Cardiovascular disease (CVD) still remains the main cause of morbidity and mortality and consequently early diagnosis is of paramount importance. Working conditions can be regarded as an additional risk factor for CVD. Since different aspects of the job may affect vascular health differently, it is important to consider occupation from multiple perspectives to better assess occupational impacts on health. Standard echocardiography has several targets in the cardiac population, as the assessment of myocardial performance, valvular and/or congenital heart disease, and hemodynamics. Three-dimensional echocardiography gained attention recently as a viable clinical tool in assessing left ventricular (LV) and right ventricular (RV) function, volume, and shape. Two-dimensional (2DSTE) and, more recently, three-dimensional speckle tracking echocardiography (3DSTE) have also emerged as methods for detection of global and regional myocardial dysfunction in various cardiovascular diseases and applied to the diagnosis of subtle LV and RV dysfunction. Although these novel echocardiographic imaging modalities have advanced our understanding of LV and RV mechanics, overlapping patterns often show challenges that limit their clinical utility. This review will describe the current state of standard and advanced echocardiography in early detection (secondary prevention) of CVD and address future directions for this potentially important diagnostic strategy. Cardiovascular disease (CVD) still remains the main cause of morbidity and mortality , 2 and cAtherosclerosis, the basis of coronary artery disease (CAD), develops into a complex process . CAD is α-amylase and cortisol diurnal slopes, reduced daily α-amylase production, elevated daily cortisol production, and reduced heart rate variability and endothelial functioning.Although stress-related disorders comprise only a small fraction of occupational injuries and illnesses , overallA deleterious effect of shift work was also shown on lipid metabolism –24. Womeμm (PM2.5) as the fifth most important risk factor for mortality worldwide and the burden from air pollution was comparable to that from hypertension and diabetes mellitus [Many features of the environment exert an important influence on CVD risk, progression, and severity. Numerous epidemiological and experimental studies showed that air pollution , 26 causmellitus ; thus itWhereas the link between occupation and cardiovascular disease has been recognized, it is unclear which role occupation plays in the progression of subclinical CVD measured as carotid intima-media thickness (CIMT). Few longitudinal studies exist about occupation and subclinical CVD. Furthermore often these studies do not examine whether occupation is only an indicator of the person's socioeconomic position or a source of potentially health-compromising exposures. While in the former approach occupational differences show the socioeconomic gradient in CVD, in the latter approach occupation represents additional damage to the risk profile.A weak positive correlation was found between CIMT and age, diastolic blood pressure, LDL cholesterol, and antiphospholipid antibodies, and a negative correlation with the presence of anti-cardiolipin antibodies and a general level of occupational stress –28. A moCoronary artery disease or ischemic heart disease (CAD or IHD) is one of the major causes of morbidity and mortality. Echocardiography provides a thorough complex assessment of structural and hemodynamic changes induced by acute or chronic CAD –32, and Myocardial ischemia impairs regional systolic contractility. Persistence of severe ischemia produces development of myocardial necrosis and scarring with permanent functional impairment . RegionaThe use of deformation (“strain”) echocardiography allows less subjective assessment of myocardial contraction as compared to simple visual evaluation –36. The Since in the normal myocardium strains and strain rates are homogenously distributed, subtle strain changes suggest myocardial contractile impairment. A good correlation has been shown between longitudinal strain decrease and reduced coronary perfusion in segments that appear visually normal. In addition to regional myocardial strain assessment, a global longitudinal strain (GLS) can be determined averaging peak longitudinal strain in all evaluable segments. GLS is compromised in CAD patients and appears as a useful index for assessment of global myocardial function. A GLS cut-point of greater than −17.77% had good sensitivity and specificity for detecting CAD and was comparable to a WMSI ≥ 1.13 measured during stress . UnfortuThree-dimensional speckle tracking echocardiography (3DSTE) has recently been regarded as a more promising technique to accurately and reproducibly evaluate the segmental and global LV function . The 3D The role of 2D stress echocardiography (SE), either exercise (exercise SE) or pharmacologic with dobutamine (DSE), is well established for diagnosis and prognosis of patients with known or suspected CAD , 37–52. The sensitivity of SE is higher for multivessel CAD and lower for single vessel disease. Sensitivity of the test is also influenced by the time between peak stress and image acquisition. It is imperative to accomplish postexercise imaging as soon as possible (≤1 min from cessation of exercise). When abnormalities recover rapidly, false-negative results occur. On the other hand, despite the excellent specificity of SE, some patients have false-positive tests  in the absence of left bundle branch morphology, right ventricular pacing, prior cardiac surgery, or abnormal wall tethering at baseline. These false-positive findings present a management challenge because it remains unclear whether these patients should be treated and how to treat them. A subset of patients has microvascular abnormalities , a hyper2D-SE has its own limitations as multiple views of the left ventricle (LV) must be obtained from more than window to completely visualize all segments. Three-dimensional stress echocardiography (3D-SE) allows assessing overall wall motion of the entire LV simultaneously in different planes . 3D imagA major limitation of echocardiographic study interpretation is the subjective visual analysis of endocardial motion and wall thickening which is only semiquantitative. The need for more quantitative techniques to objectively evaluate LV regional wall motion during DSE has led to the incorporation of new indices in the analysis of regional wall motion. Tissue Doppler imaging (TDI) is a novel echocardiographic technique that can be used to quantitatively assess low-velocity motion of myocardial walls with excellent temporal resolution . 2D-straRegional LV akinesia in CAD patients is irreversible in the presence of scarred tissue but may be reversible in stunned or hibernated myocardium –52. StunAssessment of contractile response to inotropic stimulation by low-dose dobutamine echocardiography or evaluation of myocyte metabolism with nuclear scan and positron emission tomography is used to identify hibernating myocardium. Recent clinical reports such as STICH trial suggest that we should not rely on one single imaging parameter and that optimal medical therapy may be sometimes as effective as revascularization procedures , 50. HowHypertensive heart disease represents a form of organ damage with strong independent prognostic significance. Assessment of myocardial anatomy and function is necessary to identify early cardiac alterations in hypertensive patients since left ventricular hypertrophy (LVH) is the first step toward the development of coronary heart disease, stroke, heart failure, and sudden death. Recent Guidelines of the American College of Cardiology/American Heart Association  define nEchocardiography may also give useful information on cardiac functional performance, including systolic and diastolic changes . LV diasSystemic hypertension may be a potential independent risk factor for heart failure with preserved ejection fraction, and LV diastolic filling changes can be observed even in the absence of LV remodeling. Since the left atrium (LA) is directly exposed to LV pressures during ventricular diastole, LA size is correlated with LV filling pressure. Thus, LA structural remodeling represents a stable indicator of the severity of LV diastolic dysfunction –61. BesiThe role of arterial stiffness in systemic hypertension has also been demonstrated and is based on its pathophysiological importance for overall cardiovascular performance –68. The Heart failure (HF) is a common clinical syndrome, especially in the elderly, but its diagnosis is often missed. A detailed clinical history is crucial and should address not only current signs and symptoms of heart failure but also those signs pointing to a specific cause of the syndrome, such as coronary artery disease, hypertensive heart disease, or valvular heart disease. Echocardiographic imaging has several targets in the HF population, including the assessment of myocardial structure and function, valvular disease, and hemodynamics.All modalities of echocardiography are useful in the assessment of the HF patient –73. HistTwo-dimensional echocardiographic assessment of LV ejection fraction is based on measuring end-diastolic and end-systolic volumes , 69–71 uMost HF patients have reduced LV systolic function; however a significant subset has normal or near normal resting systolic function with predominantly diastolic dysfunction , 74–77. Diastolic dysfunction causes impairment of LV relaxation and compliance and consequent elevation of LV filling pressures, left atrial pressures, pulmonary venous pressures, pulmonary capillary pressures, and right heart pressures. Cardiac performance is compromised with exercise, even in the presence of normal stroke volume and cardiac output at rest. Doppler echocardiography can help in the diagnosis by allowing assessment of indices of diastolic filling and ventricular relaxation. Myocardial hypertrophy  and/or iThe presence of RV dysfunction has important prognostic implications in patients with HF. RV dysfunction has often been evaluated qualitatively, but the development of RV annular systolic tissue velocity, RV free wall strain, and three-dimensional RV volumes  has beenSelection of patients for a wide range of device therapies needs also an accurate echocardiographic evaluation –84. ThesAdults with congenital heart disease (CHD) have increased in number due to advances in early diagnosis and treatment . CardiovApart from the assessment of postoperative complex CHD, nowadays echocardiography has gained an important role in the management of patients with patent foramen ovale (PFO) and atrial septal defect (ASD). Strokes have high rates of morbidity being the second leading cause of death, and up to 40% of ischaemic strokes are cryptogenic. A strong association has been shown between cryptogenic stroke and PFO prevalence suggesting paradoxical embolism via PFO as a potential cause. PFO closure with Amplatzer device appeared superior to medical therapy in preventing strokes in patients with cryptogenic embolism , and theQp/Qs) ratio ≥1.5 : 1 and signs of right ventricular volume overload. Indications for PFO closure are cryptogenic stroke and evidence of right to left shunt.PFO represents a remnant of the foetal foramen ovale and has a flap valve mechanism that intermittently opens a small channel between left and right atrium. It is associated with an intermittent right-to-left shunt, only rarely with a permanent left-to-right shunt, has an incidence of 20% to 35% of the general population, and is commonly treatable by device closure. On the contrary, ASD is a permanent opening characterized by left-to-right shunting with transient right-to-left shunting on the basis of the breathing cycle and accounts for nearly 10% of congenital heart disease. Different types of ASD involve particular structures such as septum primum (ostium primum ASD), septum secundum (ostium secundum ASD), sinus venosus (sinus venosus ASD), and coronary sinus (coronary sinus ASD). The ostium secundum ASD is the most frequent type and the only one treatable by percutaneous transcatheter closure. Indications for ASD closure are isolated secundum ASD with a pulmonary/systemic flow  has become an established approach  to guideTraditionally, percutaneous ASD and PFO closures are performed under 2D-TEE guidance. TEE is also employed prior to device closure to assess defect size, position, and any associated left-to-right and right-to left shunting . It is iLife-threatening acute congestive LV failure complicating surgical or transcatheter closure of ASDs in patients with LV restriction has been reported , 100. DeThree-dimensional TEE (3D-TEE) offers improved spatial orientation and better definition of ASD, “complex” PFO, or multifenestrated septal aneurysm , 102. ThPatients with valvular heart disease (VHD) can be asymptomatic or present with a series of symptoms not always related to the severity of the lesion . CurrentMitral regurgitation (MR) is the most common clinically recognizable valvular heart condition. The disease has various congenital and acquired etiologies. Mitral valve prolapse (MVP) is a primary condition  characteIt has become evident that moderate-to-severe MR, even in the absence of LV dilatation and dysfunction, may have adverse prognostic consequences. Thus, accurate echocardiographic quantification of MR is vitally important in clinical medicine, especially when planning surgery or interventional percutaneous procedures , 107 as Aortic valve stenosis (AS) represents a significant cause of morbidity and mortality . The pre2 [Complex presentations with multiple comorbid conditions make often the diagnosis and management of AS challenging. Clinical signs and symptoms are of limited use in distinguishing critical from noncritical AS due to unsatisfactory sensitivity and specificity especially in the aged. Moreover, assessment of the symptomatic status and severity of valvular lesion can be disappointing because of the subjectivity of symptoms and ambiguity of individual functional capacity. The current guidelines approve two-dimensional transthoracic echocardiography (TTE) as the diagnostic test of choice for the assessment of AS. In addition to TTE, 2D transesophageal echocardiography (2DTEE) provides images with higher resolution , while r2 . IndicatThe majority of aortic valve replacements are surgical aortic valve replacement. However, in high-risk patient groups, factors such as increasing age, prior cardiac surgery, and other comorbidities, such as heart failure, respiratory, and renal diseases, are associated with a high potential for operative mortality and morbidity. Transcatheter aortic valve implantation (TAVI) was first performed in 2002 as a less invasive approach and is now recommended as an alternative strategy for patients in high risk surgical groups –114. MulEchocardiography using both conventional and more recent modalities is the primary diagnostic tool for the assessment of early cardiac dysfunction. It is a cost-effective technique and offers real-time imaging with high spatial and temporal resolution. Three-dimensional echocardiography and two-dimensional and three-dimensional speckle tracking echocardiography may provide additional diagnostic information. It is plausible that echocardiography will further evolve in the future with improvements in technology providing better clinical help. A strong professional liaison between echocardiologists and occupational physicians aids the process of offering effective support and management for the cardiovascular patients in the workplace.


