS Statistics v.19.0.0329 software package.The study population finally consisted of 90 healthy subjects after excluding 14 due to a deficient ultrasonic window that made it impossible to obtain adequate measurements in all segments of the LV. p < 0.001) and 0.87 , respectively.PSS was observed in 48.4% of the 1620 segments analyzed . PSS type 1 was the least frequent (9.4%), while PSS type 2 and 3 represented 19.6% and 19.4%, respectively. PSS types according to LV region are shown in PSS percentage according to segment and type are shown in The mean time to aortic valve closure was 372 ± 35 milliseconds. In order to compare how our results were in line with the anatomical distribution of the apical loop described by Torrent-Guasp, we designed Special emphasis is placed on the systolic stretching and postsystolic contraction of the ascending fibers (discontinuous purple lines) during their movement. The superposition of PSS distribution  and LD sWe described the location of PSS and the temporal sequence of the left ventricle using the noninvasive technique of STE. The study population consisted of healthy subjects, so we could assume that PSS after aortic valve closure was the result of a contraction in the segment in which it was observed. PSS has been identified as a marker of myocardial dysfunction, mainly during cardiac ischemia and after infarction ,19. HoweSTE provides information about the complex mechanism of myocardial contraction and the deformation that follows. In our study, PSS was observed in all of the segments of the LV, though the percentage was highest in the interventricular septum and the basal segments . AdditioPSS was described in healthy subjects by Voigt et al. , who useThe localization of PSS and the LD sequence observed with STE provide functional data that endorse the muscle band theory of Torrent-Guasp ,4,5,6,9.According to the myocardial band model, blood is expelled as a result of the contraction of the basal loop and the descending segment of the apex loop. This contraction produces a thickening of the myocardium towards the ventricular centroid and “screws” the base to the apex by its simultaneous rotation in opposite directions (twist) , therebyWhile this occurs, the ascending portion of the apexian loop , which mainly covers the descending segment at the septum up to the aortic root and the base of the LV, is “stretched” .Torrent-Guasp’s myocardial band model describes the initial diastolic phase following ejection as a phenomenon that arises due to the muscular contraction of the ascending segment of the apexian loop ,16,17. WThis hypothesis implies a later mechanical activation at the epicardial level. Sengupta et al.  found thFonafagou et al.  used eleAshikaga et al. and Sengupta et al. described something similar with models of electrical activation, also observing that the LV subendocardium was activated before the subepicardium and the apex before the base ,26. In aNot only does the muscular component itself intervene in this process. The restoration of the potential energy that is generated when the myocardial tissue becomes deformed tends to return the myocardium to its resting form. The systolic deformation of the extracellular matrix  and myocThe presence of PSS observed with STE in myocardial segments that have initiated the relaxation process suggests the existence of an additional delayed active contraction after aortic valve closure. The anatomical arrangement of the segments in which PSS is most frequently recorded is consistent with the main path of the ascending component described by the myocardial band model of Torrent-Guasp. The postsystolic contraction of this component, which occurs later due to its epicardial situation, suggests it plays a role in the protodiastolic longitudinal elongation and untwisting of the LV and promotes the diastolic suction of the blood into the ventricular cavity.


Heart murmur was auscultated during routine examination at 6 years of age, withcomplaints of tachycardia and chest pain at that time. A diagnosis of mitralregurgitation caused by hammock mitral valve was performed and enalapril 2.5 mg/day(0.1 mg/kg) was started. She reported being asymptomatic, capable of performingphysical activity.Physical examination: good overall health status, eupneic, acyanotic,normal pulses in the four limbs. Weight: 25 kg; height: 130 cm; right upper limbblood pressure: 90 x 60 mmHg; Heart Rate (HR): 96 bpm; Oxygen Saturation(O2Sat): 97%.Precordium: diffuse apex beat, palpated in the sixth left intercostalspace, deviated from the midclavicular line and with systolic impulses in the leftsternal border. Muffled heart sounds, holosystolic murmur in the mitral and axillaryregions with a diastolic rumble after the third heart sound, both of moderateintensity. Liver palpable at the right costal margin, painless.Electrocardiogram: sinus rhythm, with signs of overload of the leftcavities. High R waves, preceded by positive Q waves and with normal T waves, inthe left leads, indicating left ventricular (LV) diastolic overload. The P wavewas negative at V1 and V2 and enlarged at the other leads. Ventricularrepolarization was normal. AQRS + 30º; AP + 50º and AP +60º.Chest X-ray: Increase in the cardiac area at the expense of the leftheart cavities and with prominent pulmonary vascular network in the upperpulmonary area, indicating of pulmonary venocapillary congestion . The mitral annuluswas thickened, with important valve regurgitation, which allowed the appearanceof a maximum diastolic gradient of 28 mmHg and a mean of 10 mmHg. The pulmonaryarteries were confluent and slightly dilated (13 mm). MPAP: 36 mmHg; RightVentricle (RV): 12; LV: 56; Left Atrium (LA): 59; Ao: 17; septum and posteriorwall: 7; LV Ejection Fraction (LVEF): 63%; mitral annulus: 30; tricuspidannulus: 21 mm (s: 21 mm .Clinical diagnosis: important mitral regurgitation caused by hammockmitral valve with enlargement of the left heart cavities in an 8-year-old girlwithout apparent symptoms.Clinical rationale: There were clinical elements pointing to adiagnosis of important mitral valve regurgitation, related to the presence of aregurgitation systolic murmur and diastolic rumble in the mitral area and in theaxillary region. The clinical effect was accentuated due to the large increaseof the left heart cavities, disclosed by the usual complementary examinations.The diagnosis was well established by the echocardiography regarding thecongenital etiology of the defect in the anatomical characterization of thehammock mitral valve. It was observed that, despite the marked consequence ofthe defect, the patient remained symptom-free and under natural evolution until8 years of age.Differential diagnosis: with the diagnostic characterization ofmarked mitral valve regurgitation, the differential diagnosis refers to thesearch for its etiology. At this age, one should remember the rheumatic cause,even without suggestive prodromes. Other causes may be related to mitral valveprolapse, valve lesion due to endocarditis or an ischemic lesion of anomalousorigin in the left coronary artery directly from the pulmonary trunk.Conduct: Considering the marked consequence of the mitral valvedefect, there was a surgical indication aimed to correct the defect and preventmore severe disease evolution alterations, such as ventricular dysfunction,pulmonary artery hypertension and cavity thrombosis with systemic embolism,among the main ones. It was presumed that the most appropriate technique wouldbe the mitral valve replacement, which was markedly affected, but with a chanceof success through a plasty procedure, to be evaluated at the time of thesurgery.The hammock mitral valve was first described as a direct connection of the papillarymuscles with the mitral leaflets, either directly or by the interposition ofunusually short chordae tendineae. This congenital malformation of the tensilesystem is sometimes called a “hammock mitral valve”, as it mimics a hammock when itis observed from the atrium. The chordae tendineae are thick and extremely short,reducing inter-cordial spaces and leading to an abnormal excursion of the leaflets,which can cause stenosis and regurgitation.1When the space between the abnormal chordae is completely obliterated, a fibrous andmuscular bridge joins the two papillary muscles. In its most severe form, with nochordae tendineae, the papillary muscles are directly fused with the free margin ofthe leaflets. Mitral regurgitation progressively worsens, with or withoutconcomitant stenosis. However, even with these anatomical alterations, the valve mayshow a relatively normal function for many years, as shown by some recentfindings.4Most reported cases are in the pediatric age group, and there are only a few reportsof hammock mitral valve anomaly in adults. In cases of hammock mitral valve, therepair can be performed through annuloplasty, commissurotomy, modified techniques ofposterior annulus shortening and papillary muscle division, according to thepresentation of the valve apparatus morphology.


