Microvascular obstruction (MVO) describes suboptimal tissue perfusion despite restoration of infarct-related artery flow. There are scarce data on Infarct Size (IS) and MVO in relation to the mode and timing of reperfusion. We sought to characterise the prevalence and extent of microvascular injury and IS using Cardiovascular magnetic resonance (CMR), in relation to the mode of reperfusion following acute ST-Elevation Myocardial Infarction (STEMI).CMR infarct characteristics were measured in 94 STEMI patients (age 61.0 ± 13.1 years) at 1.5 T. Seventy-three received reperfusion therapy: primary percutaneous coronary-intervention ; thrombolysis (n = 12); rescue PCI , late PCI (n = 6). Twenty-one patients presented late (>12 hours) and did not receive reperfusion therapy.IS was smaller in PPCI (19.8 ± 13.2% of LV mass) and thrombolysis (15.2 ± 10.1%) groups compared to patients in the late PCI (40.0 ± 15.6%) and R-PCI (34.2 ± 18.9%) groups, p <0.001. The prevalence of MVO was similar across all groups and was seen at least as frequently in the non-reperfused group  and to a similar magnitude (1.3 (0.0-2.8) v 0.4 [0.0-2.9]% LV mass, p = 0.36) compared to patients receiving early reperfusion therapy. In the 73 reperfused patients, time to reperfusion, ischaemia area at risk and TIMI grade post-PCI were the strongest independent predictors of IS and MVO.In patients with acute STEMI, CMR-measured MVO is not exclusive to reperfusion therapy and is primarily related to ischaemic time. This finding has important implications for clinical trials that use CMR to assess the efficacy of therapies to reduce reperfusion injury in STEMI. In the setting of acute ST-segment elevation myocardial infarction (STEMI), microvascular obstruction (MVO) describes suboptimal tissue perfusion despite restoration of flow in the infarct-related artery (IRA). MVO is generally thought to be related primarily to reperfusion injury -3. CardiCMR-measured MVO correlates strongly with ST-segment resolution in patients undergoing primary percutaneous coronary intervention (PPCI) but relatively weakly with myocardial blush-grade and poorly with TIMI flow . Larger The European Society of Cardiology (ESC)  advocateThis study aimed to characterise the prevalence and extent of microvascular injury (MVO) and IS using CMR, in relation to the mode of reperfusion following STEMI.Ninety-seven patients presenting to a single regional cardiac centre with a first acute STEMI from Jan 2010 to April 2012 were included. Diagnosis of STEMI was made according to ACCF/AHA and ESC definitions [‘Early-reperfused’ patients were defined as those undergoing successful initial reperfusion within 12 hours of symptoms . Thrombolysis was performed in patients presenting to non-PCI capable regional hospitals using tissue plasminogen-activator analogues. Successful thrombolysis was defined as symptom resolution and ≥50% resolution of ST-segment elevation within 90 minutes, and was followed by transfer to our centre for coronary angiography. Immediate transfer for R-PCI was undertaken for thrombolysis failure. Time to reperfusion (TTR) was measured as the time between symptom onset and successful restoration of IRA flow for PCI-related revascularisation, and time until administration of successful thrombolytic therapy for thrombolysed patients.The Thrombolysis in Myocardial Infarction (TIMI) scoring system was used to quantify angiographic IRA flow . The degCMR was performed on all subjects during the index admission on a 1.5 T scanner  with retrospective electrocardiogram gating and a 6-channel phased-array cardiac receiver coil supervised by a cardiologist with a subspecialist interest in CMR Figure . Cine imAnalysis was performed offline blinded to patient details using QMass 7.1  by two experienced observers . LV volumes and function were calculated as previously described . IschaemNormality was assessed using the Kolmogorov-Smirnov test, histograms and Q-Q plots. Normally distributed data were expressed as mean ± standard deviation and analysed using ANOVA and independent t-tests. Non-normally distributed variables were expressed as median (25%-75% interquartile range) and analysed using Mann–Whitney U-tests. Chi-squared analysis was used to compare MVO prevalence between cohorts. The association between time from symptom onset to revascularisation (TTR), AAR, time to CMR after admission, left anterior descending artery infarct related artery (LAD IRA), TIMI flow pre and post-PCI and revascularisation method with IS and MVO were assessed for reperfused patients using univariate regression. Predictors with p < 0.1 underwent stepwise multivariate analysis. Since categorical and continuous variables were used, the strength of variables was expressed according to their p-value. CMR markers were corrected for TTR using ANCOVA. Reproducibility of CMR analysis was assessed using two-way mixed-effect intraclass correlation coefficient for absolute agreement (ICC) for a subset of 10 randomly chosen studies. Statistical tests were performed on SPSS version 20. p < 0.05 was considered significant.Baseline demographics and angiography findings are summarised in Table CMR data are shown in Table LV volumes were higher and LV ejection fraction lower in the late-PCI, R-PCI groups and non-reperfused cohorts compared with the PPCI and thrombolysed patients. In reperfused patients, when corrected for TTR, the differences in LVESVI and LVEF were no longer significant Table .IS differed across the five study cohorts, being higher in R-PCI and late PCI groups compared with PPCI and thrombolysed patients . When corrected for TTR, the differences in IS in reperfused patients were no longer statistically significant (p = 0.33).AAR was significantly larger in the late PCI group compared with those undergoing the 3 alternative reperfusion techniques . When corrected for TTR, differences in AAR were only of borderline statistical significant (p = 0.054).The prevalence of MVO was similar in the 5 cohorts. There was a trend towards the extent (% of LV mass) of MVO being greatest in the late PCI group, followed by non-reperfused and R-PCI patients. When corrected for TTR, the difference in MVO with the four reperfusion techniques was not statistically significant. Representative CMR and angiography images from patients in the 5 cohorts are shown in Figure Interobserver agreement for IS, MVO, AAR and MSI was excellent, with ICCs of 0.905, 0.958, 0.888 and 0.931 respectively. Intraobserver agreement was also excellent, with ICCs as follows: (a) observer 1: IS (0.980), MVO (0.984), AAR (0.946), MSI (0.937), and (b) observer 2: IS (0.991), MVO (0.991), AAR (0.948), MSI (0.982).2 = 0.41, Table In reperfused patients n = 73), univariate predictors of IS were TTR, AAR, LAD IRA, reperfusion method, TIMI grade post-PCI and time from admission to CMR. In a stepwise multivariate model including all of the above plus TIMI grade pre-PCI, independent predictors of IS were TTR, AAR and TIMI grade post-PCI  were grouped together as the ‘early-reperfused’ group for comparison with the non-reperfused group (n = 21) and results are shown in Table per se. This may have implications for currently planned and future trials in PPCI assessing therapies specifically designed to reduce reperfusion injury.Microvascular obstruction is widely regarded as a manifestation of reperfusion injury after STEMI -3,16,17.‘No-reflow’ was first demonstrated in canine myocardium in 1974 , and is MVO is visualised on CMR by first-pass perfusion, early gadolinium imaging and LGE imaging as hypoenhanced areas within infarct cores  and is sConsistent with an extensive evidence base demonstrating correlation between the duration of ischaemia (TTR) and the extent of myocardial injury, our non-reperfused cohort had larger LV volumes and lower LVEF ,19 compaOur data suggest that CMR-measured MVO should not be used as a surrogate of subclinical angiographic ‘no-reflow’ or as a specific marker of reperfusion injury. Reperfusion injury is one component contributing to overall IS, ,17 but iCMR characteristics were similar with PPCI and thrombolysis, consistent with Bodi who demonstrated no differences in LV volumes, LVEF, IS, MVO or myocardial salvage index (MSI) . The smaPatients were not randomized. The non-reperfused group were retrospectively identified and underwent CMR later than patients receiving reperfusion, however this difference should underestimate both the prevalence and extent of MVO in this group. The numbers of patients being treated with late PCI and R-PCI are small and no definitive conclusions can be drawn on the infarct characteristics.CMR-derived MVO is highly prevalent in STEMI patients not receiving reperfusion therapy. CMR measured MVO is more closely related to ischaemic time than reperfusion therapy in STEMI and may not be a good surrogate marker of reperfusion injury.The authors declare that they have no competing interests.GPM, IBS and AHG conceived the idea for the study and developed the protocol. NR and GPM recruited patients and were present at study visits. JNK and NR performed the CMR analyses. JNK performed the angiographic analysis. JNK and NGDM performed the statistical analysis. JNK wrote the paper, which all authors critically reviewed for content. All authors read and approved the final manuscript.


