Assessment of longitudinal function with cardiovascular magnetic resonance (CMR) is limited to measurement of systolic excursion of the mitral annulus (MAPSE) or elaborate strain imaging modalities. The aim of this study was to develop a fast assessable parameter for the measurement of long axis strain (LAS) with CMR.40 healthy volunteers and 125 patients with different forms of cardiomyopathy were retrospectively analyzed. Four different approaches for the assessment of LAS with CMR measuring the distance between the LV apex and a line connecting the origins of the mitral valve leaflets in enddiastole and endsystole were evaluated. Values for LAS were calculated according to the strain formula.LAS derived from the distance of the epicardial apical border to the midpoint of the line connecting the mitral valve insertion points (LAS-epi/mid) proved to be the most reliable parameter for the assessment of LAS among the different approaches.LAS-epi/mid displayed the highest sensitivity (81.6 %) and specificity (97.5 %), furthermore showing the best correlation with feature tracking (FTI) derived transmural longitudinal strain (r = 0.85). Moreover, LAS-epi/mid was non-inferior to FTI in discriminating controls from patients (Area under the curve (AUC) = 0.95 vs. 0.94, p = NS). The time required for analysis of LAS-epi/mid was significantly shorter than for FTI . Additionally, LAS-epi/mid performed significantly better than MAPSE  and the ejection fraction .Reference values were derived from 234 selected healthy volunteers. Mean value for LAS-epi/mid was −17.1 ± 2.3 %. Mean values for men were significantly lower compared to women , while LAS decreased with age.LAS-epi/mid is a novel and fast assessable parameter for the analysis of global longitudinal function with non-inferiority compared to transmural longitudinal strain. Reduced left ventricular (LV) ejection fraction (EF) is an important predictor for cardiac mortality and morbidity . AccordiHowever, precise measurement of LV long axis function may better reflect the contractile function of the myocardium than the geometric analysis of the left ventricle, which is used for the calculation of the EF . PreviouImpairment of LV longitudinal function is recognized as an independent predictor for survival in patients with chronic heart failure  and variCardiovascular magnetic resonance (CMR) is nowadays considered as the non-invasive gold standard for the evaluation of LV function . Due to Evaluation of longitudinal deformation with different software packages is still time consuming and, more importantly, standardization of strain imaging for better comparability is urgently needed. The aim of our study was to evaluate long axis strain (LAS) with CMR as a rapid assessable and feasible parameter for the determination of LV longitudinal function.The study population consisted of 125 patients with a clinical indication for CMR and 40 healthy volunteers who were analyzed retrospectively. 60 patients had dilated cardiomyopathy (DCM), 25 patients were diagnosed with hypertrophic cardiomyopathy (HCM) and 40 patients had biopsy-confirmed systemic light-chain (AL) amyloidosis. All patients were in clinical stable condition (NYHA ≤ III) and showed sinus rhythm during the examination. For the assessment of reference values 234 healthy volunteers (101 women and 133 men) were analyzed. The investigation was carried out after approval by the local Ethics Committee of the University of Heidelberg and in accordance with the Declaration of Helsinki.2, repetition time/echo time (TR/TE) = 2.8/1.4 ms, acquired voxel size = 2.2 × 2.2 × 8 mm3, flip angle (FA) = 60°, reconstructed voxel size = 1.3 × 1.2 × 8 mm3).CMR was performed on a 1.5 T clinical scanner  equipped with a cardiac phased array 32-channel receiver coil. Cine images were obtained using a breath-hold segmented-k-space balanced fast-field echo sequence (SSFP) employing retrospective ECG gating in long axis planes  as well as in contiguous short axis slices (2 mm gap) covering the whole ventricles from the annulus of the AV valves to the apex, with 35 phases per cardiac cycle. Typical CMR imaging parameters were: field-of-view (FOV) = 350 × 350 mmAll analyses were performed on a commercially available workstation  Version 6, Philips Healthcare, Best, The Netherlands) equipped with a semi-automatic software for volumetric analysis. Results for ventricular volumes, ejection fraction and LV myocardial mass were derived from short axis slices after manually tracing of epi- and endocardial borders, excluding papillary muscles from the myocardium.For strain analysis long axis views of the ventricle in 2- and 4 chamber views were divided according to the standardized 17 segment model. The apical cap (segment 17) and the segments of the 3 chamber view were not considered for analysis. Retrospective image analyses were conducted employing the 2D CPA CMR Feature tracking software . This tool comprised a software based feature tracking algorithm, which has been validated previously in experimental and clinical studies –17. FeatIn our study global transmural longitudinal strain represents the mean values of epicardial and endocardial strain and was assessed by measuring the average peak of the mean curve of all segments. The curve represents the average of all segments over the whole cardiac cycle. This value was measured three times and then averaged, resulting in the mean transmural longitudinal strain. The technique has been described in detail in a recently published study .Long axis strain was assessed in 2 and 4 chamber views by measuring displacement of the mitral annulus. We evaluated and compared 4 different approaches for measuring LAS. All values were assessed with the IntelliSpace Portal (ISP) workspace .LAS-epi/mid: The distance between the epicardial border of the LV apex and the middle of a line connecting the origins of the mitral valve leaflets was measured in both endsystole and enddiastole Fig. .Fig. 1aLAS-endo/mid: The distance between the endocardium of the LV apex and the middle of a line connecting the origins of the mitral valve leaflets was measured in endsystole and enddiastole, respectively Fig. .LAS-epi/perp.: The distance between the epicardal border of the LV apex and a line connecting the origins of the mitral valve leaflets was measured perpendicularly in endsystole as well as in enddiastole Fig. .LAS-endo/perp.: The distance between the endocardium of the LV apex and a line connecting the origins of the mitral valve leaflets was measured perpendicularly in endsystole and in enddiastole, respectively Fig. .The value in percentage for LAS was finally measured according to the strain formula:Mean values in 2 and 4 chamber views were calculated. The mean of three measurements was then used for further analysis.CMR examinations were analyzed by the investigators in a blinded manner. For calculation of intra- and interobserver variability 20 single measurements were used. To examine intraobserver variability, a sample of 20 randomly selected CMR examinations for the measurement of LAS were randomly selected for masked review by the same investigator. The same studies were analysed by a co-investigator, who was blinded to the clinical information and the results of the first investigation, in order to measure interobserver variability.The required time for LAS analysis was registered in another 20 CMR datasets.Data are presented as mean ± standard deviation. Differences in values for LAS were evaluated using unpaired Student’s t-test with Welch correction for samples with potentially unequal variances or one-way ANOVA with Dunnett’s post-hoc test when appropriate. Pearson’s correlation coefficients were calculated since all variables showed normal distribution according to D’Agostino Pearson test. Linear regression analysis was used to model the relationship between LAS and transmural longitudinal strain. Receiver operator characteristic (ROC) curves were used to determine the optimal prognostic LAS cut-off value (highest sum of sensitivity and specificity) for discriminating healthy controls and patients. For the assessment of intra- and interobserver agreement variation coefficients were calculated. A p-value <0.05 was considered as statistically significant. All Statistics were calculated using MedCalc 12.3 .125 patients and 40 healthy subjects were retrospectively analyzed. Mean age was 55 ± 14 years and 52 ± 12 years (p = 0.15), respectively. EF was significantly lower in patients with cardiomyopathies . Mean value for body mass index (BMI) was 25 ± 3 in healthy controls and 26 ± 4 in patients (p = 0.06).Moreover 234 healthy volunteers were analyzed for the assessment of reference values. A detailed characteristic of these subjects is shown in Table We evaluated 4 different techniques for the assessment of LAS. Mean value in healthy controls was −15.9 ± 2.2 % for LAS-epi/mid, −16.4 ± 2.5 % for LAS-epi/perp, −21.0 ± 3.6 % for LAS endo/mid and −21.1 ± 3.9 % for LAS endo/perp, respectively. Mean values for patients with cardiomyopathies were significantly lower . Mean values for mean transmural strain were −19.3 ± 3.6 % in controls and −11.6 ± 4.0 % (p < 0.0001) in patients, respectively. Detailed information about the mean values of the different cardiomyopathies is shown in Table The cut-off value to discriminate healthy subjects from patients with different cardiomyopathies with the highest sensitivity and specificity was −12.4 % for LAS-epi/mid and −15.3 % for transmural longitudinal strain, respectively. Compared to strain imaging, LAS-epi/mid showed similar values for sensitivity (81.6 % vs. 84.0 %) and specificity (97.5 % vs. 92.5 %). ROC analysis revealed a comparable AUC for LAS-epi/mid (0.95) and transmural longitudinal strain , respectively.LAS-epi/mid performed significantly better than other parameters of cardiac function such as MAPSE  and the EF  in discriminating patients from healthy subjects. The corresponding ROC analysis is shown in