The influence of type 2 diabetes mellitus (DM2) on systolic function is partially determined by the coronary vasodilator function, nevertheless, an independent effect is suspected. We evaluated the relationship between DM2 and systolic function considering PET quantitative myocardial perfusion.We analyzed 585 patients without a previous myocardial infarction referred to a rest and adenosine stress Nitrogen-13 ammonia PET. A bootstrapped multiple linear regression analysis was performed using DM2, stress myocardial blood flow (sMBF), myocardial perfusion reserve (MPR), and clinical risk factors as predictors and LVEF as the outcome variable; an interaction term was additionally investigated.B = 5.830 95% CI , P = .001) and DM2  with LVEF. The interaction (DM2 × sMBF) yielded no significance (P = .512).Two hundred and ninety male and 295 female patients  were included. 57.1% presented hypertension, 16% smoking, 37.6% hypercholesterolemia, 33.8% family history for CAD, and 15.2% DM2. The mean MPR was 2.13 ± 0.48 and 2.21 ± 0.60, mean sMBF was 2.01 ± 0.51 and 2.15 ± 0.54, and mean LVEF was 63% ± 10.4 and 67% ± 10.1 for diabetics and non-diabetics, respectively. A significant relation was detected for sMBF  contains supplementary material, which is available to authorized users. The importance of type 2 diabetes mellitus (DM2) in cardiovascular disease, ranging from endothelial dysfunctionWe retrospectively analyzed a prospectively constructed database with data from 2012 to 2014. From the patients referred for PET myocardial perfusion scanning for evaluation of known or suspected CAD, we selected patients without a previous myocardial infarction as registered in the patients’ clinical history and confirmed with the absence of fixed perfusion defects in the scan results. In total, 585 patients were included for the analysis and demographic data regarding gender, age, body mass index, and cardiovascular risk factors including hypertension, hypercholesterolemia, smoking status, and DM2 were extracted from the electronic file system. DM2 was operationalized as a dichotomous variable for the presence or absence of the disease.Every patient underwent a two-phase (rest and adenosine stress) PET scan with the use of Nitrogen-13 ammonia as the perfusion radiotracer. All image data were acquired in list mode on a Siemens Biograph-16 TruePoint PET/CT  with the TrueV option . This 3D system consists of a 16-slice CT and a PET scanner with four rings of lutetium oxyorthosilicate (LSO) detectors. Patients were instructed to fast overnight and to avoid the consumption of methylxantine-, caffeine-containing beverages or medications for 24 hours before the study. Previous to the rest perfusion phase of the scans, a CT-based transmission scan  was obtained during normal breathing for correction of photon attenuation for all PET acquisitions. The automatic co-registration of the CT attenuation map with the PET images was verified visually and alignment was corrected when necessary by an experienced nuclear medicine technician. During rest, myocardial perfusion was assessed using 300 MBq of Nitrogen-13 ammonia. Imaging lasted for 12 minutes and began simultaneously with peripheral injection of the radiotracer. The Nitrogen-13 ammonia was administered as a single intravenous bolus (8-10 s with infusion rate 0.4 mL/second) followed by a 10 mL saline flush. Pharmacologic stress imaging was performed one minute later and beginning with a 6-minutes adenosine infusion through a peripheral vein (140 µg/kg/minute). A second dose of 400 MBq Nitrogen-13 ammonia was injected in the fourth minute of the adenosine administration and image acquisition was started, in the same way, simultaneously with the radiotracer bolus. Static, dynamic, and 16-bin ECG-gated images were generated from the list mode data. Patient emission data was reconstructed using 3D attenuation-weighted ordered subsets expectation maximization (OSEM3D) reconstruction with 168 × 168 matrix, zoom 2, Gaussian filter with a full width at half maximum of 5 mm, 2 iterations, and 21 subsets for gated and dynamic images and TrueX (OSEM3D with PSF) reconstruction with 256 × 256 matrix, zoom 2, Gaussian filter of 4 mm, 4 iterations, and 8 subsets for static images. CT-based attenuation, scatter, decay, and random corrections were applied to the reconstructed images. Dynamic images were reconstructed with 25 frames for rest: 1 × 10, 12 × 5, 2 × 10, 7 × 30, 2 × 60, and 1 × 180 seconds, and 26 frames for stress: delay 90, 1 × 30, 1 × 10, 12 × 5, 2 × 10, 7 × 30, 2 × 60, and 1 × 180 seconds.Based on the dynamic subsets, left ventricular contours were assigned automatically using the SyngoMBF software  with minimum observer intervention when appropriate. With a previously described 2-compartment kinetic model for Nitrogen-13 ammonia, stress and rest flow values in mL/g/minute were computed for each sample on the polar map through the resulting time-activity curves for global quantification.The list mode data were reconstructed in 16-bin ECG-gated images. The end-systolic and end-diastolic volumes were determined using Quantitative Gated SPECT 2012 (QGS) software . LVEF was expressed as the percentage of the end-diastolic volume ejected during systole.t test. Further, a multiple linear regression analysis was performed by entering gender, age, hypercholesterolemia, hypertension, smoking habit, DM2, sMBF, and MPR as predictor (independent) variables and LVEF as outcome (dependent) variable. The model was bootstrapped based on 1000 samples with bias-corrected and accelerated 95% confidence intervals (95% BCa CIs) for robustness of B coefficients and significance estimators. A second step for the model was performed for testing a possible interaction between DM2 and both sMBF and MPR. P values less than .05 were considered significant. All statistical analyses were performed using SPSS .Continuous variables were explored for sampling distribution through histograms and described as mean ± standard deviation. Dichotomous variables are described as the number of occurrences with their associated valid percentage graphically. The univariate analysis was performed through biserial correlations considering clinical variables, and a difference in means was explored through an independent samples A total of 585 consecutive patients, 290 male and 295 female, with a mean age of 65.3 ± 9.9 and 67.4 ± 10.0 years were included in our analysis, respectively. There was a high prevalence of arterial hypertension while the rate of patients who were smokers or had diagnosed DM2 was comparable. Baseline demographic and perfusion variables are depicted in Table rb = −0.14, P = .03) but not for smoking , dyslipidemia , or hypertension . The bootstrapped correlation between sMBF and LVEF was found to be significant . We evaluated the difference in mean LVEF between the patients with and without DM2 finding a statistically significant lower LVEF in the DM2 group t = −2.104 SE 1.269, P = .037, d = 0.25 , sMBF (P = .001), and the presence of DM2 (P = .034) with LVEF. The statistical values for age (P = .218), dyslipidemia (P = .086), hypertension (P = .820), and smoking (P = .152) were not significant. The overall model was assessed through the change in coefficient of determination, R2 = 0.162, P < .001. The corresponding coefficients and BCa 95% CIs are shown in Table P = .19) or between DM2 and sMBF (P = .51), and there was no significant improvement of the model according to the change R2.The bootstrapped multiple linear regression analysis determined a statistically significant relationship for gender  and additional relevant risk factors .When considering our population of patients without a previous myocardial infarction, these results line up with the current view of diabetic cardiomyopathy,Diabetic cardiomyopathy is defined as “a distinct entity characterized by the presence of abnormal myocardial performance or structure in the absence of epicardial coronary artery disease, hypertension, and significant valvular disease.”Previous research has reported a difference in systolic function measured through LVEF between patients with and without DM2 in the of setting patients without CAD.Interestingly, although there was a trend towards significance for the presence of dyslipidemia in the analysis, none of the otherwise generally considered cardiovascular risk factors yielded significance in our study. We consider that this supports the notion that the effect of DM2 may be of greater importance regarding systolic function assessment. A complementary explanation may be that other risk factors, such as age, dyslipidemia, arterial hypertension, and smoking probably hamper systolic function through their pathological effect on coronary vasodilatory function , which again was accounted for in our analysis through the included perfusion variables (sMBF and MPR). The lack of significance for the interaction term (DM2 and sMBF) suggested that the significant effect found for DM2 was not explained by mediation through myocardial perfusion. Other effects such as cardiac sympathetic innervation dysfunctionAs evidenced by the multiple regression analysis, DM2 showed a relative greater influence over LVEF than MPR, but more discrete than gender or sMBF according to the adjusted B coefficients, as shown in Table Recent evidence has demonstrated that the rate of cardiac death in diabetic patients without known CAD was low in the presence of a preserved MPRThe variable gender yielded significance in this analysis. This was expected when considering previous evidence of male-female differences in LVEF due to intrinsic anatomic and physiologic differences linked to the