T2* magnetic resonance of tissue iron concentration has improved the outcome of transfusion dependant anaemia patients. Clinical evaluation is performed at 1.5 T but scanners operating at 3 T are increasing in numbers. There is a paucity of data on the relative merits of iron quantification at 3 T vs 1.5 T.A total of 104 transfusion dependent anaemia patients and 20 normal volunteers were prospectively recruited to undergo cardiac and liver T2* assessment at both 1.5 T and 3 T. Intra-observer, inter-observer and inter-study reproducibility analysis were performed on 20 randomly selected patients for cardiac and liver T2*.R2 = 0.954, p < 0.001 for heart white-blood (WB) imaging; R2 = 0.931, p < 0.001 for heart black-blood (BB) imaging; R2 = 0.993, p < 0.001 for liver imaging). R2* approximately doubled between 1.5 T and 3 T with linear fits for both heart and liver . Coefficients of variation for intra- and inter-observer reproducibility, as well as inter-study reproducibility trended to be less good at 3 T (3.5 to 6.5 %) than at 1.5 T (1.4 to 5.7 %) for both heart and liver T2*. Artefact scores for the heart were significantly worse with the 3 T BB sequence  compared with the 1.5 T BB sequence .Association between heart and liver T2* at 1.5 T and 3 T was non-linear with good fit (Heart and liver T2* and R2* at 3 T show close association with 1.5 T values, but there were more artefacts at 3 T and trends to lower reproducibility causing difficulty in quantifying low T2* values with high tissue iron. Therefore T2* imaging at 1.5 T remains the gold standard for clinical practice. However, in centres where only 3 T is available, equivalent values at 1.5 T may be approximated by halving the 3 T tissue R2* with subsequent conversion to T2*. The transfusion dependent anemias are an important worldwide cause of morbidity and mortality. In these patients, repeated blood transfusions can lead to substantial iron tissue deposition which results in heart failure, endocrine dysfunction and death . Iron chA number of studies have assessed the robustness, reliability and reproducibility of myocardial and liver iron content quantification by T2* magnetic resonance (MR) . MyocardA total of 104 consecutive subjects were prospectively recruited from referrals for siderosis screening. Furthermore, a group of 20 healthy volunteers was included. Patients were already scheduled to undergo T2* MR myocardial and liver content assessment at 1.5 T for clinical purposes and a research scan at 3 T was performed in addition. Inclusion criteria were: 1) age >18 years old and 2) written and informed consent to participate. Exclusion criteria were: 1) claustrophobia, 2) metallic implants or permanent pacemaker and 3) inability to hold recumbent position for >15 min. The study protocol was approved by North-East Thames ethics committee.The T2* MR protocol consisted of two parts: 1) Myocardial and liver iron content assessment on a 1.5 T Sonata scanner 2) Repeated myocardial and liver iron burden assessment with a 3 T Skyra scanner .At 1.5 T, a four-element cardiac phase-array coil was used. After routine localizer acquisitions, ECG gated single breath hold multi-echo white blood (WB) and black blood (BB) sequences were acquired at a single mid-ventricular short axis slice with a 10 mm thickness at eight separate echo times . Both WB and BB sequences used a flip angle of 35°, a matrix of 128 × 256 pixels, a field of view (FOV) of 40 cm, repetition time of 20 ms between each radiofrequency pulse and a sampling bandwidth of 810 Hz per pixel. For WB imaging, all echo times were acquired exactly after the ECG R wave trigger. For BB sequence acquisition, the double inversion pulses were applied at the R wave trigger and the inversion time was set to extend into diastole.At 3 T, similar sequences were run on each patient. For WB iron content assessment, echo time ranged from 2.69 ms to 18.86 ms with 2.31 ms increments with a matrix of 256 × 256 pixels and a FOV of 40 cm. For the BB acquisition, echo times ranges from 1.57 ms to 17.74 ms with similar time increments, matrix size and FOV size. An acceleration factor of 2 was applied on all sequences. A small shimming box was used over the heart to optimize the gradients settings and minimize artefacts.At 1.5 T, a single transaxial 10 mm thick slice through the center of the liver was acquired at a succession of 20 echo times ranging from 0.97 ms to 13.89 ms with 0.68 ms increments, using a non-ECG-gated gradient echo sequence with a flip angle of 20°, a matrix of 128 × 128 pixels a 40 cm FOV and a sampling bandwidth 1950 Hz per pixel. The TR between 2 RF pulses was 200 ms. A four channel-channel array coil was used.At 3 T, sequence parameters were comparable. Echo time ranged from 1.0 ms to 16.5 ms with 1.41 ms increments. Matrix size was 128 × 128 pixels. Acceleration factor two was applied on all acquisitions. As for cardiac T2* and R2*, a small shimming box was used over the liver to improve image acquisition quality.The analysis of myocardial and liver T2* has been described elsewhere , 12. In T2* was subsequently transformed into its reciprocal R2* according to the equation:Curve fitting was done according to the truncation method . In patiIn order to compare reproducibility at 1.5 T and at 3 T, a group of 20 patients was selected for inter-observer, intra-observer variability and for inter-study variability. The 20 selected patients had levels of myocardial and liver siderosis that covered the entire range of the disease (from absent to severe iron overload). For intra-observer variability, the same investigator was asked to reassess myocardial iron content on WB and BB sequences and liver iron at 1.5 T and 3 T within a month after the first scan. For inter-observer variability two investigators experienced in MR iron content evaluation separately reported T2* at each sequence at 1.5 T and 3 T for each selected patient. Finally, patients underwent a repeated 3 T cardiac and liver iron content evaluation after a period of 1 h after the previous scan, for inter-study reproducibility assessment.U-test. Association between T2* and R2* values according to different sequence acquisition and field strengths were evaluated with the Spearman’s correlation coefficient with 95 % confidence interval (CI) or non-linear regression when appropriate. Cardiac artefact scoring between different acquisitions and field strengths were compared using a Chi-Square test. Coefficients of variation (CoV) and intra-class correlation (ICC) (with 95 % CI) analysis were conducted to assess inter- and intra-observer variability in addition to inter-study variability of cardiac and liver T2* values at 1.5 T and 3 T. For ICC, an alpha two-way mixed model with absolute agreement analysis was used. Statistical comparison between BB sequence inter-and intra-observer and inter-study reproducibility at 1.5 T and at 3 T was performed using the squared difference between the 2 observations as an estimate of between subjects variance and was multiplied by 2. A paired T-Test was done to compare the different squared difference. When appropriate, the squared differences were log transformed to allow T-test use. When the difference was zero, it was replaced by half of the next value before log transformation [P-value <0.05 was considered significant. All analyses were done using SPSS software version 22.0.0, IBM, Chicago, Illinois, USA.Imaging data were not normally distributed and are therefore expressed as median (interquartile range). Comparison of T2* and R2* values between normal volunteers and iron overload patients was performed with Mann-Whitney ormation . Finallyormation . A P-valn = 104) and normal (n = 20) patients are shown in Table A total of 124 subjects were included in the analysis. Demographics, clinical characteristics and median heart and liver T2* measurement at 1.5 T and at 3 T in both iron overload   . Good linear correlation was found for BB R2* measurements at 1.5 T and at 3 T  again with near doubling (94 %) of R2* values at 1.5 T.Using the WB sequence, the relationship between T2* values at 1.5 T and 3 T for the heart was non-linear with good fit (01) Fig. . There w01) Fig.  with neaR2 = 0.993, P < 0.001). Similar to heart R2* values, excellent linear correlation was found between R2* values at the two different field strengths  with an increase of 105 % in R2* from 1.5 T to 3 T.Regression graphs between T2* and R2* at 1.5 T and 3 T for the liver are displayed in Fig. P = 0.025) and the BB sequence at 3 T (P = 0.007). Moreover, the artefact score was significantly superior with the BB sequence at 3 T than with the WB sequence at 3 T (P < 0.001)  with the 1.5 T BB sequence, 4 (3–4) with the 3 T WB sequence and 4 (4–5) with the 3 T BB sequence. The artifact score was significantly higher (higher indicates less artefact) with the BB sequence at 1.5 T than with the WB sequence at 3 T  T2* shortening and increased B0 and B1 inhomogeneities may make T2* quantification at 3 T difficult in high iron loading; b) The correlations between T2* and R2* values between 1.5 T and 3 T are high; c) Good image quality was achieved at 3 T but was associated with significantly more artefacts than conventional BB 1.5 T imaging; d) There was a trend towards T2* measurements at 3 T being less reproducible than at 1.5 T.R2 = 0.934) [To our knowledge, this is the largest study of transfusion dependent patients reporting the association between T2* and R2* values at 1.5 T and 3 T. Meloni reported on 38 patients transfusion dependent patients and showed good correlation between WB mid-ventricular septal cardiac R2*at 1.5 T and 3 T (= 0.934) .n = 6; liver n = 8). Thus, reliable 3 T T2* values in high-risk patients were not always obtainable. Storey also expressed concerns over T2* and R2* quantification at 3 T [Guo quantified liver and cardiac T2 and T2* at 3 T in 24 patients and eight normal subjects . The T2*n at 3 T . Indeed,n at 3 T .The present study was conducted in a single centre with experience in T2* assessment. The relatively low CoV and high ICC values obtained should ideally be compared to the reproducibility data from other centres. One advantage conferred by 3 T MR may not have been fully explored in the present study, which is the possible increase of the acceleration factor and consequent shortening of the acquisition time. Such an increase in image acquisition speed however, may lead to reduction in signal to noise ratio and loss of image quality. Only adults >18 years were studied in this research which may limit the conclusions that may be drawn in younger and smaller patients.In transfusion dependent anaemia patients, heart and liver T2* and R2* quantification is feasible at 3 T. Good associations were obtained between values at 3 T and at 1.5 T with good reproducibility at both field strengths. However, no clear advantage of T2* imaging at 3 T could be identified and the clinical routine of T2* MR being performed at 1.5 T remains clinically optimal and should continue. Where only 3 T is available, one option for iron quantification is to halve the tissue R2* found at 3 T, and divide into 1000  to estimate the equivalent T2* value which would have been found at 1.5 T. However, great care must be taken to ensure that the T2* value at 3 T is not compromised by artefact or analysis difficulty.BB, black blood; CMR, cardiovascular magnetic resonance; CoV, coefficient of variation; FoV, field of view; ICC, intraclass correlation coefficient; ROI, region of interest; T, Tesla; WB, white blood