Fig. Intra- and interobserver variability for single measurements of LAS-epi/mid were low with 5.6 ± 4.2 % and 6.3 ± 4.2 %, respectively. Intra- and interobserver variability for LAS-epi/perp were −6.1 ± 8.1 % and −6.5 ± 6.1 %, for LAS-endo/mid −7.2 ± 7.0 % and −6.1 ± 7.2 % and for LAS-endo/perp −6.0 ± 5.8 % and 5.9 ± 5.9 %.The time required for the measurement of LAS-epi/mid in 4 chamber view and 2 chamber view was 67 ± 8 s and significantly shorter than the measurement time for FTI derived transmural longitudinal strain analysis, which was also assessed in 2- and 4 chamber view .Reference values were derived from 234 healthy volunteers, the resulting mean value for LAS-epi/mid was −17.1 ± 2.3 %. Additionally, LAS-epi/mid was analyzed related to age and gender. Mean values for men were significantly lower compared to women  Fig  and decrMiszalski-Jamka et al. patients with Churgh-Strauss-Syndrom and Wegener's granumolatosis displayed reduced values for longitudinal strain measured with feature tracking software despite clinical remission, normal ECG and normal echocardiography [In our study, we demonstrated the feasibility of a novel and readily available parameter for the measurement of global longitudinal LV function using standard CMR images. LAS-epi/mid correlated strongly with FTI derived transmural longitudinal strain, while sensitivity as well as specificity data were comparable. LAS-epi/mid performed significantly better in discriminating healthy subjects from patients with cardiomyopathies than EF and MAPSE. Additionally, we provided reference values for LAS-epi/mid. Atrioventricular plane displacement, a measure for longitudinal function, is known to provide approximately 60 % of the total LV stroke volume . Differeiography . Howeveriography . Still, iography . Similariography  and obseiography . In a priography . This isIn our study we wanted to evaluate an easily reproducible and more importantly fast assessable parameter for global longitudinal function, which then can be implemented into clinical routine. A practical advantage of our technique compared to various other strain imaging modalities is that no special CMR sequences or additional software tools are needed. LAS can be assessed online during a standard CMR protocol from standard SSFP sequences. Furthermore, the time required for analysis was much shorter than measurement of transmural strain. Besides, as we could prove that single measurements of LAS showed good intra- and interobserver variability an averaged value for LAS of repeated measurements is redundant.A slight drawback of our technique compared to feature tracking imaging or the technique applied by Saba et al. is that it does not provide information about strain rate or circumferential and radial strain, which may in certain circumstances reflect cardiac function better , 33.However, since LAS showed a high sensitivity and specificity in discriminating patients with cardiomyopathies from controls, it may be a rapid and valuable screening tool for patients with cardiomyopathies in clinical routine.The investigation was carried out retrospectively. Additionally, comparison and correlation with other imaging or strain modalities were not assessed in our study. Moreover, compared to feature tracking or tagging, LAS offers only global values for longitudinal strain and provides no data about regional deformation.LAS-epi/mid is a reliable and fast assessable parameter for analysis of global longitudinal function in CMR, without the need of additional pulse sequences and off-line processing using special software tools. LAS-epi/mid showed a high correlation with feature tracking analysis while being non-inferior to strain imaging in discriminating healthy controls from patients with cardiomyopathies.


Presence of intramyocardial hemorrhage (IMH) in patients with reperfused acute ST-elevation myocardial infarction (STEMI) is associated with more severe infarcts, adverse left ventricular (LV) remodeling and worse outcome. We sought to evaluate whether traditional risk factors for coronary artery disease (CAD) are related to IMH.In this observational, three-center study, 471 patients (60.0±11.6 years) were studied 4±1 days, and 356 patients at 4 months post-infarction (75.6%) by comprehensive by cardiovascular magnetic resonance (CMR). CAD risk factors were assessed using the most recent consensus guidelines.IMH was present in 117 patients (24.8%) and associated with larger area at risk (AAR) and infarct size (IS), larger LV volumes, lower ejection fraction (EF) and higher troponin-I values at baseline . At follow-up IMH was associated with lack of functional recovery and adverse LV remodeling (p<0.001). Active smoking status was associated with a younger patient age (p<0.001) and a higher prevalence of IMH, i.e., 30.9% vs 19.3% (p=0.003), while no significant association between other CAD risk factors and IMH was found. At multivariate analysis, active smoking was a strong and independent predictor of IMH (p<0.001) even after correction for LV volumes, EF, IS, AAR and myocardial salvage index. However, at follow-up, active smoking was not associated with adverse LV remodeling (defined as in increase in LV EDVi > 20%).Active cigarette smoking is clearly associated with IMH in patients experiencing a first STEMI. However, consistent with the so-called smoker's paradox, active smoking is not associated with adverse LV remodeling after 4 months.This study was in part funded by a FWO grant.


Microvascular ischemia is one of the hallmarks of hypertrophic cardiomyopathy (HCM) and has been associated with poor outcome. However, myocardial fibrosis, seen on cardiovascular magnetic resonance (CMR) as late gadolinium enhancement (LGE), can be responsible for rest perfusion defects in up to 30 % of patients with HCM, potentially leading to an overestimation of the ischemic burden. We investigated the effect of left ventricle (LV) scar on the total LV ischemic burden using novel high-resolution perfusion analysis techniques in conjunction with LGE quantification.30 patients with HCM and unobstructed epicardial coronary arteries underwent CMR with Fermi constrained quantitative perfusion analysis on segmental and high-resolution data. The latter were corrected for the presence of fibrosis on a pixel-by-pixel basis.High-resolution quantification proved more sensitive for the detection of microvascular ischemia in comparison to segmental analysis. Areas of LGE were associated with significant reduction of myocardial perfusion reserve (MPR) leading to an overestimation of the total ischemic burden on non-corrected perfusion maps. Using a threshold MPR of 1.5, the presence of LGE caused an overestimation of the ischemic burden of 28 %. The ischemic burden was more severe in patients with fibrosis, also after correction of the perfusion maps, in keeping with more severe disease in this subgroup.LGE is an important confounder in the assessment of the ischemic burden in patients with HCM. High-resolution quantitative analysis with LGE correction enables the independent evaluation of microvascular ischemia and fibrosis and should be used when evaluating patients with HCM. Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy . While tThe hallmarks of the disease include left ventricle (LV) hypertrophy, fibrosis and microvascular ischemia  and it rHigh-resolution quantification of perfusion CMR has been shown to provide accurate perfusion estimates , 21 and,The aim of this study is to demonstrate the feasibility of combined high-resolution quantitative perfusion and LGE analysis. Specifically, we aimed to determine the effect of overt LV scar on the total LV ischemic burden.Consecutive patients with a clinical diagnosis of HCM and visually unobstructed or with minor non-obstructive atheroma  on invasive coronary angiography referred for perfusion CMR were retrospectively identified. The diagnosis of HCM was based on confirmation from genetic testing or on conventional criteria for HCM diagnosis . Patients had been scanned on clinical grounds at St. Thomas’ Hospital, London. All patients gave written and informed consent at the time of the scan . This study was performed in accordance with the principles of the Declaration of Helsinki.Scans were performed at 3.0 T  and included myocardial function, stress and rest perfusion and late gadolinium enhancement imaging using standard acquisition protocols . A 32-chThe perfusion sequences were performed during adenosine-induced hyperemia over 3 min (140 μg/kg/min) and repeated 15 min later at rest, both times using 0.075 mmol/kg gadobutrol  at 4 ml/s followed by a 20 ml saline flush. A dual bolus protocol for contrast agent injection was used as previously described . All subkt turbo-gradient echo sequence . Three short-axis slices  were acquired over every heartbeat covering 16 of the standard myocardial segments (segment 17 was excluded). A correction map was created from a proton density-based image based on the same projections as the perfusion scans for correction of spatial inhomogeneities due to surface coils [First-pass perfusion imaging consisted of a high-resolution ce coils . LGE imace coils .Image analysis was performed according to standard practice . PerfusiLV function, global LV mass and maximal segmental LV wall thickness were analyzed using commercially available software  according to standardized methods . All theTwo independent observers judged the presence of fibrosis visually and recorded LGE in terms of standard LV segments. Using commercially-available software, according to standardized methods, areas of scar were measured   of an area of myocardium lasting longer than five cardiac cycles and not related to obvious respiratory, motion or dark rim artifact.Perfusion abnormalities were classified visually in three categories: 1) subendocardial perfusion abnormalities, seen as a gradient of reduced perfusion arising from the subendocardium in absence of LGE in the same segment; 2) LGE-related