Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. In sham hearts, Myc knockout did not affect cardiac function or substrate preferences for the citric acid cycle. However, Myc knockout altered fractional contributions during TAC. The unlabeled fractional contribution increased in MycKO-TAC versus Cont-TAC, whereas ketone and free fatty acid fractional contributions decreased. Additionally, protein posttranslational modifications by O-GlcNAc were significantly greater in Cont-TAC versus both Cont-Sham and MycKO-TAC. In conclusion, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy, which may regulate Myc-induced metabolic changes.Hypertrophic stimuli cause transcription of the proto-oncogene c-Myc (Myc). Prior work showed that myocardial knockout of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we assessed the interplay between Myc, substrate oxidation and cardiac function during early pressure overload hypertrophy. Mice with cardiac specific, inducible Myc knockout (MycKO-TAC) and non-transgenic littermates (Cont-TAC) were subjected to transverse aortic constriction . Additional groups underwent sham surgery . After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with  The proto-oncogene c-Myc (Myc) is an important regulator of cardiac hypertrophy –9. AlthoN-acetylglucosamine (O-GlcNAc)  in a parasternal short axis mode for at least three heart beats. The pulsed Doppler velocity was measured across the aortic constriction site. This velocity serves as a non-invasive estimate of the peak instantaneous pressure gradient across the constriction site and is calculated by the modified Bernoulli equation (Δ pressure gradient = 4*velocity2). Clinically, the calculated mean pressure gradient is often a better estimate of the pressure gradient measured invasively from cardiac catheterization. The mean pressure gradient was estimated by dividing the modified Bernoulli equation in half.Serial echocardiograms were performed prior to and after two weeks of TAC. Mice were initially sedated with 3% isoflurane in OIn vivo afterload increases with aortic constriction. To simulate in vivo conditions, the MycKO-TAC and Cont-TAC hearts were perfused at a higher afterload than the Sham hearts. We felt that this strategy would more accurately reflect in vivo substrate utilization patterns than perfusing sham and TAC hearts at the same afterload. Additionally, studies in Langendorff (retrograde aortic) mouse heart perfusions have shown that different perfusion pressures are needed to achieve similar coronary flows between aortic constricted and sham hearts acetoacetic acid , L-lactic-3-[13C]acid , and U-[13C]-long-chain mixed free fatty acids  bound to 0.75% (wt/vol) delipidated bovine serum albumin reconstituted with deionized water. Insulin (50 microunits/ml) was included in the perfusion solutions. To establish the origin of the unlabeled fraction in the aortic constricted mice, 2 hearts each from Cont-TAC and MycKO-TAC were perfused with unlabeled lactate (1.2 mmol/l), 1-[13C]glucose (5.5 mmol/l), 1,3-[13C]ACAC (0.17 mmol/l), U-[13C]free fatty acids (0.35 mmol/l). The hearts subjected to TAC  were initially stabilized at 50 mmHg afterload and 15 mmHg preload for 10 minutes before acutely increasing afterload to 80 mmHg. Sham mice were perfused with standard loading conditions of our laboratory consisting of a 12 mmHg preload and a 50 mmHg afterload. An SPR-PV-Catheter  was inserted into the left ventricle through the apex for continuous measurement of left ventricular pressure (LVP). Only aortic outflow that bypasses the coronary arteries is recirculated. Left atrial inflow was measured with a flow probe  and aortic (not including coronary flow) flow was measured via 30 second timed collections. Coronary flow was calculated as the difference between left atrial inflow and aortic flow although this measurement is affected by perfusate leak from the left atrium. Every 10 minutes, left atrial influent and coronary effluent was collected for determination of PO2, PCO2, and pH with an ABL800 blood gas analyzer . The coronary effluent is collected as it drips from the heart. Although we attempt to limit effluent exposure time to the atmosphere, some atmospheric gas exchange likely occurs which would affect the oxygen tension levels and calculations based upon this measurement . Continuously recorded parameters are left ventricular (LV) pressure (mmHg), HR (beats/min), and rate of LV contraction and relaxation . Myocardial oxygen consumption (MVO2) was calculated as MVO2 = CF x [(PaO2—PvO2) x (c/760)] x heart weight, where CF is coronary flow (ml·min−1g wet weight−1), (PaO2—PvO2) is the difference in the partial pressure of oxygen  between perfusate and coronary effluent, and c is the Bunsen solubility coefficient of O2 in perfusate at 37°C (22.7 μl O2·atm-1·ml-1). Cardiac work was calculated as the cardiac output times the developed pressure. Cardiac efficiency was defined as cardiac work/MVO2.Experiments were performed as previously described with changes noted below ,18. The m hearts ,20. Beca13C-labeled substrates in combination with NMR spectroscopy. Glutamate isotopomer analyses provide fractional contribution of acetyl-CoA to the citric acid cycle from up to three differentially labeled substrates as well as the unlabeled components.Myocardial tissue was extracted as previously described ,18. Subs13C NMR spectral acquisition. NMR free-induction decays (FIDs) were acquired on a Varian Direct Drive (VNMRS) 600 MHz spectrometer  equipped with a Dell Precision 390 Linux workstation running VNMRJ 2.2C. The spectrometer system was outfitted with a Varian triple resonance salt-tolerant cold probe with a cold carbon preamplifier. A Varian standard one dimensional carbon direct observe sequence with proton decoupling was used to collect data on each sample. Final spectra were accumulations of 4800 individual FIDs. Each FID was induced using a nonselective, 45-degree excitation pulse (7.05 us @ 58 dB), with an acquisition time of 1.3 seconds, a recycle delay of 3 seconds, and a spectral width of 224.1 ppm.Lyophilized heart extracts were dissolved in 99.8% D2O for decoupled 2 and the stoichiometric relationships between oxygen consumption and citrate formation from the various substrates as previously described [FIDs were baseline corrected, zero-filled, and Fourier transformed. Labeled carbon resonances of glutamate were integrated with the Lorentzian peak fitting subroutine in the acquisition program . The individual integral values were used as starting parameters for the citric acid cycle analysis fitting algorithm tcaCALC, kindly provided by Drs. Malloy and Jeffrey . This alescribed ,22.Western blots were performed as previously described on freshly isolated hearts (i.e. separate from the perfused hearts) ,18. BrieReported values are means ± standard error (SE) in figures and text. Data were analyzed with two-way unpaired t-test or a single factor ANOVA (multiple comparisons). If significance was identified between the groups by ANOVA ; then a two-way unpaired t-test was performed. Criterion for significance was p < 0.05 for all comparisons.in vivo systolic function measured during TAC [in vivo systolic functional differences between MycKO-TAC and Cont-TAC hearts after TAC. Compared to baseline (pre-TAC), ejection and shortening fractions were unchanged by TAC in both groups. Left ventricular end diastolic diameter decreased in both groups after TAC whereas end systolic diameter declined in Cont-TAC only. The diameter changes are likely due to the development of hypertrophy.Prior echocardiogram studies demonstrated that Myc knockout did not affect ring TAC . We simiIn prior studies, Myc knockout during aortic constriction attenuated the ratio of heart weight to tibial length, reduced cardiomyocyte size, and decreased ANP levels ,10. To cEx vivo functional assessments were made during the working heart perfusions. All reported values are after 20 minutes of stable left atrial infusion.in vivo conditions, Cont-TAC and MycKO-TAC hearts were perfused at high afterload (80 mmHg) whereas Cont-Sham and MycKO-Sham hearts were subjected to standard afterload (50 mmHg). The different afterloads affect functional parameters; therefore we did not compare sham heart function to TAC. Ex vivo cardiac function was similar between Cont-Sham and Cont-MycKO (max (p = 0.08) and-dP/dTmin (p = 0.05) in MycKO-TAC hearts compared to Cont-TAC although other functional parameters were similar  gave an average calculated glucose fractional contribution of 0.135±0.005 in Cont-TAC and 0.22±0.02 in MycKO-TAC, which indicates that the majority of the unlabeled fraction was from exogenous glucose in the TAC groups.Next, we determined the fractional contribution of acetyl-CoA to the citric acid cycle for each studied substrate. In sham hearts, fractional contributions were unaffected by Myc knockout  . As partMyc knockout reduced global O-GlcNAc levels during pressure overload hypertrophy. Laczy et al. found that acute O-GlcNAcylation promoted fatty acid oxidation . They peMyc knockout did not affect protein levels of the key O-GlcNAc regulatory enzymes GFAT, OGT or OGA. Although Myc commonly acts as a transcription factor, our results suggest that Myc alters O-GlcNAc levels through non-transcriptional mechanisms. These mechanisms potentially include changes in GFAT, OGT and/or OGA activity by post-translational modifications. Additionally, generation of the O-GlcNAc moiety depends on shuttling glucose into the hexosamine biosynthesis pathway; an accessary pathway from glycolysis. Although O-GlcNAc may influence substrate preferences; paradoxically, metabolic changes could also influence O-GlcNAc levels by affecting hexosamine biosynthesis flux . The intAlthough we tried to limit atmospheric exposure, the oxygen tension in the coronary effluent is potentially altered by atmospheric gas exchange. This limitation would affect the oxygen consumption values used to calculate estimated flux for overall citric acid cycle and individual substrates. Accordingly, the flux values should be considered calculated estimated values. However, individual substrate fractional contributions to the citric acid cycle are not affected by this limitation.Hypertrophy often affects non-oxidative glycolysis; however, the MRS based method used in this study does not measure glycolytic flux. Thus, we cannot make conclusions on Myc’s affect for overall glucose utilization during hypertrophy.The current study demonstrates that Myc affects myocardial substrate utilization preferences for the citric acid cycle during early pressure overload hypertrophy, but not during normal physiology. However, Myc’s regulation of metabolic changes was not necessary to maintain cardiac function. Myc knockout altered global O-GlcNAc levels during aortic constriction, which may mechanistically regulate the changes in substrate preferences.S1 TableFlux units are μmol/g/min. Acetoacetate was used for ketones. Note: Sample 042213A was excluded for flux value calculations because of a perfusate leak from the left atrium, which would render the MVO2 value inaccurate. However, the leak does not affect the fractional contribution values.(XLSX)Click here for additional data file.S2 TableThe O-GlcNAc western blot and total protein quantification pictures are shown in manuscript (XLSX)Click here for additional data file.