We have developed a novel and practical cardiovascular magnetic resonance (CMR) technique to evaluate left ventricular (LV) mitral annular motion by tracking the atrioventricular junction (AVJ). To test AVJ motion analysis as a metric for LV function, we compared AVJ motion variables between patients with hypertrophic cardiomyopathy (HCM), a group with recognized systolic and diastolic dysfunction, and healthy volunteers.We retrospectively evaluated 24 HCM patients with normal ejection fractions (EF) and 14 healthy volunteers. Using the 4-chamber view cine images, we tracked the longitudinal motion of the lateral and septal AVJ at 25 time points during the cardiac cycle. Based on AVJ displacement versus time, we calculated maximum AVJ displacement (MD) and velocity in early diastole (MVED), velocity in diastasis (VDS) and the composite index VDS/MVED.Patients with HCM showed significantly slower median lateral and septal AVJ recoil velocities during early diastole, but faster velocities in diastasis. We observed a 16-fold difference in VDS/MVED at the lateral AVJ . Patients with HCM also demonstrated significantly less mitral annular excursion at both the septal and lateral AVJ. Performed offline, AVJ motion analysis took approximately 10 minutes per subject.Atrioventricular junction motion analysis provides a practical and novel CMR method to assess mitral annular motion. In this proof of concept study we found highly statistically significant differences in mitral annular excursion and recoil between HCM patients and healthy volunteers. Atrioventricular plane displacement, a measure of longitudinal left ventricular (LV) function, accounts for approximately 60% of the stroke volume . ReducedIn the current study we investigated the movement of the atrioventricular junction (AVJ) throughout the cardiac cycle. We define the septal and lateral AVJ as myocardial points at the corresponding left atrial-ventricular junctions in long axis cine images. The maximum longitudinal displacement of the AVJ in systole corresponds to peak mitral annular excursion. The maximum velocity of the AVJ in early diastole reflects peak mitral annulus recoil velocity during passive LV filling. We previously showed that AVJ MVED represents a statistically significant CMR correlate of tissue Doppler echocardiography E’ , and we To test our hypothesis that hearts with systolic and diastolic dysfunction, despite preserved EF, would demonstrate abnormal AVJ motion, we performed our analysis on patients with HCM. With the highest prevalence of any genetic cardiac disorder, HCM affects approximately 1 in 500 individuals and may cause considerable morbidity and mortality . The disAtrioventricular junction motion tracking software, developed in our laboratory, measures the longitudinal position of the AVJ on routinely obtained long axis cine images as a function of time during the cardiac cycle. Analysis of steady state free precession (SSFP) cine images provides better temporal resolution compared to conventional phase-contrast imaging techniques  used to We retrospectively identified 30 consecutive patients between the ages of 21 and 64 with known or suspected HCM who underwent CMR as part of their routine clinical assessment at one of three affiliated hospitals  between February 2006 and July 2011. Eligible patients demonstrated LV hypertrophy (LVH) of at least 15 mm, not attributable to another etiology such as hypertension or diabetes, in a minimum of one myocardial segment. We excluded 5 patients without significant LVH, and one patient with concomitant evidence of left ventricular non-compaction. Prior to inception of the current study, healthy volunteers with no significant past medical history had been recruited to establish baseline AVJ motion variable values. A total of 14 healthy volunteers without hypertension, diabetes mellitus, coronary artery disease or other significant past medical history, and all with normal CMR examinations, were matched for mean age and used for comparison with the 24 HCM patients. Institutional review board approval was granted, and informed consent was obtained from all healthy volunteers.As part of routine clinical protocol, HCM patients underwent CMR evaluation on 1.5 T or 3 T systems  using a torso phased-array receiver coil. Two-dimensional SSFP pulse sequence cine imaging with electrocardiographic gating was performed in multiplanar short and long axis views, for evaluation of LV wall thickness, mass, segmental wall motion and global systolic function. Contrast-enhanced T1-weighted inversion-recovery late gadolinium enhancement (LGE) imaging was acquired for evaluation of myocardial fibrosis. Delayed imaging was performed 10 minutes after patients received intravenous gadolinium-diethylenetriamine penta-acetic acid (0.15 mmol/kg) contrast agent. Quantitative measurements of LV volumes, EF and mass, as well as qualitative assessments of LA size, severity of mitral regurgitation and systolic anterior motion of the mitral valve leaflets were performed. Post-processing, including the measurement of LV wall thickness, was performed on each segment of a 17-segment LV model, excluding the apical cap.Healthy volunteers were imaged with a 3 T CMR system , using standard phased-array coils. Typical imaging parameters for patients and healthy volunteers included: TR = 2.4 ms, TE = 1.4 ms, flip angle 51°, slice thickness = 6 mm, in-plane spatial resolution = 1.6 mm × 1.6 mm, receiver bandwidth = 930 Hz/pixel, 20–30 phases (average 25 phases) per cardiac cycle and temporal resolution ~ 45 ms. To cover late diastolic filling, image acquisition was performed throughout the cardiac cycle with retrospectively gated reconstruction.Atrioventricular motion was measured at the septal and lateral junction points between the left atrium and ventricle in the 4-chamber cine view. A reference line was placed through the LV apex and the midpoint of the mitral annulus Figure . The AVJAll distances measured were divided by the longitudinal length of the LV at end diastole to provide an approximate correction for individual heart sizes. The AVJ was identified and marked on each of the cine phases obtained Figure , and sevU test. Box-and-whisker plots were generated to graphically represent differences between the two groups. Inter-reader variability analysis was performed on the healthy volunteer cohort data obtained by two independent observers. To assess intra-study reproducibility, intraclass correlation coefficients were also obtained in a separate cohort of patients that was previously described [The continuous AVJ motion variables are presented as medians and IQR. Comparisons between AVJ motion variables in healthy volunteers and HCM patients were made using the Mann–Whitney escribed . SPSS StThe mean age of the HCM patients and healthy volunteers in the study was 45 (range 25–59) and 46 range 31–64), respectively. The mean thickness of the maximally hypertrophied segment was found to be 23 mm (range 16–32 mm). On average, each patient had 4.5 segments of myocardial hypertrophy (range 2–9). All HCM patients were found to have normal or increased EF  demonstrated regions of LGE consistent with myocardial fibrosis. None of the lateral wall segments showed evidence of LGE. The most common location of fibrosis was found to be in the basal anteroseptum , followed by the mid anteroseptum . The majority of hypertrophied segments demonstrated LGE. Of the 19 patients with basal anteroseptal hypertrophy, 14 (74%) were found to have LGE.-1) in early diastole relative to healthy volunteers. Conversely, during diastasis, AVJ motion showed significantly faster normalized velocities in patients with HCM at both the septal and lateral AVJ. We found a 16-fold difference in the VDS/MVED ratio at the lateral AVJ and a 4-fold difference at the septal AVJ. Despite the far fewer number of hypertrophied segments and no evidence of LGE in the lateral wall, there were no statistically significant differences between the septal and lateral AVJ motion variables within the HCM group. Similarly, when comparing septal to the lateral AVJ motion variables within the healthy volunteers, we observed no significant differences. Twenty of 24 (83%) HCM exhibited LGE. Comparing HCM patients with and without LGE, we found no statistically significant differences in any of the AVJ motion variables  at either septal or lateral AVJ. In comparison to healthy volunteers however, both HCM patients with and the four patients (17%) without LGE demonstrated statistically significant differences in MVED, VDS and VDS/MVED  and the composite index VDS/MVED, in patients with HCM when compared to healthy volunteers Table  and 5. Py of 24 8% HCM exhWe have demonstrated the feasibility of a novel and practical CMR technique, developed in our laboratory, to track longitudinal AVJ motion throughout the cardiac cycle. Using this technique, several AVJ motion variables relating to LV function can be measured. While novel to CMR, these variables are derived from principles relevant to assessment of systolic and diastolic function by established echocardiographic measurements.The MD, measured from the displacement-versus-time curve at end systole, reflects longitudinal mitral annular excursion and corresponds to echocardiographic MAPSE.Since mitral annular excursion occurs with longitudinal LV contraction and MAPSE predicts EF , the MD We also measured MVED, the maximum normalized velocity of the AVJ during the early, passive phase of diastole. This variable is measured from the AVJ normalized velocity-versus-time curve, which is derived by measuring the slope between sequential time points on the normalized displacement-versus-time curve. As we previously showed, MVED represents a statistically significant CMR correlate of mitral annulus E’ measured by tissue Doppler echocardiography . Since wWe also measured the normalized velocity of the AVJ in diastasis, VDS, by finding the best-fit line through the normalized velocity-versus-time curve during the quiescent phase of diastole. The composite index VDS/MVED was calculated to accentuate the individual differences in the AVJ motion variables we noted when comparing patients with HCM to healthy volunteers.While all HCM patients in our study demonstrated normal or increased EF, they showed decreased MD for both the septal and lateral AVJ. As the MD corresponds to longitudinal mitral annular excursion of a single point at the AVJ, this may reflect altered regional rather than global systolic function. Similar discrepancies between global and regional systolic function had previously been observed used tagged-CMR sequences in patients with HCM . In a peAs expected, we noted slower velocities of the septal AVJ in HCM patients compared to healthy controls. Somewhat unexpectedly, however, we also found slower velocities of the lateral AVJ, despite the relative sparing of hypertrophy and fibrosis in this region. When comparing the septal and lateral AVJ velocities within the HCM group, we again found no significant differences. These findings agree with the significantly lower septal and lateral E’ velocities noted by Severino et al.  when comWe noted significantly higher normalized velocities of both septal and lateral AVJ during diastasis in HCM patients, indicating the extension of relaxation and passive filling into the normally quiescent phase of diastole. Elevations in left atrial pressure may account in part for the persistence of blood flow across the mitral annulus during diastasis, and the correspondingly higher AVJ velocities in this phase of diastole. The higher velocities could also represent a prolongation of the initial, normally rapid relaxation phase of early diastole into the normally quiescent period of mid-diastole. The increased mid-diastolic velocities may be analogous to the L wave noted on mitral inflow in certain patients with elevated filling pressures. Interestingly, a small subset of patients noted to have triphasic mitral inflow by Ha et al.  carried Our retrospective proof-of-concept study has several limitations, including a small sample size of HCM patients, which included only 4 women (17%). The cardiac MR studies performed on healthy volunteers did not include short axis cine images, so LV EF, although qualitatively normal, was not quantified. Although we previously demonstrated a statistically significant correlation between MVED and tissue Doppler echocardiography E’, AVJ motion and echocardiography variables were not directly correlated in this HCM cohort. However, the known E’ velocity reduction in patients with HCM, in conjunction with the decreased MVED we found associated with HCM and the two previous studies correlating E’ and MVED, indicate the relevance of AVJ motion tracking findings in HCM.Atrioventricular junction motion tracking, a practical technique developed in our laboratory, assesses mitral annular excursion and recoil by CMR. Using this novel approach, we observed highly statistically significant differences in AVJ motion variables in HCM patients compared to healthy volunteers. Even with relative sparing of hypertrophy and LGE, the morphologically normal-appearing HCM lateral wall also showed abnormal AVJ motion. Atrioventricular junction motion analysis can be performed efficiently on cine sequences that are obtained in nearly all CMR evaluations, without the need for additional acquisition time.AVJ: Atrioventricular junction(s); CMR: Cardiovascular magnetic resonance; EF: Ejection fraction; HCM: Hypertrophic cardiomyopathy; IQR: Interquartile range; LA: Left atrium; LGE: Late gadolinium enhancement; LV: Left ventricle/ventricular; LVH: Left ventricular hypertrophy; MAPSE: Mitral annular plane systolic excursion; MD: Maximum displacement; MVED: Maximum velocity early diastole; NS: Not significant; SSFP: Steady state free precession; VDS: Velocity diastasis.The authors declare that they have no competing interest.SGS helped conceive the study design, analyzed the results and wrote the manuscript. SC and SB co-wrote the atrioventricular junction motion tracking software and applied their program to obtain all data analyzed. RD, MBS, MS and SDK helped conceive the study design, interpret the data and critically revise the manuscript. LA developed the technique of atrioventricular junction motion tracking and served as the Principal Investigator for the study. All authors read and approved the final manuscript.


