The left ventricular performance index (LVGFI) as a comprehensive marker of cardiac performance integrates LV structure with global function within one index. In a prospective cohort study of healthy individuals the LVGFI demonstrated a superior prognostic value as compared to LV ejection fraction (LVEF). In patients after ST-segment elevation myocardial infarction (STEMI), however, the role of the LVGFI is unknown. Aim of this study was to investigate the relationship between the LVGFI and infarct characteristics as well as prognosis in a large multicenter STEMI population.In total 795 STEMI patients reperfused by primary angioplasty (<12 h after symptom onset) underwent cardiovascular magnetic resonance (CMR) at 8 centers. CMR was completed within one week after infarction using a standardized protocol including LV dimensions, mass and function for calculation of the LVGFI. The primary clinical endpoint of the study was the occurrence of major adverse cardiac events (MACE).p < 0.001 for all). MACE and mortality rates were significantly higher in the LVGFI < median group . The LVGFI had an incremental prognostic value in addition to LVEF for prediction of all-cause mortality.The median LVGFI was 31.2 % (interquartile range 25.7 to 36.6). Patients with LVGFI < median had significantly larger infarcts, less myocardial salvage, a larger extent of microvascular obstruction, higher incidence of intramyocardial hemorrhage and more pronounced LV dysfunction (The LVGFI strongly correlates with markers of severe myocardial and microvascular damage in patients with STEMI, offering prognostic information beyond traditional cardiac risk factors including the LVEF.ClinicalTrials.gov: NCT00712101 Myocardial damage following an acute myocardial infarction (MI) is accompanied by significant changes in left ventricular (LV) mechanical function and myocardial structure . NumerouRecently, a novel LV global function index (LVGFI) that integrates LV structure with global function has been introduced as a marker for comprehensive characterization of cardiac performance. In a multicenter prospective cohort study of healthy individuals, the LVGFI was independently associated with the occurrence of hard cardiovascular events and had a superior prognostic value as compared to LVEF . In patiCardiovascular magnetic resonance (CMR) has emerged as the gold standard for measuring LVEF, LV volumes and mass. Moreover, other clinically important infarct characteristics including infarct size (IS) and reperfusion injury (microvascular obstruction [MO]) can be visualized, providing a comprehensive assessment of patients sustaining myocardial injury . TherefoThe aim of our study was to investigate the relationship between the LVGFI and infarct characteristics as well as prognosis in a large multicenter ST-segment elevation MI (STEMI) population treated with primary percutaneous coronary intervention (PCI).This prospective CMR study was a predefined substudy of the AIDA STEMI (Abciximab Intracoronary versus intravenously Drug Application in STEMI) trial, which compared intravenous versus intracoronary abciximab application in STEMI patients and did not show a difference in IS, reperfusion injury and clinical outcome between the treatment groups. The detailed design and main results of the trial have previously been published , 11. Brin = 1.032], intravenous abciximab [n = 1.033]). The study was approved by national regulatory authorities and Ethical committee of the University of Leipzig. All patients provided written informed consent. This trial is registered with ClinicalTrials.gov, NCT00712101.Patients were enrolled at 22 sites in Germany, with a final enrolled trial population of 2.065 patients . LV enddiastolic (LVEDV) and endsystolic volumes (LVESV) as well as LV mass were assessed according to standard definitions from functional images. Semiautomated computer-aided threshold detection was used to identify regions of edema, MO and infarcted myocardium. A myocardial region was regarded as affected if at least 10 adjacent myocardial pixels revealed a signal intensity of >2 standard deviations (SD) of remote myocardium for edema and >5 SD in late gadolinium enhancement (LGE) images . The hypThe LV stroke volume (LVSV) was calculated by LVEDV-LVESV. The LV global volume was defined as the sum of the LV mean cavity volume ([(LVEDV + LVESV)/2] and the myocardium volume. LV myocardial volume was calculated as LV myocardial mass divided through the specific myocardial density (1.05 g/mL). The LVGFI was thus defined according to the following established formula and expressed as a percentage:  LVGFI = The primary clinical endpoint of this substudy was a composite of all-cause death, reinfarction, and new congestive heart failure within one year after infarction. All components of the combined clinical endpoint were adjudicated by a clinical endpoints committee, blinded to the patient's assigned treatment, based on data provided by the clinical trial sites. To avoid double counting of patients with more than one event, each patient contributed only once to the composite major adverse cardiovascular event (MACE) endpoint (death > reinfarction > congestive heart failure). Detailed outcome definitions have been reported previously –12.t test for continuous data with normal distribution. Otherwise the non-parametric Wilcoxon rank-sum test was used. Hazard ratios (HR) with 95 % confidence intervals were calculated for binary outcomes. Univariate and stepwise multivariate Cox regression analyses were performed to identify predictors of MACE. Multivariate regression was performed using only variables with a p-value <0.05 in univariate regression analyses. For univariate analyses, all variables of Table Patients were grouped by the median of the LVGFI into a less than the median and a median or above LVGFI group. Baseline patient characteristics, procedural details, and CMR findings are described according to the median of the LVGFI. Data for continuous variables are presented in medians with 25th and 75th percentiles. Categorical variables are presented as frequencies and percentages. Differences between groups were assessed by Fisher’s exact or the chi-square test for categorical variables and by the Student’s The incremental additive information of the LVGFI over LVEF was assessed using c-statistics. C-statistic results were compared using the nonparametric method previously described by De Long et al. . A two-tFrom July 2008 to April 2011, 795 patients were enrolled in the AIDA STEMI CMR substudy , and were more likely to have hypertension (p = 0.05), anterior infarctions (p < 0.001), or to present with a higher Killip-class (p < 0.001). Consequently, the TIMI-risk score was significantly higher in the LVGFI < median group (p < 0.02).Baseline characteristics of the total study population and their association with the LVGFI are displayed in Table p < 0.001). There was also a significantly impaired TIMI-flow grade before PCI (p = 0.001) and ST-segment resolution (p = 0.02) after PCI in patients with LVGFI < median.Symptom-onset to reperfusion time was significantly longer in patients with LVGFI < median. Use of thrombectomy devices or stents were similar between groups. Patients with LVGFI < median had significantly more often left anterior descending culprit lesions (p = 0.70). In all patients, the median LVGFI was 31.2 % (interquartile range 25.7 to 36.6). Patients with LVGFI < median had significantly larger infarcts, less myocardial salvage, a larger extent of MO, higher incidence of intramyocardial hemorrhage and more pronounced LV dysfunction  for both LVGFI groups  as well as LV mass were also significantly larger in patients with a LVGFI < median Table .p < 0.001) and LVEF   Fig. .Fig. 3LiMultivariate analyses were performed to assess independent predictors of the LVGFI. In our regression model adjusted for significant variables in univariable regression analysis using the LVGFI as the dependent variable, male sex, symptom-onset to reperfusion time, culprit lesion left anterior descending, Killip-class on admission and IS were the strongest predictors of the LVGFI Table .Table 3Up < 0.001). Figure At 12-month follow-up, there were 53 clinical events. MACE and mortality rates were significantly higher in the LVGFI < median group. Consequently, patients who died had a significantly lower LVGFI  and 0.93  respectively.C-statistic demonstrated that inclusion of the LVGFI in addition to LVEF for prediction of mortality resulted in a significant increase of the c-statistics, thus demonstrating an additive prognostic value of the LVGFI over LVEF Table . There wThis large multicenter CMR study is the first that evaluates the prognostic significance of the LVGFI in patients with acute reperfused STEMI. The main findings can be summarized as follows: First, there was a marked reduction of the mean LVGFI in STEMI patients. Second, a significant relation between the LVGFI and the incidence of future cardiovascular events was observed. Third, the LVGFI has an incremental prognostic value in addition to LVEF for prediction of all-cause mortality. Therefore, these results highlight the importance of a comprehensive assessment of cardiac performance including LV function and LV mass following MI and argue for their routine assessment in patients with MI.Based on limitations of the measurement of systolic function (LVEF), investigators have developed a new index which integrates global function (LVEF) with heart size, including LV mass . In patiIn line with the data of Reinstadler et al.  we foundThe LVGFI is appealing because it is a simple concept and integrates prognostically important parameters. Although the LVGFI is strongly related to LVEF, it carries additional information by accounting for ventricular mass and hypertrophy. Previous studies have shown that the risk of death or MACE is significantly increased in the presence of LV hypertrophy in patients with hypertension, coronary artery disease, or MI , 6. CardThe current study clearly demonstrates for the first time that the LVGFI is associated with significantly increased MACE rates in patients with STEMI. Therefore, these data underscore the importance of the LVGFI as a marker of poor outcome in the post-MI phase. The LVGFI is correlated with established prognostic markers, such as delayed reperfusion, severe myocardial damage (IS), and reperfusion injury (MO), and might carry prognostic information of these outcome markers . HoweverOur work emphasizes the important association between myocardial function, structure and cardiovascular outcomes. Thus, aggressive medical heart failure therapy  may be started in patients with decreased LVGFI but yet preserved LVEF. Moreover, our findings may help to identify novel treatment targets and potentially more powerful efficacy markers  to reduce the incidence of cardiovascular events.Our study has several limitations worth emphasizing. First, our results are based on relatively small patient numbers, despite being the largest CMR study to date assessing the prognostic impact of the LVGFI. Second, the optimal time point for assessment of the LVGFI is unknown. We cannot exclude the possibility that later assessment of the LVGFI (e.g. 1 or 3 months after infarction) would have resulted in an even better prognostic value. Moreover, the LVGFI might change over time after reperfusion because of ongoing remodeling processes. Third, although T2-weighted CMR approaches for assessing the myocardium at risk are successfully applied in clinical settings and studies, some questions have been raised regarding physiological and mechanistic assumptions underlying this application , 22. TheIn conclusion, the LVGFI strongly correlates with markers of severe myocardial and microvascular damage in STEMI with superior prognostic information beyond traditional cardiac risk factors including the LVEF.


