Surrogate circulatory efficiency was decreased in AS, 8.6%  and AS/AR, 5.4%  when compared to controls, 11.8% (9.8–16.9). Surrogate external myocardial efficiency was higher in AS, 15.2% (11.9–18.6) than in AS/AR, 12.2%  and was significantly lower compared to controls, 12.2% (10.7–18.1) in patients with reduced ejection fraction (EF), 9.8% . In 16% of all cases, left ventricular mass/volume indices and EF were within normal ranges, wheras surrogate LV myocardial power was elevated and patients were symptomatic. Although influenced by pressure/volume load, the myocardium is additionally affected by remodelling processes. Surrogates for circulatory efficiency and LV myocardial power gradually reflect alterations in patients with AS and AS/AR, even when surrogate external myocardial efficiency, EF, mass and volume indices still remain compensated.We aimed to assess surrogate markers for left ventricular (LV) myocardial power and efficiency in patients with isolated aortic stenosis (AS) and combined stenosis/regurgitation (AS/AR). In AS (n = 59), AS/AR (n = 21) and controls (n = 14), surrogates for LV myocardial power and circulatory/external myocardial efficiency were obtained from cardiac MRI. Median surrogate LV myocardial power was increased in AS, 7.7 W/m The degree of hypertrophy is conventionally described by muscle mass and chamber size. However, large variability exists, how patients respond to pressure-volume overload and neither the onset of clinical symptoms nor the degree of hypertrophy  are exclusively and directly related to the degree of external load4.In aortic valve disease (AVD) pressure-volume overload conditions trigger cardiac remodeling causing concentric or eccentric hypertrophy5 and arrhythmia with an increased risk for sudden cardiac death can evolve7. Methods that can help to better recognize the underlying mechanisms are therefore of high clinical relevance. There is growing evidence, that in valvular heart disease myocardial efficiency is reduced9. Hence, the myocardium will need more energy to pump a given amount of blood against the vasculature10. New pharmacological or interventional therapeutic concepts aim to enhance myocardial efficiency and/or reduce energy demand likewise11.If left untreated, hypertrophy can lead to irreversible heart failure14. Increased energy requirements are known to result in adaptive changes in myocardial mass, left ventricle (LV) chamber size and interstitial fibrosis in order to maintain the pump function of the heart. Furthermore, in the resulting mechanisms of hypertrophy, the ventricle requires more energy for contraction and becomes less energetically efficient16. These changes are associated to stiffening of the heart and to decreased efficiency of the LV14. Underlying biochemical processes include an increase in cellular energy demand in the hypertrophied heart17 and a metabolic switch from mitochondrial fatty acid oxidation to anaerobic glycolysis16.From a pathophysiological perspective, alterations in heart disease can occur at the mechanical and biochemical level19. In addition, most existing methods also measure cardiac work/energetics at different levels that are not directly comparable to each other. For example, conductance catheter techniques focus on the assessment of “mechanical” circulatory energy components whereas combined Magnetic Resonance Imaging (MRI)20 and Positron Emission Tomography (PET) methods have been used to describe energy efficiency between metabolic  measures in relation to circulatory output 9.The assessment of cardiac energy expenditure is challenging. Available methods are either invasive or associated to ionizing radiation and thus are limited in their clinical useIn this study, the aim was to assess surrogate markers for LV myocardial power and the resulting efficiency, using a non-invasive MRI technique without direct measurements of biochemical or cellular mechanisms of energy consumption. The objective was to apply this method in a cohort of patients with isolated aortic stenosis (AS) and combined aortic stenosis/regurgitation (AS/AR) in order to assess potential differences of these surrogate markers between groups.21 in the absence of moderate or severe aortic regurgitation . The AS/AR group included patients with moderate and severe AR (RF ≥ 30%)23 in the presence of AS. The control group included participants without any type of aortic valve disease. Ejection fraction (EF) sub-analyses were performed in patients with reduced  and normal EF . In patients where NT-pro-BNP laboratory data was available, information were included in the dataset (n = 32).The study was conducted in 80 patients with aortic valve disease (AVD) and 14 heathy volunteers. AVD patients were assigned to two groups: Patients with isolated aortic stenosis (n = 59), patients with combined aortic stenosis and regurgitation (n = 21). Furthermore, patients were compared to a group of volunteers (n = 14). The aortic stenosis (AS) group included patients with moderate or severe stenosis (mean gradient ≥20 mmHg)24 were used to assess the presence or absence of abnormalities in parameters typically associated with left ventricular (LV) remodeling: LV muscle mass per body surface area (hypertrophy), LV end-diastolic and end-systolic volumes per body surface area (dilatation), LV EF. Measurements were considered within normal ranges if they were within two standard deviations of reference values24. An ejection fraction <50% was defined as functional impairment.The pressure gradient across the aortic valve was assessed using Doppler echocardiography. Cuff-based blood pressure measurements were obtained from the patient’s right arm before Magnetic Resonance Imaging (MRI). Clinical symptoms of heart failure were assessed using the New York Heart Association (NYHA) classification. In controls, an identical protocol was applied, and the absence of AS was confirmed using four-dimensional velocity encoded MRI (4D-VEC MRI). Age and gender specific reference values from healthy volunteersMRI examinations were performed using a whole body 1.5 Tesla MR system  using a five-element cardiac phased array coil. All MRI examinations lasted 45 to 60 minutes and were performed successfully.25. All images were analyzed using View Forum . The entire ventricle and the myocardium without the papillary muscles were segmented during diastole and systole.Epicardial and endocardial segmentations as well as LV volumetry and anatomical measurements were performed based on previously described gapless balanced Turbo Field Echo (bTFE) cine two-dimensional short axis sequencesABC, isovolumetric contraction time tIVC and the aortic pressure gradient, respectively: acquired voxel 2.5 × 2.5 × 2.5 mm, reconstructed voxel 1.7 × 1.7 × 2.5 mm, TR 3.5msec, TE 2.2msec, FA 5°, 25 reconstructed cardiac phases, retrospective gating, one signal average. 4D data were analyzed using GT Flow . Total systolic contraction time tCS is the sum of tABC and tIVC measurements obtained directly from 4D flow.According to clinical standards aortic regurgitation was quantified in the ascending aorta distally to the valve using (a) two-dimensional phase contrast MRI: repetition time (TR) 3.9msec, echo time (TE) 2.4msec, flip angle (FA) 15°; 30time steps, voxel size 1.1 × 1.1 mm. Furthermore, (b) Four-dimensional velocity-encoded MRI (4D-VEC MRI) was used to quantify blood flow across the aortic valve, the mitral valve and the ascending aorta in order to assess auxobaric contraction time t29. Previous studies have also shown the accuracy and reproducibility of 4D-VEC MRI-based flow measurements and demonstrated good agreement to 2D flow data31.High intra- and interobserver reproducibility of MRI-based volumetric LV and 2D flow measurements has been demonstratedCS of 174.5 ms (error <6%), making 4D flow measurements with 25 phases a feasible alternative to higher temporal resolution 2D flow if e.g. further post-processing is needed.As an alternative to 2D flow MRI, contraction time assessment included the quantification of the time to maximum aortic flow from 4D flow MRI sequences with 25 phases in order to allow for an optimal angulation . To exclude any methodological bias and to ensure sufficiently resolved data we performed a quality experiment in 15 aortic flow curves by comparing time measurements to higher temporal resolution 2D flow measurements with a temporal resolution of 75 phases. High temporal resolution flow curves were down-sampled to the resolution of the 4D flow MRI (25 phases) and the error for the peak flow time was evaluated. The median absolute error was 9.12 ms (interquartile range 9.1ms-18.2 ms) and thus was within acceptable range in our patients regarding an averaged t32. Since the applied method is an estimation, we defined it as a surrogate for myocardial power. The surrogate marker is a dimensional parameter [Watt] calculated as a product of the three parameters - myocardial wall stress σwall, myocardial volume Vwall and the contraction time. Surrogate left ventricular myocardial power, sLVMP, was calculated in our study using the equation:wall is myocardial wall volume, σwall is peak systolic wall stress, and tCS is the systolic contraction time (period between start of the contraction to peak systole) of the left ventricle. Peak systolic wall stress σwall was defined as:wall is the mean systolic myocardial wall thickness, PSYS is the peak systolic pressure in the left ventricle and RBP is the mean radius of the blood pool in peak systole. In order to correct for potential regional differences, mean myocardial wall thickness and mean radius of the blood pool estimations during peak systole were based on myocardial segmentations considering the LV as a cylindrical geometry. We then used a spherical Laplace-based approach as a very simplified model to estimate wall stress. Compared to finite element models, the combination with the spherical approach was demonstrated to provide a good approximation of the global mean stress in the circumferential‐longitudinal plane of the LV33. Psys is the sum of the systolic pressure in the right arm and the peak systolic pressure gradient across the aortic valve. Surrogate LV myocardial power was indexed to body surface area (BSA) allowing inter-individual comparison. The concept of the surrogate LV myocardial power and power efficiency is summarized in Fig. The surrogate for left ventricular myocardial power estimates the power of the LV myocardium required to perform contraction generating LV peak systolic pressure during a contraction timementclass2pt{minimeff): COeff = (forward flow volume – backward flow volume) * HR (heart rate). The ratio between circulatory power and the surrogate LV myocardial power (CP/sLVMP*100 [%]) is defined as the surrogate circulatory efficiency (sCircE) of the heart.Circulatory power defines the hydrodynamic power distally to the valve and represents the power needed to maintain effective blood flow against systemic vascular resistance Fig. . Circulavalve is the pressure gradient across the aortic valve in peak systole and COtotal is the total (forward flow) stroke volume  multiplied by HR. The ratio between EMP and the surrogate LV myocardial power (EMP/sLVMP*100 [%]) was defined as surrogate external myocardial efficiency (sEME). sEME is the surrogate parameter for the level of efficiency of the myocardium to provide effective cardiac output against the diseased valve and systemic pressure.External myocardial power defines the hydrodynamic power at the outlet of the LV Fig. . It reprData are presented as median and interquartile range  unless stated otherwise. Shapiro-Wilk, Shapiro-Francia and Kolmogorov-Smirnov tests were used to test data for normality. Analysis of covariance (ANCOVA) in conjunction with Bonferroni correction was used as appropriate to adjust inter-group tests  for age, gender as well as the presence of bicuspid valves. Dunn’s test was used as an appropriate nonparametric pairwise multiple comparison procedure of baseline data following a Kruskal-Wallis test of stochastic dominance among groups – it also included Bonferroni correction of p-values. Pearson’s chi-squared test was used in conjunction with Fisher´s exact test to test for differences in categorical data. Robust regression was used to assess multifactorial effects . The significance level was set at 0.05. Data were analyzed using Stata .The study was carried out according to the principles of the Declaration of Helsinki and approved by the local ethics committee (Ethics committee - Charité Universitätsmedizin Berlin). Written informed consent was obtained from the participants and/or their guardians. Trial Registration: clinicaltrials.gov NCT03172338, June 1, 2017.total) was the highest in patients with AS/AR while there were no significant differences for efficient cardiac output (COeff) between the groups. No significant differences for heart