Tissue Doppler imaging (TDI) can be used to assess fetal cardiac function and it has been shown to detect changes associated with hypoxia in animal models. However, the analysis is cumbersome and time consuming. The main objective of this study was to evaluate the feasibility of a new algorithm developed for the automated analysis of color TDI velocity recordings of the fetal myocardium. Furthermore, we wanted to assess the effect of different sizes of region of interests (ROI) on the measurement of cardiac cycle time intervals and myocardial velocities at different gestations.This study included analysis of 261 TDI velocity traces obtained from 17 fetal echocardiographic examinations performed longitudinally on five pregnant women. Cine-loops of fetal cardiac four chamber view were recorded with color overlay in TDI mode and stored for off-line analysis. ROIs of different sizes were placed at the level of the atrioventricular plane in the septum and in the right and left ventricular walls of the fetal heart. An automated algorithm was then used for the analysis of velocity traces.Out of the total 261 velocity traces, it was possible to analyze 203 (78 %) traces with the automated algorithm. It was possible to analyze 93 % (81/87) of traces recorded from the right ventricular wall, 82 % (71/87) from the left ventricular wall and 59 % (51/87) from the septum. There was a trend towards decreasing myocardial velocities with increasing ROI length. However, the cardiac cycle time intervals were similar irrespective of which ROI size was used.An automated analysis of color TDI fetal myocardial velocity traces seems feasible, especially for measuring cardiac cycle time intervals, and has the potential for clinical application. Tissue Doppler imaging (TDI) is a technique that is used to evaluate the movements of the myocardial walls. In adults, it appears to facilitate the diagnosis of subclinical myocardial disease and helps in predicting the prognosis of major cardiac diseases, such as acute myocardial infarction –5. The mStudies on adults during hypoxia have found prolongation of ventricular isovolumic relaxation time measured by TDI . This coThere are two main echocardiographic approaches to assess myocardial motion, i.e. spectral (pulsed wave) TDI and color TDI. In both techniques, the region of interest (ROI) is generally placed at the level of the atrioventricular plane (AV-plane) in order to assess the longitudinal motion executed by subendocardial longitudinal myocardial fibers that are considered to be most susceptible to hypoxia , 16. HigTo perform the automated analysis with this new method, well-defined velocity traces are required. Acceleration traces with distinct shifts that represent the changes in myocardial work can then be derived and used to define time intervals. The resolution of traces might be influenced by several factors including the size of the ROI, frame rate, size of the color box, sector width and line density. A larger ROI size has been shown to reduce the variability and diagnostic inconsistency in adults with dyssynchrony  and a smClinical application of TDI for assessing and monitoring fetal wellbeing could be simplified and improved by automation of image analysis. Thus, the main objective of this study was to evaluate the feasibility of a new algorithm developed for the automated analysis of color TDI velocity recordings of the fetal myocardium. Furthermore, we wanted to assess the effect of different ROI sizes on the measurement of cardiac cycle time intervals and myocardial velocities at different gestations.This study included analysis of 261 TDI velocity traces obtained from 17 fetal echocardiographic examinations performed on five pregnant women with uncomplicated singleton pregnancies. These five women were randomly selected from a group of 120 women with uncomplicated pregnancies included in a larger longitudinal study investigating fetal cardiac function during 18–40 weeks of gestation. Ultrasound examinations were performed serially at approximately 4-weekly intervals by an experienced operator using a Vivid 7 Dimension ultrasound machine equipped with a M4S sector transducer with frequencies of 1.5–4.3 MHz  Pregnancies were dated based on the measurement of biparietal diameter in the second trimester. The study was approved by the Regional Committee for Medical and Health Research Ethics – REK Nord  and an informed written consent was obtained from all the participants.At each examination, a four chamber view of the fetal heart with color overlay in TDI mode was obtained and cine loops of 5-10 consecutive cardiac cycles were recorded. The ultrasound beam was aligned parallel to the interventricular septum with an insonation angle close to zero (<10°). An attempt was made to keep the frame rate >180 frames/s. An off-line analysis was performed using quantitative analysis  in EchoPAC  Fixed ROIs of different sizes were placed at the level of the AV-plane in the septum and in the right and left ventricular wall of the fetal heart. ROIs were placed manually at the level of the AV-plane  groups: GA I (18-24 weeks), GA II (25–32 weeks) and GA III (33–41 weeks). The largest ROI widths of 2 mm, 3 mm and 4 mm were chosen for GA I, GA II and GA III, respectively as estimated to cover the entire thickness of the myocardium. The ROI length was increased in steps to cover different proportions of the ventricular length. The length of the septum was measured from the AV-plane to the apex in end-diastole and ROI sizes compared to this as an estimate of proportion of myocardial ventricular length occupied by each ROI size. The largest ROI length in this study was 4 mm, 6 mm and 8 mm in GA I, GA II and GA III respectively. A ROI of 2×2 mm was analyzed for all recordings to enable comparison of myocardial velocities between different ROI sizes.Dynamic Adaptive Piston Pump (DAPP) principle describing the heart as a mechanical pump controlled by its inflow [DAPP principle, is initiated by the movement of the AV-piston (the AV-plane), the atrial contraction is considered as the starting point of the cardiac cycle. The terms pre- and post-ejection are used instead of isovolumic contraction and relaxation as they are defined by shifts in myocardial work rather than by the valve opening and closure.The myocardial velocity traces were transferred to GHLab software  for visual identification and manual definition of cardiac cycle time intervals –22. GHLas inflow . This meThe acceleration shifts were assessed by two investigators (LH and JJ) and the traces were divided into three categories depending on the degree of well-defined shifts. An acceleration score of 3 represents clear and well-defined shifts, a score of 2 less well-defined, often with a biphasic appearance, and a score of 1 with indistinct shifts, generally with a flat appearance , atrial contraction (Am) and systole (Sm) were automatically extracted from the traces by the GHLab software as soon as the time intervals were defined. All measured velocity parameters were compared to the 2×2 mm ROI as the smallest ROI size is expected to record the highest velocities being closest to the AV-plane and averaging a smaller area. The differences in velocities and time intervals measured using different ROIs were calculated as the percent change in relation to the reference ROI of 2×2 mm.A newly developed automatic algorithm was then used to analyze the original TDI velocity traces and obtain cardiac cycle time intervals using MATLAB . The automated algorithm consists of approximately 100 pages of MATLAB code, encompasses four different filter settings and uses pattern recognition to detect time events.In order to assess limitations, extended information was extracted from the DICOM files. For the evaluation of axial resolution the points/mm along the ultrasound beam was measured, for temporal resolution the frame rate and for the spatial resolution the line density was noted. The traces were smoothed by a three point moving average filter in EchoPAC.Data analysis was performed using IBM SPSS Statistics for Windows, version 23.0 . Continuous variables are presented as mean ± SD or median (range) as appropriate. Categorical variables are presented as (n %).2 and all women had uncomplicated pregnancies with normal perinatal outcome. The median gestational age at examination was 21 weeks in GA I, 29 weeks in GA II and 38 weeks in GA III. The total number of analyzed traces including all walls and ROI sizes were 45, 72 and 144 respectively. The axial resolution of images estimated by the median number of points/mm was 1.46 , the median frame rate  was 190  per second, and the line density  was 20 . The median height of the color box during the examination was 10.8 cm (7.2–12.7 cm).The mean age of the pregnant women was 29 ± 4.4 years, BMI was 23.7 ± 2.6 kg/mThe different ROI sizes used in each gestational age group, the total number of traces with an acceleration score of 3, mean ventricular length of the septum and percentage of the ventricular length occupied by each ROI size are presented in Table The percent differences in velocities measured using different ROI lengths compared to the reference ROI of 2×2 are shown in Table Functional fetal echocardiography using TDI is a promising tool in experienced hands for a selected group of patients. However, its introduction to more general clinical practice is hampered partly because it is cumbersome and time consuming. Our study indicates that automated analysis of fetal cardiac function assessed by color TDI is feasible using a newly developed algorithm. If the automated method could be used for instantaneous on-line display of results it could prove to be clinically useful. The automated technique requires substantially less time to analyze the TDI velocity traces compared to the manual method. The method is not dependent on an ECG in order to define time intervals and therefore suitable for antenatal assessment of human fetuses. As the automated method uses enhanced acceleration shifts rather than crossing points of velocity traces with the baseline for defining different phases of the cardiac cycle, it can be expected to reduce the errors related to fetal breathing and movements. Furthermore, multiple cardiac cycles can be evaluated quickly and averaged, which could result