This study aimed to investigate the effect of left ventricular aneurysm (LVA) volume and left ventricular global torsion on cardiac function by real time three-dimensional echocardiography (RT-3DE) and two-dimensional speckle tracking imaging(2D-STI), to determine the accuracy of RT-3DE and 2D-STI in assessing LV function.Thirty New Zealand rabbit models of with LVA were prepared by ligation of the middle segment of the left anterior descending and left circumflex arteries. Four weeks post-procedure, RT-3DE was conducted to obtain data on LVEF, left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and LVA volume (LVAV), Peak rotation angles at the mitral valve annulus level (MV-ROT), peak rotation angles at the apical level (AP-ROT), and left ventricular global torsion angles (LV-TOR) were measured by 2D-STI.p<0.01). Moreover, LVEF correlated with LVA volume and LV torsion angle . LVA volume/LVEDV had the strongest inverse relationship with LVEF .Compared with controls, LVEDV and LVESV were significantly increased in the LVA group, while LVEF, MV-ROT, AP-ROT, and LV-TOR were consistently reduced (LVA volume, LVA volume/LVEDV, and LV torsion may be used as an indicator for evaluation of cardiac function after LVA. Moreover, LVA volume/LVEDV may be a more sensitive and reliable marker of cardiac function after LVA formation. Left ventricular aneurysm (LVA), one of the most important complications of myocardial infarction (MI), was defined as expansion of the dyskinetic area of the left ventricular wall. Aneurysms usually arise from a portion of weakened tissue in the ventricular wall, resulting in a reduction of the left ventricular ejection fraction (LVEF) –2.Recently, assessing cardiac function has been addressed using real time three-dimensional echocardiography RT-3DE) [DE [3]. TThe recent development of two-dimensional speckle tracking imaging (2D-STI) may also provide another means of assessing left ventricular function –13. 2D-SPrevious research has shown that the development of LVA closely correlated with deterioration of cardiac function –19, as LIn addition, left ventricular torsion plays an important role in LV ejection and filling –21; it iThus, we hypothesize that LVA volume and LV torsion may be more powerful variables for evaluating cardiac function after LVA formation. We aimed to investigate the relationship between cardiac function, LVA volume, and LV torsion using RT-3DE and 2D-STI, to determine the accuracy of RT-3DE and 2D-STI in assessing LV function, as well as to address the correlation between these echocardiographic variables and left ventricular function in the rabbit model, thus providing some useful parameters for clinical treatment of LVA.30 New Zealand rabbits of both genders (weight 2.3–2.5 kg) were provided by the Experimental Animal Center of Xinjiang Medical University . Rabbits were anesthetized with pentobarbitone sodium (30 mg/kg IV). Rabbit models of LVA were prepared by ligation of the middle segment of the left anterior descending artery and left circumflex artery, as previously described . PreoperAll animal experiments were performed in strict accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals  and with the approval of the Animal Care Committee of the First Affiliated Hospital, Xinjiang Medical University, P.R. China.In order to observe LVA formation and measure LVA volume, RT-3DE was used at postoperative days 1, 2 and 3, and weeks 1, 2, 3, and 4. This study found that the LVA of most animals were completely formed at postoperative 4 week and the LVA volume was the largest at postoperative 4 week. So the rabbits which had formed LVA were enrolled in this study at postoperative 4 week. The criteria for determination of LVA by echocardiography were: 1) marked thinning of the ventricular wall at the MI zone, with outward bulging of the ventricular wall in both systolic and diastolic phases; 2) the bulging wall displayed conflicting motion.Four weeks postoperatively, the rabbits were re-anesthetized and echocardiography was performed using the iE33 dimension system , with an X3-1 probe(volume rate was 24 Hz). RT-3DE images were acquired and left ventricular end-systolic and end-diastolic volume (LVESV and VLVEDV) and LVEF were calculated as described in our previous study . BrieflyTwo-dimensional echocardiography and 2D-STI studies were performed using the iE33 dimension system , equipped with an S12-4 probe(frame rate was 70–90 Hz). The parasternal mitral valve annulus and apical short-axis view were used for measurement of the mitral valve annulus level and apical level rotation. The QLAB software automatically segmented each short axis of the LV into 6 segments . LV rotation at the mitral valve level (MV-ROT) and at the apical level (AP-ROT) in each segment were calculated, as previously described . The netContinuous variables were presented as the mean and standard deviation. Statistical comparisons of echocardiographic variables between the LVA and control groups were made by analysis of variance with the Student’s t-test. Correlation coefficients between LVEF and LVA volume, and LV torsion angles were calculated by linear regression analysis. A p-value of less than 0.05 was considered statistically significant. All data analyses were performed by SPSS 11.5 software .Of the 30 New Zealand rabbits in the experimental group, 4 died within 4 weeks and 26 survived. Of these survived, 20 developed LVA and 6 did not , S1 Fig.Compared with controls, LV volume was significantly increased at both the end-systolic and end-diastolic phase in the LVA group . Conversely, the LVA group had a lower LVEF than the control group , .Compared with controls, the rotation angles of the 6 segments of the LV short-axis were significantly reduced in the LVA group. At the MV level, anterior septal rotation: -0.89±0.42° vs. -2.37±1.26°; anterior rotation: -0.37±0.08° vs. -2.03±1.01°; lateral rotation: -0.42±0.18° vs. -2.25±1.13°; posterior rotation: -0.75±0.26° vs. -2.81±1.52°; inferior rotation: -0.91±0.45° vs. -3.45±1.72°; inferior septal rotation: -0.73±0.33° vs. -3.34±1.15°. At the AP level, anterior septal rotation: 0.58±0.31° vs. 2.67±1.66°; anterior rotation: 0.22±0.22° vs. 2.32±1.11°; lateral rotation: 0.27±0.18° vs. 2.43±1.47°; posterior rotation: 0.51±0.46° vs. 3.65±1.42°; inferior rotation: 0.68±0.35° vs. 4.21±1.72°; inferior septal rotation: 0.60±0.37° vs. 3.12±1.15°. , .Compared with controls, the torsion angle of the 6 segments of the LV short-axis were significantly reduced in the LVA group, .Compared with controls, the LV global rotation angle at the mitral valve annulus (MV-ROT), the LV global rotation angle at the apical level (AP-ROT), and the LV global torsion angle (LV-TOR) were significantly reduced in the LVA group, especially at the apical level , , S2 Fig.Significant correlations between LVEF and LVA volume, LV-TOR, LVAV volume/LVEDV were observed , , S3 Fig.This study found that the development of LVA was associated with an increase in LVEDV and LVESV, and a reduction in LVEF. Meanwhile, there was a significant reduction in LV global rotation and torsion angle in all segments. Moreover, LVEF and LVA volume, LV global torsion, and LVAV/LVEDV strongly correlated. The LVA volume/LVEDV ratio presented the tightest inverse relationship with LVEF.Our study confirmed findings of previous investigations that LVA formation, as a complication of MI, can be attributed to left ventricular remodeling . UnfavorPrevious studies have consistently shown an impairment in LV torsional deformation in the setting of acute and chronic MI –31. HoweRecently, the prognostic value of the LV volume in assessing cardiac function was addressed using RT-3DE –3. HowevThis study had several limitations. The first, our sample size was small so we were not able to make continuous observations of the process of ventricular aneurysm formation, In future studies, we plan to increase sample size in subsequent studies. Second, the invasive measurements of cardiac output and LV pressure were not performed, and some parameters, such as LV volume and LVEF by 3DE were not compared with other results by magnetic resonance tomography in the present study. In this study, the term “torsion” is applied to mean the net difference between the rotation of the base and the apex. However, more correctly, the net difference should be indexed by the length of the ventricle, which was not done in this study.This study demonstrated that LVA volume on RT-3DE and LV torsion on 2D-STI are closely associated with LVEF. Accordingly, these parameters may be used in clinical practice as an indicator for the evaluation of cardiac function after LVA. Moreover, LVA volume/LVEDV measured with RT-3DE may be more sensitive and reliable than LVA volume and LV torsion in evaluating cardiac function after myocardial infarction followed by LVA.S1 FigA: Marked arrow in the cardiac apex shows left ventricular aneurysm formation. B: Marked arrow in the cardiac apex shows left ventricular aneurysm formation at 2-chamber view.(DOC)Click here for additional data file.S2 FigA: Green curve of the marked arrow shows the apical rotation curve in control group at left ventricular short-axis view. B: Green curve of the marked arrow shows the apical rotation decrease in LVA group at left ventricular short-axis view.(DOC)Click here for additional data file.S3 FigA: Correlation between LVEF and LVEDV, B:Correlation between LVEF and LVAV, C: Correlation between LVEF and LV-ROT,D:Correlation between LVEF and LVAV/LVEDV.(DOC)Click here for additional data file.S1 TableLVEDV: left ventricular end-diastolic volume; LVESV: left ventricular end-diastolic volume; LVEF: left ventricular ejection fraction; LVAV: left ventricular aneurysm volume.(DOC)Click here for additional data file.S2 TableMV level: at mitral valve annulus level; AP level: at apical level; Anterior sept rotation: the rotation angle of anterior septum; Anterior rotation: the rotation angle of anterior wall; Lateral rotation: the rotation angle of lateral wall; Posterior rotation: the rotation angle of posterior wall; Inferior rotation:the rotation angle of inferior wall; Inferior sept rotation:the rotation angle of inferior septum wall.(DOC)Click here for additional data file.S3 TableAnterior sept TOR: the torsion angle of anterior septum; Anterio TOR: the torsion angle of anterior wall; Lateral TOR: the torsion angle of lateral wall;Posterior TOR: the torsion angle of posterior wall; Inferior TOR: the torsion angle of inferior wall; Inferior sept TOR:the torsion angle of inferior septum wall.(DOC)Click here for additional data file.S4 TableMV-ROT: peak rotation angle at mitral valve annulus level; AP-ROT: peak rotation angle at apical level; LV-ROT: left ventricular global rotation angle.(DOC)Click here for additional data file.


