The aim of our study was to establish the technical feasibility of fast continuous T2*/T2 mapping throughout renal I/R. MRI was combined with a remotely controlled I/R model and a segmentation model based semi-automated quantitative analysis. This technique enabled the detailed assessment of in vivo changes in all kidney regions during ischemia and early reperfusion. Significant changes in T2* and T2 were observed shortly after induction of renal ischemia and during the initial reperfusion phase. Our study demonstrated for the first time that continuous and high temporal resolution parametric MRI is feasible for in-vivo monitoring and characterization of I/R induced AKI in rats. This technique may help in the identification of the timeline of key events responsible for development of renal damage in hypoperfusion-induced AKI.Ischemia/reperfusion (I/R) injury, a consequence of kidney hypoperfusion or temporary interruption of blood flow is a common cause of acute kidney injury (AKI). There is an unmet need to better understand the mechanisms operative during the initial phase of ischemic AKI. Non-invasive  Magnetic resonance imaging (MRI) meets the needs of non-invasive renal in-vivo imaging. Parametric MRI can provide maps of the MR relaxation parameters T2* and T2, which are known to be blood oxygenation level-dependent (BOLD) 2*-weighted MR images occurs if the volume fraction of deoxygenated hemoglobin increases. T2* or its reciprocal value (R2* = 1/T2*) have been used in numerous clinical and preclinical studies as a surrogate of renal (blood) oxygenation 2* has even been suggested to display a close correlation with renal tissue pO2 levels 2*-mapping has been deemed ideally suited for the evaluation of intra-renal oxygenation 2*/T2 mapping remained as yet untapped 2*/T2 measurements in renal ischemia models in-vivo monitoring during ischemia – and in particular during early reperfusion of the kidney. We sought to establish the feasibility high temporal resolution longitudinal T2*/T2 mapping throughout I/R. To meet this goal an I/R model that affords remote induction of ischemia/reperfusion inside an MR scanner is implemented together with a standardized segmentation model of the rat kidney. This integrated approach enabled for the first time the monitoring of renal T2* and T2 in the initial reperfusion phase.Non-invasive Landesamt für Gesundheit und Soziales Berlin . All experiments were carried out under urethane anesthesia , and all efforts were made to minimize suffering. Animals were kept under constant thermal conditions: 37°C body temperature was maintained by warming the animal beds using a circulating heated water system . Rectal temperature and respiratory motion/rate were monitored  throughout the imaging experiments.Animal experiments were carried out in accordance with the guidelines provided and approved by the Animal Welfare Department of the All imaging experiments were carried out on a 9.4T small animal MR system  equipped with a linear polarized birdcage RF resonator for transmission in conjunction with a curved four channel receive RF coil array  customized for rats.2* and T2 were tailored for fast measurements in the rat kidney at a magnetic field strength of 9.4 Tesla. T2-weighted pilot scans and local B0 shimming that uses a voxel enclosing the kidney only were performed first. Subsequently, parametric T2* and T2 mapping using respiratory gated imaging techniques was performed. For T2* mapping a multi gradient echo (MGE) sequence  was employed with a total acquisition time of approx. 1 min 20 s (respiratory rate dependent). For T2 mapping a multi spin echo (MSME) sequence  was used with a total acquisition time of approx. 1 min 40 s. A coronal oblique image slice was acquired with a spatial in plane resolution of (226×445) µm2 (field of view = (38.2×50.3) mm2, matrix size = 169×113 zero-filled to 169×215) and a slice thickness of 1.4–1.5 mm.MRI protocols for parametric mapping of T2) with 15 slices of 1.0 mm thickness placed perpendicular to the major renal blood vessels, acquired in 24 seconds.Renal blood flow during I/R experiments was monitored by time-of-flight (TOF) MR angiographies of the kidney. TOF angiography consisted of an untriggered spoiled gradient echo sequence  µm2* and T2 values were calculated by pixel-wise mono-exponential fitting to the signal intensities of the T2*- and T2-weighted images acquired at different echo times . The relaxation times T2* and T2 were chosen over the relaxivities (i.e. R2* = 1/T2* and R2 = 1/T2), as they allow for a better visualization of changes in the parameter maps for the different kidney regions and stimuli. In quantitative data representations such as value tables or bar charts the relaxation times are complemented by the corresponding relativities, which were also derived on a pixel-by-pixel basis.Parametric maps of absolute Twww.fmrib.ox.ac.uk/fsl) using the first echo images of the multi-echo MGE or MSME acquisitions. Images were registered onto a baseline scan and the resulting spatial transformation matrices applied to the corresponding parameter maps.Movements of the kidney during I/R experiments were compensated by image registration  and T2 (R2) values for several regions-of-interest (ROI) within the renal cortex, outer medulla and inner medulla were calculated from the parameter maps. To reduce operator-induced variability in the ROI placement a standardized segmentation model of the rat kidney was developed. For this purpose special care was taken with regard to the location of the ROIs in the kidney. The aim was to determine ROIs strictly according to morphological kidney features, i.e., the distinct renal layers: cortex, outer medulla, and inner medulla (http://imagej.nih.gov/ij) limited user interaction to the placement of the rectangular reference frame around the kidney. The automatically placed ROIs were overlaid onto the parameter maps and their position was visually validated. ROIs that included artifacts were excluded from further analysis.Mean T medulla Figure 12* time courses were linearly interpolated and T2* calculated for time points at exact intervals of 180 seconds. Group mean values and standard errors of the mean (SEM) were then calculated for each time point and T2*  plotted versus time. In all other cases  the original, non-interpolated, data were used.Due to the need for respiratory triggering the time intervals between MRI scans (∼180 seconds) varied slightly during the imaging experiments and between animals. To allow for a comparison between different animals the acquired T2* and T2 mapping at 9.4 Tesla in rats under variable physiological conditions has not been reported so far. Hence, the sensitivity of T2* and T2 to renal blood oxygenation changes was demonstrated by examining the changes induced in these parameters by externally controlled variations of blood oxygenation. Blood oxygenation level changes (hypoxia or hyperoxia) were induced in six male rats  by adapting the inhaled gas composition.Renal T2*/T2, hypoxia was induced by adjusting the gas mixture to 10/90% O2/N2. T2*/T2 measurements were conducted throughout 8 minutes after induction of hypoxia. The final T2*/T2 scans during hypoxia were started exactly 5 minutes after hypoxia onset, to ensure equal hypoxia durations and comparable timing of the MR scans. On completion of these MR scans, inhaled gas mixture was changed back to air and T2*/T2 continuously monitored for another ∼9 minutes. The same protocol was followed for the hyperoxia experiments by setting the inhaled gas to 100% O2. 2*-weighted MR images together with calculated T2* parameter maps acquired prior, during and after hypoxia/hyperoxia.A respiratory mask was used, which provided air (normoxia) at a flow rate of 1000 ml/min. Following baseline measurements of TSix male rats  underwent experimental ischemia-reperfusion inside the MR scanner.The abdominal cavity was opened by a midventral incision and the right kidney was removed. A remote controlled hydraulic occluder was placed around the renal artery and vein of the remaining left kidney to allow induction of renal ischemia. The hydraulic occluder Figure 32* and T2 were continuously monitored by interleaved T2*/T2 mapping with a temporal resolution of ∼3 minutes. After a baseline of five T2*/T2 measurements the hydraulic occluder around the aorta was temporarily closed and a vehicle  administered. Thereafter, ischemia was induced by closing the hydraulic occluder around the renal artery and vein for 45 minutes, followed by a reperfusion phase of ∼100 minutes. Renal blood flow during the three phases of the I/R experiment was monitored by time-of-flight (TOF) MR angiographies of the kidney, acquired prior and immediately after ischemia induction, as well as after onset of reperfusion. The absence of the flow-dependent intra-vascular signal during ischemia served to confirm complete occlusion of the renal artery and vein. 2*-weighted and T2-weighted MR images for six time points, together with T2* and T2 parameter maps.Directly following surgery the animal was transferred to the warmed MRI animal bed. For the remainder of the experiment T2* and T2 derived from the nine kidney ROIs were statistically analyzed using SPSS . Data are expressed as mean±SEM. Normal distribution was confirmed by a one-sample Kolmogorov-Smirnov test. Tests of significance (2-tailed t-test) were performed for the last time points in each experimental phase  following Levene’s test for equality of variances. A probability value of ≤0.05 was considered significant.T2*, T2 were explored during variations of inspiratory gas composition  and during renal ischemia/reperfusion.Changes in renal T2* and T2 to renal blood oxygenation changes. Parametric mapping revealed a decrease in T2* and T2 for hypoxia and an increase for hyperoxia in all kidney layers  according to the proposed standardized renal segmentation model. Under hypoxic conditions T2* decreased by 35–49% (COR), 53–62% (OM), and 53–64% (IM), while T2 decreased by 25–29% (COR), 29–33% (OM), and 29–31% (IM). The observed increase during hyperoxia was 18–23% (COR), 31–42% (OM), 38–45% (IM) for T2* and 3–8% (COR), 11–20% (OM), 11–16% (IM) for T2.The variations in inspiratory gas composition demonstrated a high sensitivity of Ty layers Fig. 2. 2* and T2 were monitored before and during ischemia/reperfusion with a temporal resolution of ∼3 minutes. 2*-weighted and T2-weighted MR images for six time points, together with T2* and T2 parameter maps. The six time points represent last baseline, onset of ischemia and end of ischemia after 45 minutes, onset of reperfusion, and 12 minutes and 100 minutes after onset of reperfusion. T2* and T2 parameter maps of an entire ischemia reperfusion experiment are presented in Figures S1 and S2. These parametric maps demonstrated immediate changes in T2*/T2 after onset and end of ischemia.T2* and T2 changes used the standardized renal segmentation model. Plots of T2*  versus time for these ROIs are shown in 2* time courses revealed an immediate drop in T2* after onset of ischemia followed by a slow and steady decrease in T2*. During ischemia T2* was significantly reduced in all ROIs , which clearly distinguished this condition from baseline. The time courses of T2 were very similar to those of T2*. During reperfusion, T2* and T2 did return to baseline in the cortex, but not in the medulla. While no major differences among the cortical, outer medullary, and inner medullary T2* changes were found during ischemia, there was a clear regional dynamics during reperfusion. After onset of reperfusion T2* returned close to baseline for cortical segments (p = 0.97 (C1), p = 0.22 (C2), p = 0.65 (C3)). For the outer medulla T2* remained below baseline throughout reperfusion and was at 40–47% below baseline after 100 minutes (p≤0.05 (C1), p≤0.001 (C2), p≤0.01 (C3)). T2 was 19–21% below baseline at 100 minutes reperfusion. In the inner medulla T2* and T2 exceeded baseline by 17–28% and 14–18% respectively (non-significant) at the end of reperfusion. These differences among the layers were pronounced during early reperfusion and remained stable throughout reperfusion. The assessment of the heterogeneity among segments within one kidney layer revealed an almost equal time course in T2* for the cortical, outer medullary and inner medullary segments, respectively.Quantitative examination of T2* and T2 during hypoxia, hyperoxia, ischemia and reperfusion are illustrated in 2* and T2 difference maps. Hypoxia/hyperoxia led to a rather uniform T2*/T2 reduction/rise across the kidney. The T2*/T2 reduction in ischemic kidneys exceeded that during hypoxia. Changes