rate were observed between the groups.The analysis was performed in all included participants (N = 94). Table 2 = 0.82) was found between surrogate LV myocardial power and: (1) indexed myocardial mass  (2) indexed left ventricular end-diastolic volume  (3) mean pressure gradient across the valve , (4) age  and (5) contraction time . There was no significant correlation between surrogate LV myocardial power and sex (p = 0.087).Figure Circulatory power and external myocardial power were assessed in all three groups. There were no significant differences for circulatory power in AS, 1.3 W , and AS/AR, 1.0 W  when compared to control group, 1.2 W (1.1–1.3). When comparing AS and AS/AR, circulatory power was higher in AS than in AS/AR (p = 0.003). External myocardial power was higher in AS, 2.1 W  and in AS/AR, 2.4 W  when compared controls, 1.3 W (1.2–1.3). There were no significant differences for external myocardial power between AS and AS/AR (p = 0.085).Figure In AS and AS/AR, surrogate LV myocardial power was significantly higher in patients with reduced EF, 12.1 W/m2 (10.8–13.6) than in patients with normal EF, 7.9 W/m2 (6.4–10.5) (p < 0.001). sCircE was decreased in patients with reduced EF, 4.9% (4.1–5.9) compared to patients with normal EF, 8.0% (6.1–10.6) (p < 0.001). sCircE was lower in patients with normal EF (p < 0.001), and was lower in patients with reduced EF (p < 0.001), when compared to controls. sEME did not differ in patients with normal EF, 14.9% (12.9–17.9) when compared to controls (p = 0.218). sEME was significantly reduced in patients with reduced EF, 9.8% (8.1–11.7) when compared to patients with normal EF (p < 0.001) and compared to controls (p = 0.025).2 = 0.37, p < 0.001). Furthermore, there were significant negative correlations between NT-proBNP and: (1) sCircE  and (2) sEME  in patients with AVD. Besides NT-proBNP, significant correlations between sLVMP, sCircE and sEME to established clinical standards for pressure-volume load assessment (LV mass/volume indices and EF) can be found  and surrogate LV myocardial power  and patients were symptomatic .Hypertrophy was present in 32/80 (40%), dilatation in 37/80 (46%) and an EF impairment in 12/80 (15%) patients. In 13/80 (16%) of all cases, left ventricular volume indices, EF and mass were within normal ranges10, including aortic valve disease where the heart is exposed to chronic pressure/volume overload. The patient-specific response to such overload conditions can vary substantially. Whereas some patients present with signs of hypertrophy, myocardial thickening and ventricular dilation, others may show alterations in contraction time or only modest signs of remodeling4. In addition to pressure/volume overload, these adaptive processes can contribute to changes in energy efficiency of the heart.Information about LV myocardial energy demand and efficiency are valuable for the understanding of heart disease2) in hypertensive patients with LV hypertrophy34. The MVO2 is determined mainly by three factors: heart rate, velocity of contraction and systolic wall tension together with the myocardial mass35. The major part of myocardial energy is used for the contraction of the myocardial muscle and approximately 50% of the total MVO2 is required during the isovolumetric phase of contraction35. Experimental studies found that MVO2 correlates linearly with wall tension as well as the velocity of contraction, which inversely correlates to the generated tension37. This tension-velocity relationship is also affected by heart disease38. In order to estimate MVO2 in patients, recent studies proposed the use of a LV mass-wall stress-heart rate product and already demonstrated its association to mortality and heart failure in aortic valve stenosis39. The proposed surrogate LV myocardial power in our study can be of potential advantage, as (i) the use of myocardial volumes in our approach results in the power dimension [Watt] of the marker, that allows its direct use for the normalization of external and circulatory power and thus (ii) the calculation of the resulting surrogate efficiency. Furthermore, the integration of the contraction time instead of the heart rate (iii) corresponds with the major part of MVO2 demand35 and (iv) correlates better to the actual velocity of contraction.The study follows previous research, which found increased LV myocardial oxygen demand  parameters and have shown interesting – though not yet fully uniform – results in valvular heart disease. In an MRI-PET study, Güclü et al. have combined biochemical measures in a ratio with the individual’s mechanical external (circulatory) power in a small cohort of N = 10 patient. They demonstrate the resulting efficiency of the myocardium to be reduced in AS and a predictor of exercise capacity after aortic valve replacement8. In another combined MRI-PET study, Hansson et al. found reduced efficiency in patients with combined heart failure and low-flow low-gradient AS defined by indirect measurements of myocardial oxygen consumption in N = 59 patients9. In addition, the efficiency of compensated AS was reported to be at control levels. In our non-invasive approach, we also demonstrate (1) sEME to maintain normal in patients with compensated disease and (2) a similar decrease in sEME in patients with reduced EF. In our combined disease group (AS/AR), sEME was lower and surrogate LV myocardial power was substantially higher. These findings are in line with previous concepts of an accentuated degree of ventricular hypertrophy under combined pressure-volume load conditions40.Cardiac energy demand and efficiency can be divided into biochemical and biomechanical components. PET and MR-spectroscopy3. By the law of Laplace, an enlarged heart also attempts to maintain wall stress, amongst others, by changing its shape, increasing myocardial wall thickness or fibrous tissue content. By the same law, all adaptive changes necessarily go along with an increased energy demand. In line we noted in our study an increase in ventricular volume and mass (hypertrophy) to be an important determinant of the surrogate LV myocardial power. Further determinants were the pressure gradient and the regurgitation fraction across the aortic valve.Biomechanical stress due to pressure/volume overload triggers remodeling processes that lead to eccentric or concentric hypertrophy41. Comparably, In AS/AI even when the EF is normal, sCircE is reduced as soon as ventricular mass, volume and contraction start to alter. During this gradual process, it would be of high interest to determine the tilting point from an efficient (adaptive) to an inefficient  myocardium. However, this question cannot be answered without performance of longitudinal studies.In patients with chronic heart failure exercise capacity can be reduced even before the onset of EF impairment42. Therefore, in heart disease, including AS/AI, it would be desirable to understand, to which extent and at which pace increases in energy demand cause energy starvation at the cellular level and in turn impair excitation-contraction coupling. Even if the proposed concepts of myocardial power and efficiency are still at an early stage, together with PET, spectroscopy and more detailed finite element approaches33 and further experimental research they open the possibilities for future studies, that combine mechanical concepts at the organ level with molecular studies at the cellular level.Several biochemical cellular processes require energy for cell excitation, contraction, active relaxation and protein turnover44. More recent approaches applied combined MRI-PET methods. PET is used to determine the myocardial oxygen consumption that is considered being an estimate of myocardial energy utilization9. MRI-spectroscopy can assess metabolic processes, yet remains limited in its application as it typically requires higher magnetic field strengths. In the current study, we used a fully non-invasive MRI method without additional PET or spectroscopy with the advantage that it can be easily applied in clinical studies or even in the clinical routine. The method used in our study relies on an accurate and reproducible segmentation of the LV. Although echocardiography is able to assess flow, and thus can help estimating external power, it will be more dependent on image quality with larger heterogeneity between patients and observers, making the calculation of LV metrics and thus surrogate LV myocardial power more prone to errors. Nevertheless, recent and future technical improvements including the availability of 3D/4D echo may allow a translation to echocardiographic methods.Earlier concepts for measuring parameters of myocardial energy demand and efficiency mainly required an indirect assessment of metabolic measures and/or involved the use of invasive methods. Conductance catheter derived pressure-volume-loops depict the external energy generated during one cardiac cycle and allow determining the mechanical efficiency of ventricular-arterial couplinget al. have shown AS patients are able to maintain normal energy efficiency until EF is reduced9, which corresponds to our findings regarding EME. In addition, the present MRI-based method permits assessing sCircE, that is able to detect imbalances between the circulatory power demand and the state of the myocardium, as soon as surrogate LV myocardial power increases due to alterations in underlying geometrical or functional measures.So far, we demonstrated a simplified approach for computing cardiac energetics. In this study, surrogate LV myocardial power was considered the potential energy of the LV myocardium generated by myocardial contraction and was based on geometrical parameters of the LV. Measures are, to some extent, comparable to those published in other studies. In a combined MRI-PET approach, Hansson et al. have described a detailed methodology how mechanical power can be assessed using a finite element (FE) approach33. The approach can have several advantages over the method presented here for the calculation of wall stress, as the FE method can be of high accuracy and considers the entire heart cycle as well as spatially resolved myocardial wall deformations. If segmentation and simulation resources as well as the necessary expertise are available, the method of Gsell et al. showed a benefit over more simplified Laplace law based approaches in 5 in-silico cases. External mechanical efficiency, using physically correct internal mechanical power, will be 100% in idealised conditions of FE simulations by Gsell et al. In our work a surrogate internal myocardial power is estimated, without the same physical meaning, and as such this fundamental mechanical balance does not hold.Gsell 35. The energy for this will always be higher than the actual mechanical energy of the contraction. The loss of energy or higher MVO2 demand is a function of the contraction time, as faster contraction will be less efficient for the ventricle and it also accounts for differences found in AS and AS/AR compared to controls. Thus, the surrogate LV myocardial power as presented here is higher than the energy calculated by the approach of Gsell et al. When compared to circulatory power, the resulting ratio is defined as the surrogate circulatory efficiency. Whereas the different mechanical approaches carry the potential for clinical application, their correlation to biochemical and catheterization based methods as well as their comparative accuracy needs to be further investigated in future clinical studies.In contrast, the here presented approach estimates the power of the LV myocardium required to generate such mechanical power during systole (contraction) and its efficiency respectively. The deviating idea of our approach is that during isovolumetric contraction and systolic ejection the major part of myocardial oxygen consumption takes places2 since the exact correlation between MVO2 LV myocardial volume, wall stress and the contraction time is not yet known. In contrast, PET at an aerobic state already allows quantifying oxygen consumed from the coronaries at the costs of using ionizing radiation. Additionally, surrogate LV myocardial power as evaluated in this study differs by definition from FE approaches that require wall stresses and myocardial wall strain rate33, as the approach by Gsell et al. represents the hydraulic pump power of the left ventricle, whereas surrogate LV myocardial power estimates the power of the LV myocardium required to perform contraction generating LV peak systolic pressure during a contraction time that also includes isovolumetric contraction (associated with zero resulting hydraulic pump power during this phase).While external power is based on mean arterial pressure and cardiac output , the surrogate LV myocardial power calculations are focused on the systole as this cardiac phase accounts for the majority of the heart’s