The ability to predict RVEF < 45 % in HCM patients was best for TAPSEout. In patients with hypertrophic obstructive cardiomyopathy (HOCM), RVEF showed a significant but weak correlation with TAPSEout  and no correlation with TAPSEin  and RVFS . In patients with hypertrophic non-obstructive cardiomyopathy (HNCM), there was a moderate correlation between RVEF and TAPSEout  and a weak correlation with TAPSEin  and RVFS . In the 20 healthy controls, there was a strong correlation between RVEF and all semi-quantitative measurements.105 patients with HCM and 20 healthy subjects underwent CMR. In patients with HCM, TAPSEin is not suitable to determine right ventricular function in HCM patients. TAPSEout showed a good correlation with RVEF in HNCM patients but only a weak correlation in HOCM patients. TAPSEout might be used for screening but the detection of subtle changes in RV function requires the 3D volumetric approach.CMR-derived TAPSE Hypertrophic cardiomyopathy (HCM) presents with a wide range of phenotypes. Apart from perturbed contractility, HCM mutations may affect energy homeostasis . Besidesin) or with one outside the ventricle (TAPSEout) and RV fractional shortening (RVFS) derived from CMR images in comparison to RV volumetry in patients with HCM. Furthermore, we performed a subgroup analysis in patients with hypertrophic obstructive cardiomyopathy (HOCM), as well as in patients with hypertrophic non-obstructive cardiomyopathy (HNCM) to test these measurement approaches.Thus, the aim of our study was to evaluate the accuracy of semi-quantitative methods to assess RV function using TAPSE with a reference point within the ventricle , normal ECG findings, no history of chest pain or dyspnoea, no diabetes, no hyperlipidaemia and normal 2D echocardiography and Doppler examination. None of the control subjects were on medication. Exclusion criteria for healthy controls were the presence of signs or symptoms of cardiac diseases, hypertension, diabetes, smoking, or participation in competitive sports.All patients and volunteers gave informed consent and the study was approved by the local ethics committee.All studies were performed using a 1.5 Tesla whole body imaging system  using a four-element (Sonata) or a six-element (Avanto), phased-array body coil. Images were acquired with ECG gating and during breath-holds in mild expiration.Cine images were acquired using a balanced segmented steady state free precession (trueFISP) sequence in three long-axis views  and in multiple short-axis views, covering the entire left ventricle from base to apex. Typical image parameters were: TE = 1.2 ms, TR = 3.2 ms, temporal resolution 35 ms, in-plane spatial resolution 1.4 × 1.8 mm2, slice thickness 8 mm, interslice gap 2 mm.CMR data were analysed using commercially available software .For RV volumetry the short-axis cine loops were reviewed and the end-diastolic and end-systolic frames were identified for each short-axis section position. The first frame of each cine image showing the largest RV cavity area was defined as end-diastole. The phase of end-systole was defined as the frame showing the smallest cavity area. The most basal section was the area of the RV outflow tract below the level of visible pulmonary valve tissue. At the inflow portion of the RV, only the area of the blood pool surrounded by trabeculated ventricular myocardium was included in the RV volume. Identification of the tricuspid valve annulus was facilitated by the simultaneous display of a cross-referenced four-chamber cine image. Endocardial contours were outlined manually at the boundary between the blood pool and the compact myocardium on each end-diastolic and end-systolic short-axis view CMR image. Trabeculations and papillary muscles were included as part of the RV volume. The workstation calculated end-systolic and end-diastolic RV volumes using a modification of the Simpson rule. The RV stroke volume was calculated by subtracting the end-systolic volume (ESV) from the end-diastolic volume (EDV). The RV ejection fraction (RVEF) was calculated by dividing the stroke volume by the EDV.in or EDLout) and end-systole (end systolic length (ESL)in or ESLout). The point outside the RV apex was chosen in extension to the RV apex and had to stay unchanged at end-diastole and end-systole. In order to ensure that the reference point outside the RV apex stayed unchanged during end-systole, we left the curser at the point of the chosen reference point while scrolling from end-diastole to end-systole. TAPSEin  as the difference between EDLout and ESL. The RVFS was calculated as follows: RVFS (%) = [(EDLin –ESLin)/EDL in] × 100  × 100 .Fig. 1Scin and TAPSEout were measured in the first 20 HCM patients twice by the first observer and once by a second observer. A period of at least 1 week passed between the two measurements made by the first observer.To determine interobserver and intraobserver reliability, TAPSEt-test. Pearson’s correlation coefficients (r) were calculated for the relation between TAPSEin, TAPSEout, RVFS and RVEF. Additionally, Pearson’s r was transformed to z using the following formula: z = 0.5*[ln(1 + r)-ln(1-r)], where ln is the natural logarithm. Fisher’s z was then used for computing 95 % confidence intervals (CI) on the difference between correlations. Lower limit of the 95%CI = z-1.96*σ, upper limit of the 95%CI = z + 1.96*σ, σ = 1/√(n-3), whereas r is the correlation coefficient and n = number of observations. Agreement between the measurement of TAPSEin and TAPSEout was assessed using the Bland-Altman method of analysis [t-test against zero for the statistical significance of the observed differences in intraobserver and interobserver variability was performed.All data are presented as a mean ± standard deviation. Continuous parameters were compared using a two-tailed student’s analysis , providianalysis  A one onin, TAPSEout, and RVFS to predict an RVEF <45 % was calculated using receiver-operating characteristic (ROC) analysis [p < 0.05. Analyses were performed with Statistical Package for Social Sciences .The ability of TAPSEanalysis . All resn = 105), RVEF determined by CMR revealed a weak correlation with TAPSEin  and RVFS  but a moderate correlation with TAPSEout . Comparison of TAPSEin and TAPSEout showed a weak correlation .Baseline patients’ and RV CMR characteristics are displayed in Table n = 40), RVEF showed a significant but weak correlation with TAPSEout  and no correlation with TAPSEin  and RVFS . In patients with HNCM (n = 65), there was a moderate correlation between RVEF and TAPSEout  but a weak correlation with TAPSEin  and RVFS . In healthy controls, there was a good correlation between RVEF and both TAPSEin  and RVFS . Furthermore there was a strong correlation between RVEF and TAPSEout .In the subgroup analysis of patients with HOCM . The area under the ROC curve for TAPSEin  and RVFS  were inferior. With a cut-off value TAPSEout of 1.5 cm, the sensitivity and specificity to detect an RVEF ≤ 45%was 67 % and 82 %, respectively.Figure in) are not suitable in patients with HCM. CMR TAPSE measurements with a reference point outside the right ventricle (TAPSEout) showed a good correlation with the standard RV volumetric approach in patients with HNCM, but only a weak correlation in patients with HOCM. Comparison of TAPSEin and TAPSEout showed a weak correlation in the whole population.Our study demonstrates that CMR-derived TAPSE measurements using a reference point in the RV apex . This approach showed a good correlation with quantitative assessment of RV function in patients with heart failure due to ischaemic heart disease [Echocardiographically assessed TAPSE represents a quick semi-quantitative approach to assess information about the RV function –24. Usin disease , 14, 25, disease , 13, Bru disease , dilated disease . The autin) are different. The echocardiographic TAPSE measurement takes into account only movements of the tricuspid annular base. The CMR approach uses a reference point in the RV apex. Thus, the longitudinal TAPSE measurement may be falsified by the movement of the RV apex out of the central plane. Therefore, we introduced a new CMR method to determine TAPSE with a reference point chosen outside the RV which is unaffected by the contraction and the torsion of the apex and is more comparable with the echocardiographic measurements. In this context our results showed that in patients with HCM, TAPSE measurements with a fixed reference point outside the RV (TAPSEout) correlated best with the standard RV volumetric approach and seem to reflect more accurately the tricuspid annular systolic excursion than the measurements with the reference point within the right ventricular apex (TAPSEin). These findings were more pronounced in the subgroup analysis. In patients with HNCM there was a good correlation between RVEF and TAPSEout and a weak correlation with TAPSEin and RVFS. Furthermore, in patients with HOCM, RVEF showed a significant but weak correlation with TAPSEout and no significant correlation with TAPSEin and RVFS. One could assume that in patients with HCM and especially in patients with HOCM who have a predominantly hypercontractile right ventricle and a significantly greater apical torsion at end-systole [The two approaches to determine TAPSE using either echocardiography or CMR-derived TAPSE with a reference point in the RV apex  the above-described pronounced apical torsion of the right ventricle in patients with HCM and b) the fact that the right ventricle is also hypertrophied in patients with HCM which makes it more difficult to identify the RV apex, particularly in end-systole. Furthermore, we investigated for the first time whether a semi-quantitative approach using TAPSE or RVFS derived by CMR is suitable to describe RV function in patients with HCM.To the best of our knowledge the present study is the first to compare CMR-derived TAPSE measurements using either a reference point inside or outside the RV apex. To date, no data were available on which method to use to achieve the most reliable and reproducible results for RV longitudinal function analysis using CMR. The clinical value of a specific analysis method is determined not only on the basis of its accuracy but also on its reproducibility. Therefore, we sought to analyse which method was superior in terms of reproducibility. The interobserver and intraobserver variability of TAPSEIn terms of acquisition, images required for the gold standard volumetric 3D approach and for the semi-quantitative 2D analysis are actually both part of the routine CMR imaging protocol. The difference is mainly due to the post-processing. The 3D approach requires outlining the endocardial border of the right ventricle on each slice of the short-axis stack which takes up to 10 min, depending on the experience of the observer, whereas the 2D approach only requires to determine in end-diastole and end-systole the distance between the cutting edge of the tricuspid annulus with the RV free wall and a reference point outside the right ventricle which can be done in 1 min. Thus, it is advantageous to have a quick 2D screening tool to identify patients with RV dysfunction and to select patients in whom a more detailed analysis would be beneficial. Furthermore, 2D TAPSE or RVFS measurements can easily be assessed by less experienced readers whereas 3D RV volumetry requires more experience.In our cohort of patients with HCM, there was only a small number of patients with reduced RVEF. Thus, the suggested TAPSE cut-off values to discriminate between patients with normal and reduced RVEF should be tested in further larger HCM populations.in) are not suitable in patients with HCM. CMR TAPSE measurements with a reference point outside the RV (TAPSEout) showed a good correlation with the 3D volumetric determined RVEF in patients with HNCM but only a weak correlation in patients with HOCM. TAPSEout might be used to screen for RV dysfunction in patients with HCM. However, the detection of subtle changes in RV function requires the more time-consuming standard 3D quantitative approach.CMR-derived TAPSE measurements using a reference point in the RV apex (TAPSE