in the course of reperfusion clearly differentiated cortex and medulla. In accordance with the ROI data medullary T2*/T2 remained reduced throughout reperfusion, cortical T2* returned to baseline and cortical T2 even rose markedly above baseline.Changes in renal T2* and T2 with standard errors (SEM) are surveyed for all regions-of-interest in 2* and R2. Relative changes in these parameters are summarized in 2* (ΔR2*) and ΔT2 (ΔR2) derived from the outer/inner medulla exceeded those observed in the cortex (except for ΔT2 (ΔR2) during reperfusion). For all regions the T2* (R2*) changes during ischemia were more pronounced than during hypoxia. T2 (R2) effects during ischemia were comparable to hypoxia.For a quantitative synopsis of the ischemia-reperfusion results together with the hypoxia/hyperoxia results the MR parameter values at baseline, end-hypoxia/hyperoxia, end-ischemia and end-reperfusion were chosen. The group mean Tin-vivo monitoring and characterization of ischemia/reperfusion (I/R) induced AKI in rats. Fast T2*/T2 mapping was combined with a remotely controlled I/R model and a segmentation model based semi-automated quantitative analysis. This approach allowed tracking of T2*/T2 in the kidney during I/R with a high spatial and temporal resolution. Our study provides a technical advance in the field, as only snapshot images acquired before and after induction of injury were previously analyzed in I/R models Our study demonstrates that continuous and high temporal resolution parametric MRI is feasible for The proposed segmentation model of the rat kidney served to reduce operator-induced variability compared to manually drawn regions-of-interest used in similar studies 2* and T2 changes were observed for all kidney regions shortly after induction of renal ischemia and during the initial reperfusion phase, which remained stable throughout the monitored reperfusion period. These findings could help to support the hypothesis that key events for the initiation of injury occur immediately after reperfusion, if a link to observations at later time points (e.g. 6–48 hours) can be established in future studies. In this study the surgical/experimental procedures were adapted for performing in vivo I/R experiments inside of an MR scanner; they do not allow for a recovery of the animal and additional MRI at later time points.T2* (R2*) measurements during hypoxia, the immediate decline of T2* at the onset of ischemia, and the accordance with reports on invasively measured tissue pO2 during ischemia 2* (R2*) changes primarily to variations in intrarenal blood oxygenation. Still, T2* and T2 may only be surrogates for physiological parameters of interest, such as renal blood oxygenation. The influence of numerous other physical and physiological parameters on T2*/T2 variations in vivo, and in particular on the absolute values of these parameters, must be taken into account when comparing parametric MRI data with other quantitative measures of blood (or even tissue) oxygenation. For this reason it is conceptually appealing for future studies to combining invasive techniques and non-invasive MRI in a hybrid setup with the goal to calibrate, monitor and interpret parametric MR and physiological parameters by means of standardized interventions. Absolute values of baseline renal R2* were found to be lower in the inner medulla versus outer medulla and cortex, which is in agreement with previous reports 2 levels measured by invasive methods 2 levels in the inner medulla. One reason behind what seems to be a discrepancy is that the blood oxygenation dependence of R2* (T2*) does not relate to the deoxyhemoglobin/oxyhemoglobin ratio, but to the absolute amount of deoxyhemoglobin per tissue volume. Thus, besides being dependent on blood oxygenation, R2* (T2*) is influenced by the blood vessel volume fraction and the hematocrit. Both, vessel volume fraction and hematocrit are low in the inner medulla Considering the oxygenation-sensitivity of T2* In our study complete occlusion of the renal artery and vein were confirmed by MR angiography, rendering potentially confounding changes in global renal blood volume unlikely. Two possibly involved physiological factors are alterations in pH and fluid shifts. A significant drop in pH during renal artery occlusion in rats has been reported earlier 2* indicating lower renal oxygenation. The observed increases in R2* during ischemia (180–500% of baseline) are comparable with previous reports During hypoxia and ischemia MRI revealed significantly higher R2* during I/R show similarities to invasively measured medullary pO2 time courses previously reported 2* effects of hyperoxia on renal oxygenation were much smaller compared to hypoxia, which might be due to the already high arterial oxygen saturation of hemoglobin during normoxia. The amount of oxygen not bound to hemoglobin but dissolved in blood, which is expected to increase during hyperoxia, contributes only a rather small fraction to the overall oxygen supply.Our findings regarding R2* and T2 may provide complementary information about the (patho)physiological conditions in the kidney as both MR parameters are affected by changes in blood oxygenation and water content to different degrees. Variations in the volume fraction of deoxygenated hemoglobin impact on the MR signal stemming from intra-vascular spaces of large vessels or capillaries as well as regions around these vessels. These intra- and extra-vascular signal components contribute differently to T2* and T22 is sensitive to water content 2* and T2, changes observed in this study will inspire further explorations into MR methodology suitable for simultaneous T2*/T2 mapping.Interleaved mapping of T2* and T2 throughout an I/R experiment in rats is feasible and provides a temporal resolution of approximately 80–100 seconds for each read-out resulting in 3 minutes for alternating T2*/T2 measurements. The proposed MRI approach enables the detailed assessment of in vivo changes in all kidney regions during ischemia and early reperfusion. Observations in the early reperfusion phase promise to offer new insights into the pathogenesis of ischemia induced AKI and might help to identify the timeline of key events responsible for development of hypoperfusion-induced renal damage. The established method of parametric MR monitoring holds the promise to be a useful investigational tool for other models of AKI such as x-ray contrast agent induced AKI, rhabdomyolysis-induced AKI, or sepsis-induced AKI.In conclusion, continuous parametric MR monitoring of TFigure S12* parameter maps of an entire ischemia reperfusion experiment.55 T First row: After a baseline of 6 time points ischemia started at time point 7. Second row: onset of reperfusion after 45 minutes ischemia at time point 19. Rows 3–5: remaining time points of 100 minutes reperfusion. The parameter maps demonstrate immediate changes in T2* after onset of ischemia and onset of reperfusion.(TIF)Click here for additional data file.Figure S22 parameter maps to Corresponding T First row: After a baseline of 6 time points ischemia started at time point 7. Second row: onset of reperfusion after 45 minutes ischemia at time point 19. Rows 3–5: remaining time points of 100 minutes reperfusion. Also in T2 immediate changes are visible directly after onset of ischemia and onset of reperfusion.(TIF)Click here for additional data file.Table S1Summary of the hypoxia/hyperoxia and ischemia/reperfusion results. Mean (±SEM) of T2* (R2*) and T2 (R2) of all regions-of-interest in the cortex , in the outer medulla  and inner medulla . Shown are the values for the last time point in each experiment phase (e.g. end-baseline).(TIF)Click here for additional data file.


Cardiac and systemic hemodynamics have been historically in the domain of invasive cardiology, but recent advances in real-time 3-Dimensional echocardiography (RT3D echo) provide a reliable measurement of ventricular volumes, allowing to measure a set of hemodynamic parameters previously difficult or impossible to obtain with standard 2D echo.To assess the feasibility of a comprehensive hemodynamic study with RT-3D echo.We enrolled 136 patients referred for routine echocardiography: 44 normal (N), 57 hypertensive (HYP), and 35 systolic heart failure patients (HF). All patients underwent standard 2D echo examination followed by RT3D echo examination, including measurement of left ventricular (LV) end-diastolic and end-systolic volumes and derived assessment of LV elastance (an index of LV contractility), arterial elastance ; ventricular-arterial coupling ; systemic vascular resistances. Blood pressure was derived from cuff sphygmomanometer and heart rate from ECG.-1 m-2, p <0.001 vs N = 3.8 ± 1.3 and HYP = 3.8 ± 1.3) and ventricular-arterial coupling . Systemic vascular resistances were highest in HYP . The LV elastance was related to EF  and arterial pressure was moderately related to vascular elastance . The ventricular-arterial coupling was unrelated to systemic vascular resistances .A complete 2D echo was performed in all 136 patients. 3D echo examination was obtained in 130 patients (feasibility = 95 %). Standard 2D echo examination was completed in 14.8 ± 2.2 min. Acquisition of 3D images required an average time of 5 ± 0.9 min (range 3.5-7.5 min) and image analysis was completed in 10.1 ± 2.8 min (range 6–12 min) per patient. Compared to N and HYP, HF patients showed reduced LV elastance (1.7 ± 1.5 mmHg mLRT-3D echo allows a non invasive, comprehensive assessment of cardiac and systemic hemodynamics, offering insight access to key variables – such as increased systemic vascular resistances in hypertensives and reduced ventricular-arterial coupling in heart failure patients. LV function, ventricular volumes, and ejection fraction are routinely assessed by standard 2D echo for early detection of cardiac disease, to monitor disease progression and to assess response to treatment. Standard echocardiographic evaluation of hemodynamic parameters shows an acceptable correlation with invasive measurements in population studies. However, in the individual patient, the dispersion of values may be so wide to limit clinical applications, mostly due to intra- and inter-observer variability of volumes measurements . RT-3D iThe underlying idea of the present study was to take advantage of the superiority of 3D over 2D echocardiography in assessing LV volumes to derive more accurate non invasive estimates of cardiac-vascular function ,7.The purpose of this study was to evaluate the feasibility and time cost of RT-3D echo, as compared to standard 2D echo, in the setting of a primary care echocardiography laboratory.We also evaluated RT3D derived cardiac and vascular hemodynamics in hypertensive and heart failure patients. In fact, RT3D-derived parameters such as left ventricular elastance or systemic vascular resistances reflect the complex interactions between the heart and its internal and external loads and are of emerging importance in the assessment and management of hypertension and heart failure .The study has been conducted in 3 different primary care cardiology outpatients clinic . All exams were performed by the same cardiologist-echocardiographer who performed both 2D and 3D echo examinations. To minimize variability the same observed, acquired and analyzed all studies. The observer had undergone a dedicated 9 month training on 3-D and the variability observed in a consecutive set of 10 studies was consistently < 10 % for LV volumes. We initially considered 400 patients, referred for clinically driven Echo evaluation between May 2009 and June 2011. Sixty patients denied the consent to enter the 3D part of the study, 50 had technically difficult 2D-Echo examination; 154 had exclusion criteria conditions . One hundred and thirty six patients were eventually included in the study. They complied with the inclusion criteria:1. Sinus Rhythm;2. Willingness to enter the study;3. Technically good 2D echo study;4. Clinical-echocardiographic diagnosis of no structural heart disease , free from major coronary risk factors, including diabetes, hypercholesterolemia, and cigarette smoking;5. Clinical-echocardiographic diagnosis of essential hypertension (HYP), previously made according to standard criteria : history6. Clinical-echocardiographic diagnosis of heart failure (HF): history of dyspnea on effort, under active treatment with ACE-inhibitors (86 %), and/or diuretics (78 %), and/or ARBs (28 %), and/or β-blockers (68 %), with EF < 40 %.Following standard 2D echo examination, patients underwent RT-3D echo with measurement of raw data of LV EDV and ESV and derived