in a potentially higher accuracy of measurements compared to a manual analysis.The automated method appears to be dependent on the quality of velocity traces and its derivatives, i.e. acceleration traces, and these seem to vary with the size of the ROI. The fetal heart grows considerably throughout gestation. Tan et al. have measured the thickness of the septum in a fetal four chamber view at end-diastole giving wall dimensions of 1.8 mm, 2.9 mm and 3.6 mm at a gestational age of 20, 30 and 40 weeks respectively. Studies of the right ventricular cavity at end-diastole demonstrate the length to be 12 mm, 20 mm and 26 mm at 20, 30 and 40 weeks respectively , 25. As TDI might be a useful method in assessing fetal cardiac function, but there is a lack of standardization concerning image acquisition, data analysis and post-processing. As we use a fixed (stationary) ROI placed at the level of the AV-plane at end systole, the myocardium apical to the original position will be interrogated during the rest of the cardiac cycle. Therefore, it might be important to choose a reasonably large ROI to reduce the variability associated with operator placement of the ROI . Substann = 261) to evaluate. However, all color TDI recordings are unlikely to be adequate for evaluation even by manual method in a larger unselected population. The accuracy of the automated algorithm should be tested in a larger population including pathological pregnancies.Although only a small number of women with normal pregnancies were examined, for a feasibility study we had a reasonable number of traces (An automated analysis of color TDI fetal myocardial velocity traces seems feasible, especially for measuring cardiac cycle time intervals, and has the potential for clinical application.


Left ventricle (LV) remodeling associated with lower LV ejection fraction after successfully treated ST-elevation myocardial infarction (STEMI) may occur in some patients. We investigated the prognostic value of intramyocardial hemorrhage (IMH) as assessed by T2* images beyond a comprehensive CMR assessment with late gadolinium enhancement (LGE) imaging including microvascular obstruction (MVO) evaluation.A total of 110 patients with STEMI were prospectively recruited and were examined with CMR at Day 4 ± 2 and Month 6 after reperfusion for measurement of LV end-diastolic (EDV) and end-systolic (ESV) volumes, LV ejection fraction (LVEF) infarct size (IS) and presence and extent of MVO and IMH. Adverse remodeling was defined as dilated left ventricular end-systolic volume indexes (EDV) at 6 months CMR.All patients were analysed. 41 patients (45%) presented with Anterior AMI, 26 with Lateral (23%) and 29 with Inferior MI (32%). Mean age was 54 +/- 12 y.o . Mean delay for reperfusion therapy was 115 +/- 100 min. LV remodelling was observed in 39 patients (36%). Despite identical EDV, patients with LV remodelling had lower LVEF at baseline , a bigger IS  and MVO extent (p < 0.01). By multivariate analysis, IMH (OR = 2.8[1.3-6.0]) and IS (OR = 3.2[1.8-12.5]) were identified as independent predictors of LV remodelling.Presence of IMH after STEMI assessed by T2* CMR predicts LV adverse remodeling.Research Grant from the french Society of cardiology (SFC)


To assess the impact of left ventricular (LV) diastolic dysfunction on left atrial (LA) phasic volume and function using dual-source CT (DSCT) and to find a viable alternative prognostic parameter of CT for LV diastolic dysfunction through quantitative evaluation of LA phasic volume and function in patients with LV diastolic dysfunction.Seventy-seven patients were examined using DSCT and Doppler echocardiography on the same day. Reservoir, conduit, and contractile function of LA were evaluated by measuring LA volume (LAV) during different cardiac phases and all parameters were normalized to body surface area (BSA). Patients were divided into four groups  according to echocardiographic findings. The LA phasic volume and function in different stages of LV diastolic function was compared using one-way ANOVA analysis. The correlations between indexed volume of LA (LAVi) and diastolic function in different stages of LV were evaluated using Spearman correlation analysis.P < 0.05). For LA conduit function, there were no significant differences between the patients in the pseudonormal group and restrictive filling group (P = 0.195). There was a strong correlation between the indexed maximal left atrial volume , minimal left atrial volume , left atrial volume at the onset of P wave , and different stages of LV diastolic function. The LAVi increased as the severity of LV diastolic dysfunction increased.LA ejection fraction (LAEF), LA contraction, reservoir, and conduit function in patients in impaired relaxation group were not different from those in the normal group, but they were lower in patients in the pseudonormal and restrictive LV diastolic dysfunction groups (LA remodeling takes place in patients with LV diastolic dysfunction. At the same time, LA phasic volume and function parameters evaluated by DSCT indicated the severity of the LV diastolic dysfunction. Quantitative analysis of LA phasic volume and function parameters using DSCT could be a viable alternative prognostic parameter of LV diastolic function. The left atrium serves as a reservoir, conduit, and booster pump during the cardiac cycle . With itCoronary CT angiography (CCTA) examination has been widely used in clinical settings. Information regarding cardiac function can also be collected as a by-product of CCTA and can be used to evaluate heart function accurately –12. In aTo date, there has been no report regarding the relationship of LA phasic volume and function with LV diastolic dysfunction using DSCT measurement. The purpose of this study was to assess the impact of LV diastolic dysfunction on LA phasic volume and function using DSCT and to find a viable alternative prognostic parameter of CT for LV diastolic dysfunction through quantitative evaluation of LA phasic volume and function in patients with LV diastolic dysfunction.The study protocols and written informed consent forms were approved by the local ethics committee of Beijing Anzhen Hospital associated with Capital Medical University in China. Written informed consent for information to be used for the study was obtained from all participating patients.Those patients who were referred for a clinically indicated CCTA were prospectively enrolled for possible participation in this study. The patients with arrhythmias, cardiac valvular heart diseases, congenital heart diseases, or implanted pacemakers or defibrillators were excluded. Additionally, patients were excluded if they could not undergo CCTA examination because of renal dysfunction (serum creatinine levels higher than 1.5 mg/dl) or a previous allergic reaction to iodinated contrast media. Only patients with normal LV systolic function were included (LVEF > 50%). A total of 77 patients  met the study’s inclusion criteria. Of these, 49 had hypertension, 7 had history of myocardial infarction, 15 had coronary artery disease, and 26 had diabetes mellitus. For all the included patients, Doppler echocardiography was performed after CT on the same day. The subjects’ heart rates were continuously monitored throughout image acquisition by two modalities. No additional ß-blockers were administered in the current study.A commercially available system, Philips IE33, was used for imaging. Pulsed wave (PW) Doppler and tissue Doppler (TD) were obtained using a S5-1 electronic transducer (1.7–3.4 MHz) and data were obtained from apical four-chamber view . PW DoppThe LV diastolic function was divided into four groups according to the recommendations for the Evaluation of Left Ventricular Diastolic Function by the American Society of Echocardiography and European Society of Echocardiography . If e′ sCT examination was performed using a 64-slice DSCT scanner . The scanning range covered the entire heart from 1 cm below the level of the tracheal bifurcation to the diaphragm. A 50–75 ml bolus of Iopamidol 370  followed by 20 ml of saline solution was continuously injected into an antecubital vein at a rate of 4–5 ml/s via a dual-head power injector . The CT angiography was triggered automatically and image acquisition started 4 s after the attenuation reached the predefined threshold of 100 HU at the aortic root. The data were acquired in a craniocaudal direction with a tube voltage of 100 kV—135 kV and tube current of 350 mAs—420 mAs. The other scan parameters were as follows: slice collimation of 2 × 32 × 0.6 mm, slice acquisition of 2 × 64 × 0.6 mm by means of a z-flying focal spot, detector collimation of 64 × 0.5 mm, a gantry rotation time of 330 ms, pitch of 0.2–0.5 (depending on the heart rate), reconstructed slice thickness of 0.75 mm (at 0.4 mm increments), and B26f kernels. Electrocardiography (ECG)-gated tube current modulation was used to reduce the required dose of radiation during scanning for all the patients, as recommended [Two independent observers with more than 5 years experience in cardiovascular imaging evaluated the images and measured the parameters of the left atrium. Assessment of the LAV was performed with a dedicated software package for cardiac function analysis  with threshold-based region-growing 3D segmentation of the LA cavity. When necessary, the LA endocardial contours were manually corrected frame by frame on 360° rotational MPRs to make sure that all the CT images had a discernible cardiac cavity Figs  and 2. Tleft atrial reservoir function = (LAVmax—LAVmin)/LAVmin × 100%left atrial conduit function = (LAVmax—LAVp)/LAVmax × 100%left atrial active contractile function = (LAVp—LAVmin)/ LAVp × 100%LAEF = (LAVmax—LAVmin)/LAVmax × 100%.The left atrial function was defined as follows :left atAll the volumes were normalized to the body surface area (BSA).LAVmax = maximal left atrial volumeLAVmin = minimal left atrial volumeLAVp = left atrial volume at the onset of P waveLAEF = left atrial ejection fraction.P values below 0.05 was considered significant.Results are presented as mean ± SD for continuous variables. The statistical software was SPSS version 18.0 . Differences in indexed LAV and function between groups with different levels of left ventricular diastolic dysfunction grade were analyzed using one-way