Images were acquired on 1.5T Siemens systems (Sonata and Avanto) using the SASHA T1 mapping method[1 variability with ROI placement. Late gadolinium enhancement (LGE) and diastolic regional wall thickness (WT), measured on bSSFP cine images, were assessed at a comparable slice location.In images from 20 subjects with FD and 7 subjects with pulmonary hypertension (PH), the inferior RV wall was assessed for the appearance of hypertrophy, to identify subjects with sufficient wall thickness for Tng method for all (LV-FD) = 11.7 mm, WT(RV-FD) = 5.7 mm, WT(LV-PH) = 10.8 mm, WT(RV-PH) = 7.5 mm), as the remaining cases had inadequate hypertrophy and spatial resolution to proceed with analysis. Sample SASHA images are shown in Figure 1 values for all subjects, demonstrating lower myocardial T1 in both the LV and RV for all FD subjects (p = 0.0143 for either ventricles). Interobserver agreement (coefficient of variation) was 4.0% and 2.41% for the RV and septum, respectively. No FD subjects were positive for LGE in the inferior RV or septum; however one was positive at the RV insertion point. No PH subjects were positive for LGE in the inferior wall; however 2 showed mid-wall septal enhancement at locations within ROIs and all were positive at the RV insertion site. However, as indicated in Figure 1 values are similar in those positive (1340.7 & 1249.7 ms) and or negative (1459.4 & 1215.0 ms) for LGE.Analysis was performed in 5 patients with FD and 4 patients with PH (WT1 values are reduced as compared to patients with PH and RV hypertrophy. Significant improvement in spatial resolution is required for T1 mapping of the normal right ventricle to establish healthy native RV T1 values.In FD patients with RV hypertrophy, both RV and LV native TThe authors acknowledge financial support from CIHR, AIHS, WCHRI.


Thirteen patients (7.8%) developed CIN. Left ventricular dysfunction and intraoperative blood transfusion were significantly more frequent in the CIN group . Multivariate analysis showed that left ventricular dysfunction had the strongest influence on CIN development . Patients with CIN also experienced longer ICU and hospital stays. Measures to improve renal perfusion flow should be considered for patients with left ventricular dysfunction who are undergoing endovascular stent graft placement. Endovascular stent graft placement has become a major treatment for thoracic and abdominal aneurysms. While endovascular therapy is less invasive than open surgery, it involves the use of a contrast medium. Contrast media can cause renal impairment, a condition termed as contrast-induced nephropathy (CIN). This study sought to evaluate the incidence and risk factors of CIN following endovascular stent graft placement for aortic aneurysm repair. The study included 167 consecutive patients who underwent endovascular stent graft placement in our hospital from October 2013 to June 2014. CIN was diagnosed using the European Society of Urogenital Radiology criteria. Patients with and without CIN were compared. Chi-squared tests,  Compared with open repair, endovascular stent graft placement is a minimally invasive procedure with low rates of perioperative mortality and complications, including low rates of renal dysfunction , 2. HoweCIN is the third most common cause of renal failure that occurs during hospitalization . In variThe present study included 184 patients who underwent endovascular stent graft placement in our hospital from October 2013 to June 2014. Of these, we excluded 12 patients who received operative treatment for aortic aneurysm rupture, three patients in whom acute aortic dissection was performed, one patient who received operative treatment including thoracotomy, and one patient with chronic renal failure who had received preoperative hemodialysis.All clinical data were collected from the patients' medical records.μmol/L (0.5 mg/dL) indicates CIN” ). Continuous variables such as age, surgical duration, amount of contrast medium used, and length of stay in the ICU and hospital were analyzed using Student's P value < 0.05 in the univariate analyses to examine the factors with the greatest influence on the onset of CIN.We performed a multiple logistic regression analysis that included all items with a All statistical analyses were performed on a personal computer using the statistical software package SPSS for Mac .P = 0.017; P = 0.032). No significant differences were noted for operative time or quantity of contrast medium used . No cases of acute renal failure that required postoperative renal replacement therapy were observed. No significant differences in age, gender, history of hypertension, surgical procedure, preoperative serum creatinine level, or preoperative eGFR were observed between the CIN and non-CIN groups. Three patients (23%) in the CIN onset group had impaired left ventricular function, compared with five patients (3.2%) in the non-CIN group; thus, impaired left ventricular function was significantly more prevalent in the CIN onset group  used to treat heart failure and found that a past history of heart failure is a risk factor for CIN . AdditioWhen decreased renal perfusion flow caused by a contrast medium occurs, patients with impaired left ventricular function have poorer perfusion flow compared to those with normal ventricular function. This may be why it is a risk factor for CIN onset.These findings suggest that the intraoperative and postoperative use of catecholamines to increase cardiac output and improve the patient's hemodynamics and renal perfusion flow could prevent and treat CIN in patients with impaired left ventricular function. This should be explored in future studies.Intraoperative blood transfusion was a risk factor for CIN. There are no reports concerning CIN associated with procedures in which blood transfusions were necessary. In the present study, only 1.80% of the total number of patients needed a blood transfusion; thus blood transfusions were generally not performed during endovascular stent graft placement. It appears that, in such procedures, intraoperative hemodynamic instability requiring blood transfusions led to a decrease in renal perfusion flow. No intraoperative aneurysm ruptures or conversions to open repair occurred during the study procedures. In our experience, the most common sites of hemorrhage during endovascular stent graft placement in patients who do not have a ruptured aortic aneurysm are the sheath placement site and the sheath retraction site. From the viewpoint of CIN prevention, it is necessary to thoroughly manage the sheath placement site in order to limit the amount of intraoperative hemorrhaging, as well as to retract the sheath with extreme care during the procedure.It is thought that intravenous hydration provides effective prophylaxis against CIN . A studyA high preoperative creatinine level has been reported to be a risk factor for CIN . HoweverIt has been reported that the ratio of contrast volume divided by eGFR (CV/eGFR ratio) in PCI is a useful predictive factor of CIN . A compaAdditionally, because the CIN onset group tended to be elderly, in the present study we also examined the age × CV interaction. These values were also significantly higher in the CIN onset group; thus it appears that a high value for this parameter can also be a risk factor.High-density contrast media are used during endovascular stent graft placement in our hospital. The use of a high-density contrast medium in animal experiments was reported to cause a higher level of renal impairment . It is pCIN is associated with poor mortality and morbidity as well as an increased length of hospitalization . In the It is possible that intravenous hydration prevents CIN: the results of the present study concerning impaired left ventricular function and intraoperative blood transfusion as risk factors are similar to the results of previous clinical studies from other fields and studies concerning the pathology of the condition. Factors leading to decreased renal perfusion flow are similarly considered to be risk factors for the development of CIN.It is possible that, by obtaining the needed circulation serum and maintaining favorable intraoperative and perioperative hemodynamics, renal perfusion flow can be improved, leading to the prevention of CIN.In the present study, our diagnoses were based on the definition of CIN put forth by the European Society of Urogenital Radiology. However, elements that are extremely difficult to evaluate, such as the effects of device manipulation and micro embolism proximal to the renal artery associated with the stent graft, are likely involved in the development of renal dysfunction occurring after stent graft placement. The inflammatory reaction is a well-known factor causing renal dysfunction, and inflammatory reactions also occur after placement of the stent graft . Thus, fImpaired left ventricular function and intraoperative blood transfusion were risk factors for CIN associated with endovascular stent graft placement. Impaired left ventricular function had the strongest influence on CIN risk. The CV/eGFR ratio and age × CV/eGFR ratio were significantly higher in the CIN onset group. The length of ICU stay and length of postoperative hospitalization tended to be longer in the CIN onset group. Preventive measures, such as catecholamine administration and intravenous hydration, should be explored for their use in patients with impaired left ventricular function who are undergoing endovascular stent graft placement.