Anthropometric characteristics, echocardiography and arterial pressure were measured. The independent t-test was used for statistical comparisons between groups. Stepwise multivariate regression analysis was applied to investigate associations between various variables. Results: The two groups used training equipment with different weights (p < 0.001). Female adolescent finswimmers presented signs of myocardial hypertrophy depicted by the increased left ventricle myocardial mass indexed to body surface area (101.34 ± 23.65). Different patterns of myocardial hypertrophy were observed for the two groups; MF swimmers presented concentric hypertrophy, while BF swimmers presented eccentric hypertrophy . MF swimmers had also higher left ventricular posterior wall diameters (p < 0.05), lower stroke volume values (p < 0.05) and lower ejection fraction (p < 0.05) compared to BF athletes. Conclusion: Adolescent female finswimmers presented different patterns of myocardial hypertrophy possibly related to different training protocols and modes of exercise.Background: The purpose of our study was to investigate early differences in the adolescent female finswimmers’ echocardiography parameters, possibly associated with different swimming-style training and different training equipment (monofin (MF) versus bifin (BF)). Method: Forty-three female finswimmers participated in our study (age: 15.6 ± 2.1 years, body mass index: 20.4 ± 2.2 kg/m Finswimming is a speed competition sport practiced at the surface or underwater with different monofins (MFs) or bifins (BFs) of variable rigidity. In MF, swimmers’ lower limbs are used for propulsion purposes  and in BF swimming athletes crawl with snorkel and fins.Echocardiography is a noninvasive technique to evaluate the cardiac adaptations associated with training in people practicing sports . Accordi−1; and bifins (BFs): two fins with approximate weight 1.1 kg−1 : fin with approximate weight 3.5 kg1.1 kg−1 ).group: n = 26 vs BFgroup: n = 17). Inclusion criteria include athletes involved in 50, 100 and 200 m events with MF on the surface and BF, training for at least 3 years, 10-h training per week and no medical history. All participants trained after school between 14:30 to 16:30, 5 to 6 days per week, and used equipment in accordance with the World Underwater Federation rules (CMAS) [Forty-three Caucasian young women from Greek finswimming sports clubs were included in the study on a voluntary basis  and divi2), body surface area (BSA = (height (cm) × weight (kg))/3600 ½) [1: forced expiratory volume in 1st second, FVC: forced vital capacity, PEF: peak expiratory force; MasterScreen-CPX, VIASYS HealthCare, Hochberg, Germany) [Anthropometric characteristics as body height, body mass (Seca 700), body mass index (BMI = kg/m/3600 ½) , percent/3600 ½)  and pulmGermany)  were recEchocardiographic studies were performed in the morning hours and all participants did not compete or train for at least 12 h before the study. A certified cardiologist performed the echocardiography examinations and analyzed the echocardiographic findings. A second certified cardiologist blinded to the athletes reviewed the results. Two-dimensional echocardiography was performed, with the subjects resting in a left lateral decubitus position, using a Vivid BT08 . Heart images were obtained in the standard parasternal long-axis and short-axis and apical four-and-two chamber planes. Left ventricle wall thickness (LVWT) was measured from 2D short-axis views at enddiastole, with the greatest measurement within the left ventricular (LV) wall defined as the maximal wall thickness. M-mode echocardiograms derived from 2D images in the parasternal long axis were used for the measurement of LV end-diastolic and systolic dimensions according to EAE/ASE  and the Relative wall thickness (RWT) was calculated with the use of the formula RWT = 2 × /, and consequently, any observed increase in LV mass was categorized as either concentric (RWT > 0.42) or eccentric (RWT ≤ 0.42) hypertrophy . Arteriat-test was used for statistical comparisons between groups. Stepwise multivariate regression analysis was used to investigate associations between various variables. The level of significance was set to p < 0.05 and the data are presented as mean value and standard deviation (mean ± SD). The SPSS 15 statistical package  was used for the statistical analyses. Study power calculations were made with the use of Java Applets for Power and Sample Size [The Kolmogorov-Smirnov test was used to evaluate the normality of the distribution. The independent ple Size .−1, p < 0.001). Female adolescent finswimmers presented signs of myocardial hypertrophy evident by the increased left ventricle myocardial mass indexed to body surface area (101.34 ± 23.65 g/m2), with different patterns of myocardial hypertrophy for the two groups. MF swimmers presented concentric hypertrophy while BF swimmers presented eccentric hypertrophy , lower stroke volume values  and lower values in ejection fraction  compared to BF athletes. Pulmonary function tests found that the two groups had comparable FVC and PEF but differed in FEV1 with the BF group presenting higher values .MF swimmers had also higher left ventricular posterior wall diameters  and not significantly with pool training hours per week . At the same time, multivariate stepwise regression analysis showed that RWT was associated (R = 0.59 for the model) with age , training hours spent at the gym , and PEF measured by spirometry , but not significantly with BMI (p > 0.05) and not significantly with swimmers’ height (p > 0.05).Multivariate stepwise regression analysis found that LV myocardial hypertrophy and specifically LV mass indexed to BSA was weakly (R = 0.42 for the model) associated only with swimmers’ age  to swimmers’ myocardium, leading to concentric hypertrophy. In finswimming and especially in athletes who use the monofin, the thighs have more activation during swimming compared to other muscle groups . IsometrPrevious studies demonstrated that changes in left ventricular mass and ventricular cavity size with physical training and conditioning take place simultaneously with augmented oxygen uptake, suggesting that ventricular hypertrophy is associated with better cardiopulmonary measures . ExercisResults from our study reveal differences between groups because of equipment. During the training but not the race, finswimmers’ periods of apnea may be used to cover short distances underwater. This practice, which is characterized as dynamic apnea, is beneficial for performance in sports .Previous study reveals that different breathing techniques during finswimming can affect differently the heart rate, arterial oxygen saturation and the maximal inspiratory pressure . The sai2 [The mechanisms underlying strength improvements in prepubertals arise through an interaction between neural and hormonal mechanisms, and affect the cardiovascular system, during endurance training in adult athletes, with major changes in morphological and functional adaptations of the heart. In the present study, myocardial hypertrophy of female finswimmers was evident compared to published data on relevant age groups with the use of magnetic resonance imaging . In an e2 .The findings of the current study could also permit clinicians to accurately diagnose and treat BF swimmers presenting themselves as patients, since the observed concentric hypertrophy is part of the adaptive physiology and not a pathological condition. The overlap between physiology and pathology is important in clinical medicine and especially in cases of myocardial hypertrophy in athletes where highly trained athletes present themselves to primary care providers for clearance to participate in sports or with the question of returning to training after minor events or symptoms .A limitation of the present study is that the adolescent female finswimmers studied were all Caucasians, meaning that the results may not apply to other ethnic groups. Moreover, athletes were evaluated only by echocardiography and not with the use of magnetic resonance imaging. Finswimmers’ myocardial right ventricle function was not investigated in the current study and LV function was only investigated with “classical parameters”.Adolescent female finswimmers presented different patterns of myocardial hypertrophy possibly related to different training programs and modes of exercise. MF swimming induced concentric cardiac hypertrophy, while BF induced eccentric hypertrophy. The said myocardial adaptations to exercise could be attributed to the different physiological demands imposed by the two swimming styles.