Myocardial vasodilator reserve is an important surrogate marker of normal and abnormal cardiac physiology. Pharmacological vasodilator agents such as adenosine increase myocardial blood volume, which is expected to prolong the observed T1-relaxation. We explored the novel application of stress T1-mapping by assessing the response of myocardial T1 to the administration of adenosine in healthy volunteers.Healthy volunteers without history of cardiovascular disease, not on cardiovascular medications with a normal ECG underwent CMR studies at 1.5T  and 3T . T1-maps were acquired using the shortened Modified Look-Locker Inversion recovery  sequence at rest and under adenosine stress (140 μg/kg/min IV for at least 3 min) in 3 short-axis  slices. Mean T1 values were derived for whole-heart, per-slice and segmental analyses (AHA 16-segment model). Stress/rest first-pass myocardial perfusion imaging was performed in matching short-axis slices. Left ventricular function and viability were assessed by CINE and late gadolinium enhancement (LGE), respectively.All healthy volunteers had normal left ventricular function (66±5%), myocardial perfusion reserve indices 2.0±0.3) and no LGE. Mean resting ShMOLLI T1 values were normal: 954±20 ms (1.5T) and 1188±33 ms (3T). Compared to rest, mean myocardial T1 values under adenosine stress increased significantly at both 1.5T and 3T  and myocardial slice or segment positioning. This is likely due to the inherent intra-scan compensation of reported known variation sources in T1-mapping. With the presumed vascular origin of the response, the stress T1 holds promise for becoming a novel biomarker for mapping regional ischaemia and for detecting significant coronary artery disease in future studies.The research was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre based at the Oxford University Hospitals NHS Trust, University of Oxford. AL is a National Institute for Healthy Research (NIHR) funded Academic Clinical Fellow, UK. SN acknowledges support from the British Heart Foundation Centre of Research Excellence, Oxford.


Within the last few decades the pre-natal echocardiographic diagnosis of congenital heart defects has made substantial progresses, particularly for the identification of complex malformation. “Functionally” univentricular hearts categorize a huge variety of heart malformations. Since no one of the patients with these congenital heart defects can ever undergo a bi-ventricular type of repair, early recognition and decision-making from the neonatal period are required in order to allow for appropriate multiple-step diagnostic and treatment procedures, either of interventional cardiology and/or surgery, on the pathway of “univentricular” heart. In the literature strong disagreements exist about the potential impact of the pre-natal diagnosis on the early and late outcomes of complex congenital heart defects. This review of the recent reports has been undertaken to better understand the impact of pre-natal diagnosis in “functionally” univentricular hearts taking into consideration the following topics: pre-natal screening, outcomes and survival, general morbidity, neurologic and developmental consequences, pregnancy management and delivery planning, resources utilization and costs/benefits issues, ethical implications, parents counseling, and interruption of pregnancy versus treatment. Within the last few decades the pre-natal echocardiographic diagnosis of congenital heart defects has made substantial progresses, allowing the recognition of virtually almost all heart malformations between the 16th and 18th week of pregnancy, with a sensibility over 96% and a specificity close to 100% .in utero,”knowledge of the natural history of the congenital heart defects “potential pre-natal medical or interventional cardiology therapeutic interventions in the case of diagnosed heart failure, arrhythmias, or malformations with poor neonatal prognosis,safer management of the pregnancy itself,organization of the peri-natal period in or close to institutions with facilities available for the immediate management in the case of life-threatening heart malformations,parental counseling.The potential impact of pre-natal diagnosis of congenital heart defects includes:“Functionally” univentricular hearts categorize a huge variety of heart malformations, including but not limited to mitral atresia, tricuspid atresia, hypoplastic right or left heart, pulmonary atresia with intact ventricular septum and hypoplastic right ventricle, aortic atresia, double outlet right ventricle with hypoplastic right or left ventricle, complete atrio-ventricular septal defect with unbalanced ventricles, double inlet right or left ventricle.Since no one of the patients with these congenital heart defects can ever undergo a bi-ventricular type of repair, early recognition and decision-making from the neonatal period are required in order to allow for appropriate multiple-step diagnostic and treatment procedures, either of interventional cardiology and/or surgery, on the pathway of “univentricular” heart.In the literature strong disagreements exist about the potential impact of the pre-natal diagnosis on the early and late outcomes of complex congenital heart defects. This review of the recent reports has been undertaken to better understand the impact of pre-natal diagnosis in “functionally” univentricular hearts.Of course it has to be taken into account the difficulty of having meaningful inferences from the literature, because of different inclusion criteria, relative small numbers of patients, different peri-operative managements, different end-points, and frequently insufficient statistical analysis.pre-natal screening,outcomes and survival,general morbidity,neurologic and developmental consequences,pregnancy management and delivery planning,resources utilization and costs/benefits issues,ethical implications, parents counseling, interruption of pregnancy versus treatment.The reported studies have been analyzed, taking into consideration the impact of the pre-natal diagnosis on the following topics:Since any of the above topics presents direct implications with most of the other, the analysis has been performed trying to separately concentrate on each of the specific matters.The pre-natal echographic screening is, by necessity, the first step in the process of pre-natal diagnosis and management of complex congenital heart defects, and therefore several reports are available in the literature, focused on the pre-natal screening, with considerations on general and specific issues –24.A higher incidence of chromosomal disorders has always been found in fetuses with complex congenital heart defects , 8, 16, The incidence of complex congenital heart defects, including “functionally” univentricular hearts, has been observed as higher in the fetal pre-natal cardiac screening than in the post-natal diagnosis , 21, 23.The pre-natal cardiac screening can also been useful to detect fetal arrhythmias . Of courThe most important information provided by the pre-natal echocardiographic screening is relative to the morphology, size, shape, and function of the ventricular chambers, even given the known difficulties in evaluating the ventricular performance based only on pre-natal echocardiography , 19, 20.Data on the morphology and functioning of the right atrio-ventricular valve are also relevant , 18, 20.In the specific cases of pre-natal diagnosis of hypoplastic left heart, the presence of restrictive inter-atrial communication, and the type and direction of the flow through the inter-atrial communication itself , 9, 15, Useful information on the expected pathophysiology are the type and direction of flow through the patent ductus arteriosus , and parA recent report proved the feasibility of pre-natal echocardiographic demonstration of the presence of ventriculo-coronary connections .Survival is of course the most important parameter when evaluating the impact of the pre-natal diagnosis on the outcomes, and this issue has been addressed by many studies , 25–32.While for a relatively simple congenital heart defect, such as aortic coarctation, the pre-natal diagnosis can contribute to improve the outcomes, including the survival , for a mWhen dealing with the most complex congenital heart defects, such as “functionally” univentricular hearts, because of the presence of multi-factorial elements influencing the outcomes, the discrepancy on the opinions about the impact of pre-natal diagnosis on survival becomes even more evident , 29–32.In the past clinical studies failed to show an improved overall survival when the diagnosis of hypoplastic left heart syndrome was made pre-natal , 34.In the more recent period, with substantially improved the peri-operative care, a dichotomy clearly divided the reports demonstrating improved survival with pre-natal diagnosis , 30–32 fDespite this discrepancy regarding the survival, almost all studies showed the improved pre-operative conditions obtained thanks to the pre-natal diagnosis and the subsequent timely transfer to tertiary referral hospital for intensive care treatment. General agreement exists on the observations that prompt referral after pre-natal diagnosis allows reducing the pre-operative metabolic acidosis and the subsequent need for bicarbonate administration, minimizing the needs for pre-operative inotropic support, reducing the incidence and degree of ventricular dysfunction and right atrio-ventricular valve regurgitation, and almost abolishing the occurrence of end-organs dysfunction , 29–32. It is very interesting to note that, despite in the vast majority of the reported studies, the pre-operative conditions were significantly better in the cases with pre-natal diagnosis versus the post-natal diagnosis, this improvement failed to provide improved operative survival in about half of the clinical observations.The impact of the pre-natal diagnosis has not yet been evaluated on the outcomes of the hybrid approach for hypoplastic left heart syndrome, with bilateral pulmonary artery banding and stenting of the patent ductus arteriosus. This treatment option is increasingly considered or used in the recent years in the patients considered with high-risk for the conventional surgical management –43.The comparison between the two groups with pre-natal and post-natal diagnosis with regard to the post-operative morbidity showed discrepancies exactly as for the survival , 29, 31.Few studies showed reduced post-operative morbidity in the group with pre-natal diagnosis , 6, 31. Other researchers failed to observe reduced morbidity in the group of patients with pre-natal diagnosis , 29.Among the studies investigating the early and late neurocognitive development in children with complex congenital heart defects, very few had taken into consideration the impact of pre-natal diagnosis , 44, 45.In fetuses with hypoplastic left heart syndrome, a significant decrease in head growth and chronic diffuse white matter injury of variable severity have been reported . The preDespite it is well known that children with complex congenital heart defects present an increased prevalence of central nervous system abnormalities, due to inadequate development, pre-natal ischemia, post-natal cyanosis, and exposure to cardio-pulmonary bypass, it seems that pre-natal diagnosis, allowing the reduction of the peri-operative multi-organ injuries, can also improve the long-term beuroligic outcome , 30, 45.Quite evident is the agreement on the positive impact of pre-natal diagnosis of complex congenital heart defect, particularly “functionally” univentricular heart, in the management of the pregnancy and the appropriate planning of the delivery , 46–49.After pre-natal echocardiographic diagnosis of “functionally” univentricular heart, a maternal-fetal care program can be established, with the pregnancy follow-up and the mode of elective delivery, either cesarean or vaginal with induced or spontaneous labor, timely planned and organized in a tertiary referral hospital. This allows appropriate multi-disciplinary management of the neonate from the delivery room to the operating room, including echocardiographic confirmation of the cardiac diagnosis shortly after birth, and immediate transfer to the neonatal intensive care unit for prompt administration of prostaglandins, maintenance of normal acid-base status, and tracheal intubation with mechanical ventilation to provide and maintain adequate balance between the systemic and the pulmonary circulation , 46–49.In an era of money-driven medicine, the efforts toward cost containing have reached also the potential impact of pre-natal diagnosis of complex congenital heart defects, including “functionally” univentricular hearts , 51.The costs of training ultrasound technicians and make them capable to perform pre-natal diagnosis of complex congenital heart defects have been compared with the costs of organizing the emergency transports of neonates with post-natal diagnosis to specialized care centers. The results showed a substantial saving, considering the costs of training the ultrasound technicians plus the organization of elective transfer for delivery to a tertiary referral center in the case of pre-natal diagnosis of complex congenital heart defect versus emergency transportation and care after post-natal diagnosis of similar heart malformations . The savAll these points, strictly correlated, are not quantifiable in scientific or mathematic terms, such as the sensitivity of the pre-natal screening or the percentage of survival. A very large number of studies have tried to cover the matter, taking in consideration all the various