perfusion abnormalities, seen only in the mid-myocardial layers and exclusively in correspondence with overt, confluent areas of LGE; 3) mixed perfusion abnormalities, in segments where both LGE-related and subendocardial perfusion abnormalities were observed.Two experienced operators, blinded to results of visual perfusion assessment and other clinical data, performed quantitative analysis using software and methods developed and previously validated by our group against perfusion phantom, PET data and microspheres , 27, 28.Segmental quantitative perfusion analysis was performed using spatially averaged myocardial SI curves according to standard cardiac segmentation .h(t), were fitted to the Fermi function with the following analytical expression:k, R and τ0 vary and keeping τd fixed. In the above equation, u(t − τd) is the unit step function. The τd accounts for the delay time between the appearance of the signal in the LV blood pool and myocardial region of interest (ROI) [τ0 characterizes the width of the shoulder of the Fermi function during which little or no contrast agent had left the ROI. R is the index of contrast agent influx parameter and k represents the decay rate of h(t) due to contrast agent washout. Using the above equation, myocardial blood flow (MBF) estimates are calculated as h(t) at t = 0 [Quantitative perfusion analysis was performed by Fermi deconvolution according to the methods described by Wilke et al.  and Jerost (ROI)  τ0 charat t = 0 .Myocardial perfusion reserve (MPR) was calculated as the ratio between stress and rest MBF estimates.Current two-dimensional perfusion techniques involve each slice being acquired in a different phase of the cardiac cycle while LGE is acquired in a pre-specified phase, usually in end-diastole. Therefore, prior to any quantification, the LGE and perfusion images had to be registered. Firstly an LGE slice was selected that matched the corresponding perfusion slice in terms of position within the LV. A pair of endocardial and epicardial LV contours were then drawn on rest and stress perfusion and LGE images and a deformable template segmentation method was applied to the images and optimized using a greedy optimization scheme as previously described .High-resolution quantitative MPR and fibrosis maps were generated allowing generation of high-resolution MPR maps and calculation of the ischemic burden with and without inclusion of areas of overt myocardial scar Fig. .Fig. 1ExIn order to represent and compare total ischemic burden measurements obtained using segmental and high-resolution quantitative analysis, we adopted the methods described and recommended by the ISCHEMIA Trial expert panel to compare ischemic burden measurements obtained by different imaging modalities . In briet test and categorical data were compared between groups using the Fisher exact test and Pearson chi-square test, as appropriate. Values of p < 0.05 was considered to be statistically significant. ANOVA was used to determine differences between multiple groups. Bonferroni correction was used to account for multiple testing in both segmental and high-resolution quantitative perfusion analysis. Bland-Altman and Pearson’s analysis were used to assess the interoperator reproducibility of the ischemic burden measurements.Categorical data are presented as numbers and percentages and continuous data are presented as mean ± standard deviation (SD). The normal distribution of high-resolution MPR estimated was tested with P-P plot and a skewness test. Group means were compared using an unpaired Student The study cohort comprised 30 patients . Demographics of patients are shown in Table Structural and functional CMR findings and hemodynamic parameters are also shown in Table Stress-induced perfusion abnormalities  were found in 18/30 (60 %) patients on visual assessment involving 185/304 (61 %) segments amongst positive patients. Subendocardial perfusion abnormalities were seen in 14/30 (47 %) patients and 4/30 (13 %) patients had mixed perfusion abnormalities. 1/30 (3 %) patient had only scar-related perfusion abnormalities. 11/30 (37 %) patients had visually normal perfusion.p = 0.38).No association was observed between average wall thickness of hypertrophic segments and perfusion abnormalities  had the lowest MPR values (2.2 ± 0.5). Conversely, segments negative for visual perfusion abnormalities and LGE (PERF-LGE-) had the highest MPR values (2.6 ± 0.6). Segments with visual perfusion abnormalities, but no LGE (PERF + LGE-) had MPR values of 2.3 ± 0.5. Segments with LGE and visually normal perfusion (PERF-LGE+) had MPR values of 2.4 ± 0.5. A significant difference was observed between PERF + LGE+ versus PERF-LGE- (p < 0.0001) and PERF + LGE- versus PERF-LGE- (p < 0.0001). Detailed results are presented in Fig. Using segmental quantitative analysis, segments with visual perfusion abnormalities and LGE . PERF-LGE- regions had the highest MPR values (2.5 ± 0.9). PERF + LGE- regions had MPR values of 2.1 ± 1. PERF-LGE+ regions had MPR values of 2.0 ± 0.8. A significant difference was observed between all categories (p < 0.0001).On high-resolution perfusion quantification, Comparing high-resolution and segmental perfusion quantification results, high-resolution measured significantly lower MPR values in all groups with the exception of PERF-LGE-. Detailed results are also presented in Fig. p < 0.001).Total LV ischemic burden for segmental and uncorrected high-resolution perfusion quantification are shown in Fig. p = 0.01). Correction of the results by exclusion of regions with overt LGE caused a significant reduction of the measured ischemic burden at all thresholds (p = 0.04). Despite this adjustment however, LGE+ patients had a higher ischemic burden in comparison to LGE- patients for all MPR thresholds above 1.3 (p = 0.04). In order to examine the effect of overt LGE on measured ischemic burden at different MPR thresholds, the percentage difference (or relative error) of ischemic burden between corrected and non-corrected high-resolution perfusion maps was calculated, using uncorrected results as the normalization factor  combined CMR high-resolution quantitative assessment of myocardial perfusion and LV fibrosis is feasible in patients with HCM; 2) high-resolution quantitative perfusion assessment preserves the resolution of the original imaging data, is more sensitive than segmental quantitative analysis for ischemia and allows for correction of perfusion data for LGE; 3) LV scar has a significant confounding effect on ischemic burden measurements; 4) 30 % of patients are re-classified to a lower tertile of ischemic burden if high-resolution perfusion maps are corrected by LV scar; 5) patients with LGE have larger ischemic burden in comparison with patients without LGE. This difference is maintained also after correction of high-resolution perfusion maps by LV scar, possibly indicating more severe disease.Microvascular dysfunction is an important feature of HCM and can be diagnosed non-invasively by stress perfusion CMR , 12, wheHigh-resolution perfusion CMR quantification has been proposed as an accurate method to assess microvascular ischemia in patients with HCM. Despite the lower signal-to-noise ratio, high-resolution perfusion CMR quantification is capable of very accurate estimates of MPR, as demonstrated previously by our group and by others , 35, 36.Current results confirm the feasibility of this approach and demonstrate the potential to perform a combined assessment of quantitative perfusion and LGE maps and measure the effect of the presence of overt scar on non-invasive measurements of ischemic burden.It has previously been proposed that high-resolution perfusion quantification could be more sensitive for the diagnosis of microvascular ischemia by avoiding spatial averaging of the data or arbitrary assumptions on the distribution of ischemia . To the The presence of LGE related perfusion abnormalities at rest in patients with HCM is well described in the literature –19. An eThe importance of accounting for LV scar in the assessment of the ischemic burden is further supported by the finding that almost one patient in three was re-assigned to a lower tertile of ischemic burden as result of the correction. Fig. .Another important finding of our study is that patients with LGE had larger ischemic burden in comparison with patients without LGE and that correction of high-resolution perfusion maps by LV scar did not fully eliminate this difference. This finding could be interpreted in a number of ways. It might indicate more severe disease and microvascular dysfunction in patients with LGE. It might also be explained by technical factors. We decided to correct high-resolution perfusion maps for LV scar defined as regions with signal >6SD above the average of remote normal tissue. Selecting lower thresholds would result in the exclusion of larger areas of fibrotic myocardium and in a smaller difference between LGE- and LGE+ patients. Given the complexity of histological validation on significant number of cases, we feel that this should be evaluated against outcomes in future studies. Corrected ischemic burden results proved in the current study to have a good reproducibility when LGE was quantified by different operators.This study enrolled a limited number of patients referred on clinical grounds. The prevalence of perfusion abnormalities therefore does not represent the entire population of patient with HCM but rather a group of patients with HCM and suspected microvascular angina. None of the patients included in this study had severe hypertrophy (>30 mm) and therefore we cannot comment on the effect of fibrosis correction in this subgroup.This study demonstrates the feasibility of combined high-resolution fibrosis and perfusion quantification and the potential of this method to provide more accurate information on the ischemic burden. Further studies are awaited regarding the impact of this novel approach on risk stratification.