This allowed detailed correlation between in vivo CMR parameters and ex vivo histopathology, and confirmed the need to include T2* measurements to detect tissue iron for accurate interpretation of pathology associated with CMR parameter changes. In summary, we provide detailed histological and in vivo imaging-based characterization of acute hemorrhagic myocarditis as an acute cardiac complication in the mouse model of Resiquimod-induced SLE, and a refined CMR protocol to allow non-invasive longitudinal in vivo studies of heart involvement in acute inflammation. We propose that adding T2* mapping to CMR protocols for myocarditis diagnosis improves diagnostic sensitivity and interpretation of disease mechanisms.Hemorrhagic myocarditis is a potentially fatal complication of excessive levels of systemic inflammation. It has been reported in viral infection, but is also possible in systemic autoimmunity. Epicutaneous treatment of mice with the Toll-like receptor 7 (TLR-7) agonist Resiquimod induces auto-antibodies and systemic tissue damage, including in the heart, and is used as an inducible mouse model of systemic lupus erythematosus (SLE). Here, we show that overactivation of the TLR-7 pathway of viral recognition by Resiquimod treatment of CFN mice induces severe thrombocytopenia and internal bleeding, which manifests most prominently as hemorrhagic myocarditis. We optimized a cardiac magnetic resonance (CMR) tissue mapping approach for the This article has an associated First Person interview with the first author of the paper. Summary: The authors present a mouse model of acute hemorrhagic myocarditis and a refined technique of preclinical cardiac MR imaging to allow non-invasive detection of diffuse myocardial tissue damage accounting for iron deposition. Immune-mediated damage to the heart can occur as the result of a wide variety of underlying conditions such as infectious disease, exposure to toxins, chemotherapeutic agents, immune checkpoint inhibitors and systemic inflammation caused by autoimmune disease. Besides being caused by a range of viruses known to induce severe hemorrhagic fevers, viral myocarditis can also be a complication of more common viruses, including coxsackie virus , adenoviin vivo tissue characterization under highly representative physiological conditions and is clinically used to detect tissue damage in inflammatory disease  imaging is a useful tool for non-invasive  disease . HoweverAlthough various cardiac structures have been reported to be affected in mouse models of acute systemic inflammation , the speex vivo histopathology of the heart and CMR parameters to establish a protocol for contrast agent-free CMR parametric mapping for the non-invasive in vivo detection of diffuse immune-mediated damage, taking into account the potential presence of hemorrhage.Here, we further characterize the acute response of CFN mice, a previously described recombinant inbred mouse line obtained by crossing C57BL/6J, FVB/NJ and NOD/ShiLtJ parental lines , to ResiAs also shown previously , Resiqui1 and T2 relaxation times were extracted from the mid slice of the heart for comparison with histopathological changes in corresponding histology sections (n=3 (control), n=10 (treated)]. Collagen deposition as a measure of fibrosis was negligible, which is likely owing to the early acute stage of disease  compared with values from myocardial tissue of untreated mice (1505±18.5 ms), whereas T2 did not change (28.5±0.5 versus 27±3 ms); n=7 (control and treated)  D.Fig. 21 values, particularly in the anterior part of the intraventricular septum. Regional T2 values remained largely unchanged, except for the inferior septum , n=9-10 (treated)*] was only mild for T1  and absent for T2   G. Specifltration E,F.2 values corresponding to areas of inflammatory infiltration and edema in histology, as expected  deposited in tissue (2* measurements because of large magnetic susceptibility artefacts caused by its proximity to the air-filled lung. Using ultrashort echo time (UTE) instead of the conventional gradient-echo readout , RBC extravasation (−0.685), infiltration (−0.619) and fibrosis (−0.703)  , suggesting that inflammatory damage and hemorrhage in this model are specific to the heart.Correlation analysis between regional Treated)] E. Most iHemorrhagic myocarditis is a potentially fatal complication of acute systemic inflammation. However, to date, a diagnosis is often only obtained post mortem. In addition, acute myocarditis can trigger an autoimmune reaction against the heart  and it iUnderlying mechanisms leading to hemorrhage in some myocarditis patients, but not in others, and implications on survival and subsequent development of inflammatory cardiomyopathies are far from understood. This supports the need for thorough mechanistic and therapeutic studies in well-characterized preclinical models. Although various cardiac phenotypes have been reported in mouse models of autoimmunity , the speThe mouse model used in this study has previously been described at chronic stage as a model of systemic autoimmunity . Yet, in1 and T2 relaxation times are commonly used to detect parameters of inflammatory damage in the heart, including edema, immune cell infiltration and fibrosis. 2 weighted images to detect myocardial edema by measuring the myocardial T2 intensity change normalized to skeletal muscle (T2-STIR), (2) early gadolinium enhancement (EGE) to detect reactive hyperemia and (3) late gadolinium enhancement (LGE) to assess tissue injury and/or fibrotic remodeling. Considering the possibility of hemorrhages, the approach taken in the present study includes the measurement of iron deposition through T2* myocardial mapping. Because of its high sensitivity to paramagnetic iron, T2* mapping is performed routinely in patients with suspected cardiac iron overload  increased T2 values with normal T1, T2*, detecting areas of infiltration and/or edema with normal levels of iron in the tissue, suggestive of an acute ongoing inflammatory process as seen in classical myocarditis and (2) low T2*, T1, T2 values, detecting areas of infiltration and/or edema with increased levels of iron in the tissue, suggestive of inflammatory changes including vascular damage, red blood cell extravasation and tissue iron deposition. This may need to be taken into consideration when designing myocarditis imaging protocols to avoid false negative results.Diagnosis of human myocarditis often still relies on invasive procedures to obtain biopsy material for histology. In mouse models, the need to excise hearts for histology prevents longitudinal studies, which would significantly improve experimental design. Attempts to reduce the need for heart biopsies, as well as improve animal welfare and experimental design in preclinical studies, have resulted in significant advances in CMR imaging, which is now considered the clinical gold standard for non-invasive detection of myocarditis. Changes in Toverload  and β-thoverload . A CMR ioverload . In thes readout , providiin vivo CMR parameter measurements and the underlying heart histopathology. The CMR protocol established in this study allows for detailed non-invasive characterization of diffuse myocardial inflammatory damage and controls for potential hemorrhage and iron deposition. The ability to discriminate different processes of tissue damage non-invasively by using specific MRI indices allows insight into the natural history of disease and improves our understanding of the potentially subclinical course of cardiac involvement in systemic inflammation, supporting the prognostic and diagnostic potential of this approach.In summary, we show that chronic anti-heart autoimmunity in the Resiquimod model of SLE follows acute thrombocytopenia and hemorrhagic myocarditis, and provide a thorough comparison of All mouse procedures were approved by the Imperial College Governance Board for Animal Research and in accordance with the UK Home Office Animals (Scientific Procedures) Act 1986 and Directive 2010/63/EU of the European Parliament on the protection of animals used for scientific purposes. Experimental mice were 10- to 12-week-old male and female littermates. They were housed in individually ventilated cages in temperature-controlled facilities on a 12 h light/dark cycle on standard diet. The mouse line used in these studies was derived from a triple cross between C57BL/6J, FVB/NJ and NOD/ShiLtJ parental lines (CFN line) and displays high sensitivity to treatment with TLR-7 agonist Resiquimod  . TreatmeMice were anesthetized and maintained under inhalation anesthesia via a nose cone . Respiration, ECG and body temperature were continuously monitored  through the CMR scans. Three ECG leads (SA Instruments) were placed subcutaneously on the left and right sides of the thorax and on the right back leg; animals were positioned prone in a dedicated mouse bed. Body temperature was maintained at 36.5-37°C by a circulating warm water heat