calculation of ejection fraction.B = 7.133 , P = .001) when compared to MPR (by inclusion in the same regression model). This finding is in line with recent reports proposing sMBF (hyperemic MBF) as a better measure of perfusion in patients with suspected CAD.Previous studies have repeatedly proven the relationship between PET-derived perfusion and ventricular function.Our results add to the body of evidence suggesting a decrease in systolic function in relation to the presence of DM2. Additionally, they describe proof of its statistically assessed independent influence when compared to other risk factors.This study demonstrated a relation between type 2 diabetes mellitus and systolic function in patients without previous myocardial infarction independently from and not mediated by quantitative perfusion results. Additionally, to the previously reported relationship between PET-derived perfusion and ventricular function, the present study showed a relative greater influence of stress myocardial blood flow compared to the myocardial perfusion reserve on systolic function.Our results are limited by the availability of alternative parameters to evaluate the status of the diabetic patients such as HbA1c or time from diagnosis. Also, it would have been of benefit to consider a complementary technique for the evaluation of ventricular function. Nevertheless, the technique described constitutes a valid one for the evaluation of systolic function and the reference standard for perfusion assessment in absolute terms. Another limitation would be that we did not include data related to invasive angiographic evaluation since only a small proportion of the sample underwent the procedure, even so, univariate correlations between quantitative perfusion and systolic function were similar in these patients and ischemic burden may have overshadowed other potential effects. Additionally, regional flow was not considered separately and although of interest, we aimed to account for the global perfusion status and its influence on the ventricular function. Therefore, the influence of specific regional measures cannot be evaluated from this study alone. Finally, our population showed a discrete prevalence of DM2 patients, which might not concur with DM2 prevalence in patients referred to cardiac PET imaging; nevertheless, it portraits the prevalence in the general population as well as in previous published reports.Diabetes mellitus significantly influences PET-measured systolic function in patients without a previous myocardial infarction, independently from myocardial perfusion parameters. Our study supports the importance of diabetes mellitus as an independent risk factor for deteriorating systolic function.Supplementary material 1 (PPTX 274 kb)Below is the link to the electronic supplementary material.


The increasing worldwide prevalence of childhood obesity portends the development of type 2 diabetes and cardiovascular disease (CVD) in this population. Cardiovascular Magnetic Resonance (CMR) imaging provides a sensitive imaging tool that may afford early detection of structural and functional alterations secondary to obesity. This pilot study explores the potential for CMR imaging, inclusive of left ventricular (LV) volume and mass analysis, Native T1 mapping and 4D strain analysis to identify such changes related to obesity in adolescence.th percentile of weight for their age. Fourteen age and gender-matched healthy weight control subjects were also enrolled. All subjects had baseline anthropometric and laboratory measures in addition to a standardized CMR imaging protocol, inclusive of routine multi-planar cine imaging and native T1 Mapping using the shMOLLI pulse sequence. Left Ventricular (LV) volumetric analysis and T1 mapping was blindly analyzed using cvi42 . 4D strain analysis was performed using GIUSEPPE in-house software.Eleven subjects between 10 and 20 years were prospectively recruited from a Pediatric Weight clinic, and defined as obese if they were ≥952, p < 0.0001) as was systolic blood pressure (SBP), serum lipid levels and markers of insulin resistance. LV ejection fraction was non-significantly elevated in the obese group . A trend was seen in elevation of LV Mass index  with mean segmental wall thickness being significantly elevated in the obese cohort . BMI was positively correlated with LV Mass Index , wall thickness  and mass:volume ratio . 4D strain analysis revealed significant elevations in peak circumferential endocardial strain (-20.5 ± 2.1 vs -18.7 ± 2.0% p = 0.04) and peak longitudinal endocardial strain (-16.7 ± 1.6 vs -14.4 ± 1.9% p = 0.006) in the obese cohort, consistent with a hyper-contractile state. Circumferential epicardial strain was not significantly different between groups, however, was significantly positively correlated with systolic blood pressure  and LV Mass Index . Native T1 mapping was not significantly different between the groups .The mean age of the obese group was 14 ± 1 years versus 14 ± 2 years in controls (p=0.572). BMI values were higher in the obese cohort (32 ± 6 and 21 ± 4 kg/mIn this pilot study we identify pediatric obesity to be associated with objective elevations in LV mass, wall thickness and Mass:Volume ratio. In this "early stage" of remodeling these structural changes were not associated with elevation in native T1, a surrogate marker of tissue fibrosis. Strain analysis revealed a hyper-contractile state, likely representing a combined contribution of elevated systolic blood pressure with compensatory myocyte hypertrophy.


P, LAEFA; N = 80, 79, respectively) were quantified by CMR. After adjustment for multiple testing, maximal LAVi was only associated with age (ρ = 0.39), transmitral filling patterns , and N-terminal pro-BNP . Lower LAEF was associated with older age, higher transmitral E/A ratio and higher NT-proBNP. Peak VO2 and VE/VCO2 slope were not associated with left atrial structure or function. After adjustment for age, sex, transmitral E/A ratio, CMR LV mass, LV ejection fraction, and creatinine clearance, NT-proBNP remained associated with maximal LAVi  and total LAEF . Passive and active LAEF were most strongly associated with age and NT-proBNP, but not gas exchange or other markers of ventricular structure or filling properties. Left atrial volume and emptying function are associated most strongly with NT-proBNP and diastolic filling properties, but not significantly with gas exchange, in HFpEF. Further research to explore the relevance of left atrial structure and function in HF-pEF is warranted.Given the emerging recognition of left atrial structure and function as an important marker of disease in heart failure with preserved ejection fraction (HF-pEF), we investigated the association between left atrial volume and function with markers of disease severity and cardiac structure in HF-pEF. We studied 100 patients enrolled in the PhosphdiesteRasE-5 Inhibition to Improve CLinical Status and EXercise Capacity in Diastolic Heart Failure (RELAX) trial who underwent cardiac magnetic resonance (CMR), cardiopulmonary exercise testing, and blood collection before randomization. Maximal left atrial volume index , left atrial emptying fraction (LAEF; N = 99; including passive and active components (LAEF Heart failure with preserved left ventricular ejection fraction (HF-pEF) affects nearly 50% of all patients with HF. Given the clinical heterogeneity across patients with HF-pEF, structuHere, we sought to investigate the relationship between left atrial structure and function with markers of fibrosis, hemodynamic stress, and prognostic indices of gas exchange in HF-pEF. We hypothesized that a greater left atrial volume and lower left atrial emptying function would be associated with decreased peak aerobic capacity, less ventilatory efficiency, and increased circulating biomarkers of fibrosis and N-terminal pro-BNP in HF-pEF. To address this hypothesis, we calculated left atrial volumes and emptying function by cardiac magnetic resonance (CMR) in HF-pEF patients in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) study. Ultimately, we sought to provide further evidence of the physiologic importance of left atrial structure in cardiopulmonary structure and fitness in HF-pEF.2 on cardiopulmonary exercise testing (CPET) less than 60% predicted for age- and sex-normative values (with adequate effort) and either (1) elevated N-terminal pro-B-type natriuretic peptide (NT-pro BNP) ≥ 400 pg/ml or elevated LV pulmonary capillary wedge pressure (>20 mmHg at rest or >25 mmHg during exercise). Patients were excluded if there was clinical evidence of myopericardial disease , pulmonary arterial hypertension, recent active coronary disease , or alternative, non-cardiac causes of dyspnea ; a full list of exclusion criteria is available[2 over 24 weeks of therapy. In addition to clinical evaluation , cardiac magnetic resonance (CMR) imaging was performed on a subset of patients within RELAX who satisfied the main trial inclusion criteria and: (1) no implanted non-MRI safe device, (2) no claustrophobia, (3) able to lie flat and breath-hold for at least 15 seconds, (4) adequate size for magnet bore, and (5) not in atrial fibrillation. Of the 216 patients randomized in RELAX, 117 (54%) were eligible for CMR imaging. The details of echocardiography, CPET testing, biomarker assays, and clinical end-points are described in the main RELAX manuscript[The details of the RELAX trial have been previously reported. RELAX wCMR imaging was performed using 1.5 Tesla scanners from all major vendors . The CMR protocol consisted of (1) conventional scout images for cardiac localization; (2) a complete stack of LV short-axis