Functional Mitral Regurgitation (FMR) associated with coronary artery disease affects nearly 3 million patients in the United States. Both myocardial infarction (MI) and ischemia contribute to FMR development but uncertainty as to which patients will respond to revascularization (REVASC) of ischemia alone prevents rational decision making about FMR therapy. The aim of this study was to create patient-specific cardiac MRI (CMR) informed finite element (FE) models of the left ventricle (LV), calculate regional LV systolic contractility and then use optimized systolic material properties to simulate the effect of revascularization .Tmax of each sector was a function of regional stress perfusion (SP-CMR) and myocardial infarction (LGE-CMR) scores. Sector-specific circumferential and longitudinal end-systolic strain and LV volume from CSPAMM were used in a formal optimization to determine the sector based myocardial contractility, Tmax and ischemia effect, α. Virtual REVASC was simulated by setting α to zero.We describe a novel FE method able to predict the effect of myocardial ischemia on regional LV function. CMR was obtained in five patients with multi-vessel coronary disease and FMR before and 3 months after percutaneous REVASC and a single healthy volunteer. Patient-specific FE models were created and divided into 17 sectors where the systolic contractility parameter, Tmax for the healthy myocardium for five patients and the volunteer was 495.1, 336.8, 173.5, 227.9, 401.4, and 218.9 kPa. The optimized α was found to be 1.0, 0.44, and 0.08 for Patients 1, 2, and 3, and 0 for Patients 4 and 5. The calculated average of radial strain for Patients 1, 2, and 3 at baseline and after virtual REVASC was 0.23 and 0.25, respectively.The FE optimization successfully converged with good agreement between calculated and experimental end-systolic strain and LV volumes. Specifically, the optimized We developed a novel computational method able to predict the effect of myocardial ischemia in patients with FMR. This method can be used to predict the effect of ischemia on the regional myocardium and promises to facilitate better understanding of FMR response to REVASC. Functional mitral regurgitation (FMR) associated with coronary artery disease (CAD) is a leading cause of valvular heart disease. FMR occurs in 1.2 to 2.1 million patients with CAD  in whom Both myocardial infarction (MI) and ischemia contribute to FMR development. Specifically, creation of inferior MI in large animals leads to left ventricular (LV) remodeling, papillary muscle displacement, restriction of mitral leaflets and subsequent development of FMR . ConversCardiac magnetic resonance imaging (CMR) allows LV remodeling, tissue characteristics including MI and non-ischemic fibrosis, ischemia and regional contractile function to be assessed with high precision. Cine-CMR has been employed as a reference standard for measuring LV size and function . Stress The relationship between MI fibrosis, ischemia and function and recovery of function after REVASC in chronically ischemic hibernating myocardium in which myocardial metabolism and contractile function are down-regulated  is complFinite element (FE) modeling has the unique potential to (1) determine the effect of ischemia in FMR associated with CAD and to then (2) simulate the effect of REVASC. Prior FE modeling studies by our group  and otheThis study describes a novel FE method able to predict the effect of myocardial ischemia on regional LV function. The method leverages CMR imaging data obtained from patients with multivessel CAD and FMR before and after percutaneous REVASC. It includes patient-specific FE models in which the regional systolic contractility parameter is a function of regional CMR-based tissue characteristics including stress perfusion and MI. The aim of the study is to calculate systolic material properties of ischemic myocardium and then use optimized systolic material properties to simulate the effect of REVASC .Five patients were selected from a larger group of patients prospectively enrolled in a protocol entitled “CMR Myocardial Tissue Based Prediction of Ischemic MR Revascularization Response” at Weill Cornell Medical College  examining REVASC effect in patients with FMR associated with CAD. The protocol included CMR and transthoracic echocardiography before and 3 months after percutaneous revascularization (PCI). One healthy volunteer without cardiovascular risk factors was also studied. The Cornell Institutional Review Board approved this study, and written informed consent was obtained at time of enrollment.in vivo sector-specific circumferential and longitudinal end-systolic strain and LV volume.The proposed method is summarized in CMR was performed with a 3.0 Tesla MRI scanner   both befLeft ventricular short and long axis and RV short axis Cine-CMR images were contoured at LV early diastolic filling  where the EDF phase was defined as the time step immediately prior to opening of the mitral valve. The LV and RV contours included the papillary muscle bases but excluded the trabeculae .To eliminate short axis image alignment breathing artifacts, an LV surface was created based on the three epicardial long axis contours. LV short axis contours were moved in plane so that the contour centroid was over the centroid of the corresponding plane from the long axis surface. After alignment, LV epicardial and endocardial and RV endocardial surfaces were created using the aligned short axis contours.Left ventricular function, MI scar and stress perfusion were localized using the AHA/ACC 17 segment model . LV