mat.All CMR scans were performed on a preclinical 9.4T scanner  housed at the Biological Imaging Centre, Imperial College London using an 86 mm inner-diameter volume transmit quadrature coil combined with an actively decoupled mouse heart array receiver. Data were acquired with Paravision 6.0.1 .1, T2 and T2* relaxation times to identify and characterize quantitatively the markers of inflammatory tissue injury observed in the Resiquimod-treated mice. For welfare reasons, because of the high susceptibility of Resiquimod-treated mice to acute bleeding, no contrast agent-based protocols were performed in this study.For localization of the heart, low-resolution ECG and respiratory triggered gradient-echo scout scans were acquired in axial, sagittal and coronal orientations followed by pseudo two- and four-chamber views. This allowed reproducible planning of imaging slices in the true short axis orientation at three specific locations in the left ventricle . A multiparametric MR imaging approach was adopted and included mapping of T1 mapping was performed  using a gradient echo-based look-locker inversion recovery sequence with 20 inversion times (TI) that followed an adiabatic global inversion time. All inversions were R-wave triggered to allow images to be acquired at the same part of the cardiac cycle (end diastole), with the TI points restricted to multiples of the R–R interval (∼100 ms). Additional acquisition parameters were inversion repetition time of 5 s , TR 4.5 ms, TE 2.1 ms, flip angle 7°, slice thickness 1 mm, field of view (22×22) mm2 and spatial resolution (164×164) μm2, with three slices acquired sequentially in ∼14 min. The inversion points acquired during respiratory motion were manually removed. The T1 curve fitting was subsequently performed on a pixelwise basis on the remaining measured inversion times using a nonlinear least square three-parameter fit, which accounted for Look–Locker correction. Data analysis was performed in Segment version 2.0  (TMedviso) ,b.2 mapping was performed  using a multi-echo spin-echo fat-suppressed sequence with five echo times acquired at the same part of the cardiac cycle . A pair of flow saturation bands surrounding each imaging slice was placed upstream of the blood flow to minimize misleading signal dropouts caused by flow artefacts. Additional acquisition parameters were TR/TE 3500/2.74, 5.49, 8.23, 10.98 and 13.72 ms; echo spacing 2.74 ms; slice thickness 1 mm; field of view (17×19) mm2; spatial resolution (147×167) μm2 and GRAPPA acceleration factor 1.65, with three slices acquired sequentially in a total scan time of ∼12 min. A two-parameter pixelwise T2 fit was carried out assuming a mono-exponential signal decay. Myocardial segmentation excluded the regions of bright signal caused by the stagnant subendocardial blood occasionally observed on T2 maps . For this, the sequence was performed repeatedly with various TEs  with a fixed scale of receiver gain. The other imaging parameters were TR 5.6 ms, flip angle 12°, FOV (20×20) mm2, in-plane spatial resolution (164×164) µm2, slice thickness 1 mm, bandwidth 250 kHz, projection number 352 and a scan time of 3.5 min for each individual echo image. Precise k-space trajectory measurement is crucial for obtaining good quality images when radial encoding is employed   ,b.1, T2 and T2* maps after partitioning the left ventricle wall based on the 16-segmentation model, as per recommendations by the American Heart Association   . Epicardhe apex) . Particuhe apex) . Signalsmoothing .Hearts were perfused and excised. Macroscopically visible hemorrhagic lesions were scored on a scale from 0 to 4: (0) no visible lesions, (1) lesions cover <10% of heart surface, (2) lesions cover 10-30% of heart surface, (3) lesions cover 30–50% of heart surface and (4) lesions cover >50% of heart surface.in situ perfusion with ice-cold phosphate buffered saline  through the apex of the left ventricle of the heart to clear blood from heart chambers and blood vessels. Hearts were then fixed in 4% formaldehyde overnight, dehydrated in an increasing gradient of ethanol and embedded in paraffin. Sections of 5 µm were cut, de-waxed and then rehydrated in an ethanol gradient. Sections were stained with H&E, Picrosirius Red and Perls Prussian Blue. All reagents were purchased from Sigma-Aldrich. Semiquantitative scoring was performed as established previously (http://rsb.info.nih.gov), (Hearts of treated and untreated mice were excised after eviously . H&E-staih.gov), .Blood was collected into 129 mM trisodium citrate and platelet counts were determined immediately by flow cytometry using a rat antibody recognizing mouse platelet GPIbβ  and calibrated beads  according to manufacturer's instructions. Samples were analyzed using a FACScalibur flow cytometer. Hemoglobin content in blood samples was determined by the cyan-methemoglobin method using Drabkin's reagent and bovine hemoglobin as a standard (both from Sigma-Aldrich). Blood or hemoglobin standards were diluted in 200 µl Drabkin/Brij L23 solution, incubated at room temperature for 15 min and absorbance read at 540 nm. Hemoglobin content in mouse blood samples were extrapolated from a standard curve of bovine hemoglobin by linear regression using GraphPad Prism (v7).http://www.gpower.hhu.de/, and reflect effect sizes obtained in previous experiments with comparable readouts. Scoring of histopathology was performed by a blinded researcher. Statistical analyzes were performed using SPSS or GraphPad Prism. Data are presented as mean±s.e.m. The Mann–Whitney test was used for scoring data, and one- or two-tailed unpaired or paired Student's t-tests were performed as appropriate for parametric data.Calculations of animal numbers and sample sizes were performed using G*Power 3.1 , availab


Diffuse remodeling of myocardial extra-cellular matrix is largely responsible for left ventricle (LV) dysfunction and arrhythmias. Our hypothesis is that the texture analysis of late iodine enhancement (LIE) cardiac computed tomography (cCT) images may improve characterization of the diffuse extra-cellular matrix changes. Our aim was to extract volumetric extracellular volume (ECV) and LIE texture features of non-scarred (remote) myocardium from cCT of patients with recurrent ventricular tachycardia (rVT), and to compare these radiomic features with LV-function, LV-remodeling, and underlying cardiac disease.Forty-eight patients suffering from rVT were prospectively enrolled: 5/48 with idiopathic VT (IVT), 23/48 with post-ischemic dilated cardiomyopathy (ICM), 9/48 with idiopathic dilated cardiomyopathy (IDCM), and 11/48 with scars from a previous healed myocarditis (MYO). All patients underwent echocardiography to assess LV systolic and diastolic function and cCT with pre-contrast, angiographic, and LIE scan to obtain end-diastolic volume (EDV), ECV, and first-order texture parameters of Hounsfield Unit (HU) of remote myocardium in LIE .p < 0.0005). cCT-derived ECV, HU-mean, HU-median, SD, and MAD correlated directly to EDV by cCT and inversely to ejection fraction by echocardiography (p < 0.05). SD and MAD correlated with diastolic function by echocardiography . MYO and IVT patients were characterized by significantly lower values of SD and MAD when compared with ICM and IDCM patients, independently of LV-volume systolic and diastolic function.Energy, HU mean, and HU median by cCT texture analysis correlated with ECV  was associated with LV dilatation, systolic and diastolic function, and is able to potentially identify the different patterns of structural remodeling characterizing patients with rVT of different etiology. Cardiac computed tomography (cCT) has impressively evolved in the last years, following the continuous improvement in temporal and spatial resolution. Nowadays, cCT is commonly used in the assessment of coronary artery disease . FurtherMultiple non-invasive diagnostic strategies have been tested for the non-invasive assessment of diffuse extracellular matrix remodeling. T1 mapping assessed by cardiac magnetic resonance represents the new non-invasive standard of reference. The areas of diffuse interstitial fibrosis are characterized by higher native T1 when compared to normal myocardium . MoreoveAlthough ECV has a strong prognostic meaning , its diaThe premise of this study is that the pattern and, particularly, the heterogeneity of the myocardial extracellular matrix remodeling could be extracted by texture analysis of LIE cCT images and that texture analysis of LIE may complement ECV, bacause it may reveal a non-invasive signature of different cardiac diseases.Texture analysis is a mathematical computation that allows the extraction of complex quantitative features from images, increasing the potential informative value of radiological examinations. Texture features extracted from biomedical images are extensively explored for “radiomic-phenotypization” of different solid tumors . MoreoveThe aim of this study was to extract the