assessment of : LV elasMean arterial pressure (MAP) was calculated as diastolic blood pressure + (systolic blood pressure - diastolic blood pressure/3). Mitral regurgitation and pulmonary arterial pressure were estimated from standard 2D echo. Forty four patients with no overt cardiac disease, a SBP ≤ 139 mmHg, and a BMI ≤ 30 Kg/m2, constituted the N group. Fifty seven subjects with hypertension but no HF constituted the HTN group. Thirty five patients with a clinical diagnosis of heart failure and EF below 40 % constituted the systolic HF group.Standard 2-dimensional echocardiography was performed according to the recommendation of the European Association of Echocardiography  using a Real time 3-dimensional echocardiography images were recorded with a Philips I33 equipped with a X3-1 1‐3 MHz matrix–phased array transducer in a 60 × 70 pyramid shaped volume containing the entire left ventricle. Volumetric data were obtained only from the apical window and displayed as conventional 2D apical which were digitalized with final interpretation made off –line with manual identification of chambers contours in selected image. Four cardiac cycles were stitched together to obtain LV volumes.3D-images were obtained soon after completing the 2D study using the same echocardiographic machines with a fast switch between the 2 probes .BP and HR were taken simultaneously during volume assessment, from cuff sphygmomanometer and from EKG, respectively.LV EDV and ESV were measured from apical four- and two-chamber view, using the biplane Simpson-method . Only re2. ESP was estimated as systolic pressure times 0.9 [Ventricular arterial coupling was derived by the ratio of LV systolic elastance index (systolic pressure/end-systolic volume index) to arterial elastance (ratio of end-systolic pressure by stroke volume). Effective arterial elastance (EaE), characterizing the distal impedance of the arterial system downstream of the aortic valve, was estimated as end-systolic pressure (ESP) divided by stroke volume (SV) and expressed as SP/ESV index = mmHg/mL/mimes 0.9 . Becauseimes 0.9 . Of noteSVR were calculated according to the traditional formula:5.where 5 is an approximation of the right atrial pressure and MAP is mean arterial pressure and CO is Cardiac Output. Vascular resistance is a term used to define the resistance to flow that must be overcome to push blood through the circulatory system. The resistance offered by the peripheral circulation is known as the systemic vascular resistance. Vasoconstriction  increases systemic vascular resistance, whereas vasodilatation (increase in diameter) decreases systemic vascular resistance. Units for measuring vascular resistance are dyne*s/cmSystemic arterial compliance was calculated as SV index/systemic arterial pulse pressure; where pulse pressure = SBP - DBP ,12.Software  was used for statistical analysis. The statistical analyses included descriptive statistics . One-way ANOVA was used to compare continuous variables between groups with intergroup comparisons by Newman-Keuls test. The agreement between continuous or discrete data was tested by the Bland-Altman method and by the concordance correlation coefficient comparing the mean differences between the two methods of measurements and 95 % limits of agreement as the mean difference. A p value of 0.05 was considered as statistically significant.Patients demographic and hemodynamic parameters are presented in Table Standard 2D Echo was performed in 136  patients. Diagnostic quality images with RT-3D echo were obtained in 130 patients (feasibility 95 %) that were distributed as follows: no structural cardiac disease , hypertension without heart failure , and systolic heart failure (EF < 40 %) . The commonest reason for incomplete RT3D was ventricular dimension exceeding the area covered by the probe.LV volumes obtained with standard echo and with RT-3D echo were plotted according to the Bland-Altman method. End-systolic as well end-diastolic volumes showed a significant correlation  and image analysis was completed in 10 ± 2.8 min (range 6.6 min-12.8 min) per patient. Therefore the completion of a RT3D echo study from imaging to analysis requires a time interval comparable to a standard 2D examination.A reduced ventricular elastance was found in HF patients as compared to N and HYP Table . VentricA significant relation was found between LV elastance and EF   and Gated-SPECT imaging -16.Compared to cardiac MRI, the currently accepted gold standard technique for LV quantification, 3D echo provides a good agreement for assessing EF with slightly underestimation of volumes, which may be attributed to the different modality in visualization of trabeculae and valves between the two techniques This study was not aimed to assess accuracy and reproducibility of 3D echo measurement of LV volumes, but to investigate the additional time costs of RT-3D images and its practicability .Calculation of the end-systolic pressure/volume ratio would require the measurement of LV pressure in end-systole. Because only non-invasive measurements were available, systolic cuff pressure was used as a surrogate for end-systolic pressure. This certainly introduces an approximation, however, there is a tight relationship between peak and end-systolic pressure .The conceptual novelty of the employed approach is limited, since already Bombardini et al. extensively showed that this approach can be usefully applied to non invasive ultrasound at rest and during stress such as exercise, dobutamine, dipyridamole and pacing ,12,19. HHemodynamic variables assessed in this study may be affected by drug therapy. ß-blockers may reduce aortic wave reflection and improve left ventricular/vascular coupling, and 68 % of patients in the HF group were on ß-blockers . HoweverIn this study we have shown that RT-3D can be performed in the vast majority of patients referred for echocardiographic examination at an acceptable time cost, comparable to standard 2D echo. Only patients with bad acoustic window or with markedly enlarged left ventricle may pose a difficult challenge. Reliable and detailed assessment of cardiac and systemic hemodynamics more than compensate for the time required for data acquisition and off-line analysis. Standard 2D echo will certainly remain the first line technique for LV assessment in the near future, given its large availability, its relative easiness, and the established role. However, when volumes are important and sequential testing is required, the 3D technique appears to be an attractive and practical alternative, offering also insight into variables of pathophysiological and potential clinical relevance, such as increased systemic vascular resistances in hypertensives and reduced left ventricular elastance in heart failure patients.AE, Arterial elastance; ARBs, Angiotensin receptor blockers; BSA, Body surface area; EaE, Effective arterial elastance; EDV, End-diastolic volume; ESP, End-systolic pressure; ESV, End-systolic volume; HF, Heart failure; LV, Left ventricular; MAP, Mean arterial pressure; SVR, Systemic vascular resistance; SV, Stroke volume.The authors declare that they have no competing interests.MCS, designed the study, collected and interpreted the data, carried out the statistical analysis. MB, AG and PB helped to collect the data. TB, was involved in designing of the study and revision of the manuscript critically for important intellectual content. RS, was involved in designing of the study and critical revision of the manuscript. All authors read and approved the final manuscript.


Impaired left ventricular (LV) function has been shown by strain rate (SR) imaging in patients with coronary artery disease (CAD). Our aim was to investigate global and regional, systolic and diastolic left atrial (LA) and right atrial (RA) longitudinal deformation in CAD using velocity vector imaging.s) and SR during LV systole (SRs), SR during early LV filling (SRe) and late LV filling (SRa) were measured. Longitudinal strain during atrial contraction (εa) was obtained at the onset of P-wave on electrocardiography, and εa/εs was calculated.Echocardiographic and velocity vector imaging studies were performed in 20 patients with mild CAD, 40 patients with severe CAD and 25 controls. Maximal atrial volume, peak atrial longitudinal strain . As compared with controls and patients with other single-vessel disease, LA SRa and εa/εs ratio were significantly increased among patients with exclusively left anterior descending coronary artery (LAD) stenosis .Longitudinal peak εa, SRa and εa/εs of RA were found in CAD patients with preserved LVEF and E/E' in gray zone. SRa and εa/εs of LA were found to significantly increase in those with LAD stenosis.Apparently decreased SRe of LA and increased ε Coronary artery disease (CAD) is a major public health problem with high risk of developing heart failure. Left ventricular (LV) diastolic dysfunction is often present in patients with significant CAD, even preceding regional or global LV systolic dysfunction, which therefore might serve as an early and sensitive marker of ischemia In recent years, accumulative evidence has shown that strain (ε) and strain rate (SR) are powerful echocardiographic parameters to directly reflect global and regional systolic and diastolic myocardial deformation Patients with suspected CAD and undergone coronary angiography in Huashan Hospital between May 2009 and January 2010 were continuously enrolled. To minimize the influence of some serious or complex medical conditions, we excluded patients with acute myocardial infarction or history of coronary revascularization (including coronary artery bypass grafting and percutaneous coronary intervention), diabetes mellitus, New York Heart Association (NYHA) class III–IV heart failure, abnormal cardiac rhythm (other than sinus rhythm). Also excluded were those with suboptimal angiographical or echocardiographic images. As a result, 85 participants were included in the final analysis. The study was approved by the medical ethics review committee of the Huashan Hospital and all subjects gave written informed consent.Demographic data and cardiovascular risk factors were collected, including age, gender, weight, height, systolic blood pressure (SBP), diastolic blood pressure (DBP), and the history of hypertension, status of smoking. Body mass index (BMI) was calculated as weight in kg divided by height in meters squared Standard selective coronary angiography was performed using the Judkins technique, by a qualified catheterizing cardiologist and an angiographer who were blinded to the study. CAD was defined as ≥50% lumen narrowing of at least one major coronary vessel 3– LVDd 3) –13.6, and was corrected to body surface area Transthoracic echocardiography was performed on the subjects at rest in the left lateral decubitus position by 2 professional cardiologists with a Siemens Sequoia 512 ultrasound machine using a 3V2C transthoracic transducer , 1–2 days before the angiographic studies. Complete two-dimensional, color, pulsed and continuous-wave doppler examinations were performed according to standard techniques For the assessment of longitudinal atrial deformation, two-dimensional grey-scale image of apical 4-chamber view was obtained under VVI mode with highest possible frame rate and a stable electrocardiogram recording. Special attention was paid to avoid foreshortening the atrium and to gain a reliable delineation of the atrial endocardial border. Cine loops with 2–3 consecutive heart cycles during breath hold were acquired and saved digitally.s) and peak strain rate (SRs) were measured at LV systolic phase, while peak atrial longitudinal SRe during early LV filling and SRa during late LV diastolic phase were measured. Longitudinal strain during atrial contraction (εa) was obtained at the onset of the P-wave on electrocardiography, and the εa/εs ratio was calculated . Additionally, atrial time-volume curve and dV/dt curve were rendered automatically by VVI software. Maximal atrial volume and peak atrial dV/dt at ventricular systole were determined.Strain analysis of LA and RA was performed offline with Siemens syngo US workplace . After manually defining the endocardial border of both atriums, the myocardial speckle was automatically tracked frame-by-frame by the VVI software throughout the cardiac cycle to calculate and generate strain/strain rate curves. Besides LA and RA global longitudinal function, regional atrial longitudinal strain/strain rates of the interatrial septum and lateral wall were also evaluated respectively. As shown in Interobserver and intraobserver variability for atrial strain/strain rate were examined in an analysis of 20 randomly selected patients. Measurements were performed by one observer, and then repeated two separate times by two observers who were unaware of the other's measurements. More than 4 weeks elapsed between the two readings by the same observer with blinding to the initial measurements.Statistical analysis was performed using SPSS 15.0 statistical software . Continuous data were expressed as means ± SD, and categories data as percentages. Continuous variables were compared using Student's t-test, or ANOVA when appropriate. Furthermore, Pearson's and Spearman's  coefficients of correlation were used where appropriate. All of the reported P values were two-sided with statistical significance evaluated at 0.05.P value, 0.66). There was no difference in history of medical therapy between the 3 groups.The clinical data of the 85 participants are presented in Of the 60 CAD patients, 17 had exclusively left anterior descending coronary artery (LAD) stenosis, and 10 had exclusively left circumflex coronary artery (LCX) or right coronary artery (RCA) stenosis. 