The correlation between impedance cardiography (ICG) and 6 min walk distance (6MWD) in atrial fibrillation (AF) patients remains unknown.We recruited 49 subjects in the study (21 AF patients and 28 patients without AF) and estimated hemodynamic parameters: cardiac output (CO), stroke volume (SV), stroke volume index (SVI), left stroke work (LSW), left stroke work index (LSWI), stroke systemic vascular resistance (SSVR), stroke systemic vascular resistance index (SSVRI); 6MWD, left ventricle ejection fraction (LVEF), NT-pro brain natriuretic peptide (NT-pro BNP) for the two groups.p = 0.039) and distinctly higher SVR , SSVRI  than the control group. NT-pro BNP  in the AF group was significantly higher than the control group and 6MWD  in the AF group was lower than the control group. There was no significant difference in LVEF between the two groups . Pearson correlation analysis revealed that CO , SV , LSW  and LSWI  significantly correlated positively with 6MWD in AF patients.The AF group have apparently lower CO (2.26 ± 0.14 VS 4.11 ± 0.20 L/min, AF patients had lower cardiac output, shorter 6MWD and higher NT-pro BNP than patients with sinus rhythm. The cardiac output measured by impedance cardiography significantly correlated positively with 6MWD in AF patients. Atrial fibrillation (AF) is a kind of common cardiac arrhythmia , which dA considerable proportion of previous data have stated the role of hemodynamic parameters measured by impedance cardiography (ICG) in diagnostic, prognostic, and therapeutic decision making in chronic heart failure –7 and puGilewski et al. investigated cardiovascular changes in tissue Doppler echocardiography (TDE) and ICG in AF patients subjected to cardioversion . The stun = 21) and healthy controls (n = 28). All the AF patients in our study were persistent or longstanding persistent AF according to 2014 AHA/ACC/HRS guideline [This study was approved by the Clinical Research Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. All participating persons were given informed consent and written informed consent was obtained from all subjects before enrollment. The study was performed between January 2014 and December 2015. We recruited patients with AF , hyperthyroidism, severe hepatic disease, severe renal impairment, asthma, cystic, fibrosis, arthritis, ankle, knee or hip injuries, muscle wasting, any life-threatening disease, drugs and/or alcohol abuse , 13. AddICG was performed using the Cheer Sails Medical (CSM3000 system) with electrodes placed on the neck and in the hypochondriac regions. The basic principle of this methodology is that variations in the impedance (Z) to an alternating high-frequency (75KHz) and low magnitude (1.8 mA) current, across the thorax during cardiac ejection, result in a specific waveform that can be used to calculate stroke volume . After 5CCU was performed with the aim of measuring LVEF. Diastolic left ventricular diameter (DLVD), left ventricular posterior wall thickness (LVPWT), interventricular septal thickness (IVST) and left atrial diameter (LAD) were also recorded. The 6MWT was performed according to standard guideline . A singl2 test for dichotomous variables [2 test, continuity correction was for dichotomous variables with fewer than 5 participants in a categories. Statistical significance was set to a p value less than 0.05. The strength of association between variables was performed using Pearson correlation test [Baseline subject characteristics across quartiles were compared using independent-samples t test for continuous variables and Pearson χariables , 16. Allion test .Baseline characteristics of the AF group and the control group were presented in Table p < 0.001). The patients in the AF group had apparently lower CO  and distinctly higher SVR , SSVRI  than those in the control group. NT-pro BNP  in the AF group was significantly higher than the control group. There was no significant difference in LVEF between the two groups . No significant difference was observed in other measured echocardiographic parameters (Table Table p = 0.023), SV , LSW  and LSWI  significantly correlated positively with 6MWD. LVEF did not significantly correlate with 6MWD .As shown in Table In previous published study, non-invasive impedance cardiography has been used to reveal heterogeneity of hemodynamic parameters in primary hypertension , 19 and p < 0.001) whereas LVEF had no significant difference between the AF group and the control group . Our study also found that LVEF did not correlate with 6MWD . The result suggested that LVEF could not predict cardiac function accurately in AF patients.6MWT is used to measure the distance that a patient can quickly walk on a flat, hard surface in a period of 6 min , and 6MWp < 0.001). Although the value of LVEF in AF patients remained normal in the present study, the cardiac function in the AF group was worse than the control group according to the 6MWD and NT-pro BNP.BNP levels could be higher in patients with impaired cardiac function , 28. Thep = 0.039) measured by impedance cardiography in AF patients were lower than the control group. Our data also found that CO , SV , LSW  and LSWI  correlated positively with 6MWD. Lacking of the atrial kick in late diastole [Due to great reliability and validity, ICG had been used in the diagnosis, prognosis and therapy in a variety of diseases , 21. A r6MWD had been proved to be useful and reliable in the assessment of functional capacity, evaluating exercise tolerance, prognosis and therapeutic effectiveness in patients with impair cardiac function , 29, 30.Digitalis and beta-blockers have long been used to control heart rate in AF patients in order to reduce AF-related symptoms , 32. TheOur study has limitations: (1) The study sample was relatively small, limiting the statistical power of group analyses. (2) The subjects in our study were relatively old and their parameters maybe could not represent the condition of the whole population. (3) We did not provide some important echocardiographic parameters such as cardiac index and left ventricular end-diastolic volume. Whether the diastolic dysfunction contribute to the decreased cardiac output in AF patients is not clear. Further studies are needed to determine the mechanism underlying the hemodynamic disorders observed in AF.Compared to patients with sinus rhythm, AF patients had lower cardiac output, shorter 6MWD and higher NT-pro BNP. The cardiac output measured by impedance cardiography significantly correlated positively with 6MWD in AF patients.6MWD, 6 min walk distance; 6MWT, 6 min walk test; AF, atrial fibrillation; ATS, Automatic Test System; BMI, body mass index; CCU, cardiac color ultrasound; CO, cardiac output; COPD, chronic obstructive pulmonary diseases; DLVD, diastolic left ventricular diameter; EDV, end-diastolic volume; ICG, impedance cardiography; IVST, interventricular septal thickness; LAD, left atrial diameter; LSW, left stroke work; LSWI, left stroke work index; LVEF, left ventricle ejection fraction; LVPWT, left ventricular posterior wall thickness; NT-pro BNP, NT-pro brain natriuretic peptide; SSVR, stroke systemic vascular resistance; SSVRI, stroke systemic vascular resistance index; SV, stroke volume; SVI, stroke volume index


The aims of the present study were: (a) to examine the agreement between subjective  and objective  physical activity (PA) levels in patients with rheumatoid arthritis (RA), and (b) to evaluate the associations of RA patients’ subjective and objective PA to their scores on the maximal oxygen uptake test (VO2max).The participants wore the GT3X for seven days before completing the IPAQ and VO2max test. The Bland-Altman plot was used to illustrate the agreement between the objective and subjective PA data, and the Wilcoxon test was employed to examine the differences. The association between the PA measurement and VO2max test was examined via the correlations and the magnitude was presented by the Steiger’s Z value.P < 0.01) and light PA  and more moderate PA  than was objectively indicated. Significant positive correlations were revealed between VO2max with all PA levels derived from accelerometry  rho = .33, P = .01), and a negative association to sedentary time (ST) emerged . IPAQ-reported moderate PA and MVPA positively correlated with maxV02 . Differences between the magnitude of correlations between the IPAQ-VO2 max and GT3X-VO2 max were only significant for ST .Sixty-eight RA patients  yrs) were recruited. Smaller differences between the subjective and objective measures were found when PA was assessed at the moderate level. Wilcoxon tests revealed that patients reported less time spent engaged in sedentary behaviours (Z = −6.80, Via responses to the IPAQ, RA patients reported that they were less sedentary and engaged in more higher intensity PA than what was objectively assessed. Accelerometry data correlated with VO2max at all PA levels. Only subjective moderate and MPVA correlated with VO2max. Findings suggest that self-reported PA and ST should be interpreted with caution in people with RA and complemented with accelerometry when possible.ISRCTN04121489. Registered 5 September 2012.Trial registration: ClinicalTrials.gov  Rheumatoid arthritis (RA), the most common inflammatory musculoskeletal disease, is characterized by joint swelling, pain and bone destruction but also a greater risk of cardiovascular disease (CVD) ,2. The lThere are two ways of measuring PA, namely subjective and the objective methods, which are distinguished on how the data are collected. To date, subjective PA is predominantly measured via self-reported means, given that this method is easy to administer, low cost, and more efficient at gathering data from larger samples . However2, median of disease duration = five (two to eight) years) participated in this study. The current medication of all studied participants appears in Table Sixty eight RA patients .Subjective PA was assessed using the long form of the IPAQ  which haDaily objective PA and sedentary time (ST) were measured using the ActiGraph accelerometer . Accelerometry is widely used for assessing individual levels of daily activity/time spent sedentary across different age groups ranging from children  to olderMovements recorded by the GT3X are converted into ‘counts’ within each epoch. These counts are calculated in relation to time spent at different activity intensities according to different cut-off points . Daily aParticipants in the current study were advised to wear the accelerometer on their waist at all times during a seven-day period, including their sleeping time if they did not find this uncomfortable. It was recommended to the participants that they should only take the device off during showering, bathing or engaging in any other water activities. If the participants engaged in any other water activity which was not possible to record on the accelerometer, they were requested to report the activity type, intensity and duration when they returned the device to the researchers. However, this was not the case for any of the current study participants.The VO2max test was performed using a breath-by-breath system  on a HP Cosmos mechanical treadmill . After identifying a convenient speed for each individual patient , the speed increased by 0.5 mph every minute until it reached 4 mph while inclination remain constant at 1%. Thereafter, there were only increases in inclination by 1% every 30 seconds until volitional exhaustion.Normal distribution of the variables was assessed via the Kolmogorov-Smirnov normality test. To test our first hypothesis, Bland-Altman plots  were useP <0.05.To test our second hypothesis, correlations between VO2max with subjective and objective PA at different levels were examined via Spearman correlations. Furthermore, Steiger’s Z test  was usedPatient characteristics are reported in Table Separate Bland-Altman plots were produced for ST, light PA, and moderate PA