wallMyocardial infarction was identified on LGE-CMR, for which transmural extent was graded using a 5-point segmental scale  . LGE in Ischemia was assessed semi-quantitatively on SP-CMR based on peak myocardial signal intensity during first-pass gadolinium infusion. Perfusion deficits were defined as persistent hypo-enhancement on ≥4 consecutive heart beats  and the Ecc) and longitudinal (Ell) strain for each sector were calculated from CSPAMM images. The HARmonic Phase (HARP) method developed by Regional 3D circumferential  was used to create patient-specific meshes of the LV composed of hexahedral elements as shown in Each element was assigned a material direction with a rule-based fiber angle method  where th1.Custom software  that included a ray casting method  to locatLV pressure (LVP) at end systole was obtained from a blood pressure cuff and LVP at end-diastole (ED) and RV end-diastolic and systolic pressures were estimated from concomitant transthoracic echocardiography data ; Table 1X and Y directions during passive filling and systolic contraction.Note that these models contract from the apex to the base. Specifically, nodes at the LV base (top surface) were fixed in the valve plane (Z direction movement = 0) but able to slide in the W, that is anisotropic relative to the local fiber direction:Passive and active myocardial constitutive laws described by whereE11 is fiber strain, E22 is cross-fiber in-plane strain, E33 is radial strain, E23 is shear strain in the transverse plane, and E12 and E13 are shear strain in the fiber-cross fiber and fiber-radial planes, respectively, and where bf = 49.25, bt = 19.25 and bfs = 17.44 max. Ca0 is the intracellular calcium concentration and ECa50 is length-dependent calcium sensitivity. Ct  is a time-varying variable defined as follows:where where ϖ is a time and sarcomere length dependent variable that increases from 0 at the start of contraction to π during peak contraction and then decreases to 0 during diastole.Material laws were implemented with a user-defined material subroutine in the explicit FE solver, LS-DYNA .C, was determined using the following:The LGE score was an integer from 0 to 4 and the SP score was an integer ranging from 0 to 3. In each case, a score of 0 represented the absence of disease. Further LGE and SP scoring details are described above . Passive stiffness, Cn represents the passive stiffness for each sector and CH the stiffness of a “healthy” sector with LGE = 0. Note that when LGE = 4 , Cn=10CHwhichis consistent with our prior work   . CH was n is the in vivo average strain at each sector (note the apex sector was excluded so n = 16), Ecc,n the calculated FE circumferential strain, Ell,n the calculated longitudinal strain, VES the LV end-systolic volume and W is the weight applied to the volume term. The overbar represents the experimental in vivo measurements.where W = 10 was applied to the volume term to make the strain and volume effects more balanced. For each case, the TmaxH was initially = 350 kPa. α was initially = 0.5 in the FMR patient models and = 0 in the healthy volunteer model. No constraints were applied to either TmaxHor VES.CH, TmaxH, and α within the fastest computation time. Four sets of meshes with different density were created with the transmural elements from 3 to 4, circumferential elements from 40 to 64, and longitudinal elements from 22 to 38.A mesh convergence study was performed on models of patients 2 and 5 to find the minimum number of elements needed to obtain stable calculations of H and TmaxH were set as the optimized values as presented in section “Testing With Synthetic Data” under “Results”). For each case, the simulated strain and LV end-systolic volume (ESV) were used as input in our optimization framework as “experimental data.” In addition, for Patient 2, the optimization was initiated with α set at 0, 0.5, and 1 while the TmaxH was set at 100 kPa, 350 kPa, and 600 kPa to test whether the current optimization scheme is sensitive to the initial guess of the parameters.Method accuracy was determined using idealized input data. Briefly, multiple simulations of diastolic inflation and systolic contraction for Patients 2 and 5 were firstly conducted by setting α to be 0 and 1, respectively  by setting α=0. As seen in Eq. 6, by setting α=0, Err calculated from baseline models and after virtual REVASC with a Cine-CMR wall motion based estimation of revascularization effect. Briefly, the following relationship was developed:Virtual REVASC was validated by comparing sector specific radial strain, rr_BLE is Err calculated from baseline models, ΔWM the difference between Cine-CMR wall motion scores at baseline and after revascularization and rr_WME is an estimated Err after revascularization based on the change in wall motion score. Eq. 8 is consistent with a wall motion score of 0 having a wall thickening of at least 50%. For instance, if rr_BLE = 0.2 and wall motion improved by 2 points, rr_WME would be 0.4.where >2). One of the patients had MI but no significant ischemia. Note that the wall motion scores were normal and LGE and SP scores were assumed = 0 for the healthy volunteer.Patient-specific LV and RV pressures and LV ejection fraction (EF) are shown in C, < 2% change in TmaxH and no change in α. Note that only the optimization results for using 7952 elements will be presented in the following sections.The mesh convergence study determined that 7952 elements  are requH and α accurately. The synthetic test also demonstrated that the current optimization scheme is insensitive to the selection of the initial guess of the