myocardial ECV and LIE first-order texture features from cCT of patients with recurrent ventricular tachycardia (rVT) and to compare the extracted radiomic features with left ventricle remodeling, systolic-diastolic function by echocardiography, and underlying cardiac disease.This is a single-center observational prospective study performed on 52 consecutive patients suffering from rVT, who underwent cCT for a combined assessment of coronary vessels and myocardial scars, in order to plan trans-catheter radio-frequency ablation. Three out of 52 patients were excluded due to previous cardiac surgery with myocardial patch implantation. One patient was excluded from the study because of low quality of the cCT images due to respiratory artifacts.Transthoracic echocardiography was performed in all patients before cCT examination.This study was approved by the Institutional Review Board of the San Raffaele Scientific Institute and all patients signed an informed consent form.cCT examinations were performed on a multi-detector CT  scanner. Patients were prepared with intravenous injection of beta-blockers (atenolol 1–15 mg) in the case of HR > 65 bpm. Three patients underwent cCT during continuous intravenous infusion of lidocaine hydrochloride, in order to control ventricular arrhythmias.cCT protocol included a pre-contrast (80 kVp) prospectively gated scan which was used to obtain baseline blood and myocardial attenuation, followed by two sequential contrast-enhanced acquisitions: an angiographic scan and a LIE scan. Angiographic scan was acquired during triphasic injection of high-iodine (iopromide 370 mg iodine/ml or iomeprol 400 mg iodine/ml) contrast agent (CA) . This injection was immediately followed by a second intravenous injection to reach the total dose of 0.6 mg iodine/kg of body weight . LIE scan = 27) in patients with HR ≤ 65 bpm and with retrospective gating with ECG-based tube current modulation (n = 21) in patients with HR > 65 bpm despite beta-blockers infusion. Regardless, the ECG-gating mode chosen, the detector collimation was 64 × 0.625 mm, the rotation time 0.42 s and images were reconstructed with a standard cardiac kernel (CB), with a thickness of 0.75 mm and 512 × 512 matrix.The angiographic and LIE scans were acquired with prospective gating  wall and cardiac chambers were semi-automatically segmented on the angiographic scan at 75 % of the cardiac cycle using a commercial software , as previously described . Left atDense scars were identified and segmented as previously described . BrieflySegmented scars were extracted from the LV wall volume and used for ablation planning, as previously described . The remAll pixels greater than 250 and 470 HU were excluded from the analysis for baseline and LIE, respectively, as well as all pixels lower than 0 HU. The lower cut-off of 0 HU was empirically chosen in order to automatically exclude pixels corresponding to air or adipose tissue  coming fFirst-order texture features were calculated from the segmented remote myocardium on the LIE scan, after filtration with a Gaussian kernel of standard deviation 1 voxel to reduce the image noise  accordinmyo is the change in myocardial HU attenuation after iodine injection, and ΔHUblood is the change of blood HU mean attenuation after iodine injection.Myocardial and blood pool HU were extracted from the baseline and LIE scan. ECV was calculated as follows:Image post-processing was around 30 min per patient.Ejection fraction (EF), end-diastolic diameter (EDD), and diastolic function of the LV were assessed. Diastolic function was determined through the evaluation of the mitral inflow pattern and scored in a 4-point scale , according to the current recommendations .vs retrospective) functional and volumetric parameters by cCT , and echocardiography .Spearman’s rho was used for evaluating correlations between LIE texture features , ECV and clinical features , scan protocol .The texture parameters which resulted significantly different in relation to the underlying cardiac disease were then categorized in classes defined by each tertile of their distribution in order to provide possible cut-offs. The association between the subgroups and the types of cardiac disease were assessed through Fisher’s test. Bonferroni’s correction was applied to account for multiple comparisons. A multivariate ordinal regression analysis was employed in order to evaluate whether the subgroups were predictive of heart diseases, when accounting for EDV, EF, and diastolic function. The final models were obtained using a backward selection procedure. The A total of 48 consecutive patients with rVT  were evaluated. According to previous medical records, echocardiography, invasive coronary angiography, and in most of cases, cardiac magnetic resonance, patients were classified as follows: 23 out of 48 patients (48 %) suffered from post-ischemic dilated cardiomyopathy (ICM), 9 out of the 48 patients (19 %) had idiopathic dilated cardiomyopathy (IDCM), 11 (23 %) had myocardial scars from a previously healed myocarditis (MYO), and 5 (10 %) suffered from idiopathic ventricular tachycardia (IVT) without any evidence of structural heart disease. The baseline characteristics of enrolled patients are listed in Table Values of texture features, ECV, and relative differences among groups are reported in Table vs energy: rho = 0.5650, p < 0.0001) and parameters of central tendency . No significant correlations were found between ECV and texture features of randomness and variability.ECV correlated with texture parameter of general attenuation  in relation to the underlying cardiac disease , systolic (EF), and diastolic function.p = 1.000, p = 1.000, p = 1.000, p = 1.000, p = 0.2625, respectively).ECV, energy, entropy, HU mean, and HU median were not significantly associated with different cardiac diseases  and statistical randomness (entropy), parameters of central tendency (HU mean and HU median), and parameters of scattering/variability (standard deviation and mean absolute deviation). In agreement with the previous study by Nacif , ECV corTexture parameters of general attenuation and central tendency provide information about the global accumulation of iodine in the extracellular matrix. The higher the HU mean and median are, the higher the accumulation of iodine in the extracellular matrix is. Hence, HU mean and median result correlated to ECV because they give similar information, and similarly to ECV, HU mean and median were not significantly different across patient groups, demonstrating a similar increase of the extracellular myocardial space in ICM, IDCM, MYO, and IVT.Only parameters of HU variability (SD and MAD) were correlated with diastolic function score, demonstrating that when the HU variability is higher, the diastolic function is worsen. Moreover, we found that SD and MAD values were significantly different in relation to the underlying cardiac disease. In fact, patients suffering from IVT and MYO had SD values under the 66th percentile in 100 % of the cases, and most of them were under the 33rd percentile (80 and 64 % respectively), whereas only 17 and 11 % of ICM and IDCM patients had SD values under the 33rd percentile , our results cannot demonstrate a direct cause-effect relationship between texture parameters of variability and diastolic function impairment. Nevertheless, the significant correlation of diastolic function with parameters of variability but not with ECV suggests that the structural architecture of ECM remodeling could be more important than the extracellular space enlargement Considering the emerging role of SD as texture parameter for non-invasive characterization of tissue heterogeneity in cancer , our resIn addition, recent literature provides a proliferation of evidence indicating that the diffuse structural remodeling is a key factor in the genesis of vulnerability to electrical re-entry circuits , 38 and In conclusion, our results suggest that texture analysis of LIE images may provide distinctive information about microstructural myocardial changes, which may help in the discrimination of cardiac diseases, simply by a computational analysis of conventional images acquired in the clinical routine.However, this suggestion needs to be reassured and supported by future experimental studies which will emphasize on tackling several limitations of our study, such as the relative small sample size, the focus only on patients with ventricular tachycardia, the lack of reproducibility tests, although texture analysis of CT images has been extensively validated and reproduced in many studies , and theOur results suggest that texture parameters describing the scattering of densities within the myocardium may provide a deeper characterization of the micro-architectural changes occurring in the extracellular myocardial space, impacting on the biomechanical properties of the left ventricle and potentially useful in the characterization of myocardial diseases.