Left ventricular non-compaction (LVNC) is an unclassified cardiomyopathy and there is no consensus on the diagnosis of LVNC. The aims of this study were to establish quantitative methods to diagnose LVNC using cardiovascular magnetic resonance (CMR) and to suggest refined semi-quantitative methods to diagnose LVNC.This retrospective study included 145 subjects with mild to severe trabeculation of the left ventricle myocardium . The left ventricular (LV) ejection fraction, global LV myocardial volume, trabeculated LV myocardial volume, and number of segments with late gadolinium enhancement were measured. In addition, the most prominent non-compacted (NC), compacted (C), normal mid-septum, normal mid-lateral wall, and apical trabeculation thicknesses on the end-diastolic frames of the long-axis slices were measured.p < 0.001), and 1.7 times higher than in the controls . However, there was no significant difference in TV% between the isolated LVNC and DCMNC groups . The receiver operating characteristic curve analysis using Jenni’s method for CMR classification as the standard diagnostic criteria revealed that a value of TV% above 34.6 % was predictive of NC with a specificity of 89.7 % (CI: 74.2 - 98.0 %) and a sensitivity of 66.1 % (CI: 52.6 - 77.9 %). A value of NC/septum over 1.27 was considered predictive for NC with a specificity of 82.8 % (CI: 64.2 - 94.2 %) and a sensitivity of 57.6 % (CI: 44.1 - 70.4 %). In addition, a value of apex/C above 3.15 was considered predictive of NC with a specificity of 93.1 % (CI: 77.2 - 99.2 %) and a sensitivity of 69.5 % (CI: 56.1 - 80.8 %).In the patients with isolated LVNC, the percentage of trabeculated LV volume  relative to total LV myocardial volume was 1.4 times higher than in those with DCM (30.3 ± 14.3 %, A trabeculated LV myocardial volume above 35 % of the total LV myocardial volume is diagnostic for LVNC with high specificity. Also, the apex/C and NC/septum ratios could be useful as supplementary diagnostic criteria. Left ventricular non-compaction (LVNC) is an unclassified cardiomyopathy characterized by an extremely thick endocardial layer with prominent trabeculation and a thin epicardial layer . LVNC haThere have been many attempts to establish standard diagnostic criteria in LVNC using various imaging modalities. At present, Jenni et al.’s echocardiographic criteria of a ratio over 2.0 between the thickness of the non-compacted and compacted myocardial layers in systole are widely recognized as the standard diagnostic criteria for LVNC . EchocarEven when using high-contrast imaging modalities such as CMR, however, there are still concerns about the overdiagnosis of LVNC , 16. In This study was approved by the Samsung Medical Center Institutional Review Board; informed consent was waived for this retrospective study.We queried the clinical and CMR databases at our institute for patients diagnosed with cardiomyopathy between August 2009 and December 2013. Of a total of 11,997 patients diagnosed with cardiomyopathy, we extracted consecutive patients who had CMR reports that included descriptions of non-compaction. We also included subjects with mildly or moderately increased LV trabeculation (hypertrabeculation) measuring more than 5 mm in thickness and NC/C ratios of 1.0–2.3 anywhere in the myocardial segments on the CMR images.We enrolled the LVNC group according to two inclusion criteria: CMR images with a distinct two-layered appearance of trabeculated and compacted myocardium and the fulfillment of Petersen et al.’s CMR criteria for the diagnosis of LVNC. As dilated cardiomyopathy (DCM) is a potential differential diagnosis for LVNC, we retrospectively enrolled two other groups: DCM with LVNC and DCM with hypertrabeculation. We classified patients with DCM into two groups according to Petersen et al.’s CMR criteria. The diagnosis of DCM was made on the basis of impaired global LV function with an ejection fraction of less than 40 % on CMR, LV chamber dilatation, and the exclusion of other causes of LV dysfunction.n = 24; group 2 for accompanied with other diseases , n = 33; group 3 for patients with DCM with LVNC [DCMNC], n = 30; group 4 for patients with DCM and hypertrabeculation, n = 27; and group 5 for the healthy control group with hypertrabeculation, n = 31) , coronary artery disease (CAD), and any arrhythmias. Diabetes was defined as a patient who had been diagnosed with diabetes or was taking glucose-lowering medication. Hypertension was defined as a diagnosis of hypertension or patients with systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg. Dyslipidemia was defined by laboratory findings . To assess arrhythmia, we reviewed the patients’ electrocardiographic findings, and any arrhythmia from atrial fibrillation to ventricular tachycardia was included.All patients underwent cardiac MRI using a 1.5 T scanner  with a 32-channel phased-array receiver coil during repeated breath-holds. After localization, cine images of LV were acquired using a steady-state free-precession sequence in four-, two-, and three-chamber views and in short-axis views to obtain 20–30 contiguous short-axis slices to include the entire LV with a slice thickness of 6 mm and gaps of 4 mm  using contiguous short-axis image acquisition of 10 to 12 slices at 6-mm thickness with 4-mm interslice gaps. Inversion delay times were typically 280 to 360 msec.The distribution of LVNC was assessed by the qualitative analysis of all 17 American Heart Association segments for the presence of a distinct two-layered appearance. A segment was regarded as having hypertrabeculation if the trabeculated to compacted ratio (NC/C ratio) in diastole was higher than 1.0. In addition, an NC/C ratio over 2.3 is considered as non-compaction. We excluded segments where the trabeculated area was less than 50 % of the total thickness.We also classified the distribution of trabeculation into three patterns: the global, apical, and non-apical types. The global type was defined as having over ten two-layered segments in total. The apical type was defined as involving more than three segments in the apical level (segments 13 through 17). The non-apical type was any trabeculation that did not meet the definitions of the global or apical types.During the measurement of the most prominent trabeculation to compacted ratio in three long-axis views as in Petersen’s CMR criteria , we alsoUsing short-axis cine images, we determined end-diastolic frames when the cavity sizes were largest and end-systolic frames when the cavity sizes were smallest. Trabeculated volume measurements were performed on the end-diastolic frames of each short-axis slice in the LV stack. After we identified a distinct two-layered structure, we manually measured the trabeculated area with a picture archiving and communication system . An endocardial border and non-compacted layer border were drawn to include the trabeculated area, and the papillary muscles were specifically excluded from the measurement Fig. . When thThe LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV) and LV myocardial mass were measured using an Argus workstation (Siemens). LVEDVi was calculated as LVEDV/BSA and LVESVi was calculated as LVESV/BSA.Wall thickening of compact myocardium in the non-compaction areas was measured from the short-axis cine images of the apical level using the following equation: compact myocardial wall thickening = /[end-diastolic compact wall thickness].We also assessed the number of myocardial segments with late gadolinium enhancement (LGE). LGE was defined as a signal intensity higher than three standard deviations above the mean intensity of the region of interest in the remote normal myocardium using semi-quantitative software .All continuous data are presented as means ± standard deviations (SDs), and categorical data are presented as percentages. The statistical analysis was performed using SPSS for Windows 18.0 .P < 0.05/4 = 0.0125 was considered significant. In addition, the categorical data in the patient group characteristics were compared by chi-square tests.Continuous data in the patient group characteristics were compared by the Kruskal–Wallis non-parametric tests; when results from these were significant, we compared them by the Mann–Whitney U non-parametric tests for post hoc analysis. In these cases, the Bonferroni correction was applied to ensure an overall type I error rate of 5 % and an adjusted n = 20) was randomly selected and measured by a second rater blinded to all information.The interobserver reproducibility was assessed using intraclass correlation and Bland–Altman analysis  by calcuWe used receiver operating characteristics (ROC) curves to determine the optimal cut-off values of the trabeculated volume, apex/C, apex/septum, apex/mid-lateral, and NC/septum ratios. A comparison of the areas under the ROC curves was performed using the method described by Hanley et al. . Based oThe study population was comprised of 145 patients and was homogeneous in its race and ethnicity, Asian (Korean). All four groups were matched in terms of age and sex, and all groups were also comparable in terms of height, weight, and body surface area , arrhythmia (n = 10), congenital heart diseases (n = 3), unclassified cardiomyopathy (n = 3), hypertrophic cardiomyopathy (n = 2), and Marfan syndrome (n = 1). We had four LVNC patients with ventricular arrhythmia  not associated other structural heart diseases.In the INC group, only one patient among 24 was diagnosed as having myotonic dystrophy. In the patients with LVNC and accompanying heart diseases, there were CADs including myocardial infarction , valvular heart diseases .There was no significant difference in N-terminal pro-brain natriuretic peptide (NT-proBNP) between INC group (40.5 ± 38.8 pg/mL) and control group (34.8 ± 29.8 pg/mL) by Student The patterns of distribution of the trabeculation areas with trabeculation thicknesses of more than 5 mm in the American Heart Association’s 17-segment model were almost similar among the groups. There were more basal segments in the NINC group (54.5 %) than in the INC group (33.3 %) Fig. . In the In our classification of the distribution of trabeculation (NC/C > 1.0 and trabeculation thickness > 5 mm) in 57 LVNC patients, 25 were the global type 43.9 %), 30 were the apical type (52.6 %), and two were the non-apical type (3.5 %). Of the 30 DCMNC cases, 22 were the global type (73.3 %) and eight were the apical type (26.7 %). Of the 27 DCM cases, five were the global type (18.5 %), 19 were the apical type (70.4 %), and three were non-apical type (11.1 %). Finally, of the 31 control cases, one was the global type (3.2 %) and 30 were the apical type (96.8 %) , severe trabeculation meeting Peterson’s criteria of LVNC (NC/C > 2.3) was observed most frequently in the segment 16 (77 %) followed by the segment 17 (67.8 %), segment 13 47.1 %), segment 15 (46 %), segment 12 (28.7 %), segment 11 (26.4 %), segment 10 (11.4 %), segment 7 (6.9 %), segment 1 (2.3 %), segment 8 (1.1 %), and segment 5 (1.1 %)  was 2.2 times lower than in DCMNC group (173.0 ± 56.4 mL/m2), and similar to the control group (76.5 ± 8.8 mL/m2). In INC group, LVESVi (27.7 ± 8.3 mL/m2) was 4.8 times lower than in DCMNC group (132.8 ± 53.9 mL/m2), and similar to the control group (25.7 ± 5.9 mL/m2) , DCMNC , and DCM  groups. The trabeculated LV volume was positively correlated with the number of LGE-positive segments  . In the DCM group, however, there was no correlation between the number of LGE segments and trabeculated LV volume.The proportion of patients with LGE-positive segments was 4.2 % (1/24) in the INC group. In the NINC group, however, 45.5 % (15/33) of the patients had LGE-positive segments. The mean number of segments with LGE was 0.04 ± 0.20 in INC group. However, there were statistically higher mean numbers of LGE-positive segments in the NINC  and LVESV   and LVESV  and