33 had multiple-vessel disease. Of all the patients, 33 were successfully treated by percutaneous coronary intervention with stent implant, while 7 patients needed subsequent coronary arterial bypass grafting surgery.P Value, 0.22). Compared with control group, the 2 CAD groups had lower E/A ratio and higher E/E' ratio, but the differences didn't reach statistical significance. None were found to have E/E' ratio >15. Five (8.3%) patients with CAD were found with mild mitral regurgitation, whereas none had moderate to severe regurgitation.Conventional transthoracic echocardiographic parameters of the study population are presented in 2, 33.68±9.34 mL/m2, 31.41±11.21 mL/m2 . No differences in the LA and RA Peak dv/dt were observed. Longitudinal εs and SRs of LA tended to be decreased among CAD patients, even though the differences didn't reach statistical significance. Compared with those in the control group, the 2 CAD groups had lower global and lateral SRe , without significant further decrease with increasing severity of coronary stenosis. LA lateral SRa was increased in severe CAD group. By contrast, SRe of RA didn't differ across 3 groups, whereas RA global and lateral εa, SRa and εa/εs ratio was apparently increased in mild and severe CAD groups.Data from VVI by the severity of coronary stenosis are summarised in a/εs ratio of LA were significantly increased only in LAD stenosis group . No similar patterns were found in global RA deformation properties (data not shown).The results of LA deformation analysis by the distribution pattern of involved coronary artery (left anterior descending coronary artery (LAD), left circumflex coronary artery (LCX), and right coronary artery (RCA)) are shown in −1 and 0.07±0.05 s−1, respectively.Interobserver variability for strain was 5±7%, and intraobserver variability was 1.6±0.6%. In addition, inter- and intraobserver variability for strain rate was 0.09±0.06 sa, SRa and εa/εs ratio of RA. Patients with exclusively LAD stenosis were found with significantly enhanced SRa and εa/εs ratio of LA, while patients with exclusively LCX/RCA stenosis were not.The atrium has an important role in optimizing overall cardiac function, acting as a reservoir, a conduit, and a booster pump for blood returning to the heart a/εs ratio may represent a new index of atrial contractile function that deserves further assessment. And future study is warranted to evaluate whether these novel echocardiographic parameters can predict enlargement of LA or development of LV diastolic dysfunction or arrhythmias.LA function measured as volumetric parameters by real-time three-dimenstional echocardiography is considered a robust marker of LV filling pressure and an indicator of LV diastolic function a/εs ratio of LA was significantly enhanced in patients with LAD stenosis. One explanation could be that hyperactive LA booster pump action compensated for the diminution of LV stroke work a/εs ratio of LA could be due to altered left ventricular compliance with shifting of left ventricular filling to late systole. It is somewhat unexpected that we did not observe a significant difference in the LA/RA deformation parameters between severe coronary stenosis and mild stenosis groups. The exact explanation was unclear. Further studies are necessary to investigate these issues and clarify the detailed mechanisms.Previous studies have proven that E/E' ratio in gray zone (8 to 15) are limited in the estimation of LV filling pressures The quality of speckle tracking depends highly on the spatial resolution of the image and on the frame rate of the cine-loop. Without dedicated software, measuring strain and strain rate in the atrium is challenging, and can be influenced by nonatrial physiological factors including LV compliance and mitral annular descent. However, recent work a/εs ratio of RA. SRa and εa/εs of LA was found to increase in those with LAD stenosis. Further profound studies are warranted to confirm the present findings and define the cut-off values as well as technical standards.CAD patients with normal LA size, preserved EF and E/E' in gray zone showed decreased SRe of LA and increased εa, SRa and ε


Cardiac remodelling after AMI is characterized by molecular and cellular mechanisms involving both the ischemic and non-ischemic myocardium. The extent of right ventricular (RV) dilatation and dysfunction and its relation to pulmonary hypertension (PH) following AMI are unknown. The aim of the current study was to evaluate changes in dimensions and function of the RV following acute myocardial infarction (AMI) involving the left ventricle (LV).We assessed changes in RV dimensions and function 1 week following experimental AMI involving the LV free wall in 10 mice and assessed for LV and RV dimensions and function and for the presence and degree of PH.RV fractional area change and tricuspidal annular plane systolic excursion significantly declined by 33% (P = 0.021) and 28% (P = 0.001) respectively. Right ventricular systolic pressure measured invasively in the mouse was within the normal values and unchanged following AMI.AMI involving the LV and sparing the RV induces a significant acute decline in RV systolic function in the absence of pulmonary hypertension in the mouse indicating that RV dysfunction developed independent of changes in RV afterload. Acute myocardial infarction (AMI) is associated with compensatory mechanisms involving both the left and right ventricles. In experimental models of AMI, right ventricular (RV) hypertrophy occurs even if the RV is initially spared a) Doppler analysis of the pulmonary artery (for the RV) and of the aorta (for the LV) measuring the time between the start of the QRS on the electrocardiogram and the start of the forward flow, and (b) using the M-mode echocardiography of the mitral annulus plane and tricuspidal annulus plane systolic excursion and measuring the time between the start of the QRS on the electrocardiogram and the start of the inward motion of the lateral portion of the annulus. The differences between the LV and RV delays were used as measures of dyssynchrony. The investigator performing and reading the echocardiogram was blinded to the group allocation.Adult male out-bred ICR mice were purchased from Harlan Laboratories . All animal experiments were conducted under the guidelines on humane use and care of laboratory animals for biomedical research published by the US National Institutes of Health . The study protocol was approved by the local Institutional Animal Care and Use Committee. Mice underwent experimental myocardial infarction due to permanent coronary artery ligation or sham surgery as previously described In an additional group of mice (ligation or sham [N = 5] per group) were deeply sedated and intubated 7 days after surgery, the chest was reopened, the RV or LV apex were punctured and a Millar catheter connected to a pressure transducer to measure RV peak systolic pressure, which is equivalent to pulmonary artery systolic pressure in the absence of pulmonary valve stenosis, or LV end-diastolic pressure. An additional group of mice (ligation or sham [N = 5] per group) underwent measurement of RV peak systolic pressure or LV end-systolic pressure after challenge with 0.4 ml of NaCl 0.9% or isoproterenol 10 ng  to evaluate for latent PH.The extent of the infarct was evaluated using two different methods. Triphenyl tetrazolium chloride (TTC) was used to stain viable myocardium samples at 24 hours and Masson's trichrome histochemical staining for the measurement of infarct size as reparative fibrosis (scar), as previously described The presence of pulmonary edema was assessed by measuring lung water content 7 days after AMI: the lungs were dissected, weighed, dried at 60°C (24 hrs), and then re-weighed to calculate wet-to-dry ratio.As an additional AMI model, we added a group of mice (N = 6), which underwent transient coronary artery ligation (30 min) followed by reperfusion in order to simulate a reperfused AMI, often seen in patients, which is also characterized by a smaller degree of LV injury. The surgical technique is as described above with the difference that the ligation was released 30 min later. These mice underwent echocardiography prior to surgery and 7 days later.The values are reported as mean and standard error. ANOVA for repeated measure analysing the effect of time, group and time x group interaction was used to compare variables between the animal groups. The analyses were completed using SPSS 16.0 software .Surgical ligation of the left coronary artery was associated with a significant reduction in LVFS, LVEF and LV fractional area change at 48 hours, 7 days and 10 weeks after surgery and a significant increase in LV dimensions  by day 7. At day 7, LV fractional area change velocity (a load- and rate-independent index of contractility) decreased by 45% (P<0.001). Cardiac output estimated by Doppler did not significantly change reflecting a condition of compensated LV dysfunction .RV fractional area change was significantly reduced at 48 hours , 7 days , and 10 weeks , while RV diastolic area significantly increased by day 7 , Table 1There was no evidence of interventricular dyssynchrony 7 days after surgery: the Doppler measured delay difference between aorta (LV) and pulmonary artery (RV) was 2.6±0.3 ms in the AMI group and 2.3±0.4 ms in the sham-operated mice (P = 0.67), the M-Mode measured delay difference between the mitral annulus plane (LV) and the tricuspidal annulus plan (RV) was 0±0.6 in the AMI group and 1.6±1.0 ms in the sham-operated mice (P = 0.27).Invasively measured RV systolic pressure and LV end-diastolic pressure were virtually unchanged after AMI , and unchanged after NaCl 0.9% or isoproterenol challenge (data not shown). The lung water content was not increased after AMI reflecting absence of pulmonary edema .The extent of infarct size was similar using both TTC (29±3%) and Masson's trichrome (28%±3%), and in all cases the infarct involved only the anterior and lateral wall while the RV and septum were not involved.Mice with reperfused AMI showed a significantly smaller infarct size using both TTC  and Masson's trichrome  and a smaller decrease in LVFAC  yet a similar reduction in RVFAC , whereas LVFAC correlated significantly with infarct size in the 2 groups combined  but not in the individual groups. RVFAC and LVFAC as absolute values were highly correlated in the 2 groups combined  but not in the individual groups.Post-infarction cardiac remodelling is characterized by biventricular remodelling. The occurrence of RV dysfunction and failure identifies a subgroup of patients with extremely poor prognosis, however only few clinical studies have systematically addressed RV remodelling following AMI RV remodelling and dysfunction following AMI may therefore simply be part of a global biventricular remodelling response due to altered wall stress which is further aggravated by neurohormonal activation during and after AMI In conclusion, acute myocardial infarction involving the LV and sparing the septum and the RV induces a significant acute decline in RV systolic function in the absence of pulmonary hypertension in the mouse. RV systolic dysfunction following AMI may represent an additional mechanism by which AMI may cause heart failure and increased mortality. These finding remain to be validated and to be mechanistically investigated, ultimately leading to clinical studies addressed at determining whether RV systolic function is an independent and modifiable predictor of mortality.