cine images for LV mass and function using a balanced steady state free precession technique  SSFP cine imaging of the tubular ascending aorta for measurement of aortic distensibility . Contrast was not administered routinely as prescribed by the RELAX protocol. Analysis of left ventricular function, volumes, and mass was performed on using QMass 4.2  by a Simpson’s approximation (standard Society of Cardiovascular Magnetic Resonance published guidelines). Aorticπ/3) X (Area4-chamber) X (Area2-chamber) / atrial length, using the shorter atrial length from either the 4- or 2-chamber view. Left atrial volumes were calculated at the end of ventricular systole (LAVMAX), just before atrial contraction (LAVBAC), and at the end of ventricular diastole (LAVMIN). All left atrial volumes were indexed to body surface area (LAVi). Finally, left atrial function was quantified into its component parts: 1) Passive left atrial emptying fraction (LAEFP) = (LAVMAX−LAVBAC) X 100%/ LAVMAX; 2) Active left atrial emptying fraction (LAEFA) = (LAVBAC−LAVMIN) X 100%/ LAVBAC; and 3) Total left atrial emptying fraction (LAEF) = (LAVMAX−LAVMIN) X 100%/ LAVMAX  using the 2- and 4-chamber cine SSFP sequences by way of the biplane area-length method: LA volume =  and biomarkers reflecting fibrosis and hemodynamic stress . Our secondary outcome was the association of LAVi and LAEF with selected imaging parameters physiologically central to greater left atrial pressures in HF-pEF . In a subset of individuals with available measures, we examined associations with components of left atrial emptying . Spearman bivariate correlation coefficients were estimated to measure the strength of association for primary and secondary outcomes. For those primary outcome measures that were significant in bivariate correlation , we constructed multivariable linear models to test for association between LAVi, LAEF, and its components with each outcome, adjusted for age, gender, CMR LV mass and LV ejection fraction, echocardiographic E/A ratio, and creatinine clearance . NT-proBNP was log-transformed for analysis to establish linearity. Model residuals were examined to ensure no departures from linearity. Given the multiple comparisons performed, we used a Bonferroni type 1 corrected p-value for multiple comparisons. SAS version 9.2  was used for all analyses.Continuous data were summarized using medians and interquartile ranges, and compared between groups using a Wilcoxon rank-sum test. Categorical data were summarized using percentages, and compared between groups using chi-square tests. Our primary outcome was the association of LAVi and total LAEF with two measures of gas exchange (peak VO2) with decreased cardiorespiratory fitness (median peak VO2 12.3 ml/kg/min). Of note, patients who did not have a CMR performed in RELAX were older (p = 0.02), with significantly higher NT-proBNP (p<0.0001), galectin-3 (p = 0.005) and lower peak VO2 (p = 0.03). Of the 100 individuals who had analyzable left atrial volumes by CMR, the majority had total left atrial emptying function , while active and passive left atrial emptying function was assessable in a majority . Unanalyzable images for components of atrial function were due to inability to determine precise phase of atrial contraction. CMR characteristics of the study population are shown in Baseline characteristics of RELAX patients undergoing CMR with analyzable left atrial data (N = 100) and patients who did not undergo CMR (N = 99) are shown in P with older age and both LAEFA and LAEFP with higher NT-proBNP, but not with gas exchange metrics; only the association between NT-proBNP and LAEFA withstood multivariable adjustment .Unadjusted (Spearman) associations between maximal left atrial volume and left atrial function are shown in In this report, we describe the distribution of left atrial volumes and function by cardiac magnetic resonance in a carefully phenotyped, prospective population of patients with HF-pEF. We found that left atrial volume and function were most strongly associated with circulating N-terminal pro-BNP concentrations, and more modestly with age and transmitral LV filling patterns. Importantly, after correction for multiple hypothesis testing, we did not observe an association between left atrial emptying function or left atrial volume with gas exchange. Associations between NT-proBNP and left atrial structure and function were robust to adjustment. These findings suggest that left atrial structure and function most closely reflect hemodynamic stress and remodeling in HF-pEF (by NT-proBNP and diastolic filling properties), but are not directly associated with prognostic measures of gas exchange.The recognition of a role for left atrial structure and function in HF has undergone a renaissance. The rol2 and natriuretic peptides in patients with a variety of cardiopulmonary diseases [2 in patients with HF-pEF. One possible explanation for this finding was the exclusion of patients with atrial fibrillation (AF) in the current analysis. Indeed, prior work from RELAX had demonstrated that individuals with AF  had significantly lower peak VO2 [2.One unanticipated finding from our analysis was the lack of association between left atrial emptying function or left atrial volume with measures of gas exchange. Given the relationship between peak VOdiseases ,16, our peak VO2 . Further2; total LAEF 39±17%; active LAEF: 30±14%); RELAX study participants had a lower passive LAEF relative to the Melenovsky study (26±9%). Our study additionally delineated association between left atrial structure and function with age and NT-proBNP, concordant with the invasive hemodynamic findings of Melenovsky et al. Taken together, these results suggest that impairment in left atrial structure and function (reflecting increased hemodynamic stress and higher LV filling pressure) is prevalent and plays an important role in HF-pEF physiology. Our study further demonstrates that CMR methods to interrogate the left atrium may provide a useful tool to non-invasively investigate HF-pEF physiology.Recent work from Melenovsky and colleagues investigated 198 patients (51% with HF-pEF) with integrated hemodynamic and echocardiographic measures of left atrial structure and function. These iThe conclusions of our study must be viewed in light of its design. Our study is small relative to other community-based studies of left atrial volume and function, which may contribute to modest effect sizes, lack of association after multivariable adjustment, and the potential for type 1 error with the multiple correlations investigated. However, the RELAX study population is rigorously selected for HF-pEF, which is unique, and the original study was not powered on left atrial imaging endpoints. Our results therefore may motivate additional studies utilizing this parameter as a physiologic endpoint. We recognize that mitral valve function was not quantified in CMR acquisition; however, individuals with severe valvular heart disease  were excluded from RELAX. Given the limited event rate and follow-up in RELAX, we did not report long-term rates of HF hospitalization or mortality in our cohort, which also merits investigation in larger, prospective studies of individuals with HF-pEF.In conclusion, in a well-phenotyped cohort of patients with HF-pEF, left atrial volumes and function are associated with aging, echocardiographic diastolic filling properties, and NT-proBNP. Gas exchange indices were not associated with left atrial structure or function. These results suggest that the left atrium may be a marker of hemodynamic stress and neurohormonal activation in a carefully phenotyped group of patients with HF-pEF. Further research in larger populations is warranted to investigate the role of left atrial morphology and function in cardiorespiratory fitness, dyspnea generation, and outcome in HF-pEF.


Cine DENSE MRI is an established myocardial strain imaging technique with high accuracy and rapid data analysis. Current cine DENSE protocols utilize breath-holding (BH); however, this practice limits the use of this technique to patients with good BH capabilities, excluding many pediatric and some heart failure patients. We propose a free-breathing (FB) framework for cine DENSE that uses localized excitation, self-navigated motion estimation, and k-space correction to enable FB motion-corrected (MC) imaging.2, slice thickness = 8 mm, localized excitation width = 80 mm, field of view = 160 mm, number of spiral interleaves per image = 4, and number of interleaves acquired per heartbeat = 2. Images were reconstructed offline with and without MC. Displacement and strain analysis was performed for 36 segments. To assess for variability due to respiratory motion, the coefficient of variation (CV) of end-systolic strain was compared among the three groups: BH, FB with and without MC using one-way ANOVA.A modified cine DENSE sequence was implemented on a 1.5T scanner . The sequence utilized an ECG-gated segmented acquisition with a variable-density spiral trajectory, typically requiring 14 heartbeats to acquire a full 2D cine dataset encoded for 2D in-plane displacement. Localized excitation was implemented by applying orthogonal slice-selective RF pulses in the DENSE preparation so that displacement-encoded stimulated echoes would only occur in the heart region where the slice profiles intersect. The use of localized excitation facilitated automatic estimation of heart motion due to respiration, as other tissues such as liver and chest did not generate significant signal Figure . Low-resFigure FB cine DENSE shows good potential for strain imaging in patients with sub-optimal BH capabilities.