parameters.CH was determined such that the FE model predicted LV EDV matched the patient-specific in vivo measured EDV  and minimal improvement in Err with virtual REVASC in spite of the fact that at baseline there was significant ischemia and the improvement in actual wall motion after revascularization was significant.in vivo measured strains were observed, which suggests that the optimized model was faithful to the experimental data.In this study, we demonstrated a novel method to estimate the effect of ischemia on regional LV myocardial contractility. The proposed method takes the advantage of multiple CMR sequences and the FE modeling to formally optimize the LV mechanics parameters. To the best of our knowledge, this study is the first study that incorporated 17-segment-based patient-specific perfusion and LGE scores into constitutive model, which allowed regional mechanical properties to be estimated with better physiological constraints. A linear relationship was proposed to describe the effect of LV infarct and ischemia on LV active contraction. Our approach was tested with CMR data from five patients with multi-vessel CAD and moderate FMR and a healthy volunteer. Good agreement between the FE model-predicted systolic strains and the patient-specific The effect of ischemia, α, on LV contractility was found to be >0 for Patients 1, 2, and 3, but = 0 for Patients 4 and 5. This is consistent with the patient-specific wall motion scores seen in It should be noted that stress induced perfusion defects are associated with either normal or depressed regional myocardial function and in the latter case the myocardium would be described as hibernating . First, TmaxH was higher in Patients 1, 2, and 5  than the healthy volunteer (259.4 kPa). The reason for this discrepancy is unclear but might be explained if Eq. 6 is overestimating the effect of infarct and ischemia on LV contractility. It is anticipated that future studies that measure infarct stiffness in patients with MI but without ischemia will help to better determine the relationship between infarct and myocardial contractility.Our assumption that infarct stiffness is ten times that of normal myocardium is consistent with our prior studies  and otheCH between the healthy volunteer and patients with multi-vessel CAD and FMR. We suspect this is likely a function of myocardial fibrosis (LGE scores >0) and, consistent with this, prior clinical studies have shown the extent of LGE to correspond to impaired LV relaxation . This may be due to the effect of MI fibrosis/LGE on either regional diastolic stiffness or systolic contractility or interaction between the two. In the current study we assumed that systolic contractility was affected by both LGE and SP scores but that diastolic stiffness was only affected by the LGE scores. Those assumptions about the form and amount of LGE effect on diastolic stiffness and systolic contractility may be overestimated. Furthermore, it should be noted that fibrosis (LGE) -based effect on diastolic stiffness will affect systolic Ecc through its effect on strain at ED and sarcomere stretch. The mismatch between the model-predicted Ecc and Ecc derived from CSPAMM in the regions with large LGE scores shows that a better understanding of the effect of LGE scores on the diastolic stiffness is important.It is interesting to note that in Results of a mesh sensitivity study suggest that the optimized LV material parameters are relatively insensitive to the mesh density, although slight differences were observed between FE models with different mesh density. Tmax and LGE relationship. For example, we assumed a sector with LGE = 2 had the Tmax as 50% of the Tmax for a healthy sector and this may be over-estimating the effect of infarct on the myocardial contractility. As a result, according to Eq. 6, the model-predicted ischemia effect might be smaller than reality to compensate the over-estimated LGE effect on myocardial contractility. A non-linear relationship between Tmax and LGE and a scaling factor in front of LGE score is under development.Validation of virtual REVASC using Cine-CMR wall thickening shows that the magnitude of ischemia effect is underestimated. This could be due to an incorrect Err with virtual REVASC in spite of the fact that at baseline there was significant ischemia and the improvement in actual wall motion after revascularization was significant. The reason for this is unclear but possibilities include that measured CSPAMM strain was inaccurate. In addition, patient 3 had a dilated LV and the subsequent decrease in systolic strain magnitude might make it hard to discriminate the ischemia (SP) effect. Regardless, this points out the need for accurate strain measurement with good spatial resolution as simulation input.CH was calibrated to match the measured LV end-diastolic volume. Second, the border zone effect was not taken into consideration in the current study. Third, only a linear relationship between the infarct and ischemia and the LV contractility were employed in this study. Fourth, boundary conditions near the valve plane of the LV may affect longitudinal strain calculations in that local area. However, longitudinal strain in the body of the LV is realistic. Last, the path from end-diastole to end-systole is not specified, and our models cannot therefore provide accurate simulation of isovolumic contraction and ejection. However, simulation of diastolic filling and end-systole are accurate.First, only systolic strains were calculated since the CSPAMM data were acquired during the systolic phase, which resulted in a fact that