Although obesity‐associated metabolic abnormalities (insulin resistance‐IR) may not play as marked a role in determining left ventricular (LV) diastolic dysfunction (DD) as hypertension, the impact of combinations of these risk factors on DD is unknown.We hypothesized that IR influences the impact of hypertension on DD.In 704 randomly selected participants from a community sample with a high prevalence of hypertension (50.6%) and obesity (46.5%), we determined adiposity indices, IR from the homeostasis model (HOMA‐IR) and LV diastolic function using standard echocardiographic techniques.P < 0.05 to P < 0.005) as well as a diagnosis of DD (P < 0.02). Importantly, however, an enhanced relationship between HOMA‐IR and E/e' in hypertensives  as compared to normotensives  was noted. Consequently, as compared to normotensives, with adjustments for confounders, hypertension was independently associated with DD only in those with the highest tertile of HOMA‐IR , while in those with the lowest tertile of HOMA‐IR, hypertension failed to show a higher prevalence of DD (P = 0.22).HOMA‐IR was independently associated with lateral wall e' and E/e' (Insulin resistance enhances the impact of hypertension on LV DD. Thus, DD is more likely to occur with the combination of hypertension and IR. Participants gave informed, written consent. The study design has previously been described.2.22, obese if their BMI was ≥30 kg/m2 and morbidly obese of their BMI was ≥35 kg/m2. Central obesity was defined as an enlarged WC (≥88 cm in women and ≥ 102 cm in men). Laboratory blood tests including percentage glycated hemoglobin (HbA1c) were performed. Fasting plasma insulin concentrations were determined from an insulin immulite, solid phase, two‐site chemiluminescent immunometric assay . Diabetes mellitus or an abnormal blood glucose control was defined as the use of insulin or oral hypoglycemic agents or a glycated hemoglobin  value greater than 6.5%. Insulin resistance was estimated by the homeostasis model assessment of IR (HOMA‐IR) using the formula (insulin [μU/mL] × glucose [mmol/L])/22.5.A standardized questionnaire was administered to obtain demographic and clinical data.Nurse‐derived conventional BP was measured according to guidelines using a mercury sphygmomanometer after 5 minutes of rest in the seated position as previously described.2.31.7.Echocardiographic measurements were performed as previously described2.Left ventricular diastolic function was assessed from a pulsed wave Doppler examination of the mitral inflow at rest and using tissue Doppler indices (TDI) as well as left atrial volumes (LAV).2.4r values) were compared with z‐statistics.Database management and statistical analyses were performed with SAS software, version 9.4 . Data from individuals were averaged and expressed as mean ± SD or the SE of the mean (SEM). To improve on the distribution of data, HOMA‐IR, lateral e', septal e', E/e', and LAV index were logarithmically transformed. To determine independent relations, multivariate adjusted linear (continuous data) or logistic (discrete data) regression analysis was performed. Indexes of diastolic LV function were adjusted for several confounders associated with diastolic function noted in bivariate analysis. Relationships  and 18.1% had concentric LV remodeling . A greater proportion of hypertensives than normotensives had LVH and concentric LV remodeling.Table 3.2With adjustments for confounders, systolic BP, and either WC, HOMA‐IR, or BMI were independently associated with lateral and septal wall e' and E/e' Table S2). While WC and systolic BP were independently associated with LAV index, HOMA‐IR, and BMI were not (Table S2). However, with adjustments for confounders systolic BP and HOMA‐IR, but not WC or BMI were independently associated with the presence of LV DD  as well as HOMA‐IR were independently associated with lateral wall e' Table . However4The main findings of the present study are as follows: In a community sample with a high prevalence of obesity, indices of excess adiposity and IR were independently associated with indices of LV diastolic function (e' and E/e'). However, while HOMA‐IR was independently associated with lateral wall e' in both hypertensives and normotensives, HOMA‐IR was independently associated with E/e' in hypertensives, but not in normotensives. Consequently, HOMA‐IR determined whether hypertensives developed LV DD as compared to normotensives. In contrast, adiposity indices were associated with indices of diastolic function less well in hypertensives as compared to normotensives and adiposity indices were consequently not independently associated with DD.16 in the present study conducted in a much larger study sample of the same community we show that while BP and HOMA‐IR translated into DD, adiposity indices failed to do so. The ability of HOMA‐IR to associate with DD while adiposity indices did not, we attribute to an impact of HOMA‐IR, but not adiposity indices on E/e in the hypertensive, but not in the normotensive BP range. These data therefore suggest that IR is an important contributor to DD, but mainly in those with hypertension.Although several large studies have demonstrated that indices of excess adiposity are strongly and independently associated with indices of LV DD,An important caveat of the present study is that the results do not suggest that IR mediates LV DD through hypertension. Indeed, relations between adiposity indices or HOMA‐IR and LV diastolic functional parameters were independent of systolic BP. Rather, the present study suggests that the impact of hypertension on relations between HOMA‐IR and DD should be viewed as an additive effect with systolic BP effects alone being more important, but with IR influencing whether hypertension translates into DD.The criteria for the diagnosis of LV DD have been debated over several decades. As recently highlighted,An explanation for the impact of HOMA‐IR on E/e' (an index of LV filling pressures) and hence DD in hypertensives, but not normotensives in the present study, is unclear. It is possible that because hypertension is associated with concentric LV remodeling, and as recently demonstrated, a more concentrically remodeled LV determines the impact of IR on E/e',There are several potential implications of the findings of the present study. First, in contrast to adiposity indices, which had less of an ability to determine the impact of hypertension on DD, the assessment of IR may better characterize hypertensives at risk of developing DD and hence heart failure with a preserved ejection fraction. In this regard, longitudinal studies are required to assess this question. Second, targeting IR as opposed to an excess adiposity per se with behavioral modification in hypertensives may have marked benefits to preventing the development of DD and hence heart failure with a preserved ejection fraction. In this regard, intervention studies are required to assess these hypotheses.The limitations of the present study are as follows: First, this is a cross‐sectional study and hence, we cannot draw conclusions regarding causality. Whether the development of IR influences that of LV DD in those with hypertension rather than normotension therefore requires further study. Second, we are not statistically powered to perform sex‐specific analysis and hence, it is possible that as more women than men volunteered for the study, the results may relate mainly to women.In conclusion, in a relatively large community‐based sample with a high prevalence of obesity and hypertension, we show that independent of confounders, the extent of IR influences whether hypertension translates into diastolic dysfunction. These data suggest that from a clinical perspective, hypertensives with IR may be particularly prone to the development of LV DD and thus possibly the progression to heart failure with a preserved ejection fraction. Consequently, targeting IR in hypertension may have marked benefits for preventing the development of heart failure.The authors declare no potential conflict of interests.FIGURE S1 Prevalence of left ventricular diastolic dysfunction (DD) in hypertensives as compared to normotensives across tertiles of the homeostasis model of insulin resistance (HOMA‐IR), waist circumference (WC) or body mass index (BMI) in the whole group and across similar age ranges. Tertiles of HOMA‐IR, WC, and BMI are defined in on‐line Table S3.Click here for additional data file.TABLE S1 Characteristics of community sample without tissue Doppler imaging (TDI).TABLE S2 Relative contribution (standardized β‐coefficient) of the homeostasis model of insulin resistance, waist circumference or body mass index vs alternative risk factors toward indices of left ventricular diastolic function in a community sample (n = 704).TABLE S3 Ranges of tertiles of the homeostasis model of insulin resistance, waist circumference, and body mass index in normotensives and hypertensives.Click here for additional data file.