aspects, and the unavoidable inter-relationships , 52–74.First of all, in this review all cases with the pre-natal diagnosis of “functionally” univentricular heart have been taken into consideration. In this regard, despite decent medium and long-term results obtained from few decades with the univentricular type of repair –79, the With regard to the option of heart transplant, evident discrepancies exist between the reported data in relationship with the timing of the heart transplant, if the option was utilized as first stage, after failed first stage Norwood type of procedure, after the second stage , or after failed Fontan circulation –83.In fact it has been reported , 70, 73 The decision for abstention from treatment, very difficult for all couples of parents, was generally justified by one or more of the following reasons: to avoid a described poor hospital survival and diminished quality of life, to prevent the child from suffering , 59, to In almost all cases the decision of the parents has been influenced by availability of pre-natal diagnosis of complex congenital heart defect , 70, 73.It is easy to agree about the importance of a multi-disciplinary team to assist the families after pre-natal diagnosis of complex congenital heart defect. Much more difficult is to define the “who, what, when, where and how” relative to the communication of the information to the parents.The information of pre-natal diagnosis of complex congenital heart defect is unavoidably followed by a major psychological crisis of the parents and their family: the state of shock, the short time available to make decisions, the frequently contradictory information available about early and long-term outcomes, limit to the parents the possibility for autonomous choices . FurtherThe parents’ counseling, already difficult because of the problem of communications between caregivers and families, can be further complicated by the influence of religion, culture, individual cognitive, emotional, and social processes , 69, 71.Another well-known difficulty of the parental counseling is due to the fact that nowadays the parents have easy access, through internet, to the best results reported by the best hospitals, while the same results are most probably not obtained in the local hospital. At this point it is very uneasy for a doctor to confess that the results of the local hospital are less satisfactory that the gold standard reported on the net.During the process of parents’ counseling, when considering the information received or perceived by the parents on the potential or expected outcomes, well known is the influence or the type and quality of messages received from the caregivers. While it is quite intuitive that the influence by optimistic physicians at surgical departments seemed important for a choice orientated toward surgery, less expected is the observation that the opinions offered by the professionals have offended some parents –69, 74.The importance of doctors’ belief, varying from the two extremes, optimism regarding the potential long-term outcomes, or serious suggestion to consider the option of termination of pregnancy, has determinant implications on the parental perceptions and their subsequent decision-making process , 70, 72.Also the opinion of the patients, and their families, should be taken into consideration, because there are certainly different degree of acceptance of a limited quality of life by different individuals and families.Doctor’s recommendations for treatment are consistent with selecting the option that maximizes the chance of the best outcome, without necessarily minimizing the chance of the worst outcome; even their beliefs about likely outcomes vary according to the patient group they encountered .The risk communication is particularly problematic when the evidence base is limited or when there are several options with many possible outcomes . FinallyNot easy is to find an answer to the question: “What if it were your child?” . An atteThe impact of pre-natal diagnosis of complex congenital heart defects where the only treatment option is a univentricular heart type of repair has dramatic implications for the parents, their families, and all the involved caregivers.The huge incidence of variable morphologic characteristics and subsequent pathophysiologic patterns, the potential association of chromosomal disorders, associated intra-cardiac and extra-cardiac malformation, and the several clinical reports with evolving short- and long-term outcomes make the parents counseling and the subsequent decision-making process extremely difficult.Better information, and therefore suggestions, could come from prospective data collection of the outcomes obtained with the currently available peri-operative techniques.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The origin and clinical relevance of exercise-induced premature ventricular beats (PVBs) in patients without coronary heart disease or cardiomyopathies is unknown. Cardiovascular magnetic resonance enables us to non-invasively assess myocardial scarring and oedema. The purpose of our study was to discover any evidence of myocardial anomalies in patients with exercise-induced ventricular premature beats.We examined 162 consecutive patients presenting palpitations and documented exercise-induced premature ventricular beats (PVBs) but no history or evidence of structural heart disease. Results were compared with 70 controls matched for gender and age. ECG-triggered, T2-weighted, fast spin echo triple inversion recovery sequences and late gadolinium enhancement were obtained as well as LV function and dimensions.p < 0.0001). More patients presented pericardial enhancement (35 %) or pericardial thickening (27 %) compared to controls . Myocardial oedema was present in 37 % of the patients and in only one control, p < 0.0001. Left ventricular ejection fraction did not differ between patients and controls .Structural anomalies in the myocardium and/or pericardium were present in 85 % of patients with exercise-induced PVBs. We observed a significant difference between patients with PVBs and controls in late gadolinium enhancement, that is 68 % presented subepicardial or midmyocardial lesions upon enhancement, whereas only 9 % of the controls did so (The majority of patients with exercise-associated premature ventricular beats present evidence of myocardial disease consistent with acute or previous myocarditis or myopericarditis. The origin and clinical relevance of exercise-induced premature ventricular beats (PVBs) in patients without structural heart disease such as myocardial infarction, coronary artery disease, left ventricular hypertrophy, cardiomyopathies or significant valvular disease is unknown. From a traditional perspective, PVBs at rest in individuals without structural heart disease are assumed to be benign –4. In coWe hypothesized that patients with exercise-associated premature ventricular beats would present evidence of acute or remote myocarditis or myopericarditis.We prospectively studied consecutive patients referred to our department with palpitations and exercise-associated premature ventricular beats. One hundred ninety consecutive patients who were transferred to our magnetic resonance department with confirmed exercise-associated ventricular ectopies were examined between 1.1.2008 and 30.11.2014 (end of recruitment period). The controls were prospectively scanned and recruited if they were free of atrial or ventricular premature beats and had no evidence of structural heart disease as was examined by medical history, echocardiography and exercise test before the magnetic resonance scan.Inclusion criteria for the patients were documented PVBs during exercise treadmill test with a history of palpitations, fatigue or exertional dyspnoea. Exercise-associated PVBs were defined as one or more ventricular ectopics during exercise including the first minute after exercise. Patients were excluded if they had a history or findings suggestive of or confirmed coronary artery disease , dilated or hypertrophic cardiomyopathy, congenital heart disease, pulmonary hypertension, LV hypertrophy, significant valvular regurgitation or valvular stenosis, renal failure . Further exclusion factors were: chronic alcohol abuse, use of sympathomimetic drugs, Conn syndrome, chronic loop diuretic treatment, chronic use of laxatives or any other causes of hypokalemia.Informed consent was obtained from each patient and control, and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution’s human research committee. After exclusions, our final cohort comprised 162 patients whom we compared to 70 age- and sex-matched controls without exercise-induced PVBs.All images were acquired on a 1.5 T magnetic resonance system  and specifically designed software (Release 11). We used a five-element cardiac phased-array coil combined with a homogeneity correction algorithm  . ConstanData acquisition was ECG-triggered. We took 2, 3 and 4-chamber long-axis views and 3-D short-axis volume data assessed by steady-state free precession imaging  to evaluate LV function and dimensions. Phase-contrast velocity images in the ascending aorta were obtained to measure stroke volume and rule out significant aortic insufficiency. Functional and morphological data were evaluated using view forum 6.5. .× 512, flip angle 90°, echo time 100 ms, TR 2 RR intervals). We measured signal intensity in the myocardial wall and skeletal muscle. We draw five regions of interest into the septum, five into the anterior, five into the lateral, and five into the inferior wall of the myocardium. If the regions were inhomogenous we draw five to 10 regions of interests. This was only the case in 5 % of patients. Five regions of interest were drawn into the skeletal muscles (erector spinae muscle or lattissimus dorsi) with a homogenous signal. Relative myocardial signal intensity was calculated by the ratio of myocardial signal intensity and muscle signal intensity. Resulting from our previous study findings, we set the cut-off value of an elevated ratio of signal intensity in STIR images between myocardial and skeletal muscle was at 2.14 [All patients underwent ECG-triggered, T2-weighted, fast spin echo triple inversion recovery sequences (STIR) in a short axis view covering the whole left ventricle  imaging was obtained in all patients 10 min after the iv. administration of 0.2 mmol/kg gadolinium-diethylenetriaminepentaacetate using 3D inversion recovery turbo gradient echo sequences  were optimized for each measurement to guarantee maximum myocardial signal suppression. 3D volume of the left ventricle was obtained covering the complete left ventricle without gap during two breath holds. Pericardial enhancement was defined as local or diffuse contrast enhancement. To exclude partial volume effects, pericardial thickening and enhancement were obtained in short and long axis views. Locally-thickened pericardium was defined as ≥4 mm. All CMR analysis including STIR and LGE measurements were carried out by one experienced CMR specialist who was blinded to the clinical characteristics and history of patients and controls. Clinical data were obtained and collected by our co-workers and study nurse.Data are presented as means and standard deviations for quantitative variables and as absolute and relative frequencies for categorical variables. Variables between patients and controls were compared using t-tests for quantitative and Chi-square-tests for categorical variables. All tests were two-sided and used a significance level of 0.05 to indicate statistical significance.Patient baseline characteristics are shown in Table Sixty out of 162 (37 %) patients displayed elevated T2-weighted CMR (STIR) values indicating oedema  and 102 patients had normal values. Figure p = 0.53, left ventricular enddiastolic volume 153 ± 35 ml vs. 156 ± 33 ml, p = 0.62) between patients with and without oedema. One control revealed a modestly-elevated STIR ratio but no symptoms.There was no significant difference in either LV-function or LV-volumes  primarily in the lateral or anterolateral parts of the pericardium, compared to 13 % of the controls, p < 0.001. Minor, not hemodynamically-relevant pericardial effusions were present in 18 % of patients and in 3 controls. The controls’ effusions were small enough as to be invisible on echocardiography.Contrast enhancement was present in the myocardium of 110/162 patients and only in 6/70 controls (Twenty-three patients revealed no myocardial or pericardial anomalies, whereas we detected myocardial or pericardial anomalies in 85 % of patients with exercise-induced PVBs.The present study provides evidence of myocardial anomalies in the vast majority of patients with exercise-associated premature beats. Eighty-five percent of our patients presented signs of acute or remote myocarditis or myopericardits despite having normal LV function. About two-thirds of our patients presented a subepicardial or/midmyocardial late contrast-enhancement typical of myocarditis , 24, 25.Some studies of the prognostic significance of ventricular arrhythmia during exercise have assumed that PVBs are benign –11, wherSudden cardiac death in athletes  and in tLGE has been investigated in controlled studies with patients suspected of having myocarditis , 35, 37.Pericardial effusion has been reported in 32 to 57 % of patients with myocarditis –41. A quThe aforementioned working groups , 9–13 diWe conclude that the majority of patients with exercise-associated premature ventricular beats present evidence of myocardial disease consistent with acute or previous myocarditis or myopericarditis.