only systolic myocardial material parameters can be optimized. Because of the lack of diastolic strains, the main diastolic material parameter, in vivo measured strains and is able to predict REVASC effect.This study proposed a novel FE method to predict the effect of ischemia on the LV contractility in patients with multi-vessel coronary disease and FMR. The proposed method has good agreement with patient-specific Future studies will explore the stress perfusion and contractility relationship to determine if non-linear relationships allow greater model accuracy. Flow structure models will be implemented so that mitral regurgitation effect can be directly simulated. Last, a study with larger numbers of patient-specific models will better establish the utility of our FE method.All datasets generated for this study are included in the article/supplementary material.The Cornell Institutional Review Board approved this study, and written informed consent was obtained at the time of enrollment.YZ, JW, and MR designed the study. YZ conducted simulations, analyzed results, and wrote the initial draft of the manuscript. MR created the FE models. VW, AM, and JK did data analysis. LG contributed to development of methodology. JW collected the clinical data. LG, JW, and MR supervised the study. YZ, VW, JG, JW, and MR contributed to manuscript writing/review.The 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 one and a half ventricle repair (1.5VR) is a common clinical choice for patients with right heart dysfunction. Considering the influence of blood circulation failure and reoperation in urgent need, this essay aims to explore the hemodynamic effects of different pulmonary vascular resistance (PVR) values on reoperation after 1.5VR failure.The lumped parameter model (LPM) was used to simulate the reoperation, including the return biventricular repair (2VR), ligation of azygos vein (1.5VR′) and return single ventricular repair (1.0VR). Firstly, the debugging parameters were used to simulate the hemodynamics of 2VR. Secondly, the value of PVR was changed from one to four times while the other parameters remained unchanged. Finally, 15 cardiac cycles were simulated and the 15th result was obtained. In this work, the left and right ventricular stroke work and their sum , the left and right ventricular ejection fraction , the mean Cardiac Output (mCO) and the mean pressure and flow-rate ratio of superior and inferior vena cava (mPsvc\mPivc and mQsvc\mQivc), respectively, were used to describe the hemodynamics of reoperation.With the change of PVR from one to four times, the values of Plv, Prv, Ptotal, LVEF, and RVEF gradually decreased. The change rate of Plv, Ptotal and LVEF of 1.0VR were the largest in the three kinds of reoperation. The change rate of Prv of 1.5VR′ was larger than that of 2VR, but it was the opposite for their EF change rate. The mCO of 2VR, 1.5VR′, and 1.0VR decreased by 18.53%, 37.58%, and 48.07%, respectively. The mPsvc\mPivc of 1.5VR′ increased from 3.76 to 6.77 and the mQsvc\mQivc decreased from 0.55 to 0.36, while the mPsvc\mPivc and mQsvc\mQivc of 2VR and 1.0VR remained 1 and 0.67, respectively. The peak value of the tricuspid flow-rate (Qti) waveform of 2VR and 1.5VR′ changed from “E peak” to “A peak.”The numerical results demonstrate the highly reoperation-dependent hemodynamic consequences and their responses to variations in PVR. Comprehensive analysis of EF, mCO and ventricular stroke work indicates that PVR has a greater impact on 1.5VR′ and 1.0VR. Therefore, we suggest that the selection strategy of reoperation should focus on PVR. The one and a half ventricle repair (1.5VR) is widely applied in the treatment of congenital heart disease with abnormal structure and function of the right ventricle like the Pulmonary Atresia with Intact Ventricular Septum (PA with IVS) , TetraloHowever, in patients with pulmonary vascular dysplasia or left ventricular dysfunction, complications such as the superior vena cava hypertension and Cardiac Output (CO) reduction are very likely to happen . When thFortunately, the occurrence of such adverse events can be avoided with reoperation. The clinical reoperation measures include the return biventricular repair (2VR), the ligation of the azygos vein (1.5VR′), the return single ventricular repair (1.0VR), the artificial tonic solution and many others. The selection of the reoperation in clinical practice generally takes into account the morphological parameters and physiological functions of the left and right ventricles . HoweverIn order to study various hemodynamic problems associated with congenital heart disease (CHD), a wide range of computational models have been established in the literature . This work aims to develop a simple and effective LPM closed model, which only includes systemic and pulmonary circulation. According to the 1.5VR surgery characteristics, the systemic circulation is divided into upper and lower body blood circulation. Therefore, this work builds on the modeling experience of the former report. We attempted to use the lumped parameter model (LPM) based on the lumped parameter state-variable equation  to quantThe equivalent circuit model that was used to simulate the cardiovascular system is shown in The heart is modeled as a four-chamber pump with a variable elasticity and four heart valves that control the direction of the blood flow.The pressure-volume relationship is used to describe the basic characteristics of the ventricle. Suga et al.  establiswhere E(t) represents the time-varying elasticity, P(t) and V(t) represent the instantaneous