energy expenditure. The surrogate LV myocardial power does not cover any direct metabolic measurements of myocardial energy consumption or MVOBoth patient groups and controls were not matched and thus include differences, also reflecting disease specific characteristics, such as a high rate of patients with a bicuspid aortic valve. Group selection may have impacted relationships between surrogate LV myocardial power and power efficiency with the presented known clinical parameters. Comparison between groups was therefore statistically adjusted for age and bicuspid aortic valve disease. Nevertheless, genuine age/gender/disease specific reference cohorts should be acquired in future studies.46 possibly overestimating the impact of the stenosis on surrogate LV myocardial power. It is suggested to improve the method in the future by using the continuity equation or model-based approaches47. The calculation of myocardial wall stress was simplified. Details of the geometrical shape of the LV as well as regional strain both impact myocardial wall stress and power and should be considered for more exhaustive and fine-tuned models. While higher temporal resolutions may be of help to improve contraction time measurements, their main benefit would be to increase the accuracy of the isovolumetric component, even this only accounts for 5–10% of total contraction time.All aortic pressure gradients were assessed using Doppler echocardiography, according to current clinical recommendations. Consequently, pressure recovery was not considered and the aortic pressure gradient can be overestimatedIn addition, the present concept does not integrate processes at the tissue level such as fibrosis which is rather associated to diastole, as clinical routine myocardial mass measurements are also not corrected for extracellular volumes gained from T1 mapping. Future studies need to explore these mechanisms, especially as they may help to better understand the role of functional loss due to fibrotic remodeling and its impact on the remaining myocardium.While the predictive qualities and the impact on mid-/long-term outcome or progression to heart failure need to be further investigated, we were able to demonstrate that surrogate parameters of myocardial power and efficiency can be determined non-invasively using routine MRI data.Although influenced by pressure/volume load, cardiac energetics is additionally affected by remodelling processes. As cardiac output needs to maintain stable, the surrogate circulatory efficiency starts to decrease from an early stage of the disease. Surrogate circulatory efficiency and LV myocardial power gradually reflect alterations in patients with AS and AS/AR, even when surrogate external myocardial efficiency, EF, mass and volume indices still remain compensated. This may add helpful information in future longitudinal studies and the evaluation of new treatment targets and strategies.


Left ventricular torsion is one of the most important biomechanical parameters of heart that routinely is measured in short axis view. A review of the literature has indicated that assessment of left ventricular torsion in short axis view has some limitations. In the present study, we evaluated whether torsion angle assessment in long axis view can be used as a diagnostic biomechanical marker in patients with coronary artery disease (CAD).We assessed 20 males and 15 females who suffered from CAD and 24 healthy males and females. Two dimensional echocardiography images were scanned in cine loop format position throughout four cardiac cycles at basal and apical levels in the long axis view (4CH). Peak torsion angle in long axis view was obtained by speckle tracking method under block matching algorithm.In long axis view, peak torsion angle and time of peak torsion angle were similar in female  and males  while they were significantly decreased and increased in CAD patients  in comparison to healthy subjects. The peak torsion angle reduction in CAD patients was a subsequent of reduced rotation angle of basal and apical levels (P<0.001).The results showed that sex difference did not influence torsion angle of the left ventricle. It is concluded that left ventricular torsion assessment in long axis view has the potential to distinct patients with CAD from healthy subjects in routine echocardiography evaluation. Coronary artery disease (CAD) is the most common type of heart disease and mortality causes in the world. This disorder develops with stiffness and narrowing the coronary arteries , 2. AngiSpeckle tracking echocardiography (STE) is a new method for the assessment of myocardial motion, independent of the angle between tissue and ultrasound beam , 8. NotoThere is a controversy on the torsion angle magnitude among different studies due to the dependency of basal and apical rotation on the place of reference levels in short axis view and assuming the circularity of LV ,13. MoreRecent studies have shown that the assessment of myocardial movement along the long-axis view of the LV has some advantages in comparison to short axis view and covers its limitation , 17. In Regarding to the relation of left ventricular mechanical dyssynchrony specially torsion angle with regional fibrous deformation that may occur in CAD patients and advantages of torsion angle assessment from longitudinal rather than short axis view, the aim of present study was to assess whether LV torsion parameters in long axis view can be proposed as diagnostic biomechanical marker of patients with CAD. Also, due to the hypothesis of torsion angle dependency to LV remodeling which itself is affected by gender , we evalStudy population: We assessed 20 males and 15 females with diagnosed CAD and 24 healthy subjects . The patients with atypical chest pain, electrocardiography changes, and positive exercise test were enrolled in the study besides they have documented ischemic heart disease (IHD) based on cardiac catheterization study. They did not have any kind of valvular or congenital heart disease. Healthy subjects did not have any history of heart disease such as myocardial infarction, ventricular arrhythmia, heart failure hypertension, diabetes, drug consumption, and any kind of coexisting disease. They had a normal physical examination, electrocardiogram (ECG), echocardiography and did not undergo coronary angiography selected based on Framingham study  through random sampling and informed consent was taken from all subjects prior to participation in the study.Instrument: 2-1- A vivid GE echocardiography system  with M3S transthoracic sector transducer (1.5-4MHz) was used for recording the original images. 2-2- Post processing: 4 cine-loops from each standard views were transferred to personal computer (PC) computer for post processing by experimental software, Block matching algorithm under sum absolute difference (SAD) SAD criterion, that programmed in MATLAB software Version 7.0.1   , 17, 21.Echocardiography Recordings: For each subject, we scanned long axis views using high frame rate (60-70 frame per second) harmonic B-mode imaging with transmitted and received frequency 1.7 MHz and 3.4 MHz, respectively. In long axis view, basal and apical levels have been in 1/2 high and 1/3 low of left ventricular axis, respectively (ectively . The subLVED/dLVES), interventricular septal diastole thickness (TIVSD), posterior wall thickness (TPW) were measured in the long-axis view of LV, also LV ejection fraction (LV-EF) were calculated using Simpson's biplane method by measuring end-diastolic and end-systolic volumes in 2D images. 2D Echocardiography imaging was performed using standard transthoracic apical two and four-chamber views according to guidelines of the American Society of Echocardiography (ASE)  .Image analyzing: Measuring LV torsion in long axis view by STE under block matching algorithm was performed as reported in our previous study . Basal/ apical- LV rotation in long axis view at septal wall were calculated based on the following equation, Eq. 1. Eventually torsion angle was defined as the net difference between the apical and basal LV rotation Eq. 2.Finally, we measured the magnitude of peak torsion and calculated the time to peak torsion. Statistical analysis: We employed statistical analysis software SPSS 16.0 in our study. Data were expressed as mean±SD). Data were tested for normal distribution and homogeneity of variance by the Kolmogorov-Smirnov test (K-S). The difference between two groups was tested by unpaired t-test and Mann Whitney U-tests in case of parametric and non-parametric data with confidence level of 95%.Ethics: This study was approved by the Regional Committee of Ethics in Research of Golestan University of Medical Sciences with grant number: IR.GOUMS.REC.1397.278.Conventional ultrasound examination of healthy subjects and CAD patient: The clinical characteristics and conventional echocardiographic values of the subjects were summarized in table. 1. There were no significant differences between age, sex, heart rate and body mass index (BMI) of healthy persons and CAD patients (p>0.05). Also, there were no significant differences between posterior wall, interventional septal thickness, end systolic diameter, and ejection-fraction of two mentioned groups (p>0.05).Myocardial Motion Analysis: The horizontal and vertical myocardial septal movements in basal and apical levels in long axis views of healthy subjects and CAD patients are depicted in table 2. Independent- samples t-test showed there were no significant differences between septum wall movements of healthy subjects and CAD patients in all directions except horizontal displacement of apical view. LV Rotation and Torsion angle: Rotation and torsion angles in long axis views were calculated through extraction of the instantaneous changes of the vertical and horizontal displacement vector throughout a cardiac cycle using block matching algorithm and determination of the desired level center in end diastolic phase frame. As seen from the apical level, two groups had the same rotational behavior, as in systolic phase rotated clock wise in basal level and counter-clock wise in apical level. Torsion angle of the healthy subjects and CAD patients in long-axis views throughout a cardiac cycle for both males and females were demonstrated in Time to torsion angle peak: Torsion angle peak time in long axis view was significantly longer in CAD patients than healthy subjects, whereas there was no significant difference between heart rate of two mentioned groups (d groups .  Angiographic and CT angiographic imaging have been considered as the most important procedures for diagnosis of cardiovascular issues. However, their invasive nature and risk of ionizing radiation have restricted their repeated utilization. Nowadays, appropriate biomechanical parameters of myocardium based on modern echocardiography are proposed for many cardiac lesions. Based on recent studies, biomechanical abnormalities are seen in heart wall segments of patients with CAD , 25. OneWei et al.  indicateMyocardial movements are able to affect the torsion angle of the heart; so large differences take place in the angle of torsion in response to even slight changes in the extent of myocardial movements. According to this fact, recent studies have proposed the recruitment of the maximum ventricular rotation angle in short axis view compared to the variations in movement as a predictive tool for potential heart muscle damages , 11. Comparisons between patient and healthy subjects showed the declined apical axial displacement in CAD patients in long axis views, while there was no significant reduction in basal level. It seems that this distinction is due to the nourishment of septal wall by multiple vessels in basal level and effects of stenosis in one vessel are diminished by other branches of coronary arteries. In the present study, we have demonstrated that LV rotation has been declined in basal and apical levels in long axis view under the condition of CAD occlusion. Such situation produces necrosis of the apex and anterior septum and consequently causes flatting of apical fiber and declining of apical rotation angle. Basal level may be inﬂuenced by the motion of adjacent muscle, and therefore neighboring myocardial regions have caused decline in basal rotation angle.In conclusion present study indicated that LV torsion in long axis view decreased in CAD patient independent of gender. Therefore, it seems the assessment of LV torsion in long axis view has potential to distinct CAD patients form healthy subjects and might make the assessment more valuable in clinical and research cardiology. It is notable that our study investigated only the changes of LV myocardial septal wall rotation and torsion in long axis view. If imaging could be scanned with better spatial resolution, it would be possible to study other segments of myocardial wall.