Histological composition of material obtained by thrombus aspiration during percutaneous coronary intervention (PCI) in patients with ST-segment elevation acute myocardial infarction (STEMI) is highly variable. We aimed to characterize this material using magnetic resonance imaging (MRI) and to correlate MRI findings with the success of PCI in terms of ST-segment resolution. Thrombus aspiration during primary or rescue PCI was attempted in 100 consecutive STEMI patients, of whom enough material for MRI was obtained in 59. MR images were obtained at 9.4T and T1 and T2 values were measured. Patients with (n = 31) and without (n = 28) adequate ST resolution 120 min after PCI  had similar baseline characteristics except for a higher prevalence of diabetes mellitus in the latter . T1 values were similar in both groups . T2 values averaged 31.2±10.3 and 36.6±12.2 ms; in thrombus from patients with and without adequate ST resolution (p = 0.09). After adjusting for diabetes and other baseline characteristics, lower T2 values were significantly associated with inadequate ST resolution . Histology classified thrombus in 3 groups: coagulated blood (n = 38), fibrin rich (n = 9) and lipid-rich (n = 3). Thrombi composed mostly of coagulated blood were characterized as being of short (n = 10), intermediate (n = 15) or long evolution (n = 13), T2 values being 34.0±13.2, 31.9±8.3 and 31.5±7.9 ms respectively (p = NS). In this subgroup, T2 was significantly higher in specimens from patients with inadequate perfusion . This can be of clinical interest as it provides information on the probability of adequate ST resolution, a surrogate for effective myocardial reperfusion. ST-segment elevation acute myocardial infarction (STEMI), usually caused by thrombotic occlusion of a diseased coronary artery after erosion or rupture of an atherosclerotic plaque, is a leading cause of death in the western world Magnetic resonance imaging (MRI) is a noninvasive technique not involving ionizing radiation that has proven very useful in the evaluation of patients with ischemic heart disease. In addition to giving an accurate estimation of ventricular geometry and myocardial perfusion status, MRI can provide high resolution images of the coronary arteries which allow to identify the presence of intraluminal stenoses The aim of the present work was to investigate if MRI analysis of the material obtained by thrombus aspiration during emergent percutaneous coronary intervention (PCI) in STEMI patients allowed to assess thrombus age and composition and also to correlate MRI findings with the success of primary PCI in terms of ST-segment resolution.The protocol was approved by the Hospital Vall d'Hebron Ethics Committee and all patients gave written consent to enter the study.One hundred consecutive STEMI patients undergoing emergency PCI at our hospital were included. The inclusion criteria were all the following: a) symptoms suggesting acute myocardial ischemia lasting for more than 30 minutes and ST-segment elevation of more than 0.1 mV in two or more contiguous leads on the ECG; b) clinical indication of primary or rescue PCI; and c) use of a thrombus aspiration device during PCI. Of these patients, enough material for MRI analysis was obtained by thrombectomy in 59.A 12-lead ECG was routinely recorded 120 min after primary PCI. Myocardial reperfusion was assessed according to the magnitude of ST-segment in this ECG trace in the lead with maximal ST elevation before PCI. Patients with ≥70% ST resolution were considered to have adequate myocardial reperfusion whereas no or less than 70% ST resolution was considered indicative of inadequate myocardial reperfusion After crossing the culprit lesion with the steerable guidewire, a 6-French Pronto V3 aspiration catheter  was advanced up to the distal vessel during continuous aspiration. Balloon dilation was performed before stenting only when necessary for stent delivery, but direct stenting after thrombectomy was the preferred technique. In all patients, intra coronary nitrates were given after restoration of anterograde flow to ensure maximal epicardial vasodilation. The use of bare metal or drug-eluting stents was left to the operator's discretion.Pharmacologic treatment before PCI included aspirin , clopidogrel , and intravenous unfractionated heparin (>5000 IU). Use of the glycoprotein IIb/IIIa inhibitor abciximab was left to the operator's discretion. Additional heparin was administered during the procedure according to the activated clotting time .Aspirated material was embedded in low-temperature gelling agarose (Sigma). Once the agarose solidified, it was transferred to a 9.4 T vertical bore magnet interfaced to a Bruker Avance 400 spectrometer  equipped with a 35-mm imaging probe. Sixty four images from a single slice were acquired with a spin-echo pulse sequence  that allowed for the variation of both RT (Repetition Time) and ET (Echo Time); RT varied from 4000 to 138 ms in 8 steps while ET started at 6 ms and increased 6 ms each of the 8 steps up to 48 ms. Image acquisition lasted for approximately 30 min. Slice thickness was set to 500 µm while in plane resolution was 98×98 µm.T1 and T2 (Spin-lattice and spin-spin relaxation) Once the images were acquired, thrombi were fixed in formaldehyde, embedded in paraffin, cut in 5 µm sections and stained using standard procedures with hematoxilyn and eosin and Masson's techniques. Thrombi were classified as lipid-rich, fibrin-rich (at least 30% of the area occupied by fibrin) and as blood. In turn, blood thrombi were divided between short-, intermediate- and long- evolution time; this classification is comparable to that of fresh, lythic and organised thrombus described previously Statistical analysis was performed with SPSS 13.0 software . Continuous variables are reported as mean ± SD, and categorical variables as absolute numbers and percentages (given in brackets %). Comparisons between two continuous variables were performed by Student t tests or by the Mann-Whitney U test when appropriate and comparisons between two categorical variables were performed with chi-square tests or with the Fisher exact test. A multivariable logistic regression analysis was performed to assess the association between T1 and T2 values with myocardial reperfusion status after PCI after controlling by baseline predictors. The variables of interest were selected in a single step (enter method). Adjustement was made for age, active smoking and all baseline variables attained (p<0.2) with ST resolution at univariate analysis . p values<0.05 were considered significant.Receiver operating characteristics (ROC) analysis was performed according to the method of Hanley and McNeil Of the 59 patients with MR images of aspirated material, significant ST resolution indicating adequate myocardial reperfusion was observed in 31 (52%), and in the remaining 28 (48%) myocardial reperfusion was inadequate. Clinical, electrocardiographic, and angiographic data, and the results of MRI in both groups are summarized in Examples of MR images of the aspirated material can be seen in Multivariable logistic regression analysis included age, sex, active smoking, hypertension, diabetes mellitus and MR variables. Only diabetes mellitus  and T2 value of the aspirated material  were retained as independent predictors of inadequate myocardial reperfusion. Also, there was a trend for higher T2 values in patients not attaining optimal myocardial reperfusion at angiography  than in the remaining patients .Histological analysis was completed in 50 specimens and showed three different patterns of thrombus composition, the most frequent consisting mostly of coagulated blood (n = 38), another characterized by a significant  content of fibrin (n = 9), and the most rarely seen being composed mostly of lipids (n = 3) . T2 valuT1 values follow a similar tendency as T2 values; T1 of 1141.2±474.6 vs 1257.3±403.6 ms, (p = 0.44) in cases with and without ST resolution respectively without being statistical significant.In the present study we have shown that MR analysis of the aspirated material obtained by thrombectomy during emergent coronary angioplasty in patients with STEMI, in particular T2 relaxation values, correlated with myocardial perfusion status as measured with ST segment resolution in the ECG.3 is needed; this is larger than the sample volume needed for histological studies.The group of patients included in the study is representative of the consecutive cohort treated at our institution. We were able to obtain MR images from aspirated material of 59 out of 100 patients; this percentage is slightly lower than those reported in previous histological studies In the study of all samples, logistic regression analysis showed that the presence of diabetes, as other studies found When only blood thrombi were analyzed, T2 values were not able to differentiate between short, intermediate and long-term evolution but were significantly different between patients with and without ST resolution at univariate analysis. Data obtained in lipid- and fibrin-rich thrombus is inconclusive due to the low number of samples in these groups, thus it can be suggested that the differences seen in the whole population came mainly from coagulated blood samples.Previous work on animal models has shown that both T1 and T2 values of thrombus change with time and that this change correlates with thrombus composition We have found shorter T2 values in long-term evolved thrombi (described as organized in some reports). This correlates with better PCI angiographic results and myocardial perfusion in the present work. Similarly, Kramer and cols MR angiography is able to detect coronary artery stenosis T1 values get longer and show a narrower distribution range as magnetic field increases. This could be the reason why it has been reported that thrombus composition affects T1 at 1.5 Tesla A limitation of this study is that all measures were conducted on material aspirated during angioplasty and that it is not clear up to what extent this may be reliably representative of the actual plaque/thrombus composition within the coronary artery. Also, a selection bias towards blood-rich thrombi vs. plaque-rich thrombi due to the amount of material needed for the analysis can not be discarded.Although MRI assessment of thrombus age remains challenging, patients with adequate reperfusion tend to have lower T2 values  as compared to those with inadequate reperfusion. Further studies are needed to investigate the clinical usage of MRI in patients with myocardial infarction for further risk assessment and prediction of interventional outcome.Figure S1Work flow to measure relaxation time, first an image of the aspirated material is obtained at 8 different repetition and echo time conditions (A); the second step is to select regions of interest (ROI) within each thrombus (B). To measure T2 the intensity of each ROI is plotted against echo time (C) and fitted to an exponential equation, for T1 measures (not shown) intensities are plotted against repetition time.(TIF)Click here for additional data file.