With the article by Morelli et al., a new hope has emerged.Septic shock is characterized by circulatory collapse and diminished tissueperfusion, leading to organ dysfunction in the setting of systemic infection. Themechanisms of septic shock are incompletely understood; moreover, its incidence isincreasing, and its mortality remains unacceptably high. In addition toantimicrobial and supportive treatments, no other therapy has a survival benefit,despite multiple attempts at developing one. The adrenergicsystem serves as an initial adaptive response to maintain homeostasis by elevatingheart rate, stroke volume and mean arterial pressure, keeping the balance ofinflammation and coagulation and providing sufficient nutrients to cells. However,over the long term, the high output of endogenous catecholamines causes an imbalancein this regulatory function and perpetuates organ dysfunction. To make matters worse, there isalso an adrenergic storm caused by the use of vasopressor therapy, which is themainstay of supportive treatment for fluid-unresponsive septic shock. Noradrenaline, adrenaline anddopamine are used for their α-adrenergic vasoconstrictor effects, but theyalso act upon β-adrenergic receptors, mainly β1.The adrenergic system plays a key role in modulating cardiovascular, immune,hemostatic and metabolic functions. It is upregulated in septic shock through theactivation of different adrenoreceptors that have distinct and sometimes oppositeeffects.,4 which isdeleterious.As such, they can promote tachydysrhythmias and cardiomyopathy and upregulateinflammatory and coagulation pathways, Right ventricular (RV) dysfunction and dilation are alsoobserved. Its cause isnot completely understood, but inflammatory mediators and adrenergichyperstimulation are important contributors to impairing myocyte signalingtransduction and reducing cardiac contractility. Tachycardia, which is common inseptic shock and is a known predictor of poor prognosis, promotes cardiacdysfunction by increasing oxygen requirements and diminishing diastolic cardiacfilling and coronary perfusion. An estimated 50% of septic shock patients developcardiomyopathy, as assessed by echocardiography. However, considering that the LV ejection fraction isdependent not only on LV contractility but also on pre- and afterload (that are inturn related to the quantity of fluids and vasopressors imposed on each patient),cardiac dysfunction would likely be present in virtually all patients with septicshock if they were evaluated using a method less dependent on the degree ofresuscitation. Contrary to previous beliefs, there is currently no clinical evidencethat links LV or RV systolic dysfunction or dilation to prognosis in septicshock. Nevertheless, arecent meta-analysis reported that diastolic dysfunction, which may be more common,is related to mortality.A particular occurrence in septic shock is the development of cardiac dysfunction.The definition of sepsis-induced cardiomyopathy is not established, but it ishistorically characterized by reduced left ventricular (LV) ejection fraction, LVdilation and complete recovery in 7 to 10 days. and some concerns about the danger of precipitouslyreducing cardiac output and blood pressure remained.There has been a growing interest in the use of β-blockers in septic shock. Itwas hypothesized that the administration of β1-selective blockers couldprotect patients from the toxicity of endogenous and exogenous catecholamines andameliorate cardiac function and the homeostasis of immunologic and coagulationprocesses. These effects have already been proven in animal models. However, theresults for prognosis have not been consistent,The first randomized clinical trial (RCT) conducted to assess the effect ofβ-blockade on tachycardia and other hemodynamic parameters in septic shockenrolled 154 patients who remained tachycardic (heart rate (HR) > 94 beats perminute (bpm)) and on a noradrenaline infusion after 24 hours of standardresuscitation. Half of them were randomized to receive an esmolol infusion, and allpatients in this group achieved the target HR (80 - 94 bpm) with no adverse effectson systemic or pulmonary hemodynamics. In fact, stroke volume increased, whichsuggests an optimization of cardiac efficiency and myocardial oxygen utilization.There was also an improvement in perfusion markers, such as arterial lactate and pH,oxygen consumption and estimated glomerular filtration rate. Fluid and vasopressorrequirements were decreased, and, most importantly, there was a significantly lower28-day mortality in the patients who received esmolol. The sameauthors published a pilot study that added the evaluation of the sublingualmicrocirculation to a similar design. They noted an improvement in two parameters(blood flow and heterogeneity index), whereas the other two (De Baker score andperfused vessel density) were unchanged in the group receiving esmolol. While it issafe to conclude that β-blockade poses no danger to the microcirculation, itis not possible to assume that there was an improvement in this vascularbed.While systemic hemodynamic parameters are accessible for monitoring patients withcirculatory collapse, the cornerstone of organ dysfunction in septic shock is themicrocirculation, which is less easily assessed in everyday clinicalpractice.Although it is clear that there is a theoretical rationale for using selectiveβ-blockers that is supported by animal studies, the clinical evidence isstill scarce, and many questions remain to be answered. Thisraises the concern that there might be a bias in patient selection, in which thepersistence of tachycardia after 24 hours of resuscitation is related to worseprognosis. It is not known whether less severe patients would derive a similarbenefit. Additionally, half of the patients received the inodilator levosimendan(that improves diastolic function), and its influence on outcome is unknown. Theother studies that address the influence of β-blockers on mortality eithershow a neutral effect or are flawed in their design and preclude the extrapolationof the results to the general population.The RCT by Morelli et al. showed a significant survival benefit ,but the trial was not designed for this purpose, and the mortality was extremelyhigh in the control group. It is unknown whether the mortality benefit isproduced by the treatment of tachycardia itself or by its effect on cardiacfunction. Because there is no relationship between systolic dysfunction andprognosis, it ispossible that the improvement in stroke volume is not solely responsible for themortality benefits. However, it is reasonable to hypothesize that the reduction inheart rate would have beneficial effects on diastolic function, as well byaugmenting diastolic filling time, and could potentially confer an improvement inprognosis.Unfortunately, this is only speculative, as no diastolic parameters were assessed.Additionally, no study assessed the optimal heart rate in septic shock, as thetargets for its reduction were arbitrarily set.,9,10Another issue is the fact that most studies published to date rely on reducingtachycardia to obtain an improvement in cardiac function. These factors should be frequently monitored andthoroughly addressed before true deleterious tachycardia, caused solely byhyperadrenergic status, is treated with β-blockers. The role of heart rate inguiding the management of critically ill patients would also be lost if the use ofβ-blockers in septic shock were to become widespread. In particular, volumestatus/fluid responsiveness and autonomic nervous system function are importantissues in intensive care patients. Nevertheless, static hemodynamic measurements arepresently being replaced with dynamic ones for the assessment of volume status/fluidresponsiveness, and anumber of methods for autonomic nervous system evaluation beyond those dependent onheart rate are being developed. Nevertheless, it would be useful to have a clear view of howto monitor these patients.An additional matter to be discussed is the fact that sinus tachycardia is often aresponse to an insult, such as fever, anxiety, pain, anemia, hypoxemia,thyrotoxicosis, electrolyte and acid-base abnormalities. Becausemicrocirculation appears to play a more important role than macrocirculation insepsis, it would beessential to understand the action of β-blockers on the microvascularbed.Furthermore, only one non-randomized prospective trial evaluated the effect ofβ-blockers on microcirculation, and the results were notconclusive.Lastly, given the ubiquitous distribution of the adrenergic system, it cannot beexcluded that β-blockers could also exert their influence on outcome throughtheir non-cardiac anti-inflammatory and anticoagulation effects.The potential benefits of β-blockers in septic shock patients are vast andinclude the amelioration of cardiac function and microcirculation, anti-inflammatoryand anticoagulation effects, and survival benefits. However, although verypromising, there is currently not enough evidence to advise the use ofβ-blockers in everyday practice, and there is an urgent need for morestudies. Two large RCTs (ESMOSEPSIS - Esmolol Effects on Heart and Inflammation inSeptic Shock and THANE - Hemodynamic Tolerance and Anti-inflammatory Effects ofEsmolol During the Treatment of Septic Shock) are presently recruiting and shouldprovide new insight into the effects of β-blockers on systemic hemodynamics,including diastolic function and microcirculation, as well as the immune system andmortality; hopefully, these RCTs will provide a better understanding of theselection process of the ideal patients for this therapy and how to monitorthem.


Misregistration due to cardiac motion causes artifacts in two‐exposure dual‐energy subtraction images, in both the soft‐tissue‐only image and the bone‐only image. Two previous investigations have attempted to avoid misregistration artifacts by using cardiac gating of the first and second exposures. The severity of misregistration was affected by the heart rate, the time interval between the low‐ and high‐energy exposures, the total duration of the two exposures, and the phase of the cardiac cycle at the start of the exposure sequence. We sought to determine whether a commercial phantom with a simulated beating heart can be use to investigate the factors affecting misregistration in dual‐energy chest radiography. We made dual‐energy images of the phantom in postero–anterior orientation using the indirect digital radiography system (GE XQ/i). We acquired digital images at heart rates between 40 beats per minute and 120 beats per minute and transferred them to a computer, where the area of the artifact on the silhouette of the heart was measured from both soft‐tissue‐only and bone‐only images. For comparison, we measured misregistration in clinical dual‐energy subtraction images by the same method. Generally speaking, without synchronization of the exposure sequence with the cardiac cycle, the area of the misregistration artifact increased with heart rate for both the phantom and clinical images. However, the phantom exaggerated the magnitude of misregistration relative to clinical images. Although this phantom was designed for horizontal operation and computed tomography imaging, it can be use in an upright configuration to simulate heart motion for investigation of dual‐energy misregistration artifacts and control.PACS numbers: 87.59.bf, 87.57.cf, 87.57N I.Dual‐energy subtraction (DES) X‐ray imaging offers a promising adjuvant to conventional chest radiography for accurate, early detection of lung disease. DES images reduce the influence of anatomical noise and offer the potential for analysis of nodule calcification. DES images produced from two sequential exposures are subject to artifacts in both the soft‐tissue‐only and bone‐only images because of cardiac motion, as shown in Any object that exhibits periodic motion could be use to study temporal misregistration in DES. In fact, a simple clock phantom was used previously.