However, these are not devoid of limitations. In the present review, we aim at rationalizing the applicability of the recent recommendations to the perioperative and ICU areas, discussing the clinical meaning and echocardiographic findings of different grades of LVDD, describing the impact of LVDD on patients’ outcomes and providing some hints on the management of patients with LVDD.There is growing evidence both in the perioperative period and in the field of intensive care (ICU) on the association between left ventricular diastolic dysfunction (LVDD) and worse outcomes in patients. The recent American Society of Echocardiography and European Association of Cardiovascular Imaging joint recommendations have tried to simplify the diagnosis and the grading of LVDD. However, both an often unknown pre-morbid LV diastolic function and the presence of several confounders—i.e., use of vasopressors, positive pressure ventilation, volume loading—make the proposed parameters difficult to interpret, especially in the ICU. Among the proposed parameters for diagnosis and grading of LVDD, the two tissue Doppler imaging-derived variables  The study of left ventricular (LV) diastolic function and the impact of decreased LV compliance and impaired relaxation has received growing interest. This is certainly due to not only the high incidence of LV diastolic dysfunction (LVDD) in the general population and its sensible impact on patients outcomes , but alsThe importance of LVDD is strongly emerging in the perioperative setting  and in ce′ wave and E/e′ ratio. The e′ and E/e′ ratio are two parameters derived by tissue Doppler imaging (TDI) analysis, measuring longitudinal fiber lengthening during early diastole at level of mitral valve annulus using a modified pulsed wave Doppler setting . The e′ maximal velocity reflects LV relaxation rate, while E/e′ correlates with the LV filling pressures and a ratio above 13–15 is associated with pulmonary arterial occlusion pressures > 18 mmHg [The most recent American Society of Echocardiography and European Association of Cardiovascular Imaging (ASE/EACVI) joint recommendations for the diagnosis and assessment of LVDD  made sub 18 mmHg . The cutIn patients with normal LV systolic function, abnormalities of more than half of measurable parameters  define the presence of LVDD. On the other hand, the new guidelines support that patients with structural abnormalities, known ischemic heart disease or abnormal LV systolic function will have impaired myocardial relaxation, and thus, echocardiography examination may focus on the assessment of LV filling pressures and diastolic dysfunction grade.E/A ratio are used to grade LVDD and can be found in the recently published recommendations [Once diagnosis of LVDD is made, the following step is to proceed with grading of the dysfunction itself. The four parameters indicated in Table ndations , but LVDndations , 11. In ndations .the guidelines are not necessarily applicable to children or in the perioperative setting.” The fact that applicability of these guidelines to the perioperative setting represents a challenge is not surprising. Indeed, patients undergoing major surgery are mechanically ventilated and exposed to drugs with vasoactive effects, and they easily fluctuate from hyper- to hypovolemia due to perioperative fasting, fluid shift, hemorrhage, etc. Moreover, the use of transthoracic echocardiography (TTE) is limited in the operating room, and the applicability of e′ and E/e′ ratio with transesophageal echocardiography (TEE) should consider the importance of obtaining a good alignment of TDI signal.Unfortunately, assessing LVDD is not always easy and the guidelines’ authors themselves state “…e′ values, possibly representing an impaired LV relaxation due to worse RV function (and possibly RV dilatation) [On the other hand, it is somewhat surprising that the authors did not mention the limitations of such new guidelines in the critically ill patients. Same limitations as the ones described in the perioperative setting may be also present. Moreover, in this population of patients, the TR jet velocity may worsen under the negative influence of mechanical ventilation on right ventricular (RV) function and there are a large number of factors that may increase pulmonary pressure at pre-capillary level, making the reliability of TR jet velocity at least questionable. Among these factors, pulmonary vascular resistances may increase with elevated airway pressures, although it should be kept in mind that the transmission of pleural pressure itself is reduced when lung compliance is low . Additionally, the effects of mechanical ventilation on LV diastolic function are not negligible, and one study in cardiac surgery patients showed that increasing levels of positive end-expiratory pressure (PEEP) reduced significantly both septal and lateral atation) . In othe2. However, at 1-month follow-up there was a mean change of 6 ml/m2, with no significant differences between patients with or without LA remodeling [With respect to the second parameter listed in Table modeling . Therefomodeling . In lighe′ and E/e′, see Table For the above reasons it becomes challenging the assessment of sepsis-related changes in LV diastolic function according to fluctuations in LA volume and/or TR jet velocities, while the two TDI parameters . Figure Hereby, we provide a simplified interpretation to the progression from normal LV diastolic function to different degrees of LVDD. In this context, it should be kept in mind that LV diastolic properties and LV filling pressure are closely related. In particular, Fig. E) wave over the atrial (A or late) wave, and the corresponding TDI e′ and a′ waves demonstrate a similar ratio . The corresponding echocardiographic appearance in the transmitral blood flow is a dominant early (E < A wave): This is the classical features of LVDD grade I  due to the reactive increase in LA pressures in response to worsening LVDD  with a consequent increase in LA pressure in order to restore a “pseudo-normal” LA-to-LV gradient (LVDD grade II). Thus, during this stage of LVDD there is a “pseudo-normalization” of transmitral flow pattern (E wave) quickly boosts the LV end-diastolic pressure at very high level so that the subsequent atrial contraction is unable to generate a decent filling . Consequently, the E wave is very dominant and the E/A ratio is usually > 2 , only a certain amount of blood can flow from the LA to the LV at each diastole. Importantly, such reduced amount of blood flowing into the LV during the early phase of diastole  [A wave is likely to happen earlier in the progression of LVDD, because it is related to the reduction in transmitral blood flow in the presence of very high LV filling pressure.On the other hand, as shown in Fig. l levels . It corrl levels , being ig curve) –23. On te′ and a consequent increase in a′ so that the e′/a′ ratio moves gradually from > 1 to < 1 values; however, while e′/a′ > 1 usually denotes a normal LV diastolic function and e′/a′ ≪ 1 is of restrictive pattern, it is more difficult to use the e′/a′ ratio for the distinction between LVDD grades I and II.Therefore, there is a progressive decrease in E wave). Moreover, the assessment becomes even more challenging in the ICU where the echocardiographic parameters can be affected by several confounders. For instance, the heart rate  and the use of vasopressors and/or inotropes influence the LV diastolic properties; the E/A ratio may vary according to non-hemodynamic factors such as mechanical ventilation; and it is also of limited value in patients with significant mitral and/or aortic valve disease, or before fluid