To evaluate, with different pacing modes, acute changes in left ventricular systolic function, obtained by continuous cardiac output thermodilution in various subsets of patients undergoing cardiopulmonary bypass surgery. Increments of mean arterial pressure and cardiac output were considered the end point.Fifty cases electively submitted to cardiac surgery were analyzed. Isolated valve surgery 62%, coronary revascularization 30% and 8% mixed disease. Left ventricular ejection fraction was preserved in 50%,36% had moderate depression,(EF 36%-50%) whereas 14% had severe depression (EF < 35%). Left bundle branch block occurred in 18%. Preoperatively 84% were in sinus rhythm and 16% in atrial fibrillation. The different subgroups were analyzed for comparisons. Right atrial-right ventricular and right atrial-left ventricular pacing were employed in sinus rhytm. Biventricular pacing was also used in atrial fibrillation.Right atrium-right ventricular pacing, decreased significantly mean arterial pressure and cardiac output (2.3%) in the overall population and in the subgroups studied. Right atrium-left ventricle, increased mean arterial pressure and cardiac output in 79% of patients and yielded cardiac output increments of 7.5% (0.40 l/m) in the low ejection fraction subgroup and 7.3% (0.43 l/m) in the left bundle branch block subset. In atrial fibrillation patients, left ventricular and biventricular pacing produced a significant increase in cardiac output 8.5% (0.39 l/min) and 11.6% (0.53 l/min) respectively. The dP/dt max increased significantly with both modes .Right atrial-right ventricular pacing generated adverse hemodynamic effects. Right atrium-left ventricular pacing produced significant CO improvement particularly in cases with depressed ventricular function and left bundle branch block. The greatest increments were observed with left ventricular or biventricular pacing in atrial fibrillation with depressed ejection fraction. The benefits of cardiac re-synchronization therapy (CRT) in chronic heart failure with severe left ventricular (LV) dysfunction due to ventricular dyssynchrony have been established by several randomized controlled trials-3, demonCardiac function is often diminished after cardiopulmonary bypass (CPB). The acute ventricular asynchrony and systolic dysfunction generated during this period, far exceed those seen in the setting of chronic heart failure (CHF) treated by CRT. Delayed recovery of myocardial performance following restoration of myocardial flow, referred as “stunning”, is a well documented phenomenon, associated to CPB reperfusion.The adverse movement of the interventricular septum toward the right ventricle, during systolic contraction it is another common finding after CPB. The aboPlacement of RV temporary epicardial electrodes, is a routine procedure during cardiac surgery to treat bradicardia with low cardiac output (CO) or atrio-ventricular block. This pacing site, usually generates an undesirable cardiac effect, due to the PSM created by the initial RV activation. CannessNelson et al., have deAt present, and despite recent clarifying investigations concerning pacing configurations, stimulation site, perioperative phase and simultaneous adjustments of atrioventricular (AVD) and interventricular delays (VVD)-14, therOur initial experience using biA total of 50 patients electively submitted to CPB surgery between March 2008 and May 2010 were included in the present study. Institutional ethical committee approval was obtained. All patients gave fully written informed consent. Exclusion criteria were the presence of previous pacemaker, severe tricuspid incompetence in order to maintain the accuracy of thermodilution derived CO measurements and intracardiac shunt. The development of cardiac arrhythmias in the early post-operative period, requiring antiarrhythmic drugs or postoperative low cardiac output needing mechanical support were also considered an exclusion criteriaMean age was 67.14 ± 11.18 years (range 39–82). Preoperative diagnosis included, isolated valve disease in 31 cases (62%), isolated coronary artery disease in 15 cases (30%) and mixed disease (8%) requiring valve surgery with coronary artery bypass grafting (CABG) (Table Left bundle branch block (LBBB) was present in 9 patients (18%) and RBBB in 2 (4%). Left ventricular ejection fraction (LVEF) derived from transthoracic Doppler echocardiography using the Simpson method was preserved (LVEF ≥ 50%) in 25 cases (50%); moderate depression (LVEF 3%-49%) in 18 cases (36%), and severe dysfunction (LVEF < 35%) in 7 cases (14%). Sinus rhythm (SR) was present in 84% of cases and 16% were in atrial fibrillation (AF) with depressed LVEF.Intraoperative patient monitoring included invasive blood pressure and continuous ECG registry. Following general anesthesia and orotracheal intubation, a heparin coated Swan-Ganz catheter  was placed for hemodynamic management and determinations: pulmonary artery pressures and systemic vascular resistance. The catheter was connected to a monitor  for continuous monitoring of CO and mixed venous oxygen saturation (SvO2). The use of validated automated CO method allows determinations of rapid change in CO, useful for modifying pacing parameters: atrio-ventricular delay (AVD), interventricular delay (VVD) and pacing configurations. Surgery was performed through a median sternotomy and under standard CPB. After aortic cross clamping, cold hyperkalemic antegrade blood cardioplegia was administered for cardiac arrest and repeated every 20 min. Controlled reperfusion was achieved using a single dose of warm cardioplegia. After completion of the surgical procedure, weaning of CPB and removal of atrial canulae, epicardial unipolar pacing wires  were placed at the right atrial appendage (RA), diaphragmatic surface of the RV (DSRV) and posterobasal LV wall, then passed percutaneously and sutured to the skin at the lower end of the sternotomy incision.In all cases, basal hemodynamic parameters: CO, systolic, diastolic and mean arterial pressure (MAP), pulmonary artery pressures, SvO2 and a 12 lead surface electrocardiogram were registered, 1–2 h after admission to the intensive care unit and once the patient had reached hemodynamic stability. Patients were sedated and mechanical ventilation parameters were held constant during the study. Norepinephrine was administered if required in order to reach MAP of at least 60 mmHg. No other inotropic agents were administered during the procedure. Blood pressures were determined as the mean of the values obtained at the end of three consecutive respiratory cycles. During the study, volume administration or intravenous drug infusions were held constant, whitout additional medications. Cases with a post-CPB heart rate > 120 beats/min were excluded. Stimulation was performed at a rate 10% superior to the basal rate during 6 min, using the different configurations and parameters. Then discontinued for 10 min after each period. External temporary dual-chamber generators  were employed.In AF cases, for achievement of dual cathodal BiVP with VVD adjustments, an implantable pulse generator, Biotronik Logos D, was used as an external pacemaker. The atrial port of the generator was usually connected to the LV lead and the ventricular port to the RV electrode, using the generator as the positive pole to close the circuit. In patients in SR two configurations were used: a) RA-LV bipolar anocathodal mode (cathode in LV). b) RA-RV bipolar anocathodal mode (cathode in RV)The AVD was modified within a range of 80 to 200 ms, according to the patients heart rate, MAP and CO monitoring. In AF patients, three different configurations were used :a) LV bipolar anocathodal . b) RV bipolar anocathodal .c) BiVP dual cathodal (cathodes in LV and RV) with adjustable VVD. With QRS <120 mm the delays ranged from +20-40 ms. With a wide QRS > 120 mm, the delays ranged from 0–80 ms.At least 3 settings were used in each study. The highest CO obtained was considered the optimal.Echocardiographic assessment was only performed in AF cases. Mitral regurgitation jets were imaged using colour Doppler echocardiography in parasternal long-axis and four chamber view. The maximal regurgitant jets were determined during intrinsic rhythm and with the various pacing configurations in order to calculate the dP/dt max as a contractility index. Left ventricular dyssynchrony was assessed using tissue Doppler imaging by transthoracic or transesophageal echo-doppler ultrasound.Analysis of the whole population was obtained. Several sub-groups were established for comparisons according to: LVEF, type of BBB, basal rhythm and type of surgery. Subjects served as their own control.Statistical analysis was performed with the Wilcoxon rank sum test for paired data, using SPSS software . Due to pairewise comparisons, Bonferroni correction was performed. A p-value of less than 0.05 was considered statistically significant. Continuous data were expressed as mean ± standard deviation.The analysis of the overall population comparing RA-LVP and RA-RVP modes with basal values showed a significant increase in CO and MAP in favour of RA-LVP, close to 80% of patients, whereas RA-RV, significantly decreased both parameters Table .In the subgroup with preserved LVEF, RA-LVP pacing produced a significant increase of CO, although not of MAP. With RA-RVP, a significant decrease of CO and MAP was noticed table . In the The LBBB subgroup, showed that RA-LVP increased significantly CO and MAP: 7.3% 0.43 l/min) and 8.9% respectively. In contrast, RA-RVP decreased significantly both  and MAP  with regard to basal values. With RA-RVP, CO significantly decreased  and also MAP .In the CABG sub-group, only CO increased significantly with RA-LVP , whereas RA-RVP significantly decreased CO  and MAP  relative to basal values. The combined CABG and valve surgery sub-group, showed an increase of MAP (66.6 ± 5.2 mmHg vs 71.4 ± 4.4 mmHg) and CO (5.20 ± 1.74 l/m vs 5.47 ± 1.83 l/m) with RA-LVP and a decline of CO (5.20 ± 1.74 l/m vs 4.77 ± 1.4 l/m) with RA-RVP, without statistical significance (4 cases only).In the SR group with RA-LVP, CO significantly increased 5.5%) and also MAP  and 11.6% (0.53 l/min) respectively, without significant differences between them  in all cases. LVP and BIVP produced symmetrical contraction of the LV mid-septal and lateral wall with both pacing modes. The .dP/dt max,Figure  increaseTemporary stimulation on the RVDS with epicardial electrodes after CBP is a common practice in cardiac surgery. Different studies, investigating the sites of pacing to optimize CO including: RVP at, apical, diaphragmatic surface, paraseptal and outflow tract; LVP: posterobasal, mid free-wall, apical and paraseptal, have generated controversial results-21.Vaughan et al. performeThe strategy for perioperative optimization, by means of LVP or BiVP using a LV basal cathodal electrode and adequate adjustments of AVD and VVD if feasible, is gaining progressive acceptance, to improve CO perioperatively, particularly in cases with depressed EF and LBBB,13,18,23In our study, in an heterogeneous population, RA-LVP,LVP or BiVP effectiveness, was validated by MAP and CO monitoring, proving to be beneficial in almost 80% of the whole population, with significant improvements of MAP and CO in the low EF and LBBB subgroups, being highest in the AF group with depressed EF. The increments obtained may appear rather modest but simultaneously avoid the adverse effects of RVP. Similar positive results with RA-LVP have been obtained by Flynn et al..In the average population, RA-RVP decreases CO and MAP and this effects also occurs in the different subgroups studied. Similar adverse observations have been reported in cases undergoing CABG surgery,18. BesiOur investigation, shows a 20% of non responders. They were tested only by RA-RVP or RA-LVP modes with AVD adjustments. The most delayed site on the inferolateral LV wall was not established by echocardiography and BiVP was not applied in the SR group, lacking a possible optimization of synchronicity with VVD.In the setting of postoperative CPB, there is very limited experience reported with AF, generally due to the established exclusion criteria. In an acute HD study in CHF, including AF cases, Blanc et al. observedMixed venous oxygen saturation, only showed favourable significant differences, in the group of AF with EF < 35%, using LVP or BiVP. Eberhardt el al in CABG Due to the nonexistence of an external triple chamber pacemaker, we employed only in AF cases, a biventricular dual cathodal pacing system, which iFew reports provide a precise description of the BiVP configuration used, accomplished either with the split bipole or the dual cathodal split system, but always with the drawback of not been able to adjust the VVD, to maximize the optimization benefit,12. FernOur study,in AF cases with EF < 35%, both LVP and BiVP significantly increased MAP and CO, accompanied by significant improvements of dP/dt max, without statistical differences between them. Flynn et al. in a subA recent study under acRight acute ventricular failure after CPB is an important hemodynamic complication difficult to treat effectively. BiVP with VVD adjustments, could be very helpful in that setting stressing the relevance of this pacing mode.Wang et al. in a subThese results, further stress the relevance of optimizing AVD and VVD in the perioperative CPB setting, particularly, in cases with preexisting LV dysfunction, at high risk of developing acute low-output state. Nevertheless, the mechanisms by which pacing optimization improves hemodynamics in this setting, are still not fully defined and requFuture investigations using TS to improve cardiac function, will be more feasible using external triple chamber generators with adjustable VVD and should contribute to establish pacing optimization as a routine step of perioperative protocols.The present study revealed that for the overall population and the different subgroups analyzed, RA-RVP at the diaphragmatic site induces a decrease of MAP and CO.Overall, 79% of the heterogeneous population analyzed, improved CO and MAP using RA-LVP, BiVP or LVP. In the preserved LVEF subgroup, there was an increase in CO of 4.15%. The benefits increased in the LBBB subgroup reaching 6.6%. With depressed LVEF there was a further increase up to 7.5%. The highest increase, 11.6% was obtained with BiVP in AF cases with depressed LVEF.Non responders to RA-LVP, should be tested by BiVP with VVD adjustments and with the accompaniment of individualized echocardiographic assessment.Mechanisms underlying the absence of positive response to RA-LVP in 20% of the sample remain unknown. Individual ecochardiographic assessment in SR cases was not performed and the most delayed activated site on the LV wall not determined. In addition, in these subjects BiVP was not applied.The authors declare that they have no competing interests.JBGB, ALF, and DSC have made substantial contributions to conception and design or acquisition of data, or analysis and interpretation of data.JAE, FG and JRGJ have been involved in drafting the manuscript and revising it critically.All authors have given final approval of the version to the be published.