Left ventricle (LV) regional fractional area change (RFAC) measured by cardiac magnetic resonance (CMR) allows the non-invasive localization and quantification of the degree of myocardial infarction (MI), and could be applied to assess the effectiveness of pharmacological or regenerative therapies. Here we investigate the ability of RFAC to identify regional dysfunction and discriminate the effect of pharmacological treatment with valsartan, a selective antagonist of angiotensin II type 1 receptor, in a model of MI.C57BL/6N mice, undergoing coronary artery ligation, were divided into two groups: untreated (MI) or treated with valsartan . Sham-operated mice were used as a control. Cardiac dimensions and function were assessed at baseline, 24 hours, 1 and 4 weeks post surgery by CMR and echocardiography. At sacrifice histology and whole-genome gene expression profiling were performed. RFAC was able to detect significant differences between treatment groups whereas the global ejection fraction was not. RFAC showed greater loss of regional contraction in remote non-infarcted myocardium in MI group than in MI+Val group. Consistently, in the same region MI+Val mice showed reduced myocyte hypertrophy, fibroblast proliferation, and fibrosis and modulation of target genes; in addition, left atrium volumes, appendage length and duct contraction were preserved.In this study, RFAC effectively estimated the degree of systolic dysfunction and discriminated the regions preserved by pharmacological treatment. RFAC index is a promising tool to monitor changes in LV contraction and to assess the effectiveness of therapeutic regimens in clinical settings. Myocardial infarction (MI) leads to complex structural alterations (remodeling) involving both the infarcted and non-infarcted left ventricular (LV) myocardium characterized by chambers dilatation, myocyte loss, fibroblast proliferation, scar formation , 2, and Imaging techniques play a central role in the diagnosis of acute myocardial infarction because of their ability to detect wall motion abnormalities or loss of viable myocardium. A number of reports proved the advantages of cardiac magnetic resonance (CMR) as reference tool for the non-invasive assessment of heart anatomy and function, advocating this approach as both an efficient method to monitor and an instrument to improve the therapeutic options –10. CMR Precise myocardial tissue characterization and a direct monitoring of treatment effects might be of great help in developing optimal therapeutic strategies for post-MI LV remodeling. Indeed, beneficial effects of pharmacological therapies on LV remodeling are associated with a better prognosis in MI patients: this makes maladaptive remodeling, occurring on remote non-infarcted myocardium, a therapeutic target for improving clinical outcome.a) assess qualitatively and quantitatively LV regional loss of function in infarcted and non-infarcted myocardium and (b) estimate drug effects occurring on myocardial wall motion. Imaging data were substantiated by tissue composition analysis and whole-genome gene expression profiling. Echocardiographic evaluation of left atrium (LA) volume was additionally used as index of LV performance and to indirectly monitor the LV diastolic function  .Systolic arterial blood pressure and pulse were measured by tail-cuff plethysmography . Three days of training sessions were necessary to accustom animals to the procedure. Recording sessions (5 measurements each) were then made by a single investigator, at the baseline and at the different time points during the follow-up.2 and 1M KCl, and retrogradely perfused with 0.01 M phosphate saline buffer (PBS) and then with 4% (vol/vol) phosphate-buffered formalin for 10 min each time. Hearts were collected and LAA removed; tissues were postfixed in 4% phosphate-buffered formalin for 24 hours and separately embedded in paraffin. Consecutive 8 μm heart axial (from base to apex) and LAA sections were prepared.To prepare specimens for histological analysis, abdominal aorta was cannulated and heart was arrested in diastole, with 2 mL of a solution of 0.1M CdClFor transcriptome analysis, hearts were perfused with PBS and the portion of the non-infarcted free wall corresponding to the posterior and inferior sectors was collected in RNAlater  and stored at -80°C.For collagen staining, deparaffinized and rehydrated heart sections were incubated in 0.1% Sirius Red Solution  in picric acid for 30 min, then washed, dehydrated , and mounted with DPX mountant for microscopy. Images were acquired with a high-resolution digital camera using 1:1 macro-lens. Myocardial infarct size was determined on LV axial section (one for each mm on LV) along the apex-basis axis and expressed as percentage of the length of the infarct scar on the LV total circumferential length  using the ImageJ v. 1.44o software.Immunofluorescence staining was performed on 3 tissue sections from each heart in order to assess myocyte cross-sectional area (MCSA), interstitial collagen fraction (ICF), and cell proliferation. Deparaffinized and rehydrated heart sections were incubated at room temperature in 10% normal goat serum  in 0.01 M PBS and 0.1% Triton X-100 for 45 min. Primary and secondary antibodies were prepared in PBS and 0.1% Triton X-100. To detect cardiomyocytes, fibroblasts, myofibroblasts, collagen I deposition, and cell proliferation the sections were incubated overnight at 4°C respectively with anti-α-sarcomeric actin (1:800), anti-vimentin (1:1500), anti-α-SMA mouse monoclonal antibodies , anti-collagen type I , and anti- Ki-67 rabbit polyclonal antibodies . Appropriate secondary antibodies  were applied for 2 h at room temperature. For nuclear staining, the sections were incubated with Hoechst 33258  in PBS for 15 min. Images were acquired at fixed exposure times using an inverted fluorescence microscope  equipped with the Axiovision v. 3.1 software (Zeiss).MCSA was assessed on LV tissue sections, double-labeled with anti-α-sarcomeric actin and anti-collagen type I: cardiomyocytes cut along the short axis, showing a circular profile and a visible nucleus were selected and their area was traced. ICF was measured within the LV non-infarcted zone and LAA and expressed as percentage of area occupied by collagen on total tissue area. Proliferating fibroblasts in LV remote non-infarcted myocardium were detected by double labeling with anti-Ki-67 as marker of proliferation and anti-vimentin as marker of fibroblasts. Cell proliferation was expressed as percentage of Ki-67 positive cells over the total number of cells (counting the nuclei); the rate of fibroblasts proliferation was expressed as a percentage of vimentin/Ki-67 double-positive cells over vimentin positive cells. Measurements were performed on 5 and 10 fields per section (220μm × 165 μm) for ICF and cell proliferation, respectively, whereas MCSA was based on 100 measured cardiomyocytes. All quantitative analyses were performed using Photoshop CS6 by an investigator blinded for the experimental groups.Total RNA was isolated from LV non-infarcted free wall using the TRIzol Reagent (Life Technologies) and further purified using silica-membrane RNeasy spin columns , following the manufacturers' instructions. Genomic DNA contamination was removed by TURBO DNA-free DNase (Life Technologies) treatment. Messenger RNA was reverse transcribed, labeled, and linearly amplified using the Total Prep RNA Amplification Kit (Life Technologies), and then hybridized to MouseWG-6 v.2 Expression BeadChip microarrays , according to the manufacturers' instructions. Signal detection was performed using a high resolution confocal scanner iScan, and quantitation and quality control were performed with the GenomeStudio v. 1.9.0 software (Illumina).lumi R package. To focus on the most informative probes and genes, we used the following filtering criteria: a probe was excluded if (a) the 33th percentile of intensities was less than 125  and/or (b) the p-value of the log-variation was greater than 0.05; (c) multiple probes were reduced to one per gene symbol by using the most variable probe measured by interquartile range across arrays. The number of genes that passed these filtering criteria was 8633. Differentially expressed genes among the three classes were identified by using a multivariate permutation test, based on 1000 random permutations, to provide 80% confidence (CI) that the false discovery rate (FDR) was less than 10%. The test statistics used was F-statistics for each gene; nonetheless, the multivariate permutation test is non-parametric and does not require the assumption of Gaussian distributions. We then performed a pairwise comparison (t-test) between pairs of classes, setting α = 0.01 for significantly different gene expression. Finally, to focus on the most meaningful differences, we filtered out those genes with a mean fold change (FC) ≤ ±1.2 in any of the two relevant post-hoc comparisons .Data adjustment, probe filtering, gene annotation and primary statistical analysis were performed using BRB-Array Tools v. 4.3.2, developed by Dr. Richard Simon and BRB-Array Tools Development Team, and software packages of Bioconductor v. 2.12 and R v. 3.0.1. Data variance stabilizing transformation (VST) and robust spline normalization (RSN) were conducted with the biological process and molecular functions ontologies) and corrects for multiple testing by bootstrapping (1000 bootstraps), estimating the empirical p-value distribution for the evaluated sets. A functional class was considered significantly enriched in a cluster if its corrected p-value was lower than 0.05.To identify clusters of genes with distinct expression patterns between the three conditions, we used the CLICK (CLuster Identification via Connectivity Kernels) clustering algorithm, implemented in the EXPANDER v. 6.3  software package  with theTo identify genes whose expression was significantly related to RFAC, we computed a statistical significance level for each gene using the Pearson’s correlation test. These p-values were then used in a multivariate permutation test in which the RFACs were randomly permuted among arrays. We used the multivariate permutation test to provide 80% confidence that the FDR was less than 10%.GSE68426.The data discussed in this publication have been deposited in NCBI's Gene Expression Omnibus  and are http://www.R-project.org). Values are shown as mean ± SEM (standard error of the mean), unless indicated; p<0.05 was considered significant. For measurements at the 24-hour time point, i.e. before pharmacologic treatment, we performed an ANOVA with Helmert contrast comparing (a) the sham group to the average of the MI and MI+Val groups, to assess that surgery was effective, and (b) MI group to MI+Val group, to assess that the assignment was unbiased. For measurements after the pharmacologic treatment (1 and 4 weeks), ANOVA with "treatment" contrast was performed to compare MI group either with MI+Val or sham group. Repeated measures ANOVA with post-hoc Holm adjustment was performed on the sham group to assess time constancy. RFAC values of MI and MI+Val groups were compared, sector by sector and slice by slice (on the resampled 10-slice space), using unpaired t-test. Mid-apical RFAC values were also averaged by sector excluding the apex slice  and the three at the base end of the heart not affected by infarction. Finally, Kaplan-Meier survival curves and the log-rank test were used to compare the mortality rate among groups after randomization to treatment with valsartan.Statistical analyses were performed using R: A Language and