ventricular pressure and volume, respectively, and V0 represents the corresponding ventricular volume when the ventricular pressure is 0. The ventricular model in this paper refers to that of n = t/tmaxtmax = 0.15tc + 0.2, tc = 60/HR, and refers to a typical cardiac cycle, HR is the heart rate and Emax and Emin are the end-systolic and end-diastolic elasticity of ventricles, respectively. Although the model of the right ventricle is similar to that of the left one, the coefficients of the elastic chamber are different.where En(tn) is the normalized elasticity, also known as the “double hill” function, tWith the generation of the P wave in the electrocardiogram (ECG), the atrial contraction leads to a rapid increase in the ventricular volume and pressure during diastole. This effect is sometimes referred to as the “atrial pulsation,” which accounts for 20–30% of the ventricular filling and reflects the function of the “booster pump” of the atrium . The mod∗tc is the start time of the P wave in ECG, Tpww = 0.08∗tc represents its duration time and Elamax and Elamin show the elasticity of the end-systolic and end-diastolic of the left atrium, respectively. The modeling equation of the right atrium is the same as that of the left atrium, but the parameter values are different.where Tpwb = 0.92A diode is used to control the one-way flow of blood in the LPM. The basic pressure-flow relationship of the valve is described using the “hole” model in fluid mechanics . Taking ARmi is the ratio of the valve open area to the maximum area. In this work, the movement process of the valve was ignored, and the movement of the valve was simplified into two states of being fully opened (1) and completely closed (0). Whether the valve is open or not depends on the pressure at both ends of the valve. Finally, CQmi is the valve flow coefficient, which is related to the orifice area when the valve opens.The systemic circulation was divided into systemic aortic sinus, systemic artery, systemic arterioles and systemic vein. In order to simulate the hemodynamics of the reoperation after 1.5VR failure, systemic arterioles and systemic vein were each divided into two parts: the upper loop and the lower loop . The pulIf the effect of L is to be considered, then the flow rate of each part is defined as Eq. 9. Otherwise, it is defined as Eq. 10.See The values of the physiological parameters are generally difficult to measure and vary among individuals. The parameter values in the LPM of reoperation constructed in this work are widely referenced from the literature to select appropriate values. However, in order to simulate different physiological realities, the parameters usually need to be adjusted. It is well known from the literature that the blood flow rate of the descending aorta accounts for 63.8% of CO, and the compliance of the inferior vena cava accounts for 66.6% of the total compliance . TherefoThe parameters of Plv, Prv, Ptotal, LVEF, RVEF, mPsvc\mPivc, and mQsvc\mQivc were used to describe the hemodynamics after reoperation in this essay. The ventricular work is calculated using MATLAB to integrate the area surrounding the ventricular P – V curve. EF can be calculated by dividing the ventricular stroke volume (SV) by the ventricular end-diastolic volume (Ved), while SV is equal to Ved and the ventricular end-systolic volume (Ves). The influence of PVR on the ventricular work and the ventricular EF is represented by the change rate of the ventricular work and ventricular EF, respectively. The changing rates of LVEF, RVEF, and mCO are comprehensively analyzed and can reflect the degree of impact of PVR impact on the reoperation.It can be seen from It can be seen from The results for Pa, Psvc and Pivc are shown in 1.5VR has been employed as a useful surgery in patients with CHD. The postoperative results of the surgery are highly patient-specific. In this paper, we have established three general LPM models, representing reoperation procedures after the failure of 1.5VR. They are closed-loop models that only consider the systemic and pulmonary circulation, with the exclusion of the local fine renal and liver circulation. The purpose of developing general LPM models is to mimic the postoperative hemodynamics of reoperation on specific PVR. These models are simple and effective. In addition, based on the models of this paper, we can adjust the lumped parameters of each vascular segment such as R, C, L, and others, so that clinical phenomena such as the azygos vein growth and the results of surgical procedures can be reproduced. The study parameters include Plv, Prv, Ptotal, CO, Qti, Pa, Psvc, Pivc, Qsvc, and Qivc.The ventricular stroke work can directly reflect the function of the ventricle. With the increase of PVR, The value of Prv of 2VR and 1.5VR′ gradually increased. This phenomenon is in accordance with the qualitative results inferred from general cardiovascular physiology. Furthermore, the Plv/Prv of 1.5VR′ exceeded that of 2VR, which is consistent with the purpose of the 1.5VR surgery . ConsideUnder different PVR conditions, LVEF and RVEF of the three surgeries stay around 50% in this work, while the mCO values of 1.5VR′ and 1.0VR are obviously decreased. In other words, the filling of the left ventricle decreases , which iIn turn, changes in the ventricular function affect changes in the pressure and flow in various parts of the body. The waves of Pa, Psvc, Pivc, Qsvc, and Qivc are of no pulsation in 1.0VR, which is determined by the surgical characteristics of 1.0VR  and is cIn addition, Qti is closely related to the ventricular function. The “E