Mucopolysaccharidosis type III (MPS III), or Sanfilippo syndrome, is caused by a deficiency in one of the four enzymes involved in the lysosomal degradation of heparan sulfate. Cardiac abnormalities have been observed in patients with all types of MPS except MPS IX, however few studies have focused on cardiac alterations in patients with MPS III.We reviewed medical records, echocardiograms, and electrocardiograms of 26 Taiwanese patients with MPS III . The relationships between age and each echocardiographic parameter were analyzed.n = 26) revealed that 10 patients (38%) had valvular heart disease. Four (15%) and eight (31%) patients had valvular stenosis or regurgitation, respectively. The most prevalent cardiac valve abnormality was mitral regurgitation (31%), followed by aortic regurgitation (19%). However, most of the cases of valvular heart disease were mild. Three (12%), five (19%) and five (19%) patients had mitral valve prolapse, a thickened interventricular septum, and asymmetric septal hypertrophy, respectively. The severity of aortic regurgitation and the existence of valvular heart disease, aortic valve abnormalities and valvular stenosis were all positively correlated with increasing age (p < 0.05). Z scores > 2 were identified in 0, 38, 8, and 27% of left ventricular mass index, interventricular septal end-diastolic dimension, left ventricular posterior wall end-diastolic dimension, and aortic diameter, respectively. Electrocardiograms in 11 patients revealed the presence of sinus arrhythmia (n = 3), sinus bradycardia (n = 2), and sinus tachycardia (n = 1). Six patients with MPS IIIB had follow-up echocardiographic data at 1.9–18.1 years to compare with the baseline data, which showed some patients had increased thickness of the interventricular septum, as well as more patients had valvular abnormalities at follow-up.Echocardiographic examinations (Cardiac involvement in MPS III is less common and milder compared with other types of MPS. The existence of valvular heart disease, aortic valve abnormalities and valvular stenosis in the patients worsened with increasing age, reinforcing the concept of the progressive nature of this disease. Mucopolysaccharidoses  comprise a group of lysosomal storage diseases resulting from deficiencies in specific lysosomal enzymes and involving the sequential degradation of glycosaminoglycans (GAGs), leading to substrate accumulation in various cells and tissues and progressive multi-organ dysfunction. Seven distinct types of MPS disorders  with 11 specific lysosomal enzyme deficiencies have been reported . Cardiom−/−) demonstrated the development of abnormal valve morphology and function in an age-dependent manner associated with increased myocardial vacuolization, inflammation and fibrosis, as well as a dysregulated lysosomal autophagy in the cardiac tissues [MPS III (Sanfilippo syndrome) includes four distinct diseases (types A-D) resulting from a deficiency in one of the four enzymes involved in heparan sulfate degradation as follows: heparan N-sulfatase in type A OMIM 252900), alpha-N-acetylglucosaminidase (NAGLU) in type B (OMIM 252920), acetyl CoA-alpha-glucosaminide acetyltransferase in type C (OMIM 252930), and N-acetylglucosamine 6-sulfatase in type D (OMIM 252940). MPS III has a variable age of onset and diverse rate of progression characterized by a large phenotypic heterogeneity. Patients with MPS III generally appear unaffected at birth, however clinical manifestations may emerge from 2 to 4 years of age, including intellectual disability, hyperactivity, coarse facial features with broad eyebrows, hirsutism, skeletal dysplasia, degenerative joint disease, hepatosplenomegaly, macrocephaly, and hearing loss , 19–21. 52900, al tissues . Unlike The medical records, echocardiograms, and electrocardiograms of 26 Taiwanese patients with MPS III  were retrospectively reviewed at Mackay Memorial Hospital from July 1997 to October 2018. The diagnosis of MPS III was confirmed by measurements of enzymatic activities of particular lysosomal hydrolases in leukocytes or skin fibroblasts, two-dimensional electrophoresis of urinary GAGs, and/or mutational analysis, as well as the exclusion of multiple sulfatase deficiency by the detection of normal enzymatic activities of other lysosomal hydrolases , 28. Six2 and mean gradient < 30 mmHg; moderate AS = valve area between 1.0–1.5 cm2 and mean gradient between 30 and 50 mmHg; severe AS = valve area < 1.0 cm2 and mean gradient > 50 mmHg; mild mitral stenosis (MS) = valve area > 1.5 cm2 and mean gradient < 5 mmHg; moderate MS = valve area between 1.0–1.5 cm2 and mean gradient between 5 and 10 mmHg; severe MS = valve area < 1.0 cm2 and mean gradient > 10 mmHg. As the frequency of physiological tricuspid regurgitation is high in the general population, including the pediatric population, we did not categorize tricuspid regurgitation into pathological findings in this study.We used a Philips Sonos 5500/7500 ultrasound system  equipped with electronic transducers from 2 to 8 MHz. Data were digitally stored and analyzed by one experienced cardiologist (MRC) to minimize inter-observer variations. Diastolic and systolic diameters were measured using M-mode and two-dimensional echocardiography. The systolic function of the left ventricle was assessed on the basis of the ejection fraction according to the Simpson method. For children, an ejection fraction < 50% was considered abnormal. For adults, an abnormal ejection fraction was defined as < 52% for men and < 54% for women . A shortz score with normal values according to the report of Foster et al. [z score derived by subtracting the mean reference value from an individual observed value, and then dividing the difference by the standard deviation from the reference value. A z score between − 2 and + 2 was considered to be normal. In addition, 11 patients also had available electrocardiographic (ECG) data. The pediatric values were used as a reference for children.We recorded data on left ventricular mass index (LVMI), right ventricular end-diastolic dimension (RVDd), interventricular septal end-diastolic dimension (IVSd) and end-systolic (IVSs), left ventricular end-diastolic dimension (LVIDd) and end-systolic (LVIDs), left ventricular posterior wall end-diastolic dimension (LVPWd) and end-systolic (LVPWs), aortic diameter, and left atrial dimension (LAD) acquired by echocardiographic evaluations. Relative wall thickness was calculated as (2 × LVPWd)/LVIDd. Concentric remodeling was defined as normal LV mass with relative wall thickness > 0.42 . Measurer et al. . All of r), and significance was tested using Fisher’s r–z transformations. Two-tailed p-values were calculated. All statistical analyses were carried out using SPSS version 11.5 . Differences with p < 0.05 were considered to be statistically significant.Sex, age, height, weight, and body surface area at the time of echocardiographic assessments were recorded for each patient. Descriptive statistics including means and standard deviations of all echocardiographic parameters were computed. The relationships between age and different echocardiographic parameters were established using Pearson’s correlation coefficient (n = 26) revealed that 10 patients (38%) had valvular heart disease. Four (15%) and eight (31%) patients had valvular stenosis or regurgitation, respectively (Table p < 0.05) , and the other 22 patients (85%) had normal LV geometry. E/A ratio < 1 was identified in one patient (4%), however, the ejection fraction and shortening fraction values were normal and revealed no substantial systolic dysfunction. Electrocardiograms in 11 patients revealed the presence of sinus arrhythmia (n = 3), sinus bradycardia (n = 2), and sinus tachycardia (n = 1). The ECG abnormalities were usually of minor clinical significance  Tables . The meae. Four 1% and eigAs far as we are aware, this is the first study to delineate the cardiac structure and function and natural progression of MPS III in Asian patients and compare them with normal values obtained from a population that included young adults on the basis of the report of Kampmann et al. . CompareCardiac involvement in MPS III has been reported to be less common and milder compared with the other types of MPS –23, 37. z scores of LVMI, IVSd, LVPWd, and aortic diameter of − 0.36, 1.71, 0.15 and 1.62, respectively, and z scores > 2 were identified in 0, 38, 8, and 27% of LVMI, IVSd, LVPWd, and aortic diameter, respectively. Bolourchi et al. [Echocardiographic assessments revealed mean i et al. . In our i et al. . Cardiaci et al. . Aortic There were varying degrees of valvular deformities in our patients, although most had mild stenosis or regurgitation. Valvular regurgitation (31%) was more common than valvular stenosis (15%) in our cohort, which is consistent with the study of Wilhelm et al. . They alVentricular remodeling indicates alterations in ventricular architecture with associated increases in volume and altered chamber configuration leading to myocyte hypertrophy and apoptosis, myofibroblast proliferation, and interstitial fibrosis . Few repn = 2), and sinus tachycardia (n = 1) although the clinical significance was minor. However, a respiratory arrhythmia is common amongst children. Thus these findings did not have to be pathological. Sudden and unexpected death due to heart block has been reported in isolated case reports of adults with MPS II, III and VI [Forty-five percent of our ECGs showed specific findings, including sinus arrhythmia , sinus bradycardia  varied considerably. As a result, studies with larger cohorts and longer follow-up periods are warranted.Cardiac involvement in MPS III is less common and milder compared with the other types of MPS. In this study, a substantial proportion of the patients with MPS III had aortic dilatation, increased interventricular septum thickness, and mild valvular heart disease. Our six MPS IIIB patients had worse valvular heart disease and cardiac hypertrophy according to echocardiographic examinations performed after 1.9–18.1 years of follow-up. The aortic valve abnormalities and valvular stenosis in these patients worsened with increasing age, which is consistent with the progressive nature of this disease. Thus, it is crucial to make an early diagnosis through screening programs for high-risk populations or newborns in order to initiate ERT or gene therapy before the occurrence of irreversible cardiac damage to improve the clinical outcome. These findings and follow-up data can also be used to develop quality of care strategies for such patients.