Aortic stenosis (AS) is associated with increased interstitial myocardial fibrosis (IMF). Although detectable after gadolinium administration by equilibrium-contrast CMR, protocols are lengthy. We hypothesized that pre-contrast T1 mapping, a potential surrogate measure of IMF, would demonstrate reduced T1 in patients with severe AS. We determined the T1 in patients with severe AS and controls before and after contrast, and correlated these values with myocardial strain measures using a high temporal-resolution tagging sequence.A Modified Look-Locker Inversion Recovery (MOLLI) sequence was used to generate eleven T1-weighted images and myocardial T1 derived by fitting a signal intensity-time curve using CMR42®. Short-axis T1 maps were acquired using a 1.5T scanner (Siemens) before and 1,2,5,8,15,20,25 and 30 minutes after contrast. Myocardial tagging images were acquired using single- and multiple-breath-hold CSPAMM sequences in multiple planes and analysed with inTag® .Forty one subjects (age 58 16), mean (SD); Severe AS, n= 18) were recruited. Subjects with severe AS displayed lower pre-contrast T1 values than healthy controls (791 (52) vs. 896 (49); mean (SD); Fig 6, mean (Pre-contrast myocardial T1 mapping demonstrates lower T1 values in patients with severe AS compared to controls and correlates well with both post-contrast T1 and reduced myocardial strain. Further histological validation is required; however, pre-contrast T1 mapping is clinically practical and holds promise for the detection of interstitial fibrosis in severe AS.This project was supported by the NIHR Cardiovascular Biomedical Research Unit of Royal Brompton and Harefield NHS Foundation Trust, the British Heart Foundation, and CORDA. Dr. Jabbour was supported by a Postdoctoral Research Fellowship from the National Health and Medical Research Council of Australia, a Vincent Fairfax Family Foundation Research Fellowship from the Royal Australasian College of Physicians, the St. Vincent’s Clinic Foundation, and the Victor Chang Cardiac Research Institute.


Cardiac magnetic resonance (CMR) imaging studies are increasingly being carried out in patients with cardiovascular disease. In a high throughput centre  technologists can potentially provide significant help in assisting with LV volumes analysis but the inter- and intra-observer variability of this task has not been reported.Two CMR technologists with no previous experience in analysing LV volumes assessed 20 CMR studies in ischemic heart disease patients. 10 studies were re-analysed 24 hours after the first analysis.Volumes and mass were analysed using semi-automated software  following a 2hr tutorial on how to use the software.Intra-observer variability was assessed using intraclass correlation coefficient (ICC); inter-observer variability was assessed using Bland Altman plots for agreement. Intra-observer variability was low for both observers . Inter-observer variability was lowest for volumes and highest for mass (Table Technologists with no previous experience in analysising LV parameters can analyse LV volumes after a short tutorial on a semi-automated software with good reproducibility, and a low inter- observer variability.NIHR Cardiovascular BRU, Bristol Heart Institute.


We report two cases of systemic sarcoidosis with atrial flutter as the clinical manifestation. In one patient, who had symptoms of shorter duration, the arrhythmia was no longer inducible after a course of glucocorticoid therapy. Electroanatomical mapping in the other case revealed patchy fibrosis of the left atrial myocardium and multiple macro-reentrant circuits. Sinus rhythm could be restored with ablation of these reentrant circuits. To our knowledge, this is the first report on the demonstration of atrial scarring in a patient with sarcoidosis using 3-D electroanatomical mapping. These two cases illustrate that the inflammation of atrial myocardium is the primary mechanism of atrial arrhythmias in patients with cardiac sarcoidosis. Sarcoidosis is a systemic granulomatous disease of unknown etiology, with clinical cardiac involvement varying from 20 to 60% of patients ,21, mostA 49-year-old male, with a permanent pacemaker implanted for complete heart block and history of iritis a few months before, presented with recurrent episodes of palpitation over the preceding few weeks. The 12-lead electrocardiogram was suggestive of atypical atrial flutter of probable left atrial origin . The echA 48-year-old woman was referred to us with recurrent episodes of paroxysmal atrial flutter, treated with a failed attempt at ablation and pharmacotherapy  in the past. Chest X-ray followed by CT scan of the thorax suggested type III pulmonary sarcoidosis with extensive involvement of the lung parenchyma. Echocardiography showed a mildly dilated left ventricle (LV) and left atrium  with normal LV systolic function. Electrocardiogram suggested LA flutter with varying atrioventricular conduction . After tThe tissue changes in sarcoidosis are characterized by accumulation of T lymphocytes and mononuclear phagocytes, non-caseating epithelioid granulomas, and derangements of normal tissue architecture, all leading to parenchymal damage and irreversible tissue fibrosis . GranuloThe development of atrial or ventricular arrhythmias can result in significant hemodynamic and clinical deterioration in these patients with a high incidence of co-existing systolic or diastolic dysfunction. The mechanism for ventricular tachyarrhythmias is thought to be mediated via granulomas and myocardial fibrosis, while atrioventricular block occurs presumably secondary to nodal artery ischemia or granulomas in the basal septum. Atrial arrhythmia in sarcoidosis, a less well-characterized entity, was proposed to be more due to atrial dilatation secondary to ventricular, valvular or pulmonary involvement rather than direct involvement of the atrial myocardium . Our patTo our knowledge, this is the first report on the demonstration of atrial scarring in a patient with sarcoidosis by voltage mapping using any 3-D electroanatomical mapping system. Our index patient had no other risk factors which could otherwise account for the scarring of the LA myocardium. The EP findings in this case suggest that the atrial myocardium can be directly involved in sarcoidosis resulting in patchy areas of scarring interspersed with conducting atrial myocardium, an ideal substrate for multiple macro-reentrant circuits. Recognition and ablation of these circuits can result in long-term maintenance of sinus rhythm in these patients.