(45) but neither is available in a commercial medical imaging system. It is interesting that Sabol et al.Previous investigators avoided misregistration artifacts by cardiac gating of both the first and second exposures. One use the electrocardiograph (ECG) signal,Although our hospital has been performing DES routinely on patients since 2005, the study of artifacts on clinical images is complicated by uncontrolled variables, including patient size, body habitus, cardiac health, and other medical conditions, as well as human subject controls and privacy issues. Since it is not easy to perform a systematic, well‐controlled investigation of artifacts on actual patients, we reasoned that a cardiac motion phantom might provide useful information about the factors that affect the incidence and magnitude of misregistration artifacts.In this study, we investigated a commercial phantom of the thorax that simulates a beating heart to determine its suitability for evaluating misregistration artifacts in DES. We tested whether the phantom was sufficiently patient‐equivalent with respect to AEC and morphology, and whether it could be operated in the vertical position required for upright exposure stations. We compared DES images of our phantom to clinical images to determine whether the artifacts seen with the phantom were similar to those observed in humans with respect to appearance, incidence, and magnitude. We measured the wall motion of the phantom heart and compared it to published data on the human cardiac cycle. We simulated wall motion at different heart rates, predicted misregistration, and compared phantom and human synthetic data to our experimental data.II.A.A commercial cardiac motion phantom . The images were then exported to a personal computer, where the area of the artifact on the cardiac silhouette was measured from both soft‐tissue‐only  and boneD.D.1We first determined whether the phantom could be operated in a vertical orientation, whether it would cause clinically representative exposure duration under AEC, whether the phantom images would resemble human chest images, and whether the subtracted images would exhibit misregistration artifacts that were similar to those seen on clinical images.D.2We imaged the phantom fluoroscopically to determine the time course of its motion in postero–anterior orientation. Four radioopaque nipple markers (BBs) were attached on the surface of the phantom heart, approximating the location of the left ventricle . PhantomD.33. We imaged the phantom four times at each combination of heart rate and EF and calculated the average misregistration for each combination of heart rate and EF. We use conventional statistical methods to assess correlations between the misregistration area and heart rate, and EF.We then evaluated the dependence of misregistration on heart rate, acquiring images at rates from 40 beats per minute (bpm) to 120 bpm with EFs of 40%, 50%, and 60% and without synchronization of the initiation of the exposure sequence with the cardiac cycle. Diaphragm motion was disabled. “Heart volume” (stroke volume) was fixed at 70 cmE.E.1We collected and analyzed images and data from patients undergoing DES who had also undergone prior DES exams to evaluate the relationship between misregistration and heart rate. A waiver of informed consent was granted by our center's Institutional Review Board. The subject population included both men and women. The enrollment process began by checking the list of patients who had undergone a DES exam on a chosen day, and then looking for prior DES exams for each patient without regard for the presence or absence of artifacts. Any adult patient (age ≥ 18 years) who already had undergone at least two DES exams, each of which was accompanied by a resting heart rate or ECG contemporary with the exam, was selected for this study. Exams that were not associated with a documented heart rate or ECG were excluded. If a patient underwent a new exam during the course of data collection, that exam was included if accompanied by heart rate or ECG data.Enrollment occurred on nine different days, and no more than five patients were enrolled on a single day. Because DES exams have been conducted at our institution routinely for five years, we were able to enroll 23 patients who had undergone multiple DES exams, for a total of 131 DES exams. All exams were performed between February 6, 2007 and August 22, 2012.The process for downloading images was the same as the process for creating phantom images. The patient's resting heart rate was recorded from the date closest to the DES exam, usually on the day of the exam or within one day before or after. Only a handful of exams included in the study had an interval greater than one day between the recorded heart rate and the exam.The area of misregistration was measured from DICOM images downloaded from our PACS, as already described. Misregistration could present at the silhouette of the heart in the vicinity of the right atrium, the right ventricle, the left atrial appendage, and the left ventricle. Misregistrations also occur in the region of the aortic arch, but these were not measured in this study. Misregistration at the right ventricle was difficult to assess because of the proximity to the diaphragm and was excluded. Misregistrations at the left ventricle were on average twice as large as those at the right atrium and three times those at the left atrial appendage. For these reasons, further analysis was restricted to left ventricular (LV) misregistration.The retrospective study protocol did not include recording the patient's EF. Because our patient population comprises cancer patients rather than cardiac patients, we assumed that their cardiac function varies about the same as in the general population with the same age range. The study population was not controlled for age, sex, medical condition, or reason for exam.E.2t‐test comparing misregistrations measured from these images to those measured from the retrospective review indicated no statistically significant difference between the two distributions (p=0.83), so these data were pooled for further analysis.In addition to the 131 exams chosen for the retrospective review, a number of other exams had been identified by radiologists in the course of routine clinical operations as having poor image quality secondary to misregistration artifacts. From this group, five patients who underwent a total of 27 DES exams were selected. Although misregistration was severe enough to trigger a radiologist complaint in one of each of these patients' exams, misregistration was evident in other exams for the same patient, sometimes greater than in the exam that generated the complaint. A two‐tailed The total patient population included 17 men and 11 women, ranging in age from 36 to 82 years, with an average age of 62 years. Of the clinical DES exams, 158 were performed on an XQ/i system.F.On the basis of the results of the phantom cardiac motion study, we were able to simulate the distribution of misregistration artifacts that would be expected with a fixed delay between the low‐kVp and high‐kVp exposures at a variety of phantom heart rates. Using representative data from the literatureIII.A.(±0.4%). DES images of the phantom  to synchronize the minima of the two functions. A comparison of human left ventricular motion and phantom motion is shown in 0.12±0.10 cm. Within these limits, the left ventricular wall motion of the phantom was similar to that of a human heart.For comparison, the displacement of the left ventricular wall of a human heart was calculated from left ventricular volume data reported in the literature.C.The aggregate results of phantom misregistration, summarized in These results indicate that the heart rate and EF are two variables affecting misregistration. to reveal the extent to which each variable contributes to misregistration, two‐way analysis of variance (ANOVA) was applied to the data from Multiple regression analysis was also performed on the misregistration data from D.81±19 bpm. The mode was 66 bpm and the median was 80 bpm. For any individual patient, the heart rate was not necessarily the same for all of that patient's DES examinations. The SD of each individual patient's heart rate was between 5 bpm and 20 bpm. Because of the wide variation of individual heart rates, misregistration data were pooled among all patients and sorted by heart rate. The maximum misregistration for all patients was 2.8 cm2. The average of misregistration for all patients was 0.9±0.5 cm2. The distribution of heart rates for all patients and all exams is shown in E.2. At each heart rate, a two‐tailed Student's t‐test was performed to determine whether the distributions predicted for the phantom differed from those predicted for the human heart. No statistically significant difference was found. The data from Distributions of expected misregistration were simulated for the cardiac motion phantom and the human heart at four different heart rates. Values for maximum, average, and SD of misregistration are shown in IV.A.2 cannot be distinguished easily, especially in soft‐tissue‐only images. These cases may be considered as exhibiting no misregistration. Considering a rectangular model and assuming the length of the left ventricle to be 6.9 cm, misregistration of 0. 5 cm2 corresponds to wall displacement of only 0.7 mm. This means that the projection of the wall moved less than 4 pixels away from its initial position.Misregistration less than 0.5 cmB.The misregistration of DES images could appear either black or white on the left ventricle silhouette, as seen in C.±0.7 cm2.The retrospective review did not collect each patient's EF, so EF is an uncontrolled variable. Multiple regression analysis of the cardiac phantom data pooled from both X‐ray units indicated that EF is a highly significant factor on misregistration, with a strong, linear dependence on heart rate. In general, healthy individuals have an EF between 50% and 65%.D.The apparent motion of the cardiac wall in the X‐ray units was increased by a magnification factor of 1.07 (source‐to‐image distance (SID) = 183 cm; source‐to‐object distance (SOD) = 172 cm). The apparent motion of the cardiac wall in the fluoroscopy unit was increased by a magnification factor of 1.10 . Thus, the difference of cardiac wall motion in fluoroscopy images and the X‐ray images should be on the order of 3%. Although the geometry of projection is different in the fluoroscopic image from the DES image, the apparent effect on wall motion is small enough to be negligible.E.As shown in 2, 3.0 cm2, and 1.7 cm2, respectively). The shape of the misregistration region of the cardiac phantom is similar to half of an ellipse  are smaller than those of the phantom images  by a facIn our simulation of human cardiac wall motion, we use volume to determine wall displacement and assumed incompressibility of the wall. This is a gross oversimplification. Variation in wall thickness during the cardiac cycle may have contributed to the discrepancy between the simulation and clinical data.3 set by the controller, then the wall displacement would be greater than expected.Greater wall displacement in the phantom could be caused by inaccuracy in the stroke volume in the phantom heart. If the actual stroke volume was greater than the 70 cm2, which is closer to the misregistration observed in the clinical images (2.8 cm2). This correspondence does not imply a heart rate of 80 bpm or an EF of 40% among our cohort of patients. Considering the variability in the incidence of misregistration when exposures are not synchronized with the cardiac cycle, this may be coincidental; however, our simulations, especially as shown in The magnitude and frequency of misregistration observed with the phantom did not always coincide with the magnitude and frequency of misregistrations observed in our clinical study. The data in V.The cardiac motion phantom is sufficiently realistic for the study of misregistration in DES imaging using clinical X‐ray systems. The morphology of the phantom and its radiographic appearance are similar to those of a human. The attenuation properties of the phantom are high enough to operate in AEC mode; however, the quantity of mAs delivered is closer to that typically delivered for a child than to that delivered for an adult.The phantom can be operated in vertical orientation. The periodic motion of the phantom heart differs from the pulsatile motion of the human heart; however, its misregistration artifacts are similar in appearance. The cardiac phantom exaggerates the magnitude of left ventricular misregistration artifacts observed in clinical studies. This can be minimized by operating the phantom at a low EF setting.The maximum, average, and SD of the area of left ventricular misregistration increase with heart rate and EF. This trend was observed in phantom images, clinical images, and simulations of the phantom and human heart. If two‐image DES is performed without synchronization of acquisition with the phase of the cardiac cycle or without deformation of the original images to align clinical landmarks to compensate for cardiac motion, misregistration artifacts of this scale and variability will be present.The authors would like to acknowledge Kyoto Kagaku Co., Ltd, for the loan of the dynamic chest and heart phantom and for instructing us on its configuration and operation. The authors appreciate constructive discussions about this project with Professors Tinsu Pan and Osama Mawlawi.