peak” and “A peak” of Qti waveform are generated by the active systole of the right ventricle and right atrium, respectively, so the time of occurrence of the peak is different. With the increase of PVR, the waveform peak of Qti changes from “E peak” to “A peak,” which indicates that PVR can affect the right ventricular function to some extent. In reference , the ratA major limitation of this study is related to the model we established. The model constructed in this essay is relatively simple and does not take into account the factors of interventricular interaction, valve movement and coronary circulation of the great clinical value, although it effectively captures physiological changes. Some scholars have used computational models to verify the importance of interventricular interaction  and valvBy constructing the LPM of the reoperation after 1.5VR failure, we investigated the three kinds of surgical procedures, including the 2VR, 1.5VR′, and 1.0VR. Through MATLAB simulation analysis, the hemodynamic differences among the three kinds of surgical procedures are quantitatively revealed at different PVR. In this paper, we mainly focus on some values which are the ventricular stroke work, EF, Cardiac Output and pressure and flow rate of the superior and inferior vena cava, which can directly or indirectly reflect the function of the heart. Using these values, we can describe the hemodynamics of reoperation after 1.5VR failure under different PVR. The ventricular stroke work, EF and mCO of the changing rate are important parameters that can reflect the sensitivity of different surgical procedures to PVR. Comprehensive analyses of the above-mentioned parameters show that PVR has a greater impact on 1.5VR′ and 1.0VR. Therefore, the selection of reoperation strategies should be mainly based on the development of pulmonary vasculature. To be noted, the definite outcomes of related procedures need to be verified by further experiments or clinic data.All datasets generated for this study are included in the article/supplementary material.YF designed and simulated the LPM of virtual surgery, performed the data analysis, and prepared the initial draft manuscript under the instruction of AQ. YY and XF provided the support of clinical knowledge. AQ subsequently revised the manuscript. All authors approved the final submitted version.The 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.


Recent studies have indicated that N-acetylneuraminic acid (Neu5Ac) plays a key role in severe coronary artery diseases, involving RhoA signaling pathway activation, which is critically involved in cardiac fibrosis. There is convincing evidence from many studies that left atrium fibrosis is involved in the pathophysiology of AF. Therefore, we speculated that Neu5Ac may be associated with atrial fibrillation (AF) and involved in the development of AF. This study aims to investigate the clinical relationship between Neu5Ac and AF and left atrial enlargement.  Forty-five patients with AF (AF group) and forty-five patients with non-AF (control group) matched for age, sex, and hospitalization date were recruited for our study. Plasma concentrations of Neu5Ac from peripheral venous blood were analyzed using enzyme-linked immunosorbent assay (ELISA). The baseline characteristics, plasma level of Neu5Ac, and echocardiographic characteristics were evaluated. P < 0.05); the left atrial diameters were positively correlated with the plasma Neu5Ac level . The plasma Neu5Ac level  and the left atrial diameters  were positively correlated with AF history times. Neu5Ac  and the left atrial diameter  were independent risk factors for AF in multivariate regression analysis.  The plasma level of Neu5Ac was significantly higher in the AF group than in the control group (107.66 ± 47.50 vs 77.87 ± 39.09  ng/ml;  Serum Neu5Ac is associated with atrial fibrillation, and the mechanism may involve left atrial enlargement. AF is associated with a five-fold increased risk of stroke and a three-fold increased incidence of congestive heart failure, as well as increased mortality. Hospitalization of patients with AF is also very common, accounting for approximately one-third of hospitalizations for cardiac rhythm disturbances –3. Funda changes –7.2+ [The evidence from many of the studies has confirmed that sialic acids are involved in some pathological phenomena, such as inflammation, apoptosis, growth, and aging, and sialic acids are also involved in the binding and transport of Ca2+ . N-Acety2+ –11. TherWe recruited consecutive patients with AF (AF group) who were admitted to the Renmin Hospital of Wuhan University to schedule their first AF catheter ablation between March 2019 and July 2019, and consecutive patients with non-AF were selected to form a control group; these individuals were matched with the AF group for age, sex, and hospitalization date. After assessment of detailed medical history and a complete physical examination, some clinical examinations needed to be completed within 3 days after admission, such as biochemical testing, a 12-lead electrocardiogram (ECG), and echocardiograph. The history of AF was the period from the initial episode of AF to the time of admission.The exclusion criteria were as follows: a history of prior AF catheter ablation, which might lead to atrial fibrosis and interfere with the results of study; atrial septal defect for occlusion or surgical treatment; severe coronary disease; heart valve disease; cardiac surgery, including heart transplantation and heart valve replacement; severe heart failure (might come with cardiac fibrosis which might