Figure . ResultsFigures Z = −6.80, P <0.01). In addition, self-reported light PA (median = 30 (11 to 66) minutes) was also significantly less compared to objective light PA time (median = 267 (221 to 321) minutes; Z = −6.89, P <0.01). In contrast, participants self-reported significantly more moderate PA behaviour on IPAQ (median = 55 (19 to 129) minutes) than was recorded on GT3X (median = 14 (5 to 25) minutes; Z = −6.26, P <0.01), and more vigorous PA (median = 0 (0 to 0) minutes) compared to GT3X (median = 0 (0 to 0) minutes, Z = −2.83, P = 0.01]. Subjective participation in MVPA (median = 59 (22 to 148) minutes) was also significantly elevated compared to MVPA objectively measured via GT3X (median = 14 (6 to 26) minutes; Z = −6.28, P <0.01).The results of the Wilcoxon tests between subjective and objective PA data at different PA levels and the interquartile ranges are shown in Table P = 0.01) and MVPA  levels. On the other hand, VO2max correlated significantly with all objective GT3X PA measurements , whereas objective ST was negatively associated with VO2max fitness .The average VO2max was 20.17 ± 4.60 ml/minute/kg, which is indicative of poor fitness levels . OverallP <0.001) were significant, whereas at all other levels of PA, no significant differences emerged, that is, light PA , moderate PA , vigorous PA  and MVPA .The tests of the magnitude of the differences between correlations were examined according to the results of the Steiger's Z value. Results indicated that only the differences between the correlations for ST  the agreement between subjective/self-reported (IPAQ) and objective (GT3X) PA, and 2) the associations between both of these assessments with VO2max, the gold standard assessment of cardiorespiratory fitness. Our results show that, when compared to accelerometry-derived values, RA patients under-reported ST while in contrast, they over-reported moderate PA, vigorous PA and MVPA when these behaviours are assessed using a self-report questionnaire. In addition, we found VO2max to associate more with objective, in contrast to subjective, PA.Based on the data obtained from the GT3X, the present findings indicated that this sample of RA patients had both lower PA compared to relevant guidelines of 150 minutes of moderate intensity PA or 75 minutes of vigorous PA per week  . Our resExamination of the agreement between both subjective and objective PA measurements indicated that the two measurements varied in their degree of discrepancy at the different PA levels. The Bland-Altman plots for sedentary and light PA levels revealed lower agreement between these two measurements when RA patients were less active. Similar patterns have been identified in past work in the general population ; howeverIn regards to comparing self-reported levels of PA with the gold standard measure of fitness (VO2max), only moderate PA and MVPA were significantly correlated with VO2max. In contrast, all objectively assessed PA levels as well as time spent sedentary were significantly associated with cardiorespiratory fitness in the expected directions. These results suggest that increased engagement in objectively assessed MVPA may lead to increased cardiorespiratory fitness in the RA population. Increased cardiorespiratory fitness is important to enhanced cardiovascular health in RA patients ,20, as hDespite the implications of our findings, it is equally important to acknowledge some of the limitations of the current study. The sample size was not calculated using standardized techniques and was limited to a certain geographical area within the UK. Also, previous research  has indiOverall, our findings suggest that the observed associations highlighted a discrepancy between RA patients’ perceptions of their participation in PA and ST (as determined via responses to the IPAQ) and what was the case objectively. Patients with RA self-reported significantly less engagement in sedentary pursuits and significantly more moderate and vigorous PA than what were indicated via accelerometer assessments. Moreover, the associations between IPAQ-assessed sitting time and PA levels and the gold standard assessment of PA indicated that only self-reported moderate and MPVA were correlated with maxVO2 in the expected manner. The present findings suggest that results from existing studies of RA patients’ PA and sedentary behaviour patterns that are based solely on subjective measures of PA and sedentary behaviour (such as the IPAQ) should be interpreted with caution.


A 4 year-old male presented with effort dyspnea, and was diagnosed as atrioventricular canal defects. This finding was confirmed by open heart surgery, and a congenital double orifice mitral valve was discovered. The septal defect was closed but the double orifice mitral valve was respected because of the absence of hemodynamic disturbance. We report this case with review of literature. Double orifice mitral valve (DOMV) is a rare congenital malformation characterized by a mitral valve with two orifices. This anomaly is usually detected with other cardiac malformation . AlthougA four-year old male child, product of non-consanguineous marriage, with history of effort dyspnea and recurrent respiratory infection. On physical examination, a systolic murmur was heard in the left parasternal area. Echocardiography provided a diagnosis of atrioventricular (AV) canal defects. In the operating room, the primumatrial septal defect (ASD) and the mitral cleft were seen. A congenital DOMV was fortuitously discovered . The priDOMV is a rare disorder that was first reported by Greenfield in 1876 . This anTransthoracic echocardiographic examination is a reliable, and in most cases sufficient, means of diagnosing DOMV and determining its type. This case demonstrates the necessity of careful imaging of the mitral valve apparatus in patients with AV canal defects.


Pressure overload induces stress-induced signaling pathways and a coordinated transcriptional response that begets concentric cardiac hypertrophy. Although concentric hypertrophy initially attenuates wall stress and maintains cardiac function, continued stress can result in maladaptive cardiac remodeling. Cardiac remodeling is orchestrated by transcription factors that act within the context of an epigenetic landscape. Since the epigenetic landscape serves as a molecular link between environmental factors (stress) and cellular phenotype (disease), defining the role of the epigenome in the development and progression of cardiac remodeling could lead to new therapeutic approaches. In this study, we hypothesized that the epigenetic landscape is important in the development of cardiac hypertrophy and the progression to maladaptive remodeling. To demonstrate the importance of the epigenome in HF, we targeted the PTIP-associated histone methyltransferase complex in adult cardiac myocytes. This complex imparts histone H3 lysine 4 (H3K4) methylation marks at actively expressed genes. We subjected PTIP null (PTIP-) mice to 2 weeks of transverse aortic constriction, a stress that induces concentric hypertrophy in control mice (PTIP+). PTIP- mice have a maladaptive response to 2wk of transverse aortic constriction (TAC)-induced pressure overload characterized by cardiac dilatation, decreased LV function, cardiac fibrosis, and increased cell death. PTIP deletion resulted in altered stress-induced gene expression profiles including blunted expression of ADRA1A, ADRA1B, JUN, ATP2A2, ATP1A2, SCN4B, and CACNA1G. These results suggest that H3K4 methylation patterns and the complexes that regulate them, specifically the PTIP-associated HMT, are necessary for the adaptive response to TAC. Heart failure (HF) is a major cause of morbidity and mortality in the world . In respGene expression profiles are regulated by transcription factors that act within the context of an epigenetic template that partitions the DNA into actively expressed and repressed regions . The divHistone tail methylation marks are one type of epigenetic mark that regulate chromatin structure and the accessibility of transcription factors and transcriptional complexes to enhancer and promoter regions of DNA . PreviouOne important histone tail methylation mark is tri- methylation of the lysine 4 residue of histone H3 (H3K4me3). H3K4me3 methylation is associated with transcriptionally active chromatin . High leIn this report, we build on our prior findings to explore the consequences of cardiomyocyte-specific ablation of PTIP in response to cardiac pressure overload induced by 2 weeks of TAC, a hemodynamic stress that induces concentric cardiac hypertrophy. We found that PTIP deletion results in a maladaptive response to TAC. Two weeks after TAC, PTIP- mice rapidly develop LV chamber dilation, LV systolic dysfunction, and cardiac fibrosis. This maladaptive response in PTIP- was accompanied by increased cell death, enhanced fetal gene expression, and an overall shift in gene expression profiles when compared to mice with PTIP. These results provide the first evidence that the PTIP-associated HMT that regulates H3K4me3 marks is necessary for the development of concentric hypertrophy TAC.The generation of male cardiac-specific PTIP null (PTIP-) and PTIP control (PTIP+) mice has been previously described . BrieflyEcho was performed to noninvasively assess the impact of TAC on cardiac structure and function. In sham operated PTIP+ sham and PTIP- sham mice, there were no differences in LV chamber dimensions including LVEDD (LV end-diastolic diameter) and IVSd  Fig  and 3B. Cardiac fibrosis and cell death are hallmarks of heart failure , 23. PicTo assess the impact of PTIP deletion on stress-induced cell death, we performed TUNEL staining on PTIP+ TAC and PTIP- TAC hearts. As shown in To confirm that PTIP is deleted in PTIP- mice and to determine whether PTIP levels change in response to TAC, we performed qPCR on TAC and sham animals (n = 4-6/group). As shown in LV remodeling and the development of hypertrophy and heart failure is accompanied by the induction of a fetal gene expression program. Accordingly, we measured the fetal genes ANF, β-MHC and Acta1 by qPCR in PTIP+ sham, PTIP- sham, PTIP+ TAC and PTIP- TAC  and PTIP- TAC (n = 4) at 2wk post TAC . Gene exIn order to confirm our gene expression array data and identify genes that could contribute to the maladaptive stress response observed in PTIP- TAC hearts, we performed qPCR for specific genes that were identified by gene expression array. Since our phenotype was already evident after only 2wk TAC, we rationalized that gene expression profiles would be abnormal early after TAC. Thus, qPCR was performed on PTIP+ TAC and PTIP- TAC hearts 3d after TAC. Gene array revealed that ATP1A2 was attenuated in PTIP- TAC hearts. ATP1A2 is a Na(+), K(+)- ATPase that regulates murine cardiac contraction. qPCR revealed a significant attenuation of ATP1A2 in PTIP- hearts compared to PTIP+ hearts . ATP2A2 α1-adrenergic receptors play a critical role in cardiac biology and are necessary for the adaptive response to TAC . AccordiThe PTIP-associated HMT regulates H3K4me3 marks at actively expressed genes. We have previously demonstrated that PTIP deletion results in an attenuation of global cardiac H3K4me3 marks. In order to determine the impact of TAC and PTIP deletion on global H3K4me3 marks we performed western blot analysis for PTIP and H3K4me3 in PTIP+ and PTIP- hearts after sham or TAC surgery. As demonstrated in Our data demonstrate that absence of the PTIP-associated HMT results in a maladaptive response to pressure overload. After just two weeks of TAC, PTIP- mice develop cardiac dilation, a marked decrease in LV systolic function, an increase in cardiac fibrosis, and an increase in cell death. These phenotypic consequences were underscored by an abnormal shift in gene expression profiles and altered H3K4me3 profiles.4me3, are heritable, stable, and conserved in yeast, flies and humans . Fast green/Sirius red staining sections were stained using 0.1% Fast green/0.1% Sirius red for 30 min. Wheat Germ Agglutinin staining slides were incubated with the WGA lectin , anti-H3K4me3 , and rabbit anti-PTIP. Blots were quantified by densitometry and normalized to H3 levels.Ventricles were harvested, snap frozen, pulverized, and homogenized. The cytosolic fraction was solubilized in a buffer with 25 mmol/L Tris-HCl [pH 7.4], 0.5 mmol/L EDTA, 0.5 mmol/L EGTA, 1 mmol/L PMSF, 1 mmol/L DTT, 25 μg/mL leupeptin, 25 mmol/L NaF, and 1 mmol/L Na2 pieces. For H3K4me3 marks, minced tissue was cross-linked with 1% formaldehyde in culture media for 15 minutes. The protocol was then followed as previously described.