Environment for Statistical Computing .No significant difference was found in heart rate (ranging 590–640 bpm) and in systolic blood pressure among the three groups at follow-up .During the follow-up period ventricular parameters in sham-operated mice remained unchanged compared to baseline, whereas in MI and in MI+Val mice LV EDV and LV ESV increased steadily exhibiting severe LV dilatation and a large significant reduction in LV EF . Neverthp<0.05), was attenuated by treatment .As shown in p<0.001 MI vs. sham) that was attenuated by treatment with valsartan .Echocardiography analyses of LV structure and function  confirmeDuring the follow-up, anterior myocardial infarction resulted in acute loss of LV systolic function and progression of LV impairment. At 24 hours after surgery, bull’s eye representation of regional LV contractile function showed a reduced contraction of anterior, antero-septal and lateral sectors from apex to mid papillary region  in infarcted mice  compared to sham group . At 1-weResults of the non-infarcted free wall are shown in LA and LAA parameters in sham-operated mice remained almost unchanged from baseline to follow-up . On the Concurrently, LAA length increased at week 1 and 4 in MI compared to sham group and, LAA duct contraction was significantly and progressively lost. At the follow-up, treatment significantly preserved both parameters , Fig 3.vs. 32.9 ± 1.9%, p<0.05). No damage was observed in sham mice . LAA collagen content in MI group increased 1.4-fold compared to sham, while treatment maintained it at the sham level , was 248. The number of genes with a significant difference  in any of the two relevant post-hoc pairwise comparisons  was 174 (out of 248): of these, respectively 27 and 53 genes were significantly up- or down-regulated by valsartan with respect to MI mice , and genes with relevant transferase activity, for instance, for the glutathione metabolism.The CLICK algorithm identified 2 clusters of genes, with an overall average homogeneity of 0.834 : (1) 112a) ECM genes, included those involved in integrin signaling pathway; (b) genes related to cardiac function and repair (cardiovascular system development); (c) genes that participate in calcium cell signalling pathways by binding to Ca2+; and (d) stress response genes, in particular those regulating cell death.Quantitative trait analysis showed strong negative correlations between expression levels of several genes in cluster 1 and ipRFAC, with significant correlation coefficients ranging from -0.67 to 0.94 . SpecifiCardiac magnetic resonance imaging in cardiovascular research is generally used to measure myocardial mass, LV volumes, or EF. Although such measures of global function are very useful, in the MI setting, where contractile dysfunction is generally localized to specific coronary territories, it is critically important to evaluate regional myocardial function.We already reported the CMR regional quantification of LV function by RFAC analysis where the LV cavity was divided into several regions and the RFAC computed for each sector and clearly visualized in a "bull’s eye" format . This apThis paper, while confirming that RFAC is a sensitive and accurate tool for LV endocardial wall motion characterization , clearlyThroughout the follow-up, bull’s eye visualization showed that anterior myocardial infarction resulted in acute loss of LV systolic function and progression of LV impairment. The expansion of damaged myocardium affected not only apical and anterior sectors, but also the inferior and posterior mid-papillary regions, indicating a progressive loss of contraction in remote non-infarcted tissue probably as a result of LV stiffness and remodeling. Most interestingly, RFAC analysis accurately located the regions where valsartan exerted its protective effect, highlighting the drug efficacy in improving contractile function and reducing maladaptive remodeling. At 1-week post surgery, when remodeling was still progressing, even in the presence of many processes that could act as confounding factors , RFAC was able to show significant differences in mid-apical regions between MI and MI+Val groups. At 4 weeks, when the remodeling was almost complete, differences between groups became even more significant and localized mostly in the mid apical free wall region. Tissue analysis of these latter zones showed, at the cellular level, attenuated myocyte hypertrophy, reduction in number of proliferating fibroblast and decreased deposition of interstitial collagen, which were associated with an overall beneficial effect on ventricular remodeling and with improved heart function.2+ binding, integrin-mediated signaling, ECM organization and response to stress, which were significantly altered by infarct and almost restored to the normal level by valsartan treatment  much subtler changes in cardiac performance than EF, which is the weighted average of the RFAC on the whole ventricle volume. Comparing RFAC with strain echocardiography could add more information on regional function and/or the benefits of RFAC, but unfortunately this echocardiographic tool is unavailable to us.RFAC index accurately monitored the efficacy of a pharmacological treatment during the follow-up and indicated the inferior and posterior sectors of the LV remote non-infarcted free wall as those where valsartan exerted a protective effect on contraction. This data was supported by evidences at the cellular level indicating attenuated myocyte hypertrophy, reduction in number of proliferating fibroblast and decreased deposition of fibrillar collagen, and by modulation of relevant gene pathways. The overall beneficial effect on ventricular remodeling was additionally confirmed by attenuation of LA enlargement.Taken together, these data indicate that RFAC index could be applied in studies assessing localized and global wall motion differences secondary to standard pharmacological treatment in a mouse model of infarction.This information might serve to provide a novel view on the evaluation of tissue injury and its response to ischemia, and contribute to gain new insights into the evaluation of new therapies, which in the future could be translated to acute MI patients.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


Galectin-3 as a part of this lectin family plays a very important role in development of heart failure. According to recent papers, galectin-3 plasma level correlates with heart failure outcome, primarily with rehospitalisation and death from heart failure. This paper summarizes the most recent advances in galectin-3 research, with the accent on the role of galectin-3 in pathophysiology of myocardial remodelling and heart failure development—with preserved and reduced ejection fraction, and some implication on development of new disease modifying drugs.Galectins are a family of soluble  Heart failure (HF) can be defined as a complex mechanical and neurohumoral syndrome manifested by hemodynamic congestion presenting with dyspnea, orthopnea, paroxysmal nocturnal dyspnea, or peripheral oedema, along with the presence of objective evidence of cardiac dysfunction , 2. A neGalectin-3  is a member of a galectin family involved in numerous physiological and pathological processes, some of which, inflammation and fibrosis, are pivotal contributing pathophysiological mechanisms to the development of HF. Gal-3 is a 29–35 kDa chimaera-type galectin which is unique in that it is the only member of the galectin family with an extended N-terminal domain constituted of tandem repeats of short amino acid segments linked to a single C-terminal carbohydrate-recognition domain. C-terminal domain is responsible for lectin activity, while the presence of the N-terminal domain is necessary for full biological activity of galectin-3 . It is fCardiac remodeling is a crucial element in the clinical outcome of heart failure, and therefore various drugs are administered to prevent ongoing damage to the heart. Sharma and colleagues showed that Gal-3 was the strongest differentially regulated gene by comparing compensated and decompensated left ventricular hypertension in rats , 19. TheFibrosis and scar formation are a part of maladaptive mechanism to the injury. Fibroblasts and myofibroblasts as well as macrophages have been identified as key cells in development and growth of tissue scarring , 21. Uprγ [The same authors demonstrated that disruption of Gal-3 gene did not affect macrophage recruitment or macrophage proinflammatory cytokine profiles in response to interferon γ . On the γ . We can The maladaptive changes that occur in surviving myocytes and in the extracellular matrix after myocardial injury lead to pathologic remodelling of the left ventricle, with dilatation and impaired contractility . If thesThe majorities of patients with HF have coronary artery disease and ischemic cardiomyopathy with zones of myocardial fibrosis as a respond to myocardial ischemia and infarction. Dilated cardiomyopathy may also result from a genetic cause, previous viral infection (recognized or unrecognized), alcohol abuse, or, occasionally, chemotherapy .β to increase cyclin D1 and direct the proliferation of myofibroblast and collagen deposition [Increased stress and injury of the myocardium can contribute to myocardial remodeling . Respondposition . Galectiposition . Recombiposition , 33. Proposition , 32.Diastolic dysfunction or heart failure with preserved ejection fraction (nonsystolic HF) represents an abnormality of diastolic distensibility, filling, or relaxation of the left ventricle, regardless of whether ejection fraction is normal or abnormal and whether the patients are with or without symptoms . HFpEF hZile et al. had demonstrated in one small series that galectin-3 levels were significantly elevated in cohort of patients with HFpEF . GalectiUntil recently, the goal of HF treatment was based on symptomatic relief. According to new trials and knowledge of myocardial remodelling as a crucial factor in HF development, slowing or reversing the progression of the disease is recognized as important goal of novel therapy  . IdentifBrain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) assay were a golden standard in prognosis of HF in the past years. Natriuretic peptides are relisted by the myocardium as a result of myocardial stretching. In normal condition their level vary widley. In heart diseases condition, it is a marker of worsening heart failure and can present practical tool for heart failure treatment . TroponiAs mentioned before, various fibrotic conditions are associated with upregulation of galectin-3. Not only heart fibrosis but also upregulation of galectin-3 has been described in animal model for hepatic and renal fibrosis; in human liver cirrhosis; and in idiopathic lung fibrosis and chronic pancreatitis , 46–48. In every day clinical practice Gal-3 can be used to identify those patients at highest risk for readmission or death of HF. Galectin-3 measurement may be a significant factor in making a decision regarding visit intervals of whom to admit in patients with worsening HF. Due to the fact that Gal-3 levels are directly correlated with remodelling and fibrotic process in the myocardium, Gal-3 can be used as a culprit biomarker and can contribute to heart failure treatment as a potential novel target in therapeutics. This would be a real disease-modifying therapy to inhibit the remodelling process or slow down HF progression. Galectin-3 may one day allow identification and treatment of patients with coronary artery disease with a major risk of cardiomyopathy development.