interfere with the results of study); recent or active malignancy; severe renal failure (estimated glomerular filtration rate <30  ml/min); shock and death during hospitalization and unwillingness or inability to sign the informed consent form.Venous blood samples were obtained from patients following overnight fasting (8 hours) after thirty minutes of rest in a sitting position before AF catheter ablation. Plasma concentrations of triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), creatinine, and uric acid were analyzed by an ADVIA 2400 Chemistry System .Venous blood samples were obtained from patients following overnight fasting (8 hours) after thirty minutes of rest in the sitting position before AF catheter ablation. A blood separator tube was used, and samples were allowed to clot for two hours at room temperature before centrifugation. Plasma samples were collected using a serum separator tube after centrifugation and then immediately frozen at −80°C until analysis. Later, the frozen serum samples were rapidly dissolved for analysis. Repeated freeze/thaw cycles were avoided. The plasma Neu5Ac level was evaluated with commercially available enzyme-linked immunosorbent assay (ELISA) kits according to the manufacturer's instructions .All patients underwent routine transthoracic echocardiography within 3 days after admission. Echocardiography was performed by an operator with over 5 years of experience using a GE E95 . All measurements included at least 3 consecutive beats for patients. The left atrial diameter (LAD) was measured using a trailing edge-to-leading edge convention to measure the maximal distance between the posterior aortic root wall and the posterior left atrial wall at end ventricular systole. Left ventricular diameter and right ventricular diameter  were measured at the end of ventricular diastole. The modified biplane Simpson rule was applied to calculate the left ventricular (LV) ejection fraction.t-test or chi-square test was used for comparisons of continuous and categorical variables, respectively. Correlation analysis was performed using Pearson's correlation analysis. Multivariate logistic regression analysis was used to identify risk factors. SPSS version 17.0  was used for data analysis. Differences were considered significant when a 2-sided P value was <0.05 for all the comparisons.All continuous variables are expressed as the mean ± SD for normally distributed data, and categorical variables are presented as counts (percentages). Independent-sample Student's P < 0.05). There were no significant differences in the prevalence of smoking, hypertension, diabetes, right atrial diameters, left ventricular diameters, right ventricular diameters, or left ventricular ejection fraction between the AF group and the control group. There were no significant differences in the levels of plasma triglycerides, total cholesterol, LDL-C, HDL-C, creatinine, or uric acid between the two groups.P < 0.05).P < 0.05) and left atrial diameter  were the independent risk factors for AF.The continuous variables were entered into the multivariate logistic regression analysis. R = 0.255; P < 0.05). There was no significant correlation between the plasma Neu5Ac level and the following factors: age, the level of plasma triglycerides, total cholesterol, LDL-C, HDL-C, creatinine, uric acid, and the right atrial, left ventricular, and right ventricular diameters.R = 0.368; P < 0.05) and the left atrial diameters  were positively correlated with the AF history times.Figures Many studies have been performed in regard to the mechanism and therapeutic strategies of AF. Multiple factors, including advancing age, male sex, obesity, heart failure, obstructive sleep apnea, anxiety, systemic arterial hypertension, and biomarkers such as N-terminal pro-B-type natriuretic peptide (NT-proBNP), have been identified as factors correlated with AF development –15. Our All cells of every species in nature are covered by a dense and complex coating of glycans (oligosaccharides or polysaccharides). Some glycans are sialic acids. Neu5Ac is the most widespread form of sialic acid. Sialic acids are a family of neuraminic acid derivatives, sugars with a shared nine-carbon backbone that are typically found attached to the terminal positions of several amino groups of the cell surface, and secreted glycan molecules . The amiIs Neu5Ac a risk factor or simply a marker or mediator molecule for AF? Our study indicated that LADs were positively correlated with the plasma Neu5Ac level. Previous studies have shown that LAD is associated with AF incidence and progression and is an important risk factor in the development of AF. LAD is also involved in the maintenance and recurrence of AF –20. TherThe LAD sizes were also positively correlated with the AF history times in our study. Many factors are involved in left atrial enlargement, including AF itself. Left atrial enlargement can occur as a consequence of AF , 22. Suzβ receptor [β in both atrial fibrosis and atrial remodeling, involving the RhoA signaling pathway [AF is a final common endpoint of atrial remodeling caused by a variety of cardiac diseases and conditions that contribute to the progression and maintenance of AF. Atrial remodeling includes structural remodeling and electrical remodeling. Structural remodeling is characterized by atrial enlargement and tissue fibrosis . There ireceptor , 27. Stu pathway , 29. TheSerum Neu5Ac is associated with atrial fibrillation. The elevated concentrations of plasma Neu5Ac may result in left atrial enlargement and fibrosis, which facilitate the development of AF.