resuscitation has been carried out in critically ill patients.In general, this paragraph provides a summary that may help readers in understanding the relationships between the LA-to-LV gradient and the changes in transmitral blood flow and mitral annular TDI displacement. It is mandatory to keep in mind that the interpretation of such parameters should take into account factors like patient’s history  and physiological factors  and, importantly, LVDD is an independent predictor of postoperative HF and prolonged hospital stay, and it is associated with postoperative adverse cardiovascular events and long-term cardiovascular mortality , 29.E/e′ ratio. Patients with borderline and high E/e′ had a higher incidence of perioperative complications  and longer ICU stay and hospital stay than patients with normal E/e′. Moreover, patients with high E/e′ had significantly higher mortality as compared to normal ratio  [While the impact of preoperative LVDD in these high-risk surgical specialties is not unexpected, more uncertainty reigns on the importance of LVDD in patient’s outcome in other surgical specialties. In this regard, one of the issues is the ethical concerns and potential value in performing intraoperative TEE in patients with isolated LVDD undergoing non-high-risk surgery. Cabrera-Schulmeyer and Arriaza conducted an interesting study in patients with cardiac comorbidities and undergoing non-cardiac/non-vascular  surgery. The authors stratified patients according to preoperative normal (< 8), borderline (8–15) and high (> 15) While preoperative LVDD correlates with outcome, a postoperative evaluation of patient’s diastolic function should consider ruling out first the influence of stressors that may worsen diastolic function .With respect to the role of LVDD in (non-cardiac surgery) critically ill patients, the greater amount of research is related to the role of LVDD in the outcome of sepsis and in the weaning from mechanical ventilation.Septic shock is characterized by intense vasoplegia requiring vasoactive therapy to restore blood pressure ; howevere′ and higher E/e′ ratio) are associated with mortality in septic patients [The so-defined septic cardiomyopathy may involve either the LV, the RV, or both, affecting systolic and/or diastolic function. With all the limitations coming from the use of LV ejection fraction (LVEF) for the evaluation of systolic function, a meta-analysis found no association between LV or RV systolic dysfunction and mortality in patients with severe sepsis or septic shock . On the patients . Interespatients . More reThe association between LVDD and outcome in patients with severe sepsis and septic shock may be explained looking at the pathophysiology of sepsis. In patients with LVDD, the LV filling benefits from maintenance of adequate preload, sinus rhythm and avoidance of tachycardia, while sepsis causes sequential disturbances at such levels since patients become relatively hypovolemic, tachycardic and frequently develop arrhythmias, with AF described in up to 23% of patients with septic shock , 35. SepSimilarly, patients with at-least-moderate mitral regurgitation may worsen their pulmonary function if an extra amount of fluid is administered . Not onlAnother factor that further worsens LV filling is tachycardia, mainly disproportionally reducing the LV diastolic time. Although healthy individuals compensate for by accelerating the LV relaxation process (frequency-dependent acceleration of relaxation ), this pConcerning the incidence of LVDD in sepsis, it is worth noting that a recent study by Clancy et al.  found thDuring mechanical ventilation, LV preload and afterload are decreased, and the transition from positive to negative pressure (spontaneous breathing) creates unfavorable LV loading conditions and may also trigger myocardial ischemia . There iA recent study investigated the value of a combined integrated thoracic sonographic evaluation  in predicting early post-extubation respiratory distress. The detection of lung interstitial water was the most relevant parameter detected during thoracic ultrasound, while among factors studied by echocardiography, the estimation of LV filling pressure was predictive of post-extubation distress. On the contrary, indexes of systolic function and diaphragmatic excursion had poor impact over the prediction of respiratory failure .E/e′ [E/e′ as the only factor independently associated with weaning failure possibly reflecting the association between a higher degree of LVDD and weaning failure. Moschietto et al. [E/e′ and lower e′ in the failing group and interestingly that e′ velocity increased in patients successfully weaned, while it remained unchanged in those failing.One study showed an association between weaning failure and both lower LVEF and higher E/e′ , but anoE/e′ . The preE/e′  found anE/e′  found lao et al.  found hipreload-independence and that a subsequent SBT is more likely to succeed after diuretic therapy and a more negative fluid balance (achieving preload-dependence). This study found similar LVEF and fluid balance between patients with WiPO and non-WiPO, but the first group had significantly higher E/e′ ratio, possibly reflecting a worse diastolic function [The largest study on this topic recently showed that the vast majority of patients failing a spontaneous breathing trial (SBT) and weaning from mechanical ventilation develop weaning-induced pulmonary edema (WiPO) and that structural cardiopathy, chronic obstructive pulmonary disease and obesity are the main risk factors for WiPO . In a sufunction . In suppThe management of patients with LVDD can be challenging, and unfortunately, there is no magic bullet that rapidly improves LV diastolic function, pharmacologically or non-pharmacologically. A graphical summary of suggestions to manage the critically ill patients with LVDD is provided in Fig. E < A, see Fig. In general, although LVDD can be potentially reversed or reduced in its magnitude with appropriate treatment in the long run, this seems rather difficult in the acute critically ill patients; since the pharmacological approach to the optimization of diastolic function does not offer rapid solutions at present, clinicians should probably focus on the maintenance of the best loading conditions for the patient with established LVDD. From a clinical perspective, patients with LVDD grade I are usually more easy to manage, but the dominance of the atrial filling .Patients with LVDD grade III are generally very frail patients and, for instance, severe abnormalities in LV filling pattern can explain the case of patients with HF with preserved LVEF, where patients are symptomatic despite no gross alteration in LVEF. In the outpatients, these individuals benefit from cardiology consultation and optimization, and they may also be considered for cardiac resynchronization therapy in case of prolonged QRS . HoweverFinally, because diastolic function is affected early during myocardial ischemia (earlier than systolic function) , attentiThere is growing evidence on the contribution of diastolic function to patients’ outcome both in the perioperative setting and in the ICU. The assessment and grading of diastolic dysfunction remains challenging in these patients, and the guidelines used in the outpatient setting are not fully applicable. While pharmacological optimization remains difficult, especially with time constraints (urgency/emergency cases), a proactive management aiming at maintaining adequate loading conditions and an appropriate balance between myocardial oxygen demand and delivery could be the best strategies in managing patients with left ventricular diastolic dysfunction.