Tei index, NYHA functional class, GLSsys and E/GLSRdias were independent predictors of all-cause mortality risk, and Tei index ≥0.9  was the best predictor of poor outcome. Combining Tei index and GLSsys yielded the best results on predicting death within 1 year (100% with Tei index ≥0.9 and GLSsys ≤13%) or survival (95% with Tei index ≤0.9 and GLSsys ≥13%). We conclude that 1-year mortality risk in AL-CA patients can be reliably predicted using Tei index or deformation parameters, with combined analysis offering best performance.Prognosis of patients with light-chain cardiac amyloidosis (AL-CA) is poor. Speckle tracking imaging (STI) derived longitudinal deformation parameters and Doppler-derived left ventricular (LV) Tei index are valuable predictors of outcome in patients with AL-CA. We estimated the prognostic utility of Tei index and deformation parameters in 58 comprehensively phenotyped patients with AL-CA after a median follow-up of 365 days . The primary end point was all-cause mortality. 19 (33%) patients died during follow-up. Tei index  and E to global early diastolic strain rate ratio (E/GLSR Primary amyloidosis formed from immunoglobulin light chain (AL) is one of the main types of systemic amyloidosis, most commonly involving the kidneys and the heart . CardiacEchocardiography plays an important role in the diagnosis and disease progression monitoring of CA patients. Typical morphological findings of CA include left ventricular (LV) hypertrophy, biatrial enlargement, and small pericardial effusion. Diastolic dysfunction usually occurs at the early stage, whereas LV ejection fraction remains normal until the late stage. Previous studies have reported the diagnostic and prognostic utility of conventional echocardiographic parameters and advanced deformation parameters in patients with AL-CA –5. ResulAs early as 1996, Tei and colleagues reported that the pulsed Doppler-derived Tei index, a simple parameter reflecting both systolic and diastolic myocardial performance, correlated with global cardiac dysfunction and was a valuable outcome predictor in CA patients . Tei indIn this study, we compared the prognostic utility between TD derived Tei index and STI derived deformation parameters as well as the incremental impact of these parameters in patients with AL-CA during 1-year of follow-up.A total of 58 consecutive biopsy-proven AL-CA patients referred to the University Hospital Würzburg and University Hospital Center Zagreb between January 2005 and October 2014 were enrolled in this retrospective study. Cardiac involvement was diagnosed according to echocardiographic findings as described in our previous studies , 12. PatA standard echocardiographic examination was performed in all patients . Measurements were performed off-line using a remote workstation . LV end-diastolic dimension (LVEDD), end-diastolic thickness of the posterior wall (LVPWd) and the septum (IVSd), LV stroke volume, and fractional shortening (FS) were measured using M-mode in the parasternal LV long axis view. Left atrial end-systolic diameter was measured in the parasternal long-axis view. LV biplane Simpson method ejection fraction (EF) was measured in apical 4- and 2-chamber views. Septal mitral annular plane systolic excursion (MAPSE) was measured by M-mode in apical 4-chamber view. LV filling pattern was assessed according to current guidelines . Pulsed Interval measurements were performed within one cardiac cycle as illustrated in Fig. sys) and strain (GLSsys) at the midline, and global longitudinal peak early diastolic strain rate (GLSRdias) of 6 segments were measured in the apical 4-chamber view . The E/GLSRdias ratio was calculated as the pulsed Doppler detected E velocity divided by the GLSRdias. The ratio between apical and basal LSsys (LSsysapi/bas) of the septum was calculated as septal apical LSsys divided by septal basal LSsys.Standard 2D grey scale apical 4-chamber view was recorded and STI was analyzed off-line using EchoPAC post processing program version 112  as previously described . Global dias ratio, and LSsysapi/bas, were normalized prior to analysis. Differences on continuous data between groups were compared using Student’s t test. Categorical data were compared using Chi square test.Continuous variables were expressed as mean ± standard deviation (SD) or median (quartiles). Categorical variables were presented as percentages. Non-normally distributed variables, including N-terminal prohormone brain natriuretic peptide (NT-proBNP), E/GLSRSurvival curves were plotted by the Kaplan–Meier method, and compared by log-rank tests. Cox proportional hazards regression was used in multivariable analyses, and hazard ratios (HR) with 95% confidence intervals (CI) were reported. Outcome was adjusted for age, gender, and body mass index. The performance of different prediction models was judged on the basis of the c-statistic (area under the receiver operating characteristic curves). Statistical significance was defined as p < 0.05. Statistical analysis was performed using IBM SPSS, version 23 for Windows .Fifty-eight AL-CA patients were included . Their clinical data are listed in Table Conventional echocardiographic data were listed in Table TD derived-Tei index was 0.70 ± 0.25 in the whole cohort, which is markedly higher than normal reference value (<0.40) . Tei indsys and GLSsys as well as GLSRdias were significantly lower in non-survivors than in survivors . The E/GLSRdias ratio was significantly higher in non-survivors than in survivors (p < 0.05).As shown in Table sys and GLSRsys, as well as E/GLSRsys ratio. The optimal cut-off value for Tei index was 0.9 with a specificity of 100% for predicting 1-year mortality. Increased Tei index , increased E/GLSRdias ratio , or reduced GLSsys  in patients with AL-CA was associated with significantly increased risk of all-cause death within 1 year  and Tei index demonstrated that Tei index ≥0.9 was the best independent predictor of all-cause mortality risk .Survival analysis Table  showed tsys or E/GLSRdias) only slightly increased this value (c-statistic: 0.87). Other approaches yielded no further favorable utility, e.g., GLSsys (c-statistic 0.77), E/GLSRdias (c-statistic 0.72) or GLSsys + E/GLSRdias (c-statistic 0.77).Prediction model performance statistics Table  revealedsys absolute value ≤13% died during 1-year follow up . In contrast, only 1 out of 16 (6%) patients with Tei index <0.9 and GLSsys >13% died within 1 year.As shown in Fig. As shown in Fig. sys (≤13%) yielded excellent prognostic utility allowing improved mortality risk stratification in AL-CA patients.The major findings of the present study are as follows: (1) increased Tei index (≥ 0.9) served as a valuable independent predictor of all-cause mortality during 1-year follow up in AL-CA patients, which was superior to LV-EF and other conventionally derived diastolic indices, and similar to both global longitudinal systolic strain and E to global early diastolic strain rate ratio; and (2) combining Tei index (threshold ≥0.9) and GLSThe Tei index is an easy-to-obtain parameter, it not only reflects combined systolic and diastolic myocardial function, but is also independent of heart rate and blood pressure . AlthougThe potential of the Tei index as a clinically meaningful diagnostic and prognostic marker has been reported in various reports investigating symptomatic heart failure, acute myocardial infarction, dilated cardiomyopathy, and primary pulmonary hypertension –19. Tei As stated above, the Tei index is computed by the formula (IVCT + IVRT)/ET. Tei et al. reported that the IVRT and IVCT components were significantly prolonged and the ET was significantly shortened in CA patients as compared with normal controls . Consistdias and E/GLSdias independently predicted outcome in this cohort. However, the prognostic power of all these deformation markers was somehow weaker than that of the Tei index . Since good imaging quality is the essential prerequisite of the measurements of GLSRdias and E/GLSdias, while Tei index could be reliably and easily obtained even in patients with unsatisfactory imaging condition, the present study underscores the priority of using Tei index instead of GLSRdias and E/GLSdias for the outcome assessment of AL-CA patients.As mentioned before, the longitudinal function assessed by TDI derived strain was reduced in patients with AL amyloidosis, which also had an important prognostic relevance . In the sys ≤13% were analyzed . Likewise, in patients with NYHA class III–IV, the Tei index also tended to be higher in non-survivors than survivors, but this trend did not reach statistical significance . These results suggest that the Tei index might be useful to predict prognosis of CA patients without overt clinical heart failure (NYHA class I–II), whereas the predictive value of the Tei index was somehow weaker in CA patients with more advanced heart failure symptoms (NYHA class III–IV). These findings need to be confirmed in future prospective studies with larger sample sizes.sys −10.9 ± 3.7%) and a single 4-chamber apical view . Since imaging quality of the apical 4-chamber view is in usually superior compared to apical 2-chamber and long-axis views, the evaluation was thus performed based on apical 4-chamber view in the present study to shorten the evaluation time and pave the way for broader use of this technique in real world clinical situations.In the present study, STI derived global strain was obtained from 4-chamber apical views only. In a pilot study, we compared the difference of global longitudinal strain value derived from all three apical views and a single 4-chamber apical view in 20 AL-CA patients, and observed similar strain values derived from all three apical views (GLSThe current cohort included only a relatively small sample of a single subtype of cardiac amyloidosis, AL amyloidosis. The prognostic utility of the Tei index in combination with longitudinal strain should be validated in other subtypes such as hereditary or wild-type transthyretin amyloidosis. This might have particularly clinical relevant implications, as a specific medical therapy of transthyretin amyloidosis is expected to be clinically available very soon. Future clinical studies with ideally larger sample sizes are warranted to externally validate the proposed risk stratification strategy, compare the findings between the various entities of cardiac amyloidosis, and evaluate potential implications on therapy planning.sys, provides excellent predictive utility for 1-year outcome and might therefore prove clinically valuable for risk stratification in this clinically demanding patient group.Both Tei index and STI-derived deformation parameters can be used to predict mortality risk in AL-CA patients with superior prognostic value compared to conventional echocardiographic parameters. However, the prognostic power of deformation markers is somehow weaker than that of the Tei index. The Tei index can easily be obtained, even under difficult imaging conditons. The combination of Tei index and selected deformation parameters, such as Tei index plus GLS


Dilated cardiomyopathy (DCM) is associated with a 20% 5 year mortality rate.We identified that the presence of left ventricular (LV) midwall fibrosis, detected by CMR late gadolinium enhancement (LGE), was associated with a 5 fold increased risk of cardiovascular death and adverse events, independently of established predictors of outcome.The natural course of DCM is however variable; up to 15% of patients may recover function, with normalisation of left ventricular ejection fraction (LVEF).We sought to evaluate whether LGE, a robust predictor of clinical outcome, was predictive of remodelling in DCM.130 prospectively recruited patients with DCM  underwent baseline and follow up CMR studies using a 1.5T Siemens scanner.The presence of midwall fibrosis was evaluated through the administration of 0.1 mmol/kg of gadolinium based contrast agent . Images were obtained using an inversion-recovery prepared gradient echo sequence in standard long and short axis views, with inversion times optimised to null normal myocardium. Images were repeated in two separate phase encoding directions to exclude artefact.ANCOVA was used to evaluate the significance of LGE on predicting the follow up LVEF, controlling for the baseline LVEF and other covariates. Students t-test was used to compare LVEF between groups with and without LGE. All statistical calculations were performed using R.Median follow up interval was 2.7 years between scans (IQR 1.4-4.7 years). Fifty patients (38%) had evidence of LV midwall fibrosis at baseline. The mean baseline LVEF in patients with LGE was 39.3% and 43.6% in patients without LGE .When the additional variables were also included in the model , the estimated effect of LGE was a 2% lower follow up LVEF, but this was not significant .Whilst LGE is a robust predictor of adverse outcome in DCM, in this cohort there was no evidence to suggest that the presence of LGE predicted left ventricular remodelling.These findings highlight that predictors of outcome and remodelling in DCM are not interchangeable. Our future work will explore these findings in a larger cohort with a quantitative evaluation of midwall fibrosis and to evaluate the relationship between reverse remodelling and clinical outcome in DCM.