Patients with transposition of great arteries, with intact interventricular septum (TGA-IVS) and deconditioned left ventricle, represent a considerable challenge in developing countries. The modified Mustard operation was shown to provide a significant improvement for these patients, particularly by enhancing atrial functions and left ventricular filling. Yet, the problems of the systemic right ventricular dysfunction and the resulting secondary tricuspid regurgitation (TR) remain to be of major concern. In addition, the deviation of the interventricular septum towards the left side markedly impairs ventriculo-ventricular interaction and predisposes to dynamic left ventricular outflow tract obstruction (LVOTO). We report that adding a moderately loose pulmonary artery banding to the modified Mustard operation in a case of TGA-IVS results in improvement of biventricular geometry and function, tricuspid and mitral valve functions and disappearance of dynamic LVOTO. However, the shift of the IVS is known to increase tricuspid regurgitation due to tethering of the tricuspid septal attachments. The latter can establish a vicious circle producing further dilatation of the right ventricle (RV) and tricuspid regurgitation (TR) (The modified Mustard operation is being increasingly used for patients with TGA and intact interventricular septum (TGA-IVS) with encouraging results.ion (TR) .6 In addition, in patients with dynamic left ventricular obstruction, LV filling and volume are hampered by the bulge of the interventricular septum into the LV cavity. We hypothesized that moderately loose banding of the pulmonary artery can interrupt this vicious circle and abolish the dynamic LVOTO. In support of this hypothesis, we here report the immediate hemodynamic effects of loose PA banding during modified Mustard, in a patient with severe TR and dynamic LVOTO.The shift of the IVS interferes with the physiologic ventriculo-ventricular interaction.A 6-year-old male patient presented with long-standing cyanosis and clubbing. He had a previous history of balloon atrial septostomy at the age of 5 days. Oxygen saturation was 60% and hemoglobin level was 20.3 gm/dl. Echocardiogram showed complete transposition of the great arteries with intact inter-ventricular septum and adequate-sized ASD. The right ventricle was dilated with moderate impairment of systolic function and severe tricuspid regurgitation . The IVS1 and tricuspid valve annuloplasty. After discontinuing cardiopulmonary bypass, a moderately loose pulmonary artery banding was applied under trans-esophageal echo guidance. The systolic pressure proximal to the band  was 50 mmHg, with systolic aortic pressure of 90 mmHg. The peak gradient across the band was 35 mmHg  because of the reported continued deterioration in late survival and quality of life.8Late presenters with TGA-IVS and deconditioned LV continue to represent a major challenge in developing countries.1 Yet, the failing systemic RV and significant TR continue to be major problems .11 In an attempt to solve these problems, we have used additional pulmonary artery banding in the patient described in this communication. This was accompanied by significant improvement of geometry and function of both ventricles.Trying to improve outcome, we have recently described a modification of the Mustard operation aiming to improve atrial functions and pattern of left ventricular filling.15 This was in line with studies reporting the natural history of cc-TGA, showing patients with pulmonary stenosis developed symptoms later, were less handicapped and had a better prognosis than those without pulmonary stenosis.16Interestingly, similar changes have been reported when pulmonary artery banding (PAB) was used to re-train the LV in patients who had previous atrial switch or have congenitally corrected TGA (cc-TGA) and presented with failing systemic RV.In conclusion, the findings reported in a single patient strongly suggest that additional PA banding should be considered in patients undergoing the modified Mustard operation, particularly those with impaired RV function, TR or dynamic LVOTO.


The average strain decreased , as did the average SR . The average longitudinal displacement did not differ. With the VVI technique, we could clearly observe RV functional change immediately after transcatheter closure of the ASD. RV functional change with regional difference may reflect the heterogeneity of volume reduction and suggest subclinical RV dysfunction. These findings can enhance our understanding of the physiologic changes in the RV during reverse remodeling.The functional change of the right ventricle (RV) after atrial septal defect (ASD) via transcatheter closure is well known. We assessed the immediate RV functional change using velocity vector imaging (VVI) with intracardiac echocardiography (ICE). Seventy-four patients who underwent transcatheter closure of an ASD were enrolled. VVI in the “home view” of ICE showing the RV was obtained before and after the procedure. Velocity, strain, strain rate (SR), and longitudinal displacement were analyzed from VVI data, and the changes of these parameters before and after the procedure were compared. The velocity of the RV decreased after ASD transcatheter closure (3.97 ± 1.48 to 3.56 ± 1.4,  A secundum atrial septal defect (ASD) is a common congenital heart disease with a left-to-right shunt that induces volume overload in the right ventricle (RV), and may eventually cause RV myocardial deformation. ASD is routinely treated via transcatheter closure under fluoroscopic and echocardiographic guidance with modalities such as intracardiac echography (ICE).ICE is a multielement, steerable system that yields useful images during intracardiac procedures ,2,3. ImaVector velocity imaging (VVI) is an advanced quantification method of echocardiography that can be used for cardiac function assessment by measuring the velocity of the myocardium. VVI has proven clinically useful