negatively with LVEF   and LVESV  and negatively correlated with LVEF  in the DCMNC group. In the DCM group, however, there were no significant correlations except with LVEDV .In the DCMNC and DCM groups, trabeculated LV volume correlated positively with LVEDV  Fig. . In resuThe percentage of trabeculated LV myocardial volume was not significantly correlated with LVEF, LVEDV, or LVESV in any of the groups. In the INC group, LVEF under 55 % was found in only 8.3 % (2/24) of subjects.p = 0.3478) groups by one-way analysis of variance (ANOVA).The thickness of compacted myocardium in the area of LVNC or hypertrabeculation was less than 2 mm in 91.7 % (22/24) of INC, 66.7 % 22/33) of NINC, 86.7 % (26/30) of DCMNC, 70.4 % (19/27) of DCM, 9.7 % (3/31) of control group , and 1.7 times higher than that in the controls  . In addition, the value was statistically similar between the DCM group and the controls.In the patients with INC, TV% (42.6 ± 13.8 %) was 1.4 times higher than that in DCM , 1.9 times lower than in DCMNC group , 1.3 times lower than in DCM group , and 1.3 times higher than in the controls  (Table 2) was 1.4 times lower than in NINC group , 2.0 times lower than in DCMNC group , 1.3 times lower than in DCM group  and 1.4 times higher than in the control group .The mean trabeculated myocardial volume in INC group (32.1 ± 13.8 mL) was 1.4 times lower than in NINC group  for inter-rater reliability was 0.95 [95 % confidence interval (CI): 0.89–0.98]. There was a slight bias (1.8 ± 4.7), but no tendency. In addition, only one value out of 20 was outside the limits of agreement. There was also excellent intraobserver reproducibility. The ICC for intra-rater reliability was strong, with a value of 0.98 (95 % CI: 0.96–0.99).The intraclass coefficients for intraobserver variability were 0.98 and 0.99 for LVESV and LVEDV, respectively, while the intraclass coefficients for interobserver variability were 0.95 and 0.88 for LVESV and LVEDV, respectively.r = 0.484 [95 % CI: 0.349–0.60], p < 0.001) or Petersen’s CMR criteria  for all groups. In four patients with ventricular arrhythmia, their mean TV% was 43.9 %  and their mean Petersen’s criteria measurement was 2.87 .The results of the ROC analysis for TV%, the apex/C ratio, and the NC/septum ratio for LVNC diagnosis using Jenni’s method for CMR classification or Petersen’s CMR classification as the standard diagnostic criteria were presented in Table The mean time required for the trabecular volume measurement was about three minutes (range: two to five minutes).The results of the present study can be summarized as follows. Trabeculated LV volume was significantly higher in INC patients as compared to healthy controls and DCM patients, although there was some overlap between the three groups. Patients with a TV% above 35 % could be considered as LVNC cases. Apex/C and NC/septum ratios could be supplemental diagnostic tools for LVNC, while LGE findings were rarely shown in the INC group. In DCMNC patients, trabeculated LV volume was positively correlated with LVEDV, LVESV, and the number of LGE segments, and it was negatively correlated with LVEF.The quantification of left ventricular trabeculation is an ideal method to diagnose INC in that it reflects the total volume of trabeculation and it does not depend on particular slices selected from the CMR images. The quantification of LV mass and volume with or without LV trabeculation has already been described and validated , 20. TheIn our study, TV% was significantly higher in the INC group compared to the healthy control and DCM groups. However, there was some overlap between the three groups. Interestingly, TV% in the DCM group showed a broad overlap with that of the INC group; these findings are in contrast to the results of Jacquier et al. .Petersen et al. excluded the measurement of the apex (segment 17), because the apical compacted myocardium is generally thinner than other segments, and its inclusion would have led to an artificially high NC/C ratio . HoweverIn extremely non-compacted cases, compacted myocardium was difficult to measure for the calculation of various ratios, especially Petersen’s criteria. The thickness of compact myocardium in the area of LVNC was less than 2 mm in most patients (>66 %) except the control group. The value of the non-compacted myocardium to septal wall thickness might be useful in these cases.LGE enables noninvasive assessment of cardiomyopathy for the detection of myocardial fibrosis , 24. In In the DCMNC group, we found that trabeculated LV myocardial volume was positively correlated with LVEDV and LVESV and negatively correlated with LVEF. In the DCM group, however, there was no correlation between trabeculated LV volume and LVESV or LVEF. In our study, there was also a positive correlation between trabeculated LV myocardial volume and the number of LGE segments in the DCMNC group. It has already been reported that myocardial fibrosis predicts a poor prognosis in DCM patients , 30. MasThis study has some limitations that should be acknowledged. First, it was a retrospective study. Second, because there was no standard reference for LVNC, Jenni’s method and Petersen’s CMR criteria were used to define our LVNC cases. Third, a selection bias may have been introduced, as the study population included patients presenting to a tertiary referral center. Fourth, although we excluded the papillary muscles from the measurement, we admit that poorly formed papillary muscle could be counted as trabeculation. The patients’ genetic factors were not considered in the LVNC diagnoses. A genetic factor could help to provide more accurate diagnoses for LVNC and would provide a more powerful means of validating our method. We did not use trabecula-dedicated software to measure the trabecular myocardial volume excluding the blood cavity. However, the manual measurement of trabecular volumes using PACS or workstations provided by MR equipment vendors was neither time-consuming nor difficult in our study. Future studies are expected to use some trabecula-specific software.In this study, we used cardiac magnetic resonance imaging to establish refined diagnostic criteria for LVNC. As a quantitative approach, we have shown that a TV% > 35 % of the LV myocardial volume is diagnostic for LVNC with high specificity. In addition, as a semi-quantitative approach, we propose a reproducible method of using apex/C and NC/septum ratios for supplemental diagnostic criteria for LVNC.


Right ventricular (RV) systolic dysfunction is now recognized widely as a strong and independent predictor of adverse outcomes in patients with heart failure (HF). Reduction of RV systolic function more closely predicts impaired exercise tolerance and poor survival than does left ventricular (LV) systolic function. In spite of this, there is a dearth of data on RV function in hypertensive HF which is the commonest form of HF in sub-Saharan Africa. We therefore conducted a prospective cohort study of hypertensive HF patients presenting to the University of Abuja Teaching Hospital, Abuja, Nigeria over an 8 year period.Each subject had transthoracic echocardiography performed on them according to the guidelines of American Society of Echocardiography. RV systolic function was defined as a tricuspid annular plane systolic excursion (TAPSE) <15mm using M-mode echocardiography.RV systolic dysfunction was identified in 272 (44.5%) of the 611 subjects that were studied. Subjects with TAPSE less than 15mm had worse prognosis compared to those with TAPSE ≥15mm.There was a significant correlation between TAPSE and other adverse prognostic markers including left and right atrial area, LV size, LV mass, LV ejection fraction, restrictive mitral inflow and RV systolic pressure (RVSP). However, LV ejection fraction and right atrial area were the only independent determinants of RV systolic dysfunction.Hypertensive HF is a major cause of RV systolic dysfunction even in a population with a low prevalence of coronary artery disease, and RV systolic dysfunction is associated with poor prognosis in hypertensive HF. Detailed assessment of RV function should therefore be part of the echocardiography evaluation of patients with hypertensive HF. Right ventricular (RV) systolic dysfunction is now widely recognized as an independent predictor of adverse outcomes in patients with heart failure (HF) especially in those with advanced HF. in whomFurthermore, the more widespread use of a simplified and reproducible echocardiography approach to the evaluation of RV function has substantially contributed to the greater awareness of the importance of this chamber ,6.In spite of these considerations, RV function in hypertensive HF, which is the commonest form of HF in sub-Saharan Africa , 8 has nThis prospective cohort study was approved by the University of Abuja Teaching Hospital Ethics Clearance Committee and is in compliance with the Helsinki declaration, besides when feasible adhering to the STROBE guidelines for an observational study of this nature. Written informed consent as approved by the University of Abuja Teaching Hospital Ethical Committee was obtained from all the subjects. The minimum age for participation in the study was 18 years and there was no upper age limit. Recruitment for the present study was initiated in April 2006 and data were obtained until June 2014. The main inclusion criterion was all black hypertensive subjects presenting with acute left-sided HF or biventricular HF for the first time to the emergency department of University of Abuja Teaching Hospital. Subjects with angina symptoms, those with electrocardiography changes of myocardial infarction and those with elevated troponin I were excluded from the study. Subjects with previous acute myocardial infarction, previous diagnosis of heart failure, those with regional wall motion abnormality and valvular lesions on trans thoracic echocardiography, those with diabetes mellitus, and those with serum creatinine levels greater than 170μmol/L were excluded from the study. Hypertension was defined according the JNC VII guidelines . The subAll the subjects completed a standard questionnaire. Where there was need for language interpretation, both medical and paramedical staff of the Cardiology Unit of the Department of Medicine of the University of Abuja Teaching Hospital assisted. The questionnaire requested specific answers regarding date of birth, gender, occupation, background diagnosis of hypertension, background diagnosis of diabetes mellitus, history of angina, history of alcohol consumption and history of smoking habits. Subjects’ outcome data with respect to length of hospital stay, intra-hospital mortality and one year re-hospitalization were collected prospectively from the subjects’ hospital records and was approved by the University of Abuja Teaching Hospital Ethics Clearance Committee. In keeping with the policy of University of Abuja Teaching Hospital, no informed consent was obtained from these subjects or their next of kin to obtain these records. However, patient records and information was anonymized and de-identified prior to analysis of their data.2 (m2) was calculated as (0.0001) x (71.84) x (weight in kg) 0.425 x (height in cm) 0.725The height and weight of the subjects were measured during the clinic by Nursing Staff with the participants standing and wearing indoor clothes with no shoes. Body mass index was calculated as weight in kilograms divided by the square of height in meters. Body surface area in metersBlood pressure (BP) measurements were obtained according to standard guidelines with a mercury sphygmomanometer (Accouson London). Systolic and diastolic BP were measured by cardiologists at Korotkoff sounds I and V respectively. BP was measured at the right arm three times after the patient has rested in the sitting position for 5minutes, and average of the three measurements was