Cardiovascular sequelae represent a leading cause of mortality in Fabry disease. Early detection of cardiac involvement is therefore a subject of considerable interest. Low native T1 values have been shown to be associated with echocardiographic markers of early systolic and diastolic dysfunction, even in those without left ventricular hypertrophy (LVH), and conceptually could be used to optimise the efficacy of Enzyme replacement therapy (ERT). The purpose of this study was to determine the relationship of both, native T1 and feature tracking CMR (FT-CMR) derived strain parameters, with maximal LV wall thickness and LVmass in Fabry's as a clinical marker of cardiac disease manifestation.66 genetically confirmed successive Fabry patients  underwent CMR at 1.5T . A standardised clinical CMR protocol including T1 mapping (Siemens Molli WIP 448) was used in all. A single ROI was selected in the mid-wall of a basal and mid-short axis slice, to determine a native T1 value, which was then corrected for heart rate, and averaged. Global longitudinal (GLS) and circumferential strain (GCS) parameters were derived from 4-chamber and corresponding mid-short axis SSFP cine images, using dedicated CMR feature tracking software . Maximal wall thickness was determined from the mid short axis slice, and LV mass was calculated from the short axis stack (CMR Tools). Patients were subdivided into two groups of normal LV mass and increased LV mass.Baseline characteristics are shown in table There was moderate negative correlation between LV mass and basal T1 values , with only mild positive correlation between mass and GLS . Native T1 values did not correlate with GLS . In those with normal LV mass, basal T1 values correlated better with LV mass as compared to GLS , whereas the opposite was seen in those with increased LV mass.Native T1 mapping shows stronger correlation with increased LV mass as compared to FT-MRI derived longitudinal strain. It shows promise as a potential future biomarker to detect early cardiac involvement in Fabry disease, and potentially to guide patient selection and timing of therapy.


ECMO independently increased length of stay by 17.8 days, cost of stay by approximately $415,917, and inpatient mortality 22-fold. Conclusion: Only a small proportion of CHD patients undergoing CS require ECMO, although these patients require increased resource utilization and have high mortality. Specific cardiac lesions, cardiac surgeries, and comorbidities are associated with increased need for ECMO.Introduction: This study aimed to determine factors associated with the need for extracorporeal membrane oxygenation (ECMO) in children with congenital heart disease (CHD) during admission for cardiac surgery (CS). A secondary aim was to determine how ECMO impacted length, cost, and mortality of the admission. Methods: Data from the Kids’ Inpatient Database (KIDS) were utilized. Admissions with CHD under 18 years of age with cardiac surgery were included. Need for ECMO in these admissions was then identified. Univariate analysis was conducted to compare characteristics between admissions with and without ECMO. Regression analyses were conducted to determine what factors were independently associated with ECMO and whether ECMO independently impacted admission characteristics. Results: A total of 46,176 admissions with CHD and CS were included in the final analysis. Of these, 798 (1.7%) required ECMO. Median age of ECMO admissions was 0.5 years. The following were associated with ECMO: decreased age, heart failure, acute kidney injury, arrhythmia, double outlet right ventricle, atrioventricular septal defect, transposition, Ebstein anomaly, hypoplastic left heart syndrome, common arterial trunk, tetralogy of Fallot, coronary anomaly, valvuloplasty, repair of total anomalous pulmonary venous connection, arterial switch, RV to PA conduit placement, and heart transplant ( Each year, 1% of live births are diagnosed with a congenital heart defect (CHD) . Since tOver the past four years, there have been over 20,000 neonatal and 30,000 infant patients receiving corrective surgery for CHD, with mortality rates of 8.8% and 2.8% respectively ,6. This Between 2–5% of pediatric CHD patients undergoing cardiac surgery will require ECMO . While tThere is currently a paucity of data regarding risk factors that can help identify those who will require postoperative ECMO. We conducted an analysis of the Kids’ Inpatient Database (KIDS) with the primary aim of identifying the factors associated with increased risk of ECMO in pediatric patients undergoing cardiac surgery. Secondary aims were to quantify the effects of postoperative ECMO length of stay, cost of admission, and inpatient mortality.A retrospective cohort study was conducted using the pediatric database, KIDS. Data regarding hospital admissions was obtained from the 2005–2012 KIDS iterations. Only admissions of patients under 18 years of age with congenital heart disease undergoing heart surgery were included. These were identified using International Classifcation of Diseases (ICD-9) diagnosis and procedure codes as below.Congenital heart disease was identified using ICD-9 codes: double outlet right ventricle using 745.11, atrioventricular septal defect using 745.60, partial anomalous pulmonary venous connection using 747.42, total anomalous pulmonary venous connection using 747.41, transposition of the great arteries using 745.10, congenitally corrected transposition using 745.12, hypoplastic left heart syndrome using 746.7, atrial septal defect using 745.61, ventricular septal defect using 745.5, pulmonary atresia with ventricular septal defect using 746.01, tricuspid atresia using 746.1, Ebstein anomaly using 746.2, truncus arteriosus using 745.0, and coronary artery anomaly using 746.85. Arrhythmias were identified using codes 427.0–427.42 as well as 426.0–426.13. It was not possible to distinguish between those in the absence of a spleen or multiple spleens due to the ICD-9 coding strategy.Cardiac surgery was identified using the following codes: codes 35.10–35.14 for valvuloplasty with no valve replacement, 35.20–35.28 for valvuloplasty with replacement, codes 35.50–35.73 for septal defect repair , 35.81 for complete repair of tetralogy of Fallot, 35.82 for pulmonary venous repair, 35.83 for complete repair of common arterial trunk, 35.84 for arterial switch operation for transposition, 35.91 for atrial switch operation for transposition, 35.92 for right ventricle to pulmonary artery conduit, 39.22 for Blalock-Tausig shunt, and 37.51 for heart transplant.ECMO was identified using ICD-9 code 39.65. It should be noted that timing of ECMO relative to the surgery could not be established by this database.The following syndromes were also captured: Noonan, Turner, DiGeorge, trisomy 13, trisomy 18, trisomy 21, and syndrome not otherwise specified.Demographic information including, age and race were collected for each admission. Comorbid conditions, as well as admission characteristics such as admission month, length of stay, and cost of stay, were collected and assessed. This research did not directly involve human participants, as this was previously collected data from a national registry. Informed consent was obtained by the national registry, but was not required by our specific study.t-test or the Mann-Whitney-U test as appropriate, with categorical variables being analyzed using chi-square analysis.Baseline characteristics such as age, race, and comorbid conditions were compared between those with and without ECMO . ContinuLogistic regression was then conducted to determine factors associated with an increased or decreased need for ECMO, with ECMO as the dependent variable. Finally, to determine the effects of ECMO on outcomes, linear regression analyses was conducted with ECMO as the independent variable with length of stay, cost of admission, and mortality of ECMO admissions as dependent variables.All statistical analysis was done utilizing SPSS Version 20.0 .p < 0.01). Comorbidities most likely in those with ECMO included heart failure  = 1.9–2.6, p < 0.01), acute kidney injury , and arrhythmia (not including atrioventricular block)   required ECMO. It is not possible from this database to determine the timing of ECMO relative to cardiac surgery. Those requiring ECMO were significantly more likely to be younger  .p = 0.20). No patients with Turner syndrome were placed on ECMO. Down syndrome was present in 3.5% of those who were placed on ECMO compared to 10.7% of those not requiring ECMO (p < 0.01). DiGeorge syndrome was found in 4.5% of those who were placed on ECMO compared to 2.0% of those not placed on ECMO (p < 0.01). No patients with Trisomy 13 or 18 were placed on ECMO. A syndrome not otherwise specified was present in 2.3% of those placed on ECMO compared to 1.7% of those not requiring ECMO (p = 0.20).With regard to syndromes, Noonan syndrome was present in 2.3% of those requiring ECMO compared to 1.7% of those not requiring ECMO (p < 0.01), as was cost of the admission . Inpatient mortality was also greater in those with ECMO, with 46.4% mortality compared to 1.8% in those without   .p < 0.01), total anomalous pulmonary venous connection , coronary artery anomaly , atrial septal defect , ventricular septal defect , pulmonary atresia , Ebstein anomaly , hypoplastic left heart syndrome , transposition , and common arterial trunk   .p = 0.01), valvuloplasty, with valve replacement , septal defect repair , common arterial trunk, complete repair , total anomalous pulmonary venous connection repair , transposition repair, arterial switch , transposition, atrial switch , right ventricle to pulmonary artery conduit , and heart transplant   .The following risk factors were associated with an increase in ECMO use: heart failure , acute kidney injury , arrhythmia , double outlet right ventricle (DORV) , Atrioventricular septal defect (AVSD) , coronary anomaly , Transposition , Ebstein , HLHS , HLHS , Common arterial trunk , Tetralogy of Fallot , Valvuloplasty no replacement , Valvuloplasty w/replacement , TAPVC complete repair , Arterial switch , right ventricle to pulmonary artery conduit , and heart transplant  .The following risk factors were associated with a decrease in ECMO use: Age  and Atrial septal defect .p < 0.01) increases in the length, cost, and mortality of admissions. ECMO increased the length of admission by 17.8 days, increased the cost of admission by approximately $415,917, and increased inpatient mortality approximately 22.4-fold  database from 2004–2013, Gupta and colleagues examined the relationship between the length of ECMO runs and outcomes in CHD patients after undergoing cardiac surgery . ECMO ruThe interplay between length and cost of admission is intuitive, but how both can be minimized in the context of admissions requiring ECMO is not clear. Some groups have suggested that one method by which to decrease the duration of ECMO runs, and overall admissions, may be cardiac catheterization. This can allow for the identification of residual lesions that can be intervened upon. Three studies have now demonstrated that this approach has led to improved survival and shortened ECMO runs ,29,30.Mortality rates of those afflicted with CHD have been decreasing over time . This isNonetheless, we feel that our study highlights factors associated with higher risk for ECMO, and delineates the future directions of such research. Identification of those at higher risk may allow for better understanding of how ECMO can be avoided in specific patients or how ECMO runs can be shortened.A small proportion of pediatric patients will require ECMO during admission for cardiac surgery. Specific cardiac malformations and surgeries are independently associated with increased risk of ECMO. Those requiring ECMO have increased length and cost of stay. This study found inpatient mortality to be 46.4% in pediatric patients requiring ECMO during admission for cardiac surgery.