analysis of variance followed by post-hoc test. The Spearman correlation coefficient was used to assess the correlation between the indexed LAV and different grades of LV diastolic function. For all statistical analyses, a P < 0.001) and significantly higher in the restrictive filling group (P ≤ 0.01) than in the other 3 groups. On the contrary, the A value were significantly higher in the impaired relaxation group (P < 0.001) and significantly lower in the restrictive filling group (P ≤ 0.05) than in the other 3 groups. There were significant differences in E/A ratios between the normal group and LV diastolic dysfunction groups and with the other 3 groups (P < 0.01). In addition, e′ s, e′ l, and em were significantly lower in LV diastolic dysfunction groups than in the normal (P < 0.001). In the pseudonormal filling group and restrictive filling group, the Av. E/e values were more pronounced than in the normal group and impaired relaxation group (P < 0.001). DT time was significantly greater in the impaired relaxation group than in the other 3 groups (P < 0.001), but DT time was significantly lower in the restrictive filling group (P < 0.001). LVEF > 50% in all groups, but it was significantly lower in the pseudonormal filling group (P = 0.002) and restrictive filling group than in the normal group (P = 0.009).The clinical characteristics and echocardiographic variables are listed in P < 0.001). The LA reservoir function in restrictive filling group was significantly lower than in the pseudonormal group (P < 0.001). There was no significant difference between impaired relaxation group and normal group for left atrial reservoir function (P = 0.181). There was also no significant difference between impaired relaxation group and normal group for left atrial conduit function (P = 1.000). The LA conduit function in pseudonormal group (P = 0.033) and in restrictive filling group (P < 0.001) was significantly lower than in normal group. The LA conduit function in restrictive filling group was significantly lower than in the impaired relaxation group (P = 0.001). There was no significant difference between the impaired relaxation group and normal group for LA contractile function (P = 1.000). The LA contractile function in the pseudonormal group and restrictive filling group was significantly lower than in the impaired relaxation group and normal group (P < 0.001). The LA contractile function in the restrictive filling group was significantly lower than in the pseudonormal group (P = 0.001). The indexed LAVmax, the indexed LAVmin, and the indexed LAVp in LV diastolic dysfunction groups were significantly higher than in the normal group . The LA ejection fraction (LAEF) was lower in the impaired relaxation group than in the normal group but not significantly so (P = 0.139). The LAEF was significantly lower in the pseudonormal group and restrictive filling group than in the normal group and impaired relaxation group .The differences in LA reservoir, conduit, and contractile function in different diastolic function groups as measured by DSCT are given in P < 0.001). Similarly, there was a strong correlation (r = 0.91) between the indexed LAVmin and different degrees of LV diastolic dysfunction (P < 0.001). There was also a strong correlation (r = 0.84) between the indexed LAVp and different degrees of LV diastolic dysfunction (P < 0.001).There was good correlation (r = 0.85) between the indexed LAVmax and different degrees of LV diastolic dysfunction . The indfunction . The indfunction . The indThe main findings of the current study were that (a) left atrial reservoir, conduit, and contractile function decreases as the left ventricular diastolic function worsens, and (b) there is a significant correlation between indexed left atrial volume assessed by DSCT and different stages of LV diastolic dysfunction.The current study demonstrated that there were no significant differences in LAEF between the impaired relaxation group and the normal group. There was also no significant difference in the LA contractile function, reservoir, or conduit function between these two groups. However, all these functions showed a downward trend. One explanation may be that there is a compensatory mechanism for the decreased LA functions that helps maintain total LA emptying volume . HoweverThere is a growing body of evidence demonstrating that LA enlargement is closely associated with the severity of diastolic dysfunction and can serve as predictor of future stroke, atrial fibrillation, and death –28. In aTraditionally, echocardiography is first-line imaging modality for evaluation of LA size. However, in the patients with poor echo window, LA volume is impossible to evaluate. The evaluation of LA size and function by echocardiography is not accurate since using Simpson’s method, which involves making geometrical assumptions. And 3D echocardiographic quantitation of LA volume tends to skew results lower than magnetic resonance imaging (MRI) or CT techniques ,31. CardPrevious studies involving echocardiography showed that indexed LAVmax has a strong graded correlation to the severity of LV diastolic function ,33. In tAlthough the feasibility of LA assessment by CT has been already reported ,14, mostThe current study has several limitations. First, the sample size was relatively small, because clinically, there are not as many patients with restrictive LV diastolic dysfunction as normal patients or patients with slight LV diastolic dysfunction. Second, Doppler echocardiography, not cardiac catheterization, was used to evaluate the left ventricular diastolic function for the classification of LV diastolic function grades. However, its invasive nature renders it impractical as a clinical tool. Future studies will have to be performed to demonstrate the prognostic value of LA phasic volume and function and facilitate the development of more effective strategies for the treatment and prevention of LV diastolic dysfunction.In summary, LA remodeling occurs in patients with LV diastolic dysfunction. LA phasic volume and function parameters evaluated by DSCT were found to indicate the severity of the LV diastolic dysfunction. Quantitative analysis of LA phasic volume and function parameters using DSCT was found to be a viable alternative prognostic parameter for LV diastolic dysfunction.S1 Dataset(XLS)Click here for additional data file.S2 Dataset(XLS)Click here for additional data file.


The high interindividual variability of myocardial T2 relaxation times appears to be one of the main challenges for the clinical application of cardiac T2-mapping. This study therefore aimed to evaluate potential underlying causes for this variability, analyzing the reproducibility of three different cardiac T2-mapping sequences and evaluating the influence of cofactors on T2 relaxation times30 healthy volunteers were examined three times on a clinical 1.5T scanner . In each examination three different T2-mapping sequences were acquired at three slices in short axis view: Multi Echo Spin Echo (MESE), T2-prepared balanced Steady State Free Precession  in single linear regression models. Using multiple regression models, we observed significant relations between mean T2 times and age (p < 0.005), gender (p < 0.01), and either weight or height (p < 0.005), for given values of the remaining cofactors.Intra- and inter-observer reproducibility of all tested T2-mapping sequnces is high, thereby confirming previous studies. According to our study, the high interindividual variability of myocardial T2 relaxation times is most likely due to proband-related effects such as age, gender, weight and height and other cofactors intraindividually varying with time.


Magnetic resonance imaging has become an essential tool in the management of patients with iron overload. Most of these patients are located in under-developed regions of the world where access to scanners is limited. Effective use of resources is therefore mandatory especially in very densely populated areas. We sought to assess if an accelerated protocol under ten minutes for iron overload assessment in the heart and liver using automated sequences and analysis would be feasible and accurate in a multicenter study.Seven centers participated in the study enrolling 179 patients in ten-minute slots. All patients underwent a similar protocol using different 1.5T scanners from a single vendor (Siemens AG), consisting of orthogonal localizers, two-chamber localizer, single-slice short-axis prototype T1 MOLLI and T2* multiecho acquisition of the heart and single-slice transaxial slice of the liver with T1 and T2* sequences. Automated maps for both T2* and T1 were generated by an in-line processing prototype software. T2* results were also obtained by manual calculation using a ROI-based fit and truncation. In a subgroup of sixteen patients, left-ventricle function was also assessed using a sparse sampling and iterative reconstruction cine technique with a repeat scan using traditional T2* sequences plus cine-SSFP imaging. Endpoints of the study included the time required for each exam, the accuracy of the automatically calculated T2* values compared to the manual analysis as well as factors associated with duration of the exam and successful completion of the protocol.The mean age of participants was 27.5±20.1 years (range 2 to 91 years) with 51% females and 44% children/adolescents. The median scan time was 5.2 minutes (IQR 4 to 7 minutes). For the heart, Bland-Altman plots demonstrated a mean difference of -1.2ms (95%CI -1.7 to -0.8ms) for the automated maps compared to the manual analysis. In the liver, this difference was -0.18ms (95%CI -0.30 to -0.06ms). In only 1.1% of the patients, the heart T2* values could not be calculated due to motion; all liver T2* values were obtained. Age, sex, etiology and hemoglobin levels did not affect the total exam time while significant differences were observed among the centers (P<0.001). In the subgroup of sixteen patients with repeat scans including cine imaging, there were significant differences in total time of scan .Use of an accelerated protocol for acquisition and calculation of iron overload in the liver and heart is feasible and results in successful completion of the study in the majority of patients with similar values compared to manual analysis.N/A.