obtained. Pulse pressure was calculated as systolic BP minus diastolic BP while mean arterial pressure was calculated as diastolic BP plus one third of the pulse pressure.Blood samples were collected for fasting blood sugar, fasting lipid profile, electrolytes, urea and creatinine, and full blood count.3 + 0.6g].This formula has been shown[2.7 in men and 46.7g/m2.7 in women [Subjects had transthoracic echocardiography performed on them using a commercially available ultrasound system (IVIS-60). All the studies were performed by same Cardiologist. Each study was performed with subject in the left lateral decubitus position using standard parasternal, short-axis and apical views according to the recommendations of the American Society of Echocardiography . Left veeen shown to yieldin women . The lefin women . DetailsSPSS software version 16.0 was used for statistical analysis. Continuous variables were expressed as mean± SD. Comparison of demographic, clinical, laboratory and echocardiography parameters among the three groups was performed by analysis of variance. Correlation coefficients were calculated by linear regression analysis with demographic, clinical, laboratory and echocardiography measures being evaluated by Spearman regression. Multivariate linear regression analyses were performed with TAPSE as dependent variable with inclusion of demographic, clinical and echocardiography parameters. A 2-tailed p value < 0.05 was considered significant.643 patients enrolled for the study but 32 (4.9%) of the total enrolment was excluded because patients were either diabetic, had a regional wall motion abnormality on trans thoracic echocardiography, had serum creatinine levels greater than 170μmol/L or had previous acute myocardial infarction. Therefore, 611 subjects with hypertensive HF were studied. This is shown in 2.7 between subjects with reduced RV systolic function and those with normal RV systolic function. Subjects with reduced RV systolic function, however had larger left and right atrial and ventricular dimensions, lower LV ejection fraction and were more likely to have tricuspid regurgitation (TR) compared to the subjects with normal RV systolic function.Our study has shown the influence of hypertensive HF on RV function. Although hypertensive HF has been previously identified as the commonest cause of left-sided HF in sub-Saharan Africa –19, we aWe found RV systolic dysfunction in 272 (44.5%) of the 611 subjects studied. Although coronary artery disease is a recognized confounder for the development of RV systolic dysfunction in the setting of hypertension and HF, we have previously shown that coronary artery disease is relatively uncommon in HF patients in urban Nigeria(7), and is therefore unlikely to explain our findings.The high prevalence of RV systolic dysfunction in our hypertensive HF cohort might partly explain the poor prognosis that is found in our subjects, as RV s29% of our subjects had tricuspid (TR), and expectedly, TR was more common in the subjects with RV systolic dysfunction. The mechanism of TR in our subjects was largely functional and has been linked to RV dilatation , rather On linear regression analysis, factors that were associated with abnormal RV function included dilated left atrium and LV, increased LV mass, reduced LV systolic function, restrictive filling pattern, and increased RV systolic pressure, while on multiple regression only low fractional shortening and LV ejection fraction, and increased right atrial area were determinants of right systolic dysfunction. LV dilation has been previously shown to have an impact on RV function as measured by TAPSE . A reducTAPSE correlated with markers of diastolic dysfunction and RV systolic pressure in our study, but not with RV end-diastolic diameter as previously reported . This maAt presentation, most of our subjects had chamber dilatation especially of the left-sided chambers, and with significant systolic and diastolic dysfunction with an average LV ejection fraction (LVEF) of 35% and trans mitral E/A ratio of 2.1, suggesting raised LV filling pressure. The reduced LV systolic function in our hypertensive heart failure subjects is not surprising as systolic dysfunction has been linked to hypertension in a black population . SubjectThe diagnosis of ischaemic heart disease was made clinically from history, physical examination, troponin I levels and electrocardiography with no myocardial perfusion imaging or coronary angiography, and therefore there is the possibility that subclinical coronary artery disease may have been missed similar to our previous study . HoweverHypertensive heart failure is a major cause of RV systolic dysfunction in Nigeria, which was present in over 40% of such patients. Importantly, this occurred despite a low prevalence of clinical ischemic heart disease in our cohort. In addition, RV systolic dysfunction is also associated with poorer prognosis in hypertensive HF. Detailed RV assessment should therefore be part of the echocardiography assessment of hypertensive HF.


Although surgery have improved the prognosis for patients who repaired tetralogy of Fallot (TOF); late ventricular dysfunction, scar and fibrosis remains a problem which weakens the prognosis. Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) also shows this scar tissue and fibrosis. In these patients decreasing in the right ventricular (RV) ejection fraction and an increase in end diastolic volume are indications for the pulmonic valve replacement. Fragmented QRS (fQRS) on 12-lead electrocardiogram represents myocardial conduction delays due to myocardial fibrosis.In this study we define the relationship between the fQRS and RV fibrosis, function, volume and the role of fQRS in the follow up and assessment of patients with repaired TOF.32 patients were enrolled in the study and the extent of fQRS in each patient was estimated by counting the number of electrocardiographic leads with QRS. The relation between fQRS and RV indexes and fibrosis in CMR was determined.2 were 87% and 62%, respectively; PPV=70% and NPV=83%.The relation of fQRS and RV end systolic volume index was statistically meaningful. The sensitivity and specificity of fQRS in identifying patients with RVESVI>82 ml/m2 were 80% and 66%, respectively; PPV=80% and NPV=66%.The relation of mean right ventricular diastolic and systolic diameter with RVEF was statistically considerable according to the P-value=0.0001 and 0.001, respectively; without any meaningful relationship between RV diastolic diameter and fQRS. And there was relationship between RV diastolic diameter and fQRS. There was a strong inverse linear relationship between the number of fQRS edges and RVEF  in addition to a strong positive linear correlation between the number of edges and the percentage of scar tissue .The mean percentage of scar tissue in those who had RVEF< 45% was 24% and 5/8% in patients with RVEF> 45%, that was statistically significant.. The overall accuracy of the test to identify patients with RVEF<45%, was 98%; that was statistically significant and could be generalized to the target population.  There was also a meaningful relationship between fQRS and RV end diastolic volume index.  The sensitivity and specificity of fQRS in identifying patients with RVEDVI>150 ml/mAccording to this study fQRS could suggest an acceptable screening test in the serial follow up of patients who repaired TOF, considering that CMR was costly and time consuming.


In sicker hearts, right atrial pressure (an estimation of right ventricle preload) are not equivalent to left atrial pressure (an estimation of left ventricle preload). Both right and left atrial pressures are frequently estimated using invasive techniques and also transthoracic echocardiography. While right atrial pressure is easy to obtain with transthoracic echocardiography, the assessment of left ventricle preload or filling pressures is not simple. In relation to the study of Sasai et al. (J Intensive Care 2(1):58, 2014), this paper discusses in a succinct manner how to think and assess the left ventricle preload by transthoracic echocardiography. Pablo BlancoDear Editor,In failing hearts (septic and non-septic etiology), right atrial pressure (RAP) which infers right ventricle (RV) preload is commonly not equivalent to left atrial pressure (LAP), which infers the left ventricle (LV) preload or filling pressures.As a daily example, it is not surprising to see patients presenting with cardiogenic pulmonary edema, which denotes a high LAP value, with normal inferior vena cava (IVC) analysis, which indicates a normal RAP.RAP is commonly obtained by central venous pressure (CVP) measurement or through the analysis of the IVC by transthoracic echocardiography (TTE) in spontaneous breathing patients. LAP is estimated with the wedge pressure (pulmonary artery catheter) or commonly with a set of TTE two-dimensional and Doppler parameters.At respect and as expected, the study carried out by Sasai et al.  shows noThe set of TTE parameters used for comparison with CVP, although simple and repeatable, are probably not accurate parameters of LV preload. For example, a patient with dilated cardiomyopathy and depressed LV systolic function could also present with hypovolemia. The simple inspection of the LV and LA suggests an elevated preload; however, other parameters like transmitral inflow and mitral annular velocities may aid in the correct distinction. Also, a patient with RV systolic failure and a low RV stroke volume, like in some cases of septic cardiomyopathy, also accompanied by several grades of tricuspid regurgitation, can have an elevated RAP, with normal or low LAP .These are some examples that suggest that more reliable parameters of LV filling are necessary along with two-dimensional measurements.With respect to tricuspid regurgitation, this jet allows to measure the pressure gradient between the RV and the RA (RV–RA pressure gradient). The increase of this gradient usually indicates the elevation of the right ventricle systolic pressure . As recommended in guidelines , PAsP isPulmonary artery diastolic pressure (PAdP) which is derived from the sum of RAP and the end-diastolic velocity of the pulmonary regurgitation Fig.  has showIn concrete, estimating LV preload with echocardiography is not easy and at least some measurements are necessary along with two-dimensional images, such as transmitral flow pattern , mitral annular velocities , and most importantly, the relationship between E and Ea (E/Ea) Fig. . PAsP anTakako SasaiDear Editor,We thank Dr. Blanco for his comments on our article.In our study, we revealed that transthoracic echocardiography (TTE) findings are more informative marker for fluid management than CVP findings for assessing the left ventricular (LV) preload of patients with septic shock. LV preload is defined as a tension on the LV myocardium at the end of the diastolic phase  and is clinically defined as LV end-diastolic volume (LVEDV) or LV end-diastolic pressure (LVEDP). In our study, we used LV end-diastolic diameter (LVEDD) as an index for LV preload. However, the authors have mentioned that LV preload cannot be easily evaluated with a single parameter, and a more detailed investigation is required. In daily practice, TTE findings, including LVEDD, may be used for estimating LV preload when actual LVEDV or LVEDP values cannot be easily obtained. Practically, in individual cases, we should treat patients with many indices instead of a single indicator. A complete evaluation of LV preload is difficult to perform and is complicated. However, a simple measurement may be sufficient to make the right decision in emergency or intensive care. Our aim was to assess whether CVP is a reliable marker of left ventricular preload; therefore, we used LVEDD, a relatively easier to measure standard indicator of LV preload, as a substitute for LVEDV.