[5’- CGCTCTTTTCTGTGTCCAGGAAC and 5’-GGCTCGCTTCTTGCTTCTCC and SCN4B 5’ ATTCCATCCCAAGCCCCC and 5’ AAAGCCCAGTGCCCAGCCATCTCGC.Ventricles were harvested and minced into 1- to 2-mmescribed. Antibodit test to compare 2 groups and analysis of variance with Bonferroni correction to compare multiple groups. P values of less than 0.05 were considered significant. All data shown are mean ± SD unless otherwise specified.Statistical significance was calculated using 2-tailed Student’s S1 FigPTIP+ TAC (n = 4) and PTIP- TAC (n = 5) hearts were subjected to TAC for 2 weeks. LV tissue was harvested and sent for gene expression array analysis at the University of Michigan DNA sequencing Core. Array data for the individual hearts are presented and labeled PTIP- TAC #1-#5 and PTIP+ TAC #1-#4. Data are organized such that the genes with the most significant p-value are closest to the top. “Log2 fold change” numbers that are positive represent genes that increased in PTIP- TAC hearts and negative “log2 fold change” numbers represent genes that decreased in PTIP- TAC mice.(XLSX)Click here for additional data file.S1 TableAdditional echocardiography and pathology parameters are included. Data shown are means ± SD. LVESD is LV chamber diameter in systole. PWd is posterior wall in diastole.* p<0.05 vs. PTIP-Sham; # p<0.05 vs. PTIP+ Sham; $ p< 0.05 vs. PTIP+ TAC.(DOCX)Click here for additional data file.


The specific aim of this study was to evaluate the feasibility, reproducibility and maturational changes of LV rotation, twist and torsion variables by real-time 3D speckle-tracking echocardiography (RT3DSTE) in children.A prospective study was conducted in 347 consecutive healthy subjects  using RT 3D echocardiography (3DE). The LV rotation, twist and torsion measurements were made off-line using TomTec software. Manual landmark selection and endocardial border editing were performed in 3 planes  and semi-automated tracking yielded LV rotation, twist and torsion measurements. LV rotation, twist and torsion analysis by RT 3DSTE were feasible in 307 out of 347 subjects (88.5%).2 = 0.036, P< 0.001). The normal ranges were defined for rotation and twist in this cohort, and for torsion for each age group. The intra-observer and inter-observer variabilities for apical and basal rotation, twist and torsion ranged from 7.3% ± 3.8% to 12.3% ± 8.8% and from 8.8% ± 4.6% to 15.7% ± 10.1%, respectively.There was no correlation between rotation or twist and age, height, weight, BSA or heart rate, respectively. However, there was statistically significant, but very modest correlation between LV torsion and age (RWe conclude that analysis of LV rotation, twist and torsion by this new RT3D STE is feasible and reproducible in pediatric population. There is no maturational change in rotation and twist, but torsion decreases with age in this cohort. Further refinement is warranted to validate the utility of this new methodology in more sensitive and quantitative evaluation of congenital and acquired heart diseases in children. Left ventricular (LV) rotation, twist, and torsion, due to the complex helical myocardial fiber architecture, are the result of the clockwise rotation of the base and the counterclockwise rotation of the apex of the LV and play an important role in ventricular systolic and diastolic performance –6. Only More recently, three-dimensional speckle-tracking echocardiography (3D STE) has been developed to overcome the limitations of 2D STE –17. ThisThe specific aims of our study were: 1) to evaluate the feasibility and reproducibility of LV 3D rotation, twist and torsion by RT 3D STE, and 2) to establish the maturational changes and normal values of these measures in a large prospective pediatric cohort.The study was approved by the institutional research ethics committee at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China. All data used were anonymized. The subjects gave written informed consent. All procedures and data analysis were performed by the authors; specific contributions of all enlisted authors are provided.A total of 347 consecutive subjects from birth to 18 years were prospectively enrolled at Union Hospital in Wuhan, China. The inclusion criteria included: 1) referral for echocardiographic evaluation for clinical reasons, 2) no previous history of congenital or acquired heart disease, and 3) completely normal studies on 2D and Doppler echocardiography with normal structure, chamber size, wall thickness and systolic function. Exclusion criteria included: 1) structural congenital or acquired heart disease, 2) abnormal cardiac rhythm, and 3) hypertension and/or other acute or chronic illnesses. Demographic variables, including age and gender, were collected at the time the echocardiographic studies were performed. Informed consent was obtained. Weight, height, heart rate, and blood pressure measurements were also obtained in all subjects.All subjects had a complete transthoracic echocardiogram to determine cardiac structure, chamber size, wall thickness and cardiac function according to the recommendations of the American Society of Echocardiography. –20 All sCardiac chamber size, mass, and systolic LV function were measured in accordance with the recommendations for chamber quantification of the American Society of Echocardiography. –20 LV enOffline 3D STE analysis was performed using software for echocardiographic quantification . Measurements were made using the dataset with the best image quality. The frame rate of the volumetric images was 15 to 24 frames / second. The 3D data sets were displayed as multi-planar reconstruction images corresponding to four tiles containing three standard long axis (LAX) views  and a short axis view, which is orthogonal to the LAX views . The sofBy convention, counterclockwise LV rotation as viewed from the apex was expressed as a positive value, whereas a clockwise rotation was denoted as a negative value. LV twist was defined as the net difference between the basal and apical rotation angles . LV torsion was calculated as the net LV twist normalized with respect to ventricular end diastolic (ED) longitudinal length between the LV apex and the mitral plane (LV torsion (°/cm) = LV twist /ED length). The coordinates for rotation, twist and torsion for each frame were exported to a spreadsheet .Inter-observer and intra-observer variabilities of the measurements were assessed in 50 randomly selected subjects (10 in each age group). To assess intra-observer variability, the same observer (L.Z.) measured the 3D rotation, twist and torsion analysis twice at an interval of 2 months to avoid recall bias. To assess inter-observer variability, 3D rotation, twist and torsion measurements were performed by a second observer (J.Z.), who was blinded to the results of the first observer (L.Z.).P values < .05 were considered statistically significant. Statistical analyses were performed using SPSS for Windows version 16.0 .All demographic, conventional echocardiographic, and 3D LV rotation, twist and torsion data are presented as numbers or percentages (mean ± SD). The relations between age and 3D LV rotation, twist and torsion variables were determined using scatter plots, one-way analysis of variance, and second-order polynomial regression analysis. Intra-observer and inter-observer agreements were calculated using the coefficient of variation  and intra-class correlation coefficient. A total of 347 subjects were evaluated for inclusion in the study. Of those, LV rotation, twist and torsion analysis by RT 3D STE was feasible in 307 subjects (88.5%) , whereas 40 subjects were subsequently excluded, including 15 subjects due to low frame rates as determined by the software system and 25 subjects due to the poor 3D images.On the basis of changes of somatic growth rate in infancy (rapid growth), preschool years (deceleration in growth), preadolescence (relatively steady growth), onset of puberty (beginning of growth spurt), and adolescence , the effects of age and cardiac growth on LV functional indices were examined. The final 307 study subjects were divided into 5 representative age groups : group 1P < .01), and the heart rate decreased significantly , except for LVEF which remained unchanged throughout the age groups (P > .05).Conventional echocardiographic parameters of the study subjects are presented in 2 = 0.036, P< .001). There was no significant difference in rotational and twist variables among the age groups but there were statistically significant differences in torsion (P< .001) among the 5 age groups, except for the analysis between group 5 and group 4 as well as between group 4 and group 3. Three-dimensional LV rotation, twist and torsion data are presented in Intra-observer and inter-observer variability data are shown in Tables To the best of our knowledge, this is the largest prospective pediatric study to investigate the feasibility and reproducibility of 3D STE and a modality independent software and algorithm to derive LV 3D rotation and twist variables. We also investigated normal values and maturational changes in this large pediatric cohort.Previous studies have reported an increase in LV apical, basal rotation, and twist and a deEchocardiographic speckle tracking is a technique based on a frame-by-frame tracking of speckle patterns created by interference of the ultrasound beam within the myocardial tissue,5. 2D STOur results showed measurement of LV rotation, twist and torsion is highly feasible by the 3D STE technique 88.5%). The intra-observer and inter-observer variabilities for apical and basal rotation, twist and torsion ranged from 7.3% to 15.7%. Previous studies suggested that the good reproducibility is due to the fact that 3D STE is not limited to one imaging plane and, as a result, can better track the complex 3D motion of the LV speckles%. The in,17.Although the clinical utility of rotation, twist and torsion is still unfolding, there are growing evidence and investigations using this new approach to assess LV function in various cardiovascular disorders in both adults and children–25. MoreIn addition, there are many other studies in the literature that showed that LV mechanical parameters are altered in congenital and acquired heart diseases. For example, Menting E et al found that the majority of patients with corrected tetralogy of Fallot showed a reduced LV twist mainly due to decreased apical rotation. StrikinThere are a few limitations related to this study. First, the left ventricular rotation, twist, and torsion by3D STE technology has not been validated against other reference standard. Second, the ethnic group we studied is limited to the Asian population. It has been noted in the published literature that suggested there is variability in LV volume, mass, and function among certain ethnic groups. FurtherThe measurement of LV rotation, twist and torsion by this new RT 3D STE methodology is feasible and reproducible in children. There is no maturational change in rotation and twist, but torsion decreases with age in this cohort. Further refinement is warranted to validate the utility of this new methodology in congenital and acquired heart diseases.S1 Fig(TIF)Click here for additional data file.S2 Fig(TIF)Click here for additional data file.