Abnormal splice‐out of the exon 7‐encoded segment in the N‐terminal variable region of cardiac troponin T (cTnT‐ΔE7) was found in turkeys and, together with the inclusion of embryonic exon (eTnT), in adult dogs with a correlation with dilated cardiomyopathy. Overexpression of these cTnT variants in transgenic mouse hearts significantly decreased cardiac function. To further investigate the functional effect of cTnT‐ΔE7 or ΔE7+eTnT in vivo under systemic regulation, echocardiography was carried out in single and double‐transgenic mice. No atrial enlargement, ventricular hypertrophy or dilation was detected in the hearts of 2‐month‐old cTnT‐ΔE7 and ΔE7+eTnT mice in comparison to wild‐type controls, indicating a compensated state. However, left ventricular fractional shortening and ejection fraction were decreased in ΔE7 and ΔE7+eTnT mice, and the response to isoproterenol was lower in ΔE7+eTnT mice. Left ventricular outflow tract velocity and gradient were decreased in the transgenic mouse hearts, indicating decreased systolic function. Ex vivo working heart function showed that high afterload or low preload resulted in more severe decreases in the systolic function and energetic efficiency of cTnT‐ΔE7 and ΔE7+eTnT hearts. On the other hand, increases in preload demonstrated preserved Frank‐Starling responses and minimized the loss of cardiac function and efficiency. The data demonstrate that the N‐terminal variable region of cardiac TnT regulates systolic function of the heart. Using transgenic mouse models expressing myopathic splicing variants of cardiac troponin T, we demonstrated that abnormality in the N‐terminal variable region of troponin T selectively affects the systolic function of the heart, whereas the Frank‐Starling response is preserved. Two‐month‐old female mice were used for echocardiographic measurement and 3‐ to 5‐month‐old mice of both sexes were used for ex vivo working heart studies.−1 body weight, i.p.) and the same measurement was repeated for β‐adrenergic responses. All data and images were saved and analyzed with the Advanced Cardiovascular Package Software  to evaluate cardiac function.Echocardiography studies were performed using a Vevo 770 high‐resolution in vivo imaging system  as described previously . Hearts were rapidly isolated and cannulated via aorta with a modified 18‐gauge needle to start Langendorff retrograde perfusion within 3 min after opening of the chest. A pressure sensor  was connected to the side arm of aortic cannular and placed at the level equivalent to the heart to measure aortic pressure. A 0.5 mL air bubble was introduced in the aortic trap to mimic in vivo arterial compliance. A pulmonary vein was then cannulated with a 16‐gauge needle for perfusion to the left atria in the working mode. The pulmonary artery trunk was connected to a beveled polyethylene‐25 tubing to collect the coronary effluent from the right ventricle. The coronary effluent was also measured for the O2 concentration by passing through an O2 sensor (Microelectrode). The apex was punctured using a 30‐gauge needle to make a path that allows the insertion of a 1.2‐Fr pressure–volume (P–V) catheter  into the LV. After all the cannulations were established, a water jacket was placed around the heart to maintain the surrounding temperature at 37°C before switching to left atrial perfusion to start the working mode.Transgenic and wild‐type mouse hearts were examined in isolated ex vivo working heart preparations as previously described . Preload response was tested by altering the height of preload perfusate reservoir at left atrial filling pressure of 5, 8, 10, 12.5, 15, and 20 mmHg. Afterload was adjusted by changing the height of effluent outlet equivalent to 55, 70, or 90 mmHg.Immediately after functional measurements, LV muscle tissue was collected from each heart and stored at −80°C for Western blot verification of cardiac TnT contents.Left ventricular ejection time parameters were determined as previously described  and LV total integral .2 consumption as previously described  = (PO2a−PO2v) × coronary flow × c/760 where PO2a is PO2 in the perfusate (95%), PO2v is PO2 in the coronary effluent, and c is the solubility coefficient for O2 in Krebs buffer (22.7 mL O2·atm−1·mL−1 at 37°C).Left ventricular efficiency was further calculated from O−1·g−1) = cardiac output (in mL·min−1·g−1) × aortic pressure (in mmHg) × 1.33 ×10−4 J·mmHg−1·mL−1. Kinetic work (in J·min−1·g−1) =cardiac output (in mL·min−1·g−1) × [perfusate density (in g cm−3)/980 cm s−2] × V2 × 9.8 × 10−3 J·g−1·m−1·min−1·g−1 where V (in cm s−1) = [cardiac output (in mL min−1)/aortic cross‐sectional area (in cm2)] × [cycle time (in s)/ejection time (in s)] × (1/60). Myocardial O2 consumption was converted into joules per minute per gram using a conversion factor of 20.054 J mL−1 O2 consumed  for normalizing the amount of sample loading.Cardiac muscle from left ventricular free wall was rapidly isolated postmortem and homogenized in SDS‐PAGE sample buffer containing 2% SDS and 1% −2 for 15 min. The blotted membranes were blocked in 1% bovine serum albumin (BSA) in Tris‐buffered saline  with shaking at room temperature for 30 min. The blocked membrane was probed with an anti‐TnI monoclonal antibody (mAb) TnI‐1  was employed following the manufacturer's instruction. Total cardiac muscle proteins were resolved on 14% SDS‐polyacrylamide gels as above. The SDS‐gel was fixed in 50% methanol and 10% acetic acid overnight with a change after the first 45 min. After washing in deionized water for three changes of 10 min each, the gel was stained with shaking in Pro‐Q Diamond reagent for 90 min in a dark box. Destaining was performed in 20% acetonitrile, 50 m·mol·L−1 sodium acetate, pH 4.0, for three changes of 30 min each in a dark box. The gel was then washed twice with deionized water for 5 min each in a dark box and scanned on a Typhoon 9410 fluorescence scanner  with excitation at 532 nm and recording the emission at 560 nm to reveal phosphorylated proteins. The same gel was then stained with Coomassie Blue R‐250 to visualize the total protein profile.To examine the effect of t test, or one‐way and two‐way ANOVA with a Fisher adjustment as noted in the table and figure legends.Data are presented as means ± SE or ± SD and statistical analysis was performed using Student's B‐mode and M‐mode echocardiography showed no atrial or ventricular enlargement or dilation in the transgenic mice in comparison with the wild‐type (WT) control at 2 months of age. The results in Fig. No significant change was found in mitral Doppler and tissue Doppler measurements , except To evaluate the kinetic function of the heart, left ventricular outflow tract (LVOT) velocity was measured from the apical approach in an anteriorly angulated four‐chamber view. Aortic Doppler data indicated that LVOT velocity and LVOT gradient were decreased in cTnT‐ΔΕ7 and ΔΕ7+eTnT hearts as compared to WT control Fig. C and D. β‐adrenergic signaling was preserved and the impaired systolic function may indicate direct effects of cTnT‐ΔΕ7 or ΔΕ7+eTnT on cardiac muscle contractility. Representing other phosphorylation‐regulated myofilament proteins, the phosphorylation level of myosin regulatory light chain (RLC) also had no significant change in the cTnT‐ΔΕ7 and ΔΕ7+eTnT mouse hearts  increased at higher afterloads, whereas stoke volume decreased in response to the increase in afterload  was unchanged (data no shown), indicating that the end diastolic pressure and myocardial compliance did not change in the transgenic mouse hearts under normal or increased afterloads. The inability to increase ±dP/dt in cTnT‐ΔΕ7 and ΔΕ7+eTnT hearts when afterload was increased suggests a diminished contractile capacity.cTnT‐ΔΕ7 and ΔΕ7+eTnT hearts had significantly slower systolic and diastolic velocities Fig. A and B, max Fig. C, and stmax Fig. D than thWhen afterload was increased, the time parameters of WT mouse hearts showed decreased total, rapid, and reduced ejection times Fig. A, corresIsovolumetric contraction and relaxation times (IVCT and IVRT) were longer in cTnT‐ΔΕ7 and ΔΕ7+eTnT hearts than WT controls at all afterloads tested Fig. B, indicaLVP integral and ejection integral were increased when afterload was increased in all three groups of hearts, in which the ejection integral had proportionally less increase indicating decreased pumping efficiency under high afterload Fig. A. An inc2 increased in all three groups of hearts when afterload was increased. These changes resulted in a reduction of energetic efficiency that was more severe in cTnT‐ΔΕ7 and ΔΕ7+eTnT hearts than that in WT hearts and diminished more at higher afterload in all three groups  as a result of increased contractility. Pumping efficiency deduced from the ratio of ejection integral to LVP integral increased when preload increased from 5 mmHg to 10 mmHg whereas further increases in preload did not produce significant change , the young cTnT‐ΔΕ7 and ΔΕ7+eTnT transgenic mouse hearts were at a compensated stage without anatomical dilation or clinical failure.Indicated by the similar left ventricular end diastolic dimension seen in echocardiographs  and LVPmThe results in Fig. Nonetheless, a chronic adaptive utilization of Frank‐Starling mechanism to compensate for the impaired systolic function would increase energy expenditure and induce dilatative ventricular remodeling, leading to the progression of dilated cardiomyopathy in cTnT‐ΔΕ7 and ΔΕ7+eTnT hearts .