Assessment of left ventricular (LV) systolic function can be achieved by conventional echocardiographic methods, but quantification of contractility, regional myocardial function, and ventricular synchrony is challenging. The goal of this study was to investigate the applicability of two-dimensional speckle tracking (2DST) to characterize segmental and global wall motion for assessment of LV function and LV synchrony in healthy goats. We aimed to describe the techniques, report normal values of a variety of 2DST indices, and determine the influence of general anesthesia.Prospective study on 22 healthy female Saanen goats . All goats underwent two transthoracic echocardiographic examinations, the first standing and unsedated and the second 7.4 ± 3.5 days later during isoflurane anesthesia and positioned in sternal recumbency. Data analyses were performed offline, blinded, and in random order. Left ventricular longitudinal, radial and circumferential strain and strain rate as well as longitudinal and radial displacement were measured using 2DST methods. Summary statistics were generated and differences of 2DST variables between myocardial segments and treatments  were assessed statistically .Echocardiographic analyses by 2DST were feasible in all goats and at both time points. Longitudinal systolic strain, strain rate and displacement followed a gradient from apex to base. Absolute systolic strain was generally lower and strain rate was higher in awake goats compared to anesthetized goats. Circumferential and radial indices did not consistently follow a segmental pattern. Generally, peak strain occurred later in anesthetized goats compared to awake goats. General anesthesia did not significantly influence LV synchrony.2SDT is a valid method for non-invasive characterization of LV wall motion in awake and anesthetized goats. The results of this study add to the understanding of LV mechanical function, aid in the diagnosis of global and segmental LV systolic dysfunction, and will be useful for future cardiovascular studies in this species. However, effects of anesthesia and species-specific characteristics should be considered when goats are used as animal models for human disease.The online version of this article (doi:10.1186/s12947-015-0005-8) contains supplementary material, which is available to authorized users. The echocardiographic assessment of myocardial function is a pivotal part of every clinical or experimental cardiologic examination, but still presents a considerable challenge for every cardiologist. Traditionally, myocardial function has been assessed by use of two-dimensional 2D), M-Mode, and Doppler echocardiography ,2. AlthoD, M-ModeEchocardiographic strain and strain rate imaging using two-dimensional speckle tracking (2DST) has been advocated for assessment of regional and global ventricular function beyond the conventional echocardiographic approach -9. The hTherefore, the goal of this study was to investigate the applicability of 2DST to characterize segmental and global wall motion for assessment of LV function and LV synchrony in healthy Saanen goats. We hypothesized that 2DST can be applied to characterize myocardial function in standing, awake goats as well as in anesthetized goats during general anesthesia. We aimed to describe the techniques, report normal values of a variety of 2DST indices, and determine the influence of general anesthesia. We further intended to explore the agreement of the findings of this study to other studies conducted in people and in other animal species to identify similarities and disparities with regard to the physiology of LV mechanics. The results of this study provide fundamental information on the use of 2DST for assessment of LV mechanics in goats and will be useful for future cardiovascular studies in this species.22 female Saanen goats aged 3.7 ± 1.1 [mean ± SD] years and with a body weight of 60.2 ± 10.5 kg were studied prospectively. All goats were considered healthy based upon physical examination, cardiac auscultation, and routine echocardiographic examination .The animals were fasted for 24 h and deprived of water for 2 h prior to anaesthesia. A 14 G/1.88 in catheter  was placed aseptically into the right jugular vein. All animals were premedicated intravenously with 0.1 mg/kg xylazine , diluted in 20 mL of saline  and given over 5 min with a syringe pump . Anaesthesia was then induced with either 3 mg/kg racemic ketamine  or 1.5 mg/kg S-ketamine  i.v. given by manual injection.2 > 50 mmHg. In this case, intermittent positive pressure ventilation was used with a tidal volume of 10-15 mL/kg at a rate of 10-15 breaths per minute. Anesthesia was maintained with isoflurane  delivered in oxygen and air via a semi-closed circle absorption system with a flow of 60 mL/kg/min during the first 10 min and a flow of 35 mL/kg/min thereafter. The vaporizer was initially set to 2.5% and after 15 min it was reduced and held between 1.5 and 2% to maintain an end-tidal isoflurane concentration of 1.1%. Lactated Ringer’s solution  was administered i.v. at a dose rate of 10 mL/kg/h. During anesthesia, the goats were kept in sternal recumbency.Once the animals were recumbent, they were positioned sternally, intubated, and connected to an anesthesia machine. Generally, the goats were allowed to breathe spontaneously throughout the entire duration of anesthesia. Mechanical ventilation was only applied when arterial blood gas analysis revealed a PaCO2, end-tidal isoflurane, and rectal temperature were monitored. Blood gas analysis was performed at 10 minutes after anesthesia induction and then every 30 minutes for the duration of anesthesia. Following anesthesia, the goats were placed sternally in a padded box. The endotracheal tube was removed once swallowing reflex returned.Each goat was instrumented with an electrocardiogram, a pulse oximeter and an end-tidal gas analyzer. A portable multiparameter monitor  continuously displayed the physiologic monitoring data during the anesthetic period. The ear artery was cannulated for intraarterial blood pressure monitoring and blood sampling for blood gas analyses. Heart rate (HR), respiratory rate, saturation of arterial oxygen, direct arterial blood pressures, end-tidal COTransthoracic echocardiography was performed using a high-end digital echocardiograph  with a phased array transducer  at a frequency of 1.9/4.0 MHz (octave harmonics) . A singlm). It was defined as the time interval between the peak of the electrocardiographic R wave and the closure point of the aortic valve identified on an M-mode recording of aortic valve motion. In cases, in which the closure point of the aortic valve was not clearly identifiable on the M-mode recording, anatomical M-mode was applied to the recorded two-dimensional echo loop of the LVOT, and cursor placement was adjusted to identify the point of aortic valve closure. The corresponding heart rate (HRAVCm) for each cycle was calculated as 60,000/R-R interval.The time to aortic valve closure was measured manually (tAVCThe 2D speckle tracking (2DST) analyses were performed using the 2D Strain module of the analysis software . The 2DST variables were measured as follows: (1) The appropriate long-axis or short-axis image was selected and the Q-Analysis module was started. (2) A single heart cycle was selected by moving the left and the right cursor, respectively, to the peak of the R waves of the electrocardiogram. Each cycle was identified by the image number, the time when the image was recorded, and the first and the last frame of the cycle. The R-R interval was measured and the frame rate was recorded. (3) Subsequently, the 2D Strain module was started. The long-axis  grayscale loops of the LV were analyzed using the “4CH” option, and the short-axis grayscale loops of the LV were analyzed using the “SAX-AP” , “SAX-PM” , and “SAX-MV” option , respectively. Once the option had been selected, a region of interest (ROI) was determined by tracing the endocardial border of the LV at end-systole. For the long-axis images, tracing started at the septal mitral valve (MV) annulus and ended at the lateral MV annulus; for the short-axis images, tracing was started at mid-septum and proceeded in a clockwise direction. The papillary muscles were not included in the tracings. The ROI width was adjusted, so that the entire myocardial thickness was covered throughout the cardiac cycle. Subsequently the speckle tracking analysis was started. The software algorithm automatically divided the myocardium into 6 segments, performed the speckle tracking analysis, and provided confirmation of adequate tracking for each segment , longitudinal strain rate (SRL), longitudinal displacement (DL), and transverse displacement (DT). For the short-axis images , the following variables were reported by the software: Circumferential strain (εC), circumferential strain rate (SRC), radial strain (εR), radial strain rate (SRR), radial displacement (DR). The time of aortic valve closure was automatically calculated and displayed by the software  as well as peak systolic strain . Where the highest strain value occurred before or at the time of aortic valve closure, peak strain (ε) was identical with peak systolic strain (εsys). Where 2 peaks for strain were present and εsys was followed by a 2nd, higher peak after aortic valve closure, the 2nd peak was considered ε. Where only 1 peak occurring after aortic valve closure was present, εsys was defined as strain at the time of aortic valve closure and the 2nd peak was termed ε. Post-systolic motion was diagnosed where the highest strain value occurred after automatically determined aortic valve closure (AVCa) ). Tracking was considered inaccurate in 1,869 of total 31,512 measured segments (5.93%) based on automated verification and visual assessment of tracking by the operator .a and tAVCm except for measurements obtained at the apical short-axis level during anesthesia and at the chordal short-axis level in awake and anesthetized goats  were significantly lower than those for peak strain (ε), except for circumferential strain in awake goats recorded at the SAX-AP level  and between treatments . SRL-E significantly differed between segments  but not between treatments. SRL-A significantly differed between segments (without a clear gradient) and between treatments . Longitudinal displacement differed significantly between segments  and between treatments (with varying effect of anesthesia depending on segment). Transverse displacement differed significantly between segments  and between treatments (higher displacement in anesthetized compared to awake goats).Segmental analyses are presented in Figures C significantly differed between segments and treatments (with varying effect of anesthesia depending on segment) and with an apparent gradient in anesthetized goats at PM and CH levels. At PM and CH levels, εR significantly differed between segments (without a clear gradient) but not between treatments. DR significantly differed between segments  and between treatments. SRC-sys differed significantly between segments and treatments . SRC-E differed between segments at all levels (without an obvious gradient), with a segmental effect of anesthesia at PM and CH levels. At AP level, SRC-A differed significantly between segments (without an obvious gradient), with varying segmental effects of anesthesia. SRR-sys significantly differed between segments (without an obvious gradient), with a segmental effect of anesthesia at the PM and CH level. SRR-E differed significantly between segments at the PM and CH, but not the AP level. Finally, absolute SRR-A was significantly higher in the awake state at the AP and PM level, and it differed between segments at the PM and the CH level.In SAX views Figure , εC signεL, tεC, tεR) are presented in Figure Segmental timing of peak strain values  is determined by active LV relaxation, LV compliance, and filling pressures [A) is related to active atrial contraction  and LV compliance at end-diastole [E was not significantly different in anesthetized compared to awake goats, suggesting that LV relaxation and filling was not markedly altered by anesthesia or that 2DST is not sensitive enough to detect slight alterations. Conversely, SRA was higher in awake goats in longitudinal as well as radial  and circumferential  direction, consistent with a slight depression of active atrial contraction in the anesthetized state. This was in agreement with previous findings obtained on the same population of goats, indicating that active left-atrial contraction was slightly lower in anesthetized goats [Strain rate measurements can also be applied for assessment of LV diastolic function. Early-diastolic strain rate , spatial resolution is slightly reduced when the longitudinal axis of the heart is perpendicular to the ultrasound beam. Therefore it is important to standardize imaging planes when comparing studies between individuals or over time and when comparing individual measurements to normal reference intervals.Since only female goats were included in this study, the influence of sex on 2DST variables could not be assessed. Regression analyses were not able to detect any significant relationship of 2DST variables to age and body weight, respectively (data not shown), but the study population was relatively homogenous and the range of available ages and body weights was narrow.A true limitation of this study is the lack consideration of alterations in blood pressures between the awake and the anesthetized state, since loading conditions might significantly influence strain variables. However, the current study setting did not allow invasive measurements of arterial blood pressures in awake goats.Also, this study was not designed to comprehensively assess the repeatability and reproducibility of recordings and measurements. Therefore, while significant differences between segments and treatments, respectively, can be established on a population level, the diagnostic validity for detection of subtle changes in strain and strain rate in individual goats in a clinical setting is unknown to date.In conclusion, 2SDT is a valid method for non-invasive characterization of LV wall motion in awake and anesthetized goats. In conjunction with conventional 2D, M-mode, and Doppler echocardiography, it may add to the understanding of LV mechanical function and may aid in the diagnosis of global and segmental LV systolic dysfunction in goats. However, effects of anesthesia and species-specific characteristics should be considered when goats are used as animal models for human disease. Furthermore, future studies are required to assess the reliability of 2DST measurements when used repeatedly in individual animals over time.