Cardiovascular disease is the leading cause of mortality and morbidity in end-stage renal failure (ESRF) population, mostly from coronary artery disease (CAD). Majority of CAD in ESRF patients is asymptomatic and current cardiac stress imaging modalities are sub-optimal as risk predictors. Advances in cardiovascular magnetic resonance (CMR) with the novel blood oxygen level-dependent (BOLD) technique provides unprecedented capability to assess regional myocardial deoxygenation. We hypothesized that myocardial oxygenation would be reduced in ESRF patients and may form a novel strategy to assess myocardial ischemia.Sixteen chronic renal failure (CRF) patients  with no known history of CAD underwent CMR scanning at 3.0 T. Given known reductions in BOLD signals in hypertrophied myocardium, we also assessed a control group of HT patients with no history of CAD (n = 6) Myocardial function, rest and stress BOLD was performed. To measure oxygenation, using a T2-prepared BOLD sequence, myocardial Signal Intensity (SI) was measured at adenosine stress (140 μg/kg/min) and at rest . Comparison of myocardial SI analyses were performed using multivariate linear regression.Baseline clinical characteristics were similar in both CRF case and HT control groups, except higher body mass index in HT group (p = 0.02). Left and right ventricular dimensions and functions were similar. Interventricular septal thickness and LV mass were similar in both RF case and HT control groups . Rate Pressure Product (RPP) was similar in both groups. Global myocardial BOLD SI change was significantly lower in RF case group compared to HT control group  (Figure Chronic renal failure patients have global reductions in myocardial oxygenation even controlling for the degree of LVH. BOLD CMR is a promising tool to detect myocardial ischemia in the renal failure population, and may form a novel risk predictor of cardiovascular prognosis.None.


Speckle tracking echocardiography (STE) is a relatively novel and sensitive method for assessing ventricular function and may unmask myocardial dysfunction not appreciated with conventional echocardiography. The association of ventricular dysfunction and prognosis in sepsis is unclear. We sought to evaluate frequency and prognostic value of biventricular function, assessed by STE in patients with severe sepsis or septic shock.Over an eighteen-month period, sixty patients were prospectively imaged by transthoracic echocardiography within 24 hours of meeting severe sepsis criteria. Myocardial function assessment included conventional measures and STE. Association with mortality was assessed over 12 months.Mortality was 33% at 30 days (n = 20) and 48% at 6 months (n = 29). 32% of patients had right ventricle (RV) dysfunction based on conventional assessment compared to 72% assessed with STE. 33% of patients had left ventricle (LV) dysfunction based on ejection fraction compared to 69% assessed with STE. RV free wall longitudinal strain was moderately associated with six-month mortality . No other conventional echocardiography or STE method was associated with survival. After adjustment  severe RV free wall longitudinal strain impairment remained associated with six-month mortality.STE may unmask systolic dysfunction not seen with conventional echocardiography. RV dysfunction unmasked by STE, especially when severe, was associated with high mortality in patients with severe sepsis or septic shock. LV dysfunction was not associated with survival outcomes. Characterized by hemodynamic distress, severe sepsis is frequently associated with cardiopulmonary dysfunction driven by a cascade of cellular and molecular processes . MyocardTwo-dimensional speckle tracking echocardiography (STE) has emerged as an angle-independent technique for quantifying systolic function by assessing myocardial deformation ,6: straiThe objectives of this study were to assess: the prevalence of RV and LV dysfunction in severe sepsis and septic shock assessed with STE; factors related to RV and LV longitudinal strain dysfunction; and whether myocardial dysfunction assessed by STE is associated with mortality at 30 days and 6 months.3, <4,000 cells/mm3, or >10% immature (band) forms. Severe sepsis was defined as sepsis associated with organ dysfunction  score ≥2), hypoperfusion  or hypotension (systolic blood pressure <90 mmHg or decreased 40 mmHg below baseline). Severe sepsis with hypotension resistant to intravenous fluids was considered septic shock. Exclusion criteria were supraventricular tachyarrhythmias, pregnancy, congenital heart disease, cardiomyopathy, moderate or severe valvular disease and valvular prosthesis and insufficient image quality for STE.We prospectively studied 60 adult patients (>18 years) with severe sepsis or septic shock admitted over an 18-month period at St. Mary’s Hospital, Rochester, MN, USA. The study was approved by the Mayo Institutional Review Board and written consent was obtained from all patients or authorized representatives (next of kin) before enrollment. Individuals were included by American College of Chest Physicians criteria for severe sepsis or septic shock . Sepsis Transthoracic echocardiography was performed within 24 hours of meeting sepsis criteria with a Vivid 7 echocardiography machine  by research sonographers or research fellows fully trained in echocardiography and strain imaging. A comprehensive echocardiogram was performed according to American Society of Echocardiography guidelines . PhysiolThree-beat two-dimensional digital clips were transferred to a Syngo Velocity Vector Imaging workstation  for STE analysis by SRO, who had performed more than 100 hours of analysis in STE prior to commencing the study. The endocardium was traced manually from the medial annulus with 7 to 15 points. LV values were averages of the 16 LV segments. If STE could not be calculated on one apical view, the LV was considered to have insufficient image quality. RV values were an average of the three free wall segments. Once accuracy of tracking was ensured, displacement, velocity, strain and strain rate curves were assessed for motion, smoothness, time to peak, delay and correlation . Continuous variables are expressed as mean ± standard deviation or median with interquartile range and were analyzed between groups using analysis of variance. Categorical variables are expressed as the number and percentage with comparisons by Pearson’s chi-square analysis or Fisher’s exact test. All probability values are two-sided and of n = 40) and 52% alive at 6 months (n = 31)  had supraventricular arrhythmia and 14 patients (13%) had insufficient image quality for STE analysis . The mean age was 62 years (±15) with 50% female, 67% alive at 30 days (P = 0.02). There was no difference in survivors’ LV GLS or GLS rate compared with nonsurvivors.There was no difference seen between survivors and nonsurvivors in any standard echocardiography measure of ventricle size or function at 30 days or 6 months, or in their peak systolic pulmonary artery pressures Tables . There wThe incidence of myocardial dysfunction was different based on the method of assessment Table . Based oP <0.001). Separate analysis within these groups exposed those patients with severe RV strain dysfunction as having the statistically significant association (Table P = 0.03). This subgroup was also associated with a greater severity of disease (SOFA score), lower arterial partial pressure of oxygen/fraction of inspired oxygen ratios, mechanical ventilation, worse LV GLS, reduced RV FAC, higher echo-based right atrial pressures, lower tricuspid velocity, and higher echo-based peak systolic pulmonary artery pressure  due to all patients in this subgroup dying before 6 months  were respectively: RV free wall longitudinal strain, –2 (±1.2) and −1.4 (±0.9); RV free wall longitudinal strain rate, −0.3 (±0.1) and −0.1 (±0.05); LV GLS, −0.9 (±0.9%) and −0.8 (±0.5); and LV GLS rate, −0.1 (±0.05) and −0.1 (±0.05).In this observational cohort study of 60 patients with severe sepsis or septic shock we demonstrated: frequent biventricular systolic dysfunction, occasionally severe, occurring within 24 hours of diagnosis; that STE is a more sensitive method of assessing systolic dysfunction than conventional echocardiography; and that severe RV dysfunction assessed by STE  is associated with a worse prognosis.The use of STE in the noncritically ill population is increasing because most modern high-end echocardiography machines have the software capability. These advanced machines are becoming increasingly available in the ICU and it is suggested that STE may unmask systolic dysfunction not seen by standard echocardiographic assessment . Indeed,STE is dependent on adequate image quality, and studies in the noncritically ill report a 7 to 9% suboptimal image quality for STE analysis ,20. ImagMyocardial dysfunction in sepsis is caused by a variety of factors, including direct effect by the infectious process , decreased myocardial perfusion, interventricular dependence and raised pulmonary pressures from acute lung injury, hypoxia, hypercarbia and atelectasis. Evaluation of myocardial contractile function by echocardiography is challenging, particularly for the RV due to its complex geometry, which makes volumetric assessment difficult. Several studies have found RV systolic dysfunction early in the course of sepsis to be associated with increased mortality -28. HoweThe association between 6-month mortality and severe RV free wall strain dysfunction highlights the importance of RV function analysis in the prognosis of the critically ill patient, and this supports studies in other populations such as patients with acute respiratory distress syndrome . All of This study is observational in nature and has a limited number of patients, and the imaging was not optimized for STE . One cannot exclude that weaker associations may be statistically significant in a cohort with a larger sample size. Repeated imaging and further STE analysis were not performed. Further dysfunction that would be seen by standard echo parameters may have occurred at a later stage. Larger, prospective studies with imaging focused for STE optimization and follow-up echocardiography STE analysis could be considered in future.There are several drawbacks to current STE analysis that limit its clinical utility in the ICU at this time: STE requires adequate image quality, which can be challenging particularly in the mechanically ventilated patient , STE is time consuming to perform, and normal values have been difficult to elucidate partly due to vendor differences in the software algorithms . Our cutSTE unmasks systolic dysfunction unrecognized with conventional echocardiography in patients with severe sepsis or septic shock. RV dysfunction assessed by strain appears to be correlated with worse late outcomes, especially if the dysfunction is severe. LV dysfunction assessed either by conventional imaging or STE does not appear to correlate with survival in sepsis.● STE unmasks systolic dysfunction unrecognized with conventional echocardiography in patients with severe sepsis or septic shock.● Severe right ventricular strain dysfunction is associated with worse prognosis.● LV dysfunction assessed by standard echocardiography or STE is not associated with early or late outcome.FAC: fractional area change; GLS: global longitudinal strain; LV: left ventricle; RV: right ventricle; SOFA: Sequential Organ Failure Assessment; STE: speckle tracking echocardiography.The authors declare that they have no competing interests.SRO, JNP, MM, SG, JNS, GCK and JKO contributed to data acquisition and take responsibility for the integrity and accuracy of the data and analysis. SRO, JNP, GCK and JKO had access to the data, and contributed to study conception and design, statistical analysis and preparation of the manuscript. MM and SG contributed to study conception and design, and preparation of the manuscript. JNS contributed to data analysis and interpretation, and drafting of the manuscript. All authors read and approved the final manuscript.