Athlete’s heart is a common definition for a broad spectrum of adaptations induced by intense exercise. We intended to compare left ventricular (LV) mechanics in two sports disciplines with different exercise nature: marathon runners (endurance) and bodybuilders (power).24 marathon or ultramarathon runners (R), 14 bodybuilders (B) and 15 healthy, sedentary male volunteers (N) were investigated. Beyond standard echocardiographic protocol, parasternal short-axis and apical recordings optimized for speckle tracking analysis were acquired (Esaote MyLab 25). Using dedicated software , global longitudinal (GLS), circumferential (GCS) and radial strain (GRS) were calculated by averaging the corresponding 16 LV segments. Data are presented as mean ± SD.Calculated LV mass was higher in bodybuilders compared to normal controls . We found no difference regarding conventional systolic function parameters among the groups . However, speckle tracking analysis showed a different pattern of myocardial deformation in our groups: while GRS was similar, GLS was decreased in runners, GCS was decreased in bodybuilders compared to the other two groups . Significant correlations were found in runners between GLS and end-diastolic volume , and body surface area . In bodybuilders, GCS was closely related to LV mass  and systolic blood pressure .While conventional morphological and functional echocardiographic parameters failed to distinguish between the athlete’s heart of the two different sport disciplines, deformation parameters showed a different pattern of LV mechanics in runners versus bodybuilders.The online version of this article (doi:10.1186/s12947-015-0002-y) contains supplementary material, which is available to authorized users. Athlete’s heart is a common expression for the various adaptive changes induced by intense exercise -5. HowevTraditionally, sport disciplines can be divided by their exercise nature to endurance or power groups ,4,7. AltThe complex helical myofiber architecture of the left ventricle (LV) is of great clinical interest since deformation data in multiple directions provide valuable information in numerous pathological and physiological conditions . The novOur aim was to investigate the cardiac adaptation of marathon runners and bodybuilders using speckle tracking echocardiography. We hypothesized that different deformation pattern exists in these sport disciplines.In this study highly trained male athletes were included: 24 marathon or ultramarathon runners and 14 bodybuilders. Fifteen healthy, sedentary male volunteers were also enrolled. Subjects in the athlete groups had an at least 5 year history of regular exercise and trained at least 11 months a year. The regime of marathon runners consisted of 20.0 ± 1.4 training hours/week for 7.8 ± 1.6 years, while of bodybuilders 16.8 ± 1.1 hours/week for 7.9 ± 1.4 years in average. Marathoners covered at least 50 kilometres a week and also participating in professional competitions. Bodybuilders trained at least five times a week. Healthy volunteers had no more than three hours regular physical activity a week. Exclusion criteria were any acute or chronic disease, use of any medication or performance-enhancing drugs, or suspicion of presence of any cardiovascular disease based on blood pressure measurements, ECG, laboratory tests or echocardiography. Our protocol was designed in accordance to the ethical principles of the Declaration of Helsinki and all participants provided their written informed consent before entering the study. The protocol was approved by the Semmelweis University Institutional Committee for Science and Research Ethics (TUKEB 175/2012).Before the ultrasonic assessment, detailed medical history was obtained, then subjects underwent physical examination, basic anthropometric and blood pressure measurements (office and 24 h ambulatory blood pressure monitoring as well) on the basis of current guidelines . StandarFor statistical analysis we used Statistical Package for the Social Sciences software version 20 . Normal distribution of variables was assessed by Shapiro-Wilk test. To compare variables, one-way ANOVA followed by Fisher post-hoc test was used. Relationships were calculated with Pearson correlation test. Data are presented as mean ± SD. P values under 0.05 were considered statistically significant.Basic characteristics of the study groups are summarized in Table Table However, speckle tracking analysis showed a different pattern of myocardial deformation between the groups. While radial strain was similar, longitudinal strain was lower in runners, circumferential strain was lower in bodybuilders compared to the other groups , end-diastolic volume index  and body surface area . In bodybuilders, circumferential strain was closely related to LV mass , mass index  and systolic blood pressure .We aimed to compare two very different sport disciplines in terms of myocardial mechanics: highly trained marathon runners and bodybuilders. While conventional echocardiographic parameters failed to be different between the two groups, speckle tracking derived strain indices showed a different pattern of deformation compared to each other and to healthy controls as well.The multiple helical fiber orientation of the LV is a well known phenomenon , howeverAthlete’s heart is characterized by a physiological increase in LV mass -4. A claIn contrast to our expectations, the groups of athletes were similar to each other regarding morphological features provided by echocardiography. Furthermore, conventional parameters of LV systolic function  also failed to distinguish between the two types of athlete’s heart.The novel method of speckle tracking echocardiography allows us to easily characterize myocardial mechanics on standard two-dimensional grey-scale images . We founIn bodybuilders the circumferential strain was found to be lower. In this group, the decrease in circumferential shortening strongly correlated with increased LV mass. The relationship between increased LV mass and decreased strain values is well-known from previous studies involving patients with hypertrophic cardiomyopathy, aortic stenosis, and also with hypertension-induced hypertrophy -32. BaseIn-depth analysis of myocardial mechanics raises the question whether strain parameters could be able to differentiate pathological and physiological remodelling and maybe could help to monitor the training phases of an athlete. Promising data are available regarding a classical dilemma of sports medicine: differentiation between hypertrophic cardiomyopathy and athlete’s heart ,33,34. NObvious limitations of our study are the relatively low case number and its cross-sectional approach. We used 2D speckle tracking analysis, however, the added value of 3D strain has been reported recently . RecruitWhile conventional morphological and functional echocardiographic parameters failed to distinguish between the athlete’s heart of two different sport disciplines, strain parameters showed a different pattern of LV deformation in runners versus bodybuilders. Longitudinal strain is lower in runners, whilst circumferential strain is decreased in bodybuilders. Speckle tracking analysis can be useful for identifying previously undetected differences regarding athlete’s heart.


Introduction. The presence of T-wave alternans (TWA) has been shown to correlate with a higher risk for sudden cardiac death. The mechanism of TWA may be related to abnormalities in intracellular calcium handling, which is a mechanism in heart failure and associated arrhythmias as well. However, an association between TWA and cardiac volume status has not been demonstrated. Methods Used. We report the case of a 54-year-old man with a dilated cardiomyopathy who had a biventricular defibrillator system implanted with intrathoracic impedance measurement capability. We performed baseline TWA testing, which was normal and was associated with normal clinical status and normal intrathoracic impedance. We followed intrathoracic impedance measurements, and when the measurement suggested volume overload eight months later, we repeated the TWA test. TWA was grossly positive, and volume overload was corroborated with clinical heart failure. The patient was diuresed, and when clinical status and intrathoracic impedance returned to normal a month later, we repeated TWA, which was again negative.Conclusion. This case demonstrates a correlation between cardiac volume status, as measured by intrathoracic impedance measurements, and TWA status. This data suggests that conditions of volume overload such as heart failure could be causally related to increased TWA, perhaps by the common mechanism of altered intracellular calcium handling. The presence of microvolt T-wave alternans has been shown to correlate with a higher risk of sudden cardiac death in patients with structural heart disease . The mecThe current example is a 54-year-old man with nonischemic dilated cardiomyopathy and left bundle branch block. He had well-compensated heart failure following biventricular defibrillator insertion in 2007. His intrathoracic impedance measurements and T-wave alternans tests were normal at baseline  until MaThe implantable defibrillator has become standard therapy for the prevention of sudden death in patients with severe structural heart disease. The questionable cost effectiveness of routine implantation for primary prevention has resulted in the search for better methods of risk stratification. One such modality is microvolt T-wave alternans, a test that can detect beat-to-beat variations in the T-wave that may correspond to spatial dispersion of refractoriness or alternations in repolarization that underlie a substrate that can support lethal arrhythmias . The utiThe mechanism of T-wave alternans is unclear, but data point to abnormalities in intracellular calcium handling , 3, 8. CIntrathoracic impedance measurements have been shown to correlate with cardiac fluid status and predict heart failure hospitalizations , 15. Usi


Hypertrophic cardiomyopathy (HCM) with apical aneurysm (AAn) is associated with considerable morbidity and mortality. However, the real incidence of AAn tends to be underrecognized due to the poor visualization of left ventricular (LV) apex with echocardiography. This study sought to investigate the exact incidence and associated manifestations of AAn using cardiovascular magnetic resonance (CMR) in patients with HCM.A total of 350 consecutive patients diagnosed with HCM  underwent CMR and echocardiography. We divided the subjects into 4 phenotypes according to the location of hypertrophic segment; asymmetrical septal hypertrophy (ASH), apical, concentric and septal/apical type. On CMR, the LV volumetric parameters were measured, and the amount of LGE was calculated with gray-scale thresholds of 6 SD above the mean signal intensity for normal remote myocardium. Echocardiographic evaluations included left atrial volume index, mitral inflow pattern, tissue Doppler of mitral annulus and LV dimension.The prevalence of AAn on CMR was 14.3%, which was significantly high compared to previously reported data. AAn was detected in all groups of HCM regardless of type . Clinical manifestations and LV volumetric parameters on CMR did not differ between the HCM patients with and without AAn. The frequency and the amount of late gadolinium enhancement were not different between two groups .The incidence of AAn in HCM patients was far higher than it was reported previously. Regardless of presence of AAn, initial manifestations and associated morphology of LV were similar. This means that adverse clinical outcomes in HCM patients with AAn may be a long-range problem which arises from secondary myocardial changes due to AAn.None.