We report the presence of an anomalous papillary muscle inserting into the basal antero-septum in patients with hypertrophic obstructive cardiomyopathy (HOCM) investigated by means of cardiac MRI.9 consecutive patients with HOCM and 13 age- and gender-matched controls without this condition were interrogated using a Siemens Espree MRI machine. A diagnosis of HOCM was established on the basis of asymmetric antero-septal left ventricle hypertrophy and systolic anterior motion of the mitral apparatus.100% of HOCM patients and 62%  of controls demonstrated an anomalous papillary muscle connecting the left ventricle basal antero-septum with the apex, noticeable on a long axis view acquired on an SSFP sequence. This particular structure contracts during during systole as seen in Figure An anomalous papillary muscle connecting the basal antero-septum with the left ventricular apex and contracting during systole is more commonly seen in HOCM patients than in controls. Further larger studies are needed to elucidate the importance of this anatomical finding in the physiology of left ventricle outflow tract obstruction.


The Tei index is a Doppler-derived myocardial performance index. It is a measure of the combined systolic and diastolic myocardial performance of both the left and right ventricles. The incidence of heart failure (HF) is increasing globally, and its severity can be clinically assessed using the New York Heart Association (NYHA) functional classification and more objectively using echocardiographic assessment of systolic and diastolic functions. Thus, a measure of the combined systolic and diastolic myocardial performance could be a useful predictor of the severity of the clinical status of patients with HF.Seventy-five newly presenting patients with HF of NYHA class II to IV and 60 normal controls were consecutively recruited. Using conventional two-dimensional and Doppler echocardiography techniques, the left ventricular parameters assessed were the isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), ejection time (ET), ejection fraction (EF), and end-diastolic volume (EDV). The Tei index was determined using the formula IVCT + IVRT/ET. The mean Tei index of patients was significantly higher than that of controls . The Tei index ranged from 0.33 to 1.94 in patients and from 0.56 to 1.24 in controls. The mean EF was lower in patients than in controls . The mean EDV was higher in patients than in controls . Comparison of the mean Tei indices of patients with HF of NYHA classes II, III, and IV showed statistically significant differences among all three groups (p < 0.001).The Tei index seems to be a clinically relevant indicator of cardiac function. It is reflective of the severity of HF as clinically assessed using the NYHA functional classification in patients with HF. Heart failure (HF) is one of the most common diseases of the heart in adults and accounts for an increasing number of hospital admissions in the developed world . In AfriThe ideal test for HF would be a noninvasive, integrated assessment of systolic and diastolic LV function that does not artificially uncouple systolic from diastolic function, is independent of ventricular loading conditions, and is reproducible during serial follow-up. A new Doppler-derived index combining systolic and diastolic time intervals proposed by Tei et al. in 1995 ,11 fulfiThe aim of the present study was to assess the relationship between the Tei index and HF of different severities clinically assessed using the New York Heart Association (NYHA) functional classification in patients with HF.Seventy-five consecutive patients who fulfilled the Framingham criteria  for diagThis study was conducted at the Cardiac Care Unit, Department of Medicine, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Osun State, Nigeria.This was a case–control study.a priori approval from the institution’s human research committee.Approval was obtained from the ethics and research committee of the hospital, and signed informed consent was obtained from each patient who participated in the study. The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in 2pq / d2, where z is the standard normal deviate using a 95% confidence level of 1.96; p is the proportion of the target population estimated to have a particular characteristic ; q is obtained using the formula 1.0 – p; and d is the degree of accuracy desired, set at 0.05.The minimum sample size was calculated using a formula for estimating proportions with populations of less than 10,000: nf = n/1 + n/N. The value nf is the desired sample size when the population is less than 10,000; N is the estimated population size ; n is obtained using the formula n = zThus,andThe diagnosis of HF was made using the Framingham criteria ,24 for dFor each patient, a chest radiograph (posteroanterior view) was obtained at the radiology department to assess the cardiac silhouette, aorta, and lung fields. A conventional resting 12-lead electrocardiogram was obtained with a Schiller AT-2 electrocardiographic machine. Lead II was recorded for a long rhythm strip. The recommendations of the American Heart Association  concerniTwo-dimensional (2-D), motion mode (M-mode), and Doppler studies were performed with transthoracic echocardiography using a Siemens Sonoline G60S ultrasound imaging system with a P4-2 transducer. Measurements were performed in accordance with the recommendations of the American Society of Echocardiography  with leaThe data were analyzed with a statistical computer software package (SPSS version 16.0). Continuous variables are expressed as mean ± standard deviation, and categorical variables are expressed as percentages. Student’s t-test was used to determine the difference between two means. A p-value of ≤0.05 was considered statistically significant.The sample frame comprised age- and gender-matched patient and control groups , as shown in Table The Tei index has been proven to be a reliable method for the evaluation of LV systolic and diastolic performance, with clear advantages over older established indices and prognostic value in many kinds of heart disease ,14,18,30Moreover, the mean Tei index was higher with increased HF severity, and there were statistically significant differences among all three groups . This finding is in agreement with several others, including the findings obtained by Tei et al. . Their sOur study also revealed the trend of presentation of patients with HF in our environment (41% of these patients were in NYHA class IV). In most such patients, the HF is structurally advanced with an altered LV geometric pattern, and the ellipsoid shape of the heart tends to become spherical, leading to limitations in the use of most of the traditional parameters for assessing systolic and diastolic functions. This further buttresses the relevance of the Tei index. The present study also demonstrated the usefulness of the Tei index in HF of causes other than hypertensive HF, as seen in a study of black patients in Africa . The dilFurthermore, in agreement with previous studies such as that by Bruch et al. and Ambakederemo et al. ,19, the The herein-described myocardial performance index (Tei index), which combines systolic and diastolic time intervals as an expression of global myocardial performance, correlates with cardiac function and seems to be a useful complimentary marker in the assessment of LV function. This combined measurement of ventricular chamber performance may be more reflective of overall cardiac dysfunction than systolic or diastolic measures alone. In our environment, where people present in the late stage of severe clinical HF, the Tei index may be more effective because it is not based on a geometric model or on volume measurement. A study of healthy adults and patients with congestive HF reported by Correale et al.  investigThis study has some limitations. First, the small sample size did not allow for adequate stratification for the observation of the presence or absence of statistical significance. Second, the effects of loading conditions and arrhythmias on this index remain to be elucidated. Finally, pseudonormalization of the index value was present in this study.In conclusion, this study indicates that the Tei index is a useful myocardial performance index that has a promising role in determining overall cardiac dysfunction. It is a reliable indicator of clinically assessed severe HF using the NYHA functional classification.The authors declare that they have no competing interests.OJO designed the study, was involved in the data collection and statistical analysis, wrote the protocol, and was involved in writing the first through final drafts of the manuscript. AAO was involved in designing the study and in writing the first through final drafts of the manuscript. OMA was involved in the writing of the manuscript. All authors read and approved the final manuscript.