Stress echocardiography (SE) is dependent on subjective interpretations. As a prelude to the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) Trial, potential sites were required to submit two SE, one with moderate or severe left ventricular (LV) myocardial ischemia and one with mild ischemia. We evaluated the concordance of site and core lab interpretations.Eighty-one SE were submitted from 41 international sites. Ischemia was classified by the number of new or worsening segmental LV wall motion abnormalities (WMA): none, mild (1 or 2) or moderate or severe (3 or more) by the sites and the core lab.Core lab classified 6 SE as no ischemia, 35 mild and 40 moderate or greater. There was agreement between the site and core in 66 of 81 total cases . Agreement was similar for SE type - 24 of 30 exercise  vs. 41 of 49 pharmacologic . The agreement between poor or fair image quality  was not as good as for the good or excellent image quality cases . Differences in concordance were noted for degree of ischemia with the majority of discordant interpretations (87 %) occurring in patients with no or mild LV myocardial ischemia.While site SE interpretations are largely concordant with core lab interpretations, this appears dependent on image quality and the extent of WMA. Thus core lab interpretations remain important in clinical trials where consistency of interpretation across a range of cases is critical.NCT01471522 ClinicalTrials.gov  Stress echocardiography (SE) is widely used for diagnosis, risk stratification, and prognosis of patients with known or suspected coronary artery disease and has reasonable sensitivity and specificity for clinical decision making , 2. SincInternational Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) Trial were studied. The ISCHEMIA Trial is a randomized study comparing an initial invasive strategy of cardiac catheterization, revascularization, and optimal medical therapy with a conservative strategy of optimal medical therapy alone among stable patients with at least moderate myocardial ischemia [SE exams submitted in the pre-enrollment site certification phase of the ischemia , 6. As aTwo experienced core lab echocardiographers who were blinded to the site interpretations interpreted the SE together for segmental WMAs. Standard interpretations were performed assessing each segment at baseline and peak stress using a modified 17 segment model with segment 17, the apical cap, excluded . Thus, mCore lab determination of image quality was based on adequacy of LV border definition and classified as excellent, good, fair, and poor. Excellent image quality had complete LV endocardial border definition. Good image quality had visualization of 88 - 99 % of the endocardial borders (14 or more segments). Fair image quality had visualization of 70 - 88 % of the LV endocardial borders (11–13 segments). Poor image quality had visualization of less than 70 % LV endocardial border.p-value of less than 0.05 was considered statistically significant.Concordance between site interpretation and core lab interpretations was examined in total and as a function of mode of stress, degree of myocardial ischemia, image quality, and the site’s geographic location. All categorical variables are presented as proportions. All analyses were performed using MedCalc software ver. 12.7.1.0 . Comparisons of concordance was assessed by Chi-square testing and weighted kappa coefficients (K). The value of K was graded as following: 0 to less than 0.4 was poor agreement; equal to or greater than 0.4 to less than 0.6 was moderate agreement; equal to or greater than 0.6 to less than 0.8 was good agreement; and equal to or greater than 0.8 to 1.0 was excellent agreement . A p-valAs seen in Table Table Table Table Echocardiographic contrast agents were used in only a small number of the cases. Even though there was concordant interpretations in 13 of the 14 contrast cases, when these 14 cases were excluded from the analysis there was no significant differences in the results most likely due to the small sample size.While SE is an important method to diagnose coronary artery disease, it is based on the subjective assessment of changes in LV WMA. Thus there is the potential for variability in interpretation amongst readers. In a prelude to the multicenter ISCHEMIA Trial, we examined the degree of agreement between enrolling site and core lab SE interpretations of cases that were representative of varying degrees of myocardial ischemia. We found that while agreement in aggregate is good, there are variables which are associated with lower degrees of inter-reader agreement. These include the degree of myocardial ischemia and the image quality. Such discordances highlight the importance of the use of a core lab in multicenter trials.Specifically, there was agreement between local site and core lab in the interpretation of the degree of myocardial ischemia in 81 % of the cases. In the cases where there was disagreement, the majority (87 %) of these were determined by the core lab to have no or mild myocardial ischemia  but were interpreted as more extensive ischemia by the local site. Thus while one might have hypothesized that a major source of discrepant interpretations would be when small regions of stress induced WMAs are missed, in fact the major source of discrepancy was a tendency for local interpretations to over-estimate the extent of stress induced WMA. One can speculate that this may reflect a cognitive bias as the site interpreter might have been influenced by the clinical information about the patient, exercise performance, symptoms during the test or the stress ECG to interpret the stress echocardiographic wall motion to reflect more extensive ischemia than was present. The core lab interpretation was immune to such bias as the core lab did not have access to clinical or stress test data. An alternative explanation for our findings of more disagreement when myocardial ischemia is absent or mild during SE is that larger extent of, or more severe degrees of, WMA are easier to appreciate and thus the agreement would be better in these cases. Previous studies of inter-institutional observer agreement of SE have also found better agreement when the coronary artery disease is more extensive , 10, 11.It is not surprising that 60 % of the disagreements occurred in cases where images were graded as fair or poor due to reduced visualization of left ventricular endocardium. Hoffman and colleagues previously identified image quality as an important factor influencing inter-observer variability in the interpretation of dobutamine stress echocardiograms . InteresPrior studies that have examined this issue typically have utilized single centers  or involWhile variability in discrimination of different degrees of ischemia may not be as important for the diagnosis of coronary artery disease , it does have implications for assessment of prognosis or for trial enrollment. For example, the ischemia entry criterion for the ISCHEMIA Trial is the presence of moderate or greater myocardial ischemia on stress testing. Our observations suggest that without core lab oversight, patients with less than moderate ischemia might be enrolled, and this could importantly affect the results. While the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) Trial did not show a benefit of revascularization to reduce major adverse cardiovascular events compared to optimal medical therapy in patients with stable coronary artery disease, a substudy demonstrated that the greatest reduction in ischemia as measured by myocardial perfusion imaging occurred in those with moderate to severe ischemia who underwent percutaneous revascularization , 14. AnaThe value of core lab interpretations has also been demonstrated in the interpretation of electrocardiograms in patients with acute coronary syndromes , 17. TheOur study differs from prior studies examining inter-observer variability in SE interpretation at expert centers in that technologic advances have occurred and were incorporated into our cases. While prior studies included a high proportion of videotape assessments, all of our assessments were on digital images with harmonic imaging that were formatted for side by side rest and stress comparisons . More reWhile there may be different equipment, stress protocols, scanning techniques, image acquisition protocols and levels of expertise at different sites around the world, our data did not demonstrate a difference in concordance as a function of this geographic location.Interpretation of stress echocardiograms is challenging and prior studies have shown the value of educational initiatives . An addeThere are several limitations in this study. First, due to the restrictions of the pilot phase of this trial, we did not have access to patient demographic data and thus we cannot assess if such characteristics would influence concordance. On the other hand, this enabled the core lab to remain free of bias. Also we did not have access to information about the site readers. Their years of echocardiography experience might explain differences in concordance. In fact, prior studies suggest that specific training and experience in SE is critical for accurate interpretations , 21. In We sought to assess the value of core lab interpretation in a real world experience involving multiple enrolling sites from multiple locations around the world with multiple levels of experience. While site SE interpretations are comparable to core lab interpretations in many cases, discrepancies occur in up to 20 %. The majority of the discrepancies result from local site over-estimation of the extent of ischemia. The major factors associated with discordance of interpretation are the extent of inducible ischemia and image quality. Thus, interpretations by experienced and expert core laboratories remain important in clinical trials where consistency of interpretation across a range of cases is critical.