The purpose of the present study was to evaluate the effect and predictive value of metabolic syndrome (MetS) and its components on diastolic heart failure (DHF) in patients at high risk for coronary artery disease (CAD).We enrolled 261 patients with normal left ventricular ejection fraction (≥50%) who were scheduled to undergo coronary angiography for suspected myocardial ischemia. They were categorized into three groups  based on the number of MetS criteria. Echocardiography was used to assess left ventricular (LV) diastolic function. The association between MetS and DHF was assessed by multivariate logistic regression (MLR) analysis (non-DHF patients as reference group) after controlling for confounders. The predictive performance of the MetS severity score (MSS) was evaluated using the area under the receiver-operating characteristic curve (AUC).A tendency toward increased DHF prevalence with increasing MSS was found (p < 0.001). MLR analysis showed that in patients with an MSS of 1, the odds ratio (OR) of DHF was 1.60  compared to non-DHF patients; in patients with MSS ≥4, the OR was 6.61  compared to non-DHF patients. MSSs strongly predicted DHF . MLR with MetS components as binary variables showed that blood pressure (BP) and triglycerides (TGs) were significantly associated with DHF .Our findings signify that MetS and its components of BP or TG were associated with DHF in high-risk CAD patients. DHF prevalence tends to increase with increasing MSS that has a high value in predicting DHF in high-risk CAD patients. Metabolic syndrome (MetS) is a global health concern and refers to a constellation of the risk factors of cardiovascular disease, including obesity, abdominal fat distribution, disorders of glucose and lipid metabolism and hypertension (HT) . The burPatients who are at a high risk for coronary artery disease (CAD) characteristically have HT, DM and hyperlipidemia. MetS and DHF tend to be co-prevalent in high-risk CAD patients, who account for more than half of the patients hospitalized in departments of cardiovascular disease . High-riTwo hundred and sixty-one consecutive symptomatic or asymptomatic Chinese patients who had normal LV ejection fraction  and were scheduled to undergo coronary angiography for suspected myocardial ischemia were recruited between February 2009 and March 2011 at the Huashan Hospital of Fudan University, China. Patients were excluded from the study to eliminate potential confounding factors that may have influenced heart function. The exclusion criteria were as follows: (1) history or findings of systolic heart failure (LVEF ≤ 45%), significant valvular heart disease , hyperthyroidism or hypothyroidism and dilated or hypertrophic cardiomyopathy, (2) pregnancy or lactation and/or (3) a major systemic illness, such as systemic lupus erythematosus. Written consent was obtained from all patients before the study, which was performed in accordance with the ethical standards laid down in Declaration of Helsinki and approved by the Medicine Ethical Committee of Fudan University.2, central obesity was assumed, and WC did not need to be measured. For analysis, the study subjects were grouped according to the number of MetS criteria they satisfied: non-MetS (0 criteria), pre-MetS (1–2 criteria) and MetS (≥3 criteria). MetS severity was scored on a scale of 0 to 4 according to the number of MetS components present. Three subjects met all five MetS criteria, and their MetS severity score (MSS) was set to 4.MetS was diagnosed according to the updated National Cholesterol Education Program/Adult Treatment Panel III criteria (WHO Western Pacific Region obesity criteria) in individuals meeting three or more of the following : (1) cenThe subjects were interviewed for the documentation of medical histories, medications, history of smoking habits, laboratory assessment of cardiovascular disease risk factors and standardized echocardiographic examination. BMI was calculated as the weight in kilograms divided by the square of height in meters. SBP and DBP values were the means of two physician-obtained measurements on the left arm of the seated participant. HT was diagnosed if the BP was ≥140/90 mm Hg and/or the patient was undergoing antihypertensive therapy. DM was diagnosed on the basis of the oral glucose tolerance test and either a glycosylated hemoglobin (HbAlc) level of ≥6.5% or the use of insulin or hypoglycemic medications. CAD was diagnosed if any one of the following were present: (1) history and/or treatment for angina and/or myocardial infarction; (2) history of coronary artery revascularization procedures and/or coronary angiography with ≥50% stenosis in one or more of the major coronary arteries; and (3) regional wall-motion abnormalities on rest echocardiography.Peripheral venous blood samples were collected in tubes in the fasting state in all subjects. The blood was centrifuged at 3000 rpm for 10 min for plasma separation and immediately used to measure biomarkers. FPG was measured using the glucose oxidase procedure; HbA1c was measured using ion-exchange high-performance liquid chromatography . Serum total cholesterol (TC), HDL cholesterol, TGs, creatinine (Cr) and uric acid (UA) levels were measured using an enzymatic method with a chemical analyzer . Low-density lipoprotein (LDL) cholesterol levels were calculated using the Friedewald formula, and the creatinine clearance rate (Ccr) was calculated using the Cockcroft-Gault formula. The day-to-day and inter-assay coefficients of variation at the central laboratory in our hospital for all analyses were between 1% and 3%.Echocardiography examinations were performed with a Vingmed System 5 Doppler echocardiographic unit . Conventional echocardiography measurements were performed according to American Society of Echocardiography guidelines. LV mass (LVM) was calculated using the Devereux formula. The LVM was corrected for body surface area (BSA) to obtain the LVM index (LVMI). The left atrial diameter (LAD) and aortic root dimension (AOD) were also measured. LV systolic function was assessed using the LVEF. Diastolic function was assessed by determining the E-to-A ratio (E/A) and deceleration time (DT), where E and A represent the early and late ventricular filling velocities, respectively.We used the definition of DHF recommended in the European Society of Cardiology guidelines in 2008 . The dia2 test for categorical variables. Univariate linear regression was performed to determine the variables associated with DHF and to estimate confounding factors possibly disturbing the relationship between MetS and DHF. Multivariate logistic linear regression (MLR) was carried out to determine the independent contributions of variables to DHF (non-DHF patients as reference group). Potential confounding variables, including age, gender, smoking, LAD, LVMI, UA, Ccr and Cr, were controlled in the regression model. Variables were entered into the backward stepwise regression models if a p value of <0.10 was obtained. The models were re-analyzed after substituting the continuous variables related to all MetS components with their dichotomous counterparts in the models. The predictive performance of the MSS was evaluated using the area under the curve (AUC) in a receiver operating characteristics (ROC) curve. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for the relative risk of MetS with DHF. The results were analyzed using the Statistical Package for Social Sciences for Windows, version 16.0 . The tests were two-sided, and a p value of <0.05 was considered significant.The Kolmogorov-Smirnov test was used to determine whether continuous variables followed a normal distribution. Variables that were not normally distributed were log-transformed to approximate normal distribution for analysis. The results are expressed as the mean ± SD or median, unless otherwise stated. The characteristics of the subjects according to MetS groups were assessed using one-way analysis of variance (ANOVA) for continuous variables and the χThe baseline clinical characteristics of the 261 subjects were grouped according to the type of MetS . The backward stepwise regression model showed that age, UA, LVMI and DBP were independently associated with DHF . To reduce the effect of medical therapy, MLR models with adjustments for confounders were developed to include MetS components as binary variables. The results showed that BP and TG were significantly associated with DHF (p = 0.001 and 0.043, respectively in the enter regression model; p = 0.001 and 0.038, respectively in the backward stepwise regression model; Table We first conducted a case–control study to evaluate the effect of metabolic factors on DHF in Chinese high-risk CAD patients. CAD, HT and DM were more prevalent in patients with MetS. Most of the demographic factors, biochemical characteristics and echocardiographic measurements significantly differed among the three MetS groups. Doppler echocardiography has become a well accepted, reliable, noninvasive tool to measure the LV diastolic function. In the present study, Doppler echocardiography was used to measure LV diastolic function in order to diagnose DHF.The main finding of the present study was that MetS strongly and independently predicted DHF in high-risk CAD patients. The prevalence of DHF increased with the severity of MetS. HT, insulin resistance and obesity have been associated with LV diastolic dysfunction or DHF in different populations ,12. In aIn the present study, the AUC was calculated to show that the MSS strongly predicts DHF. In patients with MSSs of up to 4, the prevalence of DHF was nearly 90%. This finding indicates that the severity of MetS is linked to the progression of DHF. This is one of interesting findings of the present study, which not only supports further studies on the mechanism of DHF but also provides evidence for clinicians to predict DHF in hospitalized patients. However, in the present study, we scored the MetS severity by simply using the number of MetS criteria. We did not consider the weights of the MetS components. For instance, the BP component of MetS makes a greater contribution to DHF. A large-scale, case–control study or cohort study with a better method of scoring MetS severity will be conducted to develop a highly sensitive and specific model that uses MetS information to predict DHF. Such a model would facilitate the prevention and treatment of DHF in clinical practice.Another interesting finding of the present study was that BP and TG were the only MetS components that contributed to DHF. This finding is inconsistent with those of some earlier studies, which had revealed that BMI, SBP, DBP and lipid profiles were significantly associated with diastolic parameters and the structure and functions of the LV ,16-18,20Several limitations of the study deserve comment. First, the design of the present study was hospital-based, which is susceptible to selection bias. Second, the sample size was moderate, limiting its ability to detect significant results. Third, the multiple regression models indicated only a moderate influence of MetS on DHF. Other environmental and genetic factors may contribute to the unexplained variation in DHF prevalence. Fourth, the association between insulin resistance and DHF was not analyzed in the present study. This is because data on fasting blood insulin levels were missing. Furthermore, most of participants were enrolled with the first diagnosis of diastolic heart failure or not. So we did not collect information of the history of diastolic heart failure. Finally, it is important to mention that our study was performed on Chinese individuals, and our findings may not be relevant to people of other ethnicities.In conclusion, individuals with MetS frequently have a higher prevalence of DHF. Our findings signify that MetS is an independent predictor of DHF, and BP and TG, as components of MetS, are independently associated with DHF. There is a tendency toward increased prevalence of DHF with increasing MSSs. This supports the hypothesis that MetS is involved in the regulation of DHF progression. The present observations provide evidence that improved metabolic control may coordinately and perhaps even synergistically inhibit the progression of DHF and also provide novel insights into biological functions, in the future.ACEI: Angiotensin-converting enzyme inhibitor; Alb/Cr: Albumin/urinary creatinine ratio; AOD: Aortic root dimension; BMI: Body mass index; BSA: Body surface area; Ccr: Creatinine clearance rate; CI: Confidence intervals; Cr: Creatinine; DBP: Diastolic blood pressure; DHF: Diastolic heart failure; DM: Diabetes; DT: Deceleration time; E/A: E-to-A ratio; FPG: Fasting plasma glucose; GLM: General linear model; HbAlc: Glycosylated hemoglobin; HDL: High-density lipoprotein cholesterol; HOMA-IR: Homeostasis model assessment insulin resistance estimate; HT: Hypertension; IDF: International diabetes federation; LAD: Left atrial diameter; LDL: Low-density lipoprotein cholesterol; LV: Left ventricle; LVEF: Left ventricular ejection fraction; LVM: Left ventricular mass; LVMI: Left ventricular mass index; MetS: Metabolic syndrome; MLR: Multivariable logistic linear regression; OGTT: Oral glucose tolerance test; OR: Odds ratios; PBG: Postprandial blood glucose; HT: Hypertension; SBP: Systolic blood pressure; TC: Serum total cholesterol; TG: Triglyceride; WC: Waist circumference; UA: Uric acid.The authors declare that they have no conflicts of interest.LZ and YS conceived of the study, and participated in its design and coordination and helped to draft the manuscript. Z-HT participated in the design of the study and performed the statistical analysis, carried out the molecular genetic studies, participated in the sequence alignment and drafted the manuscript. FZ and ZL carried out the molecular genetic studies, participated in the sequence alignment and drafted the manuscript. All authors read and approved the final manuscript.


Coronaritis, miocarditis, pericarditis, mitral insufficiency and pancarditis have been reported in Kawasaki Disease (KD). The aim was to evaluate all the cardiac involvement in children affectd by KD followed at out center during the past 20 years.The medical records of all patients diagnosed with KD at our institute between 1988 and 2010 were reviewed.45 cases of KD were identified . Heart involvement was present in 24% , 2 pancarditis, 2 pericarditis, and 8 valvulitis). Patients with heart involvement had higher mean age, higher mean C-Reactive Protein. This subset of patients was less prone to respond to the first dose of intravenous immunoglobulins. The frequency of valvulopathy was 18%. Atrio-ventricular valves  presented a mild-to moderate asymptomatic insufficiency identifiable only at the echocardiography. The valvulopathy was transient, disappearing without sequelae between the second and fourth week.According to literature the rate of coronary aneurisms was 2%, while the incidence of valvular involvement appears elevated (18%). The valvular involvement is identified at the echocardiography during the acute or subacute phase, isolated or associated to miocarditis, pericarditis or coronaritis. The mitral valve appears primarily involved. Cardiac sequelae were not reported. Indeed, the valvulopathy disappeared within four weeks. These data further enhance the importance of a prompt diagnosis of KD and the need of an appropriate therapy to reduce the risk of a coronary involvement and bring to complete regression of the heart involvement.