Understand the pathophysiology of myocardial fibrosis.Understand the core concepts of cardiovascular MRI for myocardial fibrosis.Understand the clinical implications of myocardial fibrosis imaging in common myocardial diseases.The current era has seen major advances in myocardial imaging. We are now able to assess cardiac anatomy, function, tissue composition and disease activity across a wide range of disease states. Recently, there has been major interest in imaging myocardial fibrosis, predominantly with cardiovascular magnetic resonance (CMR). Fibrosis represents a common response to injury in most cardiomyopathies, but the distribution and pattern of fibrosis differ between pathologies, underscoring its potential role as a diagnostic marker. Furthermore, fibrosis is closely associated with impaired left ventricular function, as well as cardiac arrhythmias; as such, fibrosis imaging also provides powerful prognostic information.In this review, we discuss the pathophysiology of myocardial fibrosis, review the applications of CMR in the non-invasive detection of myocardial fibrosis and provide an overview of common pathologies in which fibrosis imaging may be of clinical utility.Our understanding of myocardial function and disease is largely focused on cardiomyocytes. However, the majority of cardiac cells in the adult mammalian heart are non-myocytes. Cardiac fibroblasts are one such cell type that play a crucial role in myocardial disease and healing. These cells are responsible for the production and deposition of extracellular matrix proteins—type 1 collagen being the prototype—which serve as a scaffold for other cellular components and are integral to the structural integrity and function of the myocardium. Fibroblasts respond to cytokines and neurohormal factors, differentiating into activated fibroblasts and smooth muscle-like myofibroblasts that are critical in the healing response of diseased or injured myocardium. These cells exert their effects on the extracellular matrix via regulation of matrix metalloproteinases and fibronectin. Although the primary response to myocardial injury—wound healing, reparative scar formation and remodelling—is important in limiting tissue damage, chronic changes become maladaptive, ultimately impairing cardiac function.Myocardial fibrosis is a common final pathway in chronic myocardial disease and is the structural correlate of heart failure. It has traditionally been divided into interstitial fibrosis and replacement fibrosis, although more recent histology/CMR data have suggested considerable overlap between these two states.A non-invasive technique to assess myocardial fibrosis requires excellent temporal and spatial resolution in addition to the ability to characterise soft tissue. CMR is therefore the imaging modality of choice. Although CT has also been studied,The detection and quantification of replacement fibrosis using CMR is an established technique and has a larger evidence base than techniques which assess diffuse interstitial fibrosis. It requires the use of gadolinium-based contrast agents (GBCAs) which shorten the T1 of tissues in which they accumulate, providing a high-intensity signal on T1-weighted imaging. These large molecule agents distribute at different rates into healthy and diseased myocardium, partitioning into extracellular space and thus washing out of regions of focal replacement fibrosis at a slower rate than healthy tissue. The contrast in signal provides a visual difference between areas of replacement fibrosis (white) and healthy myocardium (black), although it is insensitive for detecting reactive interstitial fibrosis due to the diffuse nature of this type of fibrosis. Importantly, manual selection of the inversion time to null the myocardium at the time of acquisition is required to achieve this visual contrast, introducing some subjectivity. Late gadolinium enhancement  is the standard parameter and is usually presented as either a dichotomous finding or a percentage of myocardial volume. Both the presence and volume of LGE are almost universally associated with a poorer prognosis in myocardial disease. Different patterns of LGE are associated with different disease states .T1 mapping is the cornerstone of interstitial fibrosis imaging with CMR. There are several different approaches, including native T1, extracellular volume fraction (ECV%) and indexed extracellular volume (iECV). These techniques are comprehensively reviewed elsewhere2) use GBCAs to target the extracellular space. ECV% represents the extracellular matrix as a proportion of total left ventricular myocardial volume, whereas iECV adjusts for left ventricular myocardial volume  and offers a measure of absolute matrix volume.Native T1 values (milliseconds) are measured without GBCAs and reflect the combined intracellular and extracellular compartments. Values increase with a greater burden of fibrosis and are usually measured on a per-segment basis. In contrast, ECV% (percentage) and iECV  to develop and validate cross-vendor sequences that are transferable, reproducible and easy to acquire. Consequently, T1 mapping is now at the forefront of myocardial imaging research.Given the distinct differences between reactive interstitial fibrosis and replacement fibrosis, the combination of CMR T1 mapping and LGE offers a comprehensive assessment of myocardial disease that is currently unmatched by any other imaging modality.Imaging of myocardial fibrosis using CMR has been studied in a variety of cardiovascular conditions for both diagnosis and prognosis. Guidelines endorsing standardised image acquisition and analysis have been published.Myocardial infarction is the prototypical model of myocyte necrosis, apoptosis and collagen deposition with the formation of scar (replacement fibrosis). LGE in myocardial infarction occurs in epicardial coronary artery territories and may be subendocardial or transmural, often accompanied by regional wall motion abnormalities or wall thinning . The mosIn addition to the prognostic implications of LGE, it is important to appreciate the diagnostic utility of CMR in suspected myocardial infarction. In the current era of high-sensitivity cardiac troponin, there is often diagnostic uncertainty in patients with chest pain, a normal ECG and a small elevation in troponin concentration, particularly when obstructive coronary artery disease is not observed on angiography. In these cases of myocardial injury with non-obstructed coronary arteries, CMR may offer a diagnosis based on the pattern of injury and myocardial dysfunction.T1 mapping has also been investigated. Studies in patients with myocardial infarction have demonstrated the ability of T1 mapping to quantify infarct size and differentiate reversible and irreversible myocardial injury,Dilated cardiomyopathy (DCM) is a major cause of cardiovascular morbidity and mortality, with heterogeneous mechanisms governing ventricular dysfunction, arrhythmias and sudden cardiac death. CMR can aid characterisation of the underlying pathology . Around These early data highlight the need for more prospective studies of myocardial fibrosis imaging as a risk stratifying tool in DCM. In light of recent data,Aortic stenosis is the best-studied valvular heart disease with regards to myocardial fibrosis imaging. In recent years, there has been a paradigm shift in the assessment and risk stratification of aortic stenosis, with more focus on the myocardium. Current European Society of Cardiology guidelines recommend aortic valve intervention in symptomatic aortic stenosis, reflecting the standard clinical practice in place for many years.As such, there is a clinical need for more sophisticated risk stratification. CMR fibrosis imaging has the potential to fill this role.The natural progression of myocardial fibrosis imaging in aortic stenosis is the investigation of diffuse interstitial fibrosis—that is, detecting myocardial disease at an early, reversible stage. This is relevant as interstitial fibrosis can regress after aortic valve replacement.Hypertrophic cardiomyopathy is the most common genetic cardiomyopathy. It is characterised by inappropriate regional wall thickening , althougIn addition to its diagnostic role, CMR has been proposed as a means of better identifying patients at high risk of sudden cardiac death. Although individual studies have been limited by small numbers, meta-analyses have demonstrated that both the presence and quantity of LGE are independently associated with all-cause and cardiac death.T1 mapping has been investigated in hypertrophic cardiomyopathy in small studies. Native T1 and ECV are able to differentiate healthy from diseased myocardiumMyocarditis is an inflammatory disease of the myocardium which can be acute, subacute or chronic and is caused by a variety of aetiologies—most commonly viral or idiopathic. The true incidence is difficult to ascertain but there appears to be a trend of increasing hospitalisation in recent years, in part due to high-sensitivity cardiac troponin assays and access to CMR.The prognostic significance of CMR findings are restricted to LGE at present. The presence of non-infarct LGE is a powerful independent predictor of adverse events,The most commonly encountered infiltrative cardiomyopathies are cardiac amyloidosis and sarcoidosis, which will be discussed here. Others include haemochromatosis and Fabry disease, both of which have characteristic findings on LGE, T1 and T2* mapping. These disease processes differ slightly from other pathologies as their hallmark is deposition of abnormal proteins within the interstitial space, rather than reactive inflammatory fibrosis and myocyte necrosis seen in previously discussed diseases. Research into these diseases is largely limited to observational studies.The hallmark of amyloidosis is extracellular deposition of fibrils, comprising low molecular weight subunits of serum proteins. The most common types of primary amyloidosis are light-chain and transthyretin (senile) cardiac amyloidosis. The former is a plasma cell dyscrasia which leads to monoclonal light-chain deposition, with cardiac involvement occurring in up to 50% of cases. This type of amyloidosis is responsible for the majority of systemic amyloidosis. The latter results in deposition of misfolded transthyretin and may be present in up to 10%–15% of older patients with heart failure. CMR offers an ideal modality for the diagnosis and assessment of cardiac amyloidosis given its ability to interrogate the cardiac interstitium. The presence of LGE is nearly universal in patients with confirmed cardiac amyloidosis.Sarcoidosis is a multiorgan, chronic, inflammatory granulomatous disease of unknown cause. Cardiac involvement occurs in up to one quarter of patients, although more than half of these patients may have subclinical disease.Across a breadth of pathologies, myocardial fibrosis represents a final common pathway of myocardial disease, with the pattern and distribution of fibrosis differing between conditions. Irreversible replacement fibrosis, represented by LGE on CMR, is of nearly universal prognostic relevance. Meanwhile, diffuse interstitial fibrosis imaging has been shown to have great potential as a dynamic, early and reversible marker of myocardial disease. Both approaches are being used increasingly in clinical practice as diagnostic adjuncts, but data demonstrating that CMR improves outcomes in a cost-effective manner are lacking. Further clinical trials are required for this purpose, and several major observational and randomised controlled trials are currently underway.Education in Heart articles are accredited for CME by various providers. To answer the accompanying multiple choice questions (MCQs) and obtain your credits, click on the ‘Take the Test’ link on the online version of the article. The MCQs are hosted on BMJ Learning. All users must complete a one-time registration on BMJ Learning and subsequently log in on every visit using their username and password to access modules and their CME record. Accreditation is only valid for 2 years from the date of publication. Printable CME certificates are available to users that achieve the minimum pass mark.