Echocardiography is a key tool for hemodynamic assessment in Intensive Care Units (ICU). Focused echocardiography performed by nonspecialist physicians has a limited scope, and the most relevant parameters assessed by focused echocardiography in Pediatric ICU are left ventricular systolic function, fluid responsiveness, cardiac tamponade and pulmonary hypertension. Proper ability building of pediatric emergency care physicians and intensivists to perform focused echocardiography is feasible and provides improved care of severely ill children and thus should be encouraged.  Echocardiography is currently considered a key tool for the hemodynamic assessment in Intensive Care Units (ICU), able to identify causes of hemodynamic instability and to quickly guide therapy , 2. SomeSeveral studies have demonstrated the positive effect of the use of echocardiography in the management of critically ill patients, changing their treatment in 30%–60% of cases after the test is performed .In the pediatric age range, there is an important limitation of noninvasive devices for hemodynamic monitoring, and this makes the use of echocardiography even more promising. An interesting review on hemodynamic monitoring suggests using focused echocardiography with the monitoring devices already routinely used to assess the hemodynamic status of critically ill children .When compared to the full echocardiography, the purpose of the focused echocardiography is the early identification of limited hemodynamics changes thus expediting clinical decisions regarding treatment , 10.Although there is no consensus on the ideal training format for capacity building of nonechocardiographers in focused echocardiography, different training programs for physicians from different areas  to perform specific echocardiographic assessments have been published , 11–21. The most relevant parameters assessed by focused echocardiography in pediatrics are left ventricular systolic function, volemia/response to fluid resuscitation, pericardial effusion/cardiac tamponade, and right ventricular systolic function and pulmonary hypertension.p < 0.001) [Previous studies have demonstrated the inaccuracy of physical examination in the assessment of the cardiac function and hemodynamic profile of critically ill patients, even when performed by an experienced physician . The ech< 0.001) . Similar< 0.001) .In a Pediatric Intensive Care Unit, Ranjit et al.  suggesteThe left ventricular systolic function may be assessed by echocardiography both qualitatively and quantitatively.The qualitative analysis of the LV systolic function consists of the visual analysis of the examiner in relation to the myocardial contractile function and is the method of choice for the assessment of the LV function by nonechocardiographers .Left ventricular ejection fraction (EF) is estimated visually using multiple echocardiography views: the parasternal long and short views and the apical and the subcostal views. This assessment is made by analyzing the myocardial thickness during systole and the reduction of the ventricular chamber diameter during systole in comparison to diastole provided by the ventricular wall motion during systole. LV function is subjectively classified as normal (EF ≥ 55%), slightly reduced (EF 41%–55%), moderately reduced (EF 31%–40%), and markedly reduced (EF ≤ 30%) .The quantitative analysis of the LV systolic function consists of LV ejection fraction and cardiac output/index measurements. This data aids the physician in choosing between therapeutic options, like fluids and/or inotropic agents.Ejection fraction may be measured in the M mode or two-dimensional mode. EF calculation in the M mode is the most widely used in clinical practice, especially in pediatric patients, and is derived from the fractional shortening (FS) measurement. Measurements of the LV systolic (ESD) and diastolic diameter (EDD) right below the mitral valve leaflets in the parasternal short- or long-axis views are necessary to obtain the fractional shortening, which is calculated using the formula FS = EDD − ESD/EDD × 100 .The clinical usefulness of quantitative EF measurements in the management of critically ill patients is broadly accepted both in adult and in pediatric patients , 27; howSimilar to the qualitative assessment, EF is classified as normal (EF ≥ 55%), slightly reduced (EF 41%–55%), moderately reduced (EF 31%–40%), and markedly reduced (EF ≤ 30%) .The cardiac output (CO) evaluation is not recommended to all shock patients. However, a recent experts consensus was proposed as evidence level I that the CO measurement should be performed in those patients that are not responding to initial therapy to evaluate the response to fluids or inotropes . As prevπ(LVOT  diameter/2)2  by the heart rate (HR). SV is obtained by measuring the LV outflow tract (LVOT) diameter in the two-dimensional mode  and the velocity-time integral (VTI) by pulsed Doppler , with SV = VTI × LVOT area, where LVOT  area = eter/2)2 . The tarr/2)2  diameter. However, the static measurement of IVC diameter has a poor correlation with the patient's individual response to fluid resuscitation, especially in children in whom the IVC diameter is related to their weight and height . RespiraDmax − Dmin)/Dmin  × 100, showed the best cutoff value of 18% to discriminate volume-responsive individuals (dIVC > 18%) from non-volume-responsive individuals (dIVC < 18%) with 90% sensitivity and specificity. However, we should note that it was performed in sedated patients with normal sinus rhythm, no spontaneous breathing, and a tidal volume of 10 mL/kg under mechanical ventilation. For having the advantage of being a noninvasive method that can be performed quickly and serially, the use of dIVC became widespread, but the specific situation in which the study was conducted cannot be disregarded [Respiratory changes in IVC by transthoracic echocardiography were established in the clinical practice after two studies conducted in adult patients undergoing mechanical ventilation. These studies showed a strong correlation between respiratory change in IVC and the patient's fluid responsiveness , 39. Theregarded . There aregarded , 42.V = (Vpeak  max − Vpeak  min)/Vmean  peak [Another means of assessing fluid responsiveness using echocardiography is by analyzing the respiratory change of the aortic peak flow velocity on Doppler during inspiration and expiration in patients under mechanical ventilation. It is calculated as Δan  peak . The aoran  peak , 44, 45.Pericardial effusion (PE) is identified in echocardiography as an echolucent space adjacent to the cardiac structures. It may be diffuse or loculated, more frequently is diffuse and promote a clear separation between the parietal and visceral pericardia . LoculatCardiac tamponade is an emergency situation and its diagnosis is known to be clinical. However, echocardiography may suggest the existence of tamponade physiology, that is, increased intrapericardial pressure precluding the ventricular filling. The major echocardiographic signs that corroborate the clinical diagnosis of cardiac tamponade are systolic collapse of the right atrium and diastolic collapse of the right ventricle, presence of IVC dilatation with no respiratory change, and presence of respiratory change in flow velocities through the heart valves –49 Figu.Bedside echocardiography plays an important role in guiding pericardiocentesis. An extensive review from the Mayo Clinic on 1127 patients undergoing echocardiographically guided pericardiocentesis showed that the usual subxiphoid approach had been chosen in only 20% of cases after echocardiographic assessment. In most of the patients, pericardial puncture was performed using transthoracic puncture , and this reduced the complication rate of pericardiocentesis from 20% to only 4.7% .The right ventricular (RV) wall thickness and dimensions should be analyzed using all multiple views, the apical view being the most suitable for this analysis. The RV size is qualitatively analyzed and, in comparison to the LV size, is classified according to the RV and LV ratio as follows: normal, when the RV is smaller than the LV (approximately 60% of the LV size) and the RV apex is lower than the LV; slightly increased, when dilatation is present; however, RV is still smaller than LV; moderately increased, when the RV size is the same as LV; and markedly increased, when RV is larger than LV  Figure .The RV systolic function is assessed by nonechocardiographers only qualitatively, by visual estimation. Just like the assessment of LV function, ventricular wall motion and thickness should be analyzed. The classification of RV function is also similar to the LV's: normal, slightly reduced, moderately reduced or markedly reduced .Echocardiography also allows the estimative of pulmonary artery systolic pressure (PASP) in the presence of tricuspid regurgitation. Using the spectral curve of tricuspid regurgitation obtained by continuous wave Doppler, the pressure difference between RV and RA (gradient pressure) is calculated. The RV-RA gradient pressure added to the RA pressure is equivalent to PASP, when there is no RV outflow tract obstruction .Pulmonary hypertension is present in several clinical situations in Pediatric Intensive Care, especially following cardiac surgery and in neonates. This makes its bedside diagnosis by the pediatrician both interesting and useful , 52.Bedside echocardiography has become widespread in emergency and Intensive Care Units. It is a useful tool in the diagnosis and treatment of hemodynamic unstable adult and pediatric patients. Adequate training of pediatricians from Emergency and Intensive Care Units to perform focused echocardiography is feasible and provides improved care of severely ill children and thus should be encouraged.