The aim of the present study was to identify the relationship of physical activity (PA) and Health-Related Quality of Life (HRQoL) in patients suffering from low back pain (LBP).The present evaluation was conducted as a cross-sectional study based on baseline data of an randomized controlled trial on the effectiveness of an intervention promoting PA. Patients answered a questionnaire on domain specific PA (GPAQ) and HRQoL (EQ-5D-5 L). Furthermore, sociodemographic and indication-specific variables as well as work-related aspects were assessed. Associations of PA and HRQoL were estimated by means of regression analysis: one regression model only included domain specific PA (model 1) and a second regression model additionally included further variables (model 2).412 patients completed the questionnaire. Model 1 showed opposed effects of workplace and leisure time PA: while workplace PA showed a negative association , a positive association of leisure time PA could be proved . Model 2 showed that only the variables “current work ability”  and “intensity of pain”  significantly contributed to explain the variance in HRQoL (model 2).The present results indicate the necessity of a differentiation of workplace and leisure time PA in the context of assessing health-enhancing effects of PA in LBP patients. In the context of HRQoL it must be assumed that the relevance of PA might be overestimated. Further research should be performed on predictors of HRQoL and thereby particular attention should be paid on the patients’ work-related and indication-specific aspects. Physical activity (PA) is widely recognized as an important health-related lifestyle factor. The social, psychosocial and also biological health benefits of PA and exercise are well established and there is clear scientific evidence that moderate PA on a regular basis can reduce the risk of the morbidity of preventable non-communicable diseases (NCDs) ,2. OveraBesides morbidity and mortality, patient-oriented outcomes, such as Health-Related Quality of Life (HRQoL), are of utmost importance in rehabilitation and health services research . While qLow back pain (LBP) is not only one of the leading causes of pain and disability but also of a costly burden on the healthcare budget as LBP leads to a frequent demand for medical services ,15. The A better understanding of how PA is associated to HRQoL contributes to a comprehensive understanding of HRQoL and also to the development of target-group specific approaches to increase HRQoL in LBP patients. Therefore, the present paper aims to 1) explore the association between domain specific PA and HRQoL and 2) identify variables associated with HRQoL in LBP patients.Data were collected as part of a randomized controlled trial (RCT), evaluating the effectiveness of an intervention on physical activity promotion -ID: DRKS00004878). Ethical approval was granted by German Sport University Ethics Committee (reference number: 56/12). The study was conducted in compliance with the Helsinki Declaration. The present evaluation was conducted as a cross-sectional study based on baseline data of the RCT . EligiblPatients answered a questionnaire on PA, HRQoL and sociodemographic aspects. HRQoL was measured using the EQ-5D, a standardized, preference based measure of health status. Preference-based approaches are often used in cost-effectiveness analyses and incorporate values or utilities for health outcomes . The EQ-a. Therefore, vigorous intensity is described as “activities that cause large increases in breathing or heart rate”. The GPAQ is scored by multiplying the minutes per week for each domain by their associated MET to create MET-min scores per week. In the comparison with the International Physical Activity Questionnaire (IPAQ), a previously validated and accepted PA questionnaire, the GPAQ showed a moderate to strong positive relationship . Pedometer studies showed fair pooled criterion validity for total PA (r = 0.31) and reliability was of moderate to substantial strength  [r = 0.28) and vigorous (r = 0.48) PA. GPAQ data were checked for possible data entry errors by using the provided WHO CleanRecode program [PA was operationalised by Global Physical Activity Questionnaire (GPAQ) ,27. The age, gender, partnership, level of education and body mass index (BMI). BMI data were classified: BMI from 20 – 24.9 was defined “normal weight”, BMI from 25 – 29.9 “overweight” and ≥ 30 “obese” [current employment status (employed/unemployed), sick certificate before rehabilitation (<6 weeks/≥ 6 weeks), current work ability compared to highest work ability ever ) as an item from work ability index [duration of LBP (≤12 months/> 12 months) and intensity of pain. Intensity of pain during the last four weeks” was measured via a question from the SF-36 questionnaire  to 6 (very severe)) [Sociodemographic variables collected were severe)) .Physical inactivity was defined as 0 min PA/week, equivalent to not performing PA continuously for at least ten minutes in the life domain referred to in the GPAQ. For the regression models, the PA variables were classified: Transport PA was dichotomized (“no transport PA (0 min/week)”/“transport PA”), workplace PA and leisure time PA were divided into three classes each. Cut-off at workplace PA was set at “no workplace PA (0 min/week)”/“moderate or vigorous workplace PA”/“moderate and vigorous workplace PA”. Classification of leisure time PA was conducted referring to WHO-recommendations (“no leisure time PA (0 MET-min/week)”/“<600 MET-min”/“≥600 MET-min”).In order to describe the sample, means and standard deviation (SD) were calculated for continuous data and frequency tables  for categorical data. For the description of HRQoL, the frequency tables of self-reported problems across each of the five EQ-5D domains were presented. Summary index value of health status (EQ-5D-5 l) and the volume of PA at the workplace, in transport and in leisure time were described by means, SD, median, first and third quartile. The results on the volume of PA only relate to patients reporting any PA (>0 min PA/week). Prevalence of physical inactivity was presented separately by frequency of patients reporting “no PA” in each life domain.U Test.Gender and age differences between participants in the study and non-participants were tested by Pearson Chi Square Test respectively Mann–Whitney-To explore the association between PA and HRQoL (question 1) and identify variables associated with HRQoL (question 2) multiple linear regression models were calculated. In the first model (question 1), solely the different domains of PA were included. In the second model (question 2), besides PA, the sociodemographic, work-related and indication-specific variables were included stepwise to get insight in what variables explained HRQoL best. The principal assumptions of linear regression were tested. In both regression models, participants with missing values in dependent or independent variables were excluded. For all statistical tests, significance level was set at p < 0.05. All analyses were run with IBM SPSS Statistics 22.t-test p = 0.04). Most frequent reasons cited for non-participation were privacy protection  and language problems . 288 non-participants (55%) did not state a reason.Of 931 eligible patients, 412 gave informed consent and completed the questionnaire (participation rate = 44%). Compared to non-participants, there was no significant difference regarding sex (p = 0.18), but regarding age (p = 0.04). In average, participants  were one year younger than non-participants  and the mean age was 50.4 ±8.1) years. Sociodemographic and indication-specific variables as well as work-related aspects of the sample are shown in Table  years. SThe prevalence of physical inactivity across different life areas is presented in Table PA data (min/week) of patients reporting PA are displayed in Table pain and discomfort, followed by daily activities . Furthermore, severe problems in mobility are answered by 11.2%. Majority of the patients reported no problems in self-care (57.3%). The mean index value of health status (HRQoL) was 0.65 (±0.22).Table For calculation of regression models, independent variables were classified as described in statistical analysis. Table 2 = .033).In the first step, model 1, solely including dimensions of PA, was calculated Table . There w2 = 0.350). In this regression model, no domain of PA showed a significant association.In model 2  supported the assumption of opposed effects of leisure time PA and workplace PA: While “moderate and vigorous workplace PA” showed a negative association , leisure time PA “≥600 MET-min/week” showed a positive association  to HRQoL. Independently of HRQoL, Jacob et al. showed that strenuous PA at work might lead to a significantly higher risk of back pain . JunqueiHowever, the findings showed no significant association of PA and HRQoL if further variables were considered to explain influences on HRQoL. The results contradict other studies, stating a relationship between level of PA and quality of life in LBP patients  as well This research investigation has several strengths and limitations. As inclusion criteria were defined very broad, all patients prescribed inpatient rehabilitation because of LBP were included in the study. Due to logistic restrictions, specific problems related to LBP  could not be obtained. Also the participation rate of 44% and the monocentric study design are a limitation as they may cause a selection bias. Furthermore, as the present evaluation was performed in the context of an intervention study on promoting health-enhancing PA, primarily motivated patients may have responded. Due to missing values in independent variables, the regression models could only be fitted on subpopulations and therefore a further selection bias cannot be excluded. In consequence, implications for population mean of LBP patients have to be concluded very carefully. A second limitation is that the cross-sectional data cannot elucidate a possible causality of the associations. Thirdly, the self-reported operationalization of PA may induce a reporting bias due to overestimation . To miniApart from that, this study includes a number of important strengths. One such strength is the domain specific measurement of PA. By examining PA in different life areas and evaluating its domain specific associations to HRQoL, a gainful contribution assessing health-enhancing effects of PA in LBP is made. Furthermore, the comprehensive data collection enabled to capture often overlooked information such as work-related aspects. Another strength of the present study certainly is its concentration on HRQoL as an highly important outcome in rehabilitation and health services research. Whereas several studies and reviews on the relationship of PA and LBP are available, there is a lack of studies evaluating the association of PA and HRQoL in LBP patients. The present study therefore encounters the importance of the construct of HRQoL as a superior aim in rehabilitation and heath care service, as emphasized in German treaties on social law and utility analysis .Leading patients to an active lifestyle is a superior aim of exercise therapy in rehabilitation ,46. TherIn the context of HRQoL it must be assumed that the relevance of PA is overestimated. However, as HRQoL is of utmost importance in rehabilitation and health care research, further research should be performed on the prognostic influence of PA and other relevant predictors on HRQoL in longitudinal studies. Thereby, particular attention should be paid to the patients’ work-related aspects.aThe metabolic equivalent (MET) is a physiological measure expressing the expended energy of physical activities. MET is defined as the ratio of the rate of energy consumption during a specific physical activity to a reference metabolic rate. Vigorous intensity corresponded to 8 MET; moderate intensity corresponded to 4 MET.