COPD influences cardiac function and morphology. Changes of the electrical heart axes have been largely attributed to a supposed increased right heart load in the past, whereas a potential involvement of the left heart has not been sufficiently addressed. It is not known to which extent these alterations are due to changes in lung function parameters. We therefore quantified the relationship between airway obstruction, lung hyperinflation, several echo- and electrocardiographic parameters on the orientation of the electrocardiographic (ECG) P, QRS and T wave axis in COPD.1), functional residual capacity (FRC), left ventricular (LV) mass, and ECG data.Data from the COPD cohort COSYCONET were analyzed, using forced expiratory volume in 1 s (FEVp = 0.002), whereas no differences in right ventricular wall thickness were observed. All three ECG axes were significantly associated with FEV1 and FRC. The QRS axes according to GOLD grades 0–4 were (mean ± SD): 26.2° ± 37.5°, 27.0° ± 37.7°, 31.7° ± 42.5°, 46.6° ± 42.2°, 47.4° ± 49.4°. Effects of lung function resulted in a clockwise rotation of the axes by 25°-30° in COPD with severe airway disease. There were additional associations with BMI, diastolic blood pressure, RR interval, QT duration and LV mass.One thousand, one hundred and ninety-five patients fulfilled the inclusion criteria . Left ventricular (LV) mass decreased from GOLD grades 1–4  contains supplementary material, which is available to authorized users. Cardiovascular comorbidities are common in patients with chronic obstructive pulmonary disease (COPD) –3. This Verticalization of the P wave axis in COPD has been reported –10, as wWe therefore hypothesized that the electrical axes of the heart are related to lung function in patients with COPD. Airway obstruction and hyperinflation were evaluated as numerical predictors of the electrical heart axes.The study was performed using a subset of the baseline data of the German COPD cohort COSYCONET, which is a prospective, observational, multi-center cohort study in patients with stable COPD that aims to evaluate the role of comorbidities –15, inclFor the present analysis, we used data from the recruitment phase and excluded patients with more than moderate heart valve disease, heart valve replacement, or other cardiac devices such as pacemakers/cardioverter-defibrillators. The analysis was restricted to patients with sinus rhythm and several criteria of completeness and plausibility of lung function, echocardiographic and ECG data were applied , the residual volume (RV), total lung capacity (TLC), and their ratio RV/TLC and forced expiratory volume in 1 s (FEV1) for airway obstruction. The diffusing capacity for carbon monoxide (TLCO) was determined via duplicate assessments of the single-breath method, and the transfer coefficient (KCO) as ratio of TLCO and alveolar volume (VA). Echocardiography was performed as recommended by the American Society of Echocardiography and the European Association of Cardiovascular Imaging [Spirometry and body plethysmography were performed following the recommendations of the American Thoracic Society (ATS)/European Respiratory Society (ERS)  and Deut Imaging . The ass1 and FRC were evaluated as percent predicted values [2]. The RR interval was obtained as the mean of 10.88 ± 2.08 (mean ± SD) consecutive QRS complexes. The QT duration was used as measured, i.e. without heart rate correction, since heart rate was considered as distinct parameter.FEVd values –27. Card1 % predicted, FRC % predicted, BMI and diastolic blood pressure as predictors, and LV mass, RR interval, QT duration, P wave axis, QRS axis and T wave axis as dependent variables. For all estimates of regression coefficients, 95% confidence intervals were computed.For descriptive purposes mean values and standard deviations (SD) or standard errors of the mean (SE) were computed. Differences between groups were evaluated via analysis of variance (ANOVA) and by Tukey-HSD post-hoc comparisons. Univariate multiple linear regression analyses were employed to determine the influences of sex, age and medication on the different variables. Variables were adjusted for these three influencing factors via computation of non-standardized residuals and used for further analyses. Multivariate multiple linear regression analyses were used to determine the associations between FEVp < 0.05.To disentangle the multiple relationships between the measured variables, structural equation modelling (SEM) was employed , 28, 29.2; p = 0.002), whereas no differences in RV wall thickness were observed .A total of 1195 stable COPD patients were analyzed. The selection process of the cohort is depicted in Additional file p < 0.001 for each pairwise comparison).When averaged over the whole study population, the orientations of P wave, QRS and T wave axes differed significantly from each other . Pairwise post hoc comparisons of the axis orientations between GOLD grades revealed significant (p < 0.05 each) differences, except between grade 0 and 1 and between grade 1 and 2.The mean orientation of the P wave axis according to the spirometric GOLD grades 0–4 is illustrated in the left panel of Fig. p < 0.001). There was a clear trend towards an increased clockwise rotation in more severe airflow limitation. Post hoc comparisons revealed significant (p < 0.05 each) differences between a disease severity not exceeding moderate grades (GOLD 0 to 2) compared with severe to very severe COPD (GOLD 3 and 4). The relationship of the QRS orientation to FRC % predicted across GOLD grades is illustrated.In a similar manner, mean QRS axes are illustrated in Fig. p < 0.001). There were significant (p < 0.05 each) differences between all GOLD grades, except between grade 0 and 1 and between grade 3 and 4. Again, the relationship to the mean values of FRC % predicted for the different GOLD grades is shown.The results for the mean T wave axis are analogously shown in Fig. 1 % predicted and FRC % predicted as covariates. In accordance with the GOLD definition of COPD [n = 1020). Additional file 1 and FRC as predictors of the electrical axes. Since both predictors are cross-linked with each other and FRC is not always available in clinical practice, the analysis was rerun using FEV1 as predictor only. The estimated incremental rotation of the QRS axis as a function of FEV1  and as function of both FEV1 and FRC  is illustrated in Fig. We assessed the magnitude of the relationship between ECG axes and lung function using multivariate multiple linear regression analysis, with the three ECG axes as dependent variables against FEV of COPD , this su1 and FRC were subtracted, the distribution of the QRS axes shifts from a vertical type  to a normal (sector 30° to 60°) as the most frequent type (lower panel).The measured distribution of the QRS axis across standard sectors is shown in Additional file 1 % predicted and diastolic blood pressure, whereas age was significantly associated with FEV1 and FRC % predicted, diastolic blood pressure, LV mass and QRS and T wave axis. Heart rate lowering medication , was significantly related only to FEV1 and FRC % predicted (p < 0.05 each). In all following analyses we used the values that were adjusted for sex, age and medication according to these results.To account for possible effects of confounders on measured variables, we also evaluated their relationship to sex, age and heart rate-lowering medication using univariate multiple linear regression analyses. All parameters showed a significant dependence on sex except FEV1 % predicted, FRC % predicted, BMI and diastolic blood pressure as covariates was determined by multivariate multiple linear regression analysis. FEV1 % predicted was correlated with the RR interval, the QT duration and all three electrical axes. FRC % predicted correlated with the RR interval, QT duration and the three axes. BMI was associated with all dependent variables, with the exception of QT duration. Diastolic blood pressure correlated with all variables except LV mass and the T wave axis ; the CFI was 0.992, with an RMSEA of 0.024 , which indicates an acceptable model that does not significantly deviate from the data. A detailed sensitivity analysis is given in Additional file Given these multiple interdependences between parameters, we aimed to determine their relative importance in a network of associations via SEM, which is an extension of multiple regression and factor analysis , 16. The1, a measure of airway obstruction, and FRC, a measure of lung hyperinflation, but there were also indirect influences that were mediated through associations with other variables, including LV mass, the RR interval and the QT duration. This network of relationships was studied by using structural equation modelling as a statistical method designed to describe such networks. These relationships appear to be plausible from a pathophysiological point of view. Besides well-known qualitative influences of lung disease on the electrical heart axes, the present study for the first time quantifies influences of the magnitude of lung function impairment.The present study demonstrates significant associations of the degree of airway obstruction and lung hyperinflation with the orientation of the electrocardiographic heart axes in patients with COPD. The association comprised direct influences of both FEV1 only and bivariate based on both FEV1 and FRC.Determination of the QRS axis is a basic diagnostic criterion that is commonly used clinically to gain evidence, e.g. for LV hypertrophy, but also for an increased right heart load, e.g. due to pulmonary hypertension or pulmonary embolism. The large clockwise rotations of about 25 degrees on average significantly affect the judgement of the electrical type. This helps to uncover other cardiac disease and to prevent misdiagnosis, which is particularly valuable as on the one hand patients with COPD often have cardiac disease, but there are also significant numbers of individuals without such concomitant disorders . For ins1 also played a role despite the fact that a decrease of FEV1 and consecutive increases in FRC are generally related to each other; i.e. an increase in FRC may be due to expiratory flow limitation during tidal breathing in dynamic hyperinflation or reduced elastic recoil in static hyperinflation. Both mechanisms may not be strictly related to FEV1 but may affect heart function, e.g. by a reduced venous return due to increased thoracic and gastric pressure [It is conceivable that lung hyperinflation affects the anatomical axis of the heart mechanically within the thoracic cavity, and consequently the electrical axes. An interesting finding was that airway obstruction in terms of FEVpressure  and by apressure . Indeed,1. Therefore, it can be hypothesized that patients with high FRC and low FEV1 would demonstrate particularly strong effects on the rotations of the electrical axes if they also have a low BMI, e.g. in cachectic patients with pulmonary emphysema. It seems noteworthy that the direct influences of FRC and FEV1 on LV mass indicated a cardiac response to hyperinflation, which was linked to the QT duration that was also affected via the RR interval. Since the QRS axis depends on the electrical depolarization of both ventricles, one could argue that potential changes of the RV may have affected the findings. However, this appears unlikely, since no differences of the echocardiographic RV wall diameter or RV function was observed among GOLD grades. Moreover, the contributory extent of the RV to the QRS axis appears minor than that of the LV due to the much less RV mass.Interestingly, the two lung function parameters worked in parallel on the ECG axes, but were to some extent counteracted by those of BMI, which was correlated with both FRC and FEV1, FRC, and BMI on the axes were dominant over indirect effects as mediated via interposed variables


For these thresholds cardio-respiratory variables and percentages of maximum heart rate, heart rate reserve, maximum oxygen uptake and oxygen uptake reserve, and maximum power output were compared between groups. Additionally, the degree and direction of the deflection of the heart rate to performance curve (kHR) were compared between groups. Individuals with T1D had similar heart rate at LTP1 (mean difference) −11, [ −27 to 4 b.min−1], at VT1  and at LTP2 , at VT2 , and at the heart rate turn point  (p = 0.22). Heart rate expressed as percentage of maximum heart rate at LTP1, VT1, LTP2, VT2 and the heart rate turn point as well as expressed as percentages of heart rate reserve at LTP2, VT2 and the heart rate turn point was lower in individuals with T1D (p < 0.05). kHR was lower in T1D compared to CON individuals . Our findings demonstrate that there are clear differences in the heart rate response during CPX testing in individuals with T1D compared to CON individuals. We suggest using submaximal markers to prescribe exercise intensity in people with T1D, as the heart rate at thresholds is influenced by kHR.To investigate the heart rate during cardio-pulmonary exercise (CPX) testing in individuals with type 1 diabetes (T1D) compared to healthy (CON) individuals. Fourteen people  performed a CPX test until volitional exhaustion to determine the first and second lactate turn points . Low amounts of structured exercise such as 3 × 30 min per week are associated with consistent improvements in health status in already healthy and physically active individuals . In peopCurrently, standard exercise recommendations for individuals with T1D are similar to those for healthy individuals, namely 150 min or more of moderate to intense exercise and physical activity spread over at least three days per week, or a minimum of 75 min per week of vigorous-intensity exercise/physical activity , 4.HR) during CPX testing are altered in some healthy individuals  recommends prescribing exercise intensity as percentages of maximum heart rate  even thoividuals  and mighividuals .Furthermore, in T1D individuals with autonomic cardiac neuropathy, left ventricular function was found to be decreased in both systole and diastole, non-dipping was more prevalent, and pulse pressure was higher compared to patients without autonomic cardiac neuropathy . The hea1) or the first ventilatory threshold (VT1)] translates to the inability of the muscle to entirely oxidize produced lactate and therefore it is partly shifted into the blood stream and can be metabolized by other organs. At this first threshold there is still a metabolically balanced condition but on a systemic level (2) or the second ventilatory threshold (VT2)] produced lactate in the working muscles cannot be muscularly or systemically eliminated, resulting in a blood lactate accumulation   .The aim of the study was to investigate the time course of the heart rate to performance curve during CPX testing in T1D individuals compared to matched healthy individuals (CON), and to prove its influence on percentages of maximum heart rate, percentages heart rate reserve, percentages maximum oxygen uptake, percentages oxygen uptake reserve and percentages maximum power output compared to standard markers of submaximal performance between groups. We determined as a primary outcome the heart rate to performance curve during CPX testing and its impact on target training heart rate determination in comparison of T1D individuals and matched healthy individuals (CON) and as secondary outcomes the functional capacity, cardiorespiratory and metabolic markers in comparison of groups during CPX testing. We hypothesized that people with T1D show an altered heart rate to performance curve during CPX testing and this impacts target training heart rate determination.This study was carried out in accordance with the recommendations of Good Clinical Practice (GCP), “Bundesamt fuer Sicherheit im Gesundheitswesen” (BASG Austria). The protocol was approved by the ethics committee of the Medical University of Graz, AT (26-069 ex 13/14). All subjects gave written informed consent in accordance with the Declaration of Helsinki. CON individuals were matched from routine diagnostics (approved by the Ministry of Science).1c) ≤ 8% (64 mmol.mol−1), fasting c-peptide negative, treated with multiple daily insulin injections, no long-term complications and no other physical and/or mental diseases, which might influence the study results. In this primary investigation we recruited male individuals as the female menstrual cycle may influence the energy supply during CPX testing (−1) or alcohol consumption 24 h before. All data were assessed and documented in a standardized Case Report Form. CON individuals were selected with respect to T1D individuals' characteristics  from routine diagnostics data at the entry to the physical education studies. CON individuals were instructed to avoid intense or long-lasting exercise 24 h prior to the investigation and to avoid alcohol within 24 h pre-testing. Written informed consent was obtained from all participants.To be eligible for the study, T1D individuals had to be male, diagnosed with T1D for at least 12 months, aged between 18 and 35 years (both inclusive), glycated hemoglobin (HbA testing . Partici−2 (20–28), HbA1c 7.4 ± 0.6% (6.5–8) (57 ± 6.3 mmol.mol−1) (47–64), c-peptide 0.13 ± 0.19 nmol.l−1 (0–0.4) and total daily insulin dose with insulin Degludec 41 ± 16 U (27–69). Four participants used bolus insulin Aspart  and three participants used bolus insulin Lispro . Before switching to insulin Degludec, two patients used insulin Detemir  and five patients used insulin Glargine  as basal therapy. T1D participants were free of comorbidities and co-medications other than insulin. CON individuals were aged 23 ± 4 years (19–30), had a BMI of 23.4 ± 1.8 kg.m2 (21–26) and were healthy without taking any medications.T1D individuals' characteristics were: age 24 ± 5 years , BMI 23.9 ± 2.5 kg.mIn this experimental design, T1D individuals were adjusted to the same therapy with insulin Degludec  as part of a basal-bolus routine. After a run-in period of 4 weeks with insulin Degludec, a CPX test was performed. Insulin Degludec was used to achieve homogeneity for the basal insulin therapy. We have chosen insulin Degludec since its pharmacodynamic profile is flat and stable, demonstrated by an even distribution of glucose-lowering effects across the 24-h period  accompanied by an increase in VE/VO2 without an increase in VE/VCO2. VT2 was defined as the second abrupt increase in VE accompanied by an increase in both VE/VO2 and VE/VCO2. Additionally, the heart rate turn point was defined as the point of intersection of two regression lines in the heart rate to performance curve between LTP1 and the maximum power output with minimal standard deviation of the two straight lines. The degree and direction of the deflection of the heart rate to performance curve (kHR) was calculated by a second-degree polynomial function between LTP1 and the maximum power output  at the Sports Science Institute, University of Graz, Austria . Particiand LTP2  as well analysis . LTP1 war output , 21.Pulmonary gas-exchange variables were measured continuously during CPX testing via breath-by-breath measurement and 5 s average . Heart rate was measured continuously via chest belt telemetry and 5 s average . A 12-lead electrocardiogram and blood pressure measurements (every 2 min) were obtained during CPX testing for cardiac monitoring. Blood lactate and blood glucose (for safety in T1D group) concentrations were determined by taking capillary blood samples from the earlobe at the end of the rest and warm-up periods, at the end of each workload step (every minute), and at the end of active and passive recovery. Blood lactate and blood glucose were analyzed by means of an enzymatic-amperometric method .After overnight fasting, T1D individuals received a standardized meal on the day of the CPX test , which was calculated from the average pre-investigational amount of consumed carbohydrates during the last 4 weeks prior to the start of the study. The standardized meal and the reduced bolus insulin dose were administered exactly 4 h before the cycle ergometer exercise tests. The bolus insulin dose was reduced by 40% of the regular dose for the CPX testing. Both groups were informed to ingest carbohydrate enriched meals at least the day prior CPX testing to ensure adequate tissue glycogen stores.HR were compared between groups by paired students' t-test. Differences in comparison of groups for thresholds LTP1, VT1, LTP2, VT2, and heart rate turn point for relative and absolute power output, heart rate, oxygen consumption and lactate concentration were analyzed by a two-way ANOVA (group and threshold), with Bonferroni post-hoc testing. All statistics were performed with a standard software package ®Prism Software version 5.0  and SPSS 22.0 software .All data were tested with Shapiro-Wilk normality test and were found to be normally distributed. Descriptive statistics included mean and standard deviation for participant's anthropometric data, performance characteristics, and diabetes specific data. Anthropometric data and kPost-hoc power analysis was performed for the primary outcome percentages of heart rate comparing markers of lowest significant difference between groups (VT1) and revealed a post hoc power 1-β = 0.99. There were no episodes of hypoglycemia noted during the CPX testing in the T1D group. T1D individuals maintained a blood glucose steady state during CPX testing showing no significant difference between the start (10.58 ± 3.42 mmol.l−1) and the end concentrations (10.24 ± 3.48 mmol.l−1) (p = 0.86).1 and VT1  as well as LTP2, VT2 and heart rate turn point  were not significantly different within both groups.Cardio-respiratory and metabolic markers at LTP1, LTP2, heart rate turn point, and maximum power output between T1D and CON individuals, except for lactate concentration at LTP1 . No significant differences were found for the oxygen uptake at percentages of maximum oxygen uptake (p = 0.88), oxygen uptake at percentages of oxygen uptake reserve (p = 0.71) and heart rate at percentages of heart rate reserve  as well as percentages of maximum power output %P (p = 0.64) at LTP1, VT1, LTP2, VT2, and heart rate turn point when comparing T1D and CON individuals . Figure 2 for T1D individuals and clearly below LTP2 for CON individuals. Eighty-five percent of the maximum heart rate resulted in significant differences comparing T1D vs. CON for oxygen uptake at percentages of maximum oxygen uptake , oxygen uptake at percentages of oxygen uptake reserve , and power output at percentages of maximum power output , but not for heart rate at percentages of heart rate reserve .kHR was significantly different between T1D individuals and CON individuals. T1D individuals showed a lower heart rate of percentages of the maximum heart rate at the second turn points  and a significantly lower kHR  indicating the objectivity and the validity of these markers which may be used interchangeably.The aim of this study was to investigate the alterations in the heart rate during CPX testing in T1D individuals compared to matched CON individuals. k1 and VT1) were not significantly different at all submaximal markers, heart rate at percentages of maximum heart rate at LTP1, VT1 and LTP2, VT2 and heart rate turn point as well as percentages of heart rate reserve at LTP2, VT2 and heart rate turn point were significantly lower in T1D individuals compared to CON individuals. It was previously shown that these differences were also found in young healthy and trained subjects  or ventilatory variables ] for the exercise intensity prescription in T1D which were shown to be representative for constant and intermittent type exercise of various intensities .To the best of our knowledge, this is the first study investigating the differences in cardio-pulmonary responses of the heart rate, heart rate reserve, oxygen uptake, and oxygen uptake reserve as well as maximum power output in relation to objective submaximal markers LTPHR and lowered percentages of maximum heart rate / percentages of heart rate reserve at submaximal markers. We recommend additional studies to analyze e.g., HbA1c levels in relation to the heart rate to performance curve in a larger group of individuals with T1D.In conclusion, our findings demonstrate that there are clear differences in heart rate responses during CPX testing in individuals with T1D compared to CON individuals. We postulate that T1D individuals displayed an altered kBoth groups gave written signed informed consent for publication.Data will be made available on demand by the corresponding authors via email contact.All authors confirm that they meet the International Committee of Medical Journal Editors (ICMJE) uniform requirements for authorship. OM participated in the conceiving and designing the study, analyzing the data, and writing the manuscript. GT, AM, WG, and GK conceived the study and conducted the measurements. ME and RB conceived the study, analyzed data, drafted and revised the manuscript. TP and PH designed the study, supervised the measurements, and writing process. All authors have approved the final version of the manuscript to be published.OM has received lecture fees from Medtronic, travel and research fees form Novo Nordisk A/S, Novo Nordisk Austria and Dexcom Inc. and received a grant from Ser Cymru II COFUND fellowship/European Union. ME has received a KESS2/European Social Fund scholarship. RB has received educational grants from Novo Nordisk, Eli Lilly, Sanofi, Boehringer Ingelheim, and Beneo. GK has received lecture fees and has participated in advisory panels from Novo Nordisk, Bohringer Ingelheim, Novartis, MSD, and Eli Lilly. TP has participated in advisory panels and acted as a consultant for Novo Nordisk. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The progressive cardiomyopathy that develops in boys with Duchenne and Becker muscular dystrophy (DMD/BMD) is presumed to be a secondary consequence of the fibrosis within the myocardium. There are only limited data on using parametric imaging in these patients. The purpose of this study was to assess native T1 and extracellular volume (ECV) values in DMD patients.n = 23), Group D2 - DMD patients with LGE (n = 20), and Group C – gender matched controls (n = 13).The Czech population of males with DMD/BMD was screened. All eligible patients fulfilling the inclusion criteria were included. Forty nine males underwent cardiac magnetic resonance (MR) examination including T1 native and post-contrast mapping measurements. One DMD patient and all BMD patients were excluded from statistical analysis. Three groups were compared – Group D1 - DMD patients without late gadolinium enhancement (LGE) (p < 0.05). Group D2 had significantly increased global ECV  and segmental ECV in inferolateral and anterolateral segments in comparison with controls. The results were also significant after adjustment for subjects’ age.Compared to controls, both DMD groups had prolonged T1 native relaxation time. These results are concordant in all 6 segments as well as in global values (1041 ± 31 ms and 1043 ± 37 ms vs. 983 ± 15 ms, both DMD males had increased native T1 relaxation time independent of the presence or absence of myocardial fibrosis. Cardiac MR may provide clinically useful information even without contrast media administration. Muscular dystrophies mostly affect the skeletal muscles, but in the case of dystrophinopathy such as Duchenne and Becker muscular dystrophy (DMD and BMD), the heart muscle can be also seriously affected and the dystrophin deficiency in the heart manifests as a cardiomyopathy. For a long time, the cardiac impairment was significantly under-diagnosed for many reasons, even though patients suffer heart failure and also arrhythmic complications. In last years, the strong progress in cardiac management that includes first of all a regular cardiac assessment as well as early therapeutic recommendations, has been achieved , 2.The progressive cardiomyopathy that develops in male with DMD/BMD is presumed to be a secondary consequence of the fibrosis within the myocardium. As with skeletal muscle, the loss of dystrophin and the disruption of the dystrophin-glycoprotein complex (DGC) cause either fragile sarcolemma of the cardiomyocyte (CM) and muscle contraction damages, leading to small tears in the cell membrane, or stem cell depletion preventing heart muscle regeneration , 4.http://www.dmd.nl) in the Netherlands, and similar databases in Belgium and France  and angiotensin converting enzyme-inhibitors . The patients from D2 group had more often an advanced neurological stage compared to the D1 group - the difference in neurological scale was non-significant after age adjustment (p = 0.61).Of the total 44 DMD patients, 1 patient had only pre-contrast cardiac MR because of a problem with the intravenous line introduction. Of 43 patients with post-contrast MR, LGE was found in 20 subjects  and 23 boys had no LGE . Intramural and subepicardial LGE was found typically in the lateral wall   curve based on all native cardiac MR factors was 0.95 with Youden’s point (point with the highest sum of sensitivity and specificity) corresponding with sensitivity 1.00 and specificity 0.85.In our study, neither the ACE-inhibitor use nor the motor abilities (ambulatory/non-ambulatory) were associated with the T1 relaxation time. The patients that used beta-blockers had higher global and segmental native T1 values compared with those that did not. This was statistically significant in all segments except of anteroseptal and inferoseptal.p ≤ 0.05). This association did not change substantially after age adjustment. No other difference in the cardiac MRI data was observed  and the percentage of patients with regional fibrosis detected by LGE was even higher (44%). While progressive worsening of LV function in this population is already well known and several publications describing frequent LGE have also been published –17, therThese concordant results could mean that native T1 relaxation time can be a potential robust marker of very early cardiac involvement, earlier than any other imaging marker like LV functional decrease or regional myocardial fibrosis. These finding are in concordance with trails assessing T1 relaxation time in patients with non-ischemic cardiomyopathy. In several papers, native T1 correlated with LV dilatation and LV functional decline and was shown to be predictive of heart failure events and all-cause mortality –32.Native T1 relaxation time could also become a novel parameter for the optimal start and evaluation of cardiac therapy. An earlier start of therapy could have important prognostic consequences as cardiomyopathy is one of the main causes of death in DMD patients . NeverthIn contrast to native T1 relaxation time, we have found increased ECV only in DMD patients with LGE. ECV of patients without LGE did not differ from the controls. These findings are slightly contradictory with some other works. Soslow et al.  found noOn the other hand, other studies reached similar results to our study. Florian et al.  also fouThis is to authors’ knowledge first study to compare cardiac involvement assesses by MR and genetic background. Despite the progress on prediction of DMD/BMD phenotype, more detailed predictions are complicated and unreliable. It is almost impossible to predict the age until an out-patient care will remain possible and similarly it is very difficult to trace age dependency in the cardiac involvement. Nevertheless mutation position in higher exons (51st exon and higher) was found to be associated with mores severe ECV values in segments, previously described as typical for initial fibrosis identification . These rThe study has several limitations. Some of them are related to the general limitations of T1 mapping , 35. A lThe study demonstrated that cardiac mapping is a feasible, non-invasive method and provides a powerful incremental diagnostic value in the cohort of DMD patients. Regional and global native T1 relaxation time was increased independently of the presence or absence of myocardial fibrosis. Patients in late stages of DMD also had elevated ECV. Native T1 relaxation time seems to be a potential novel robust marker of very early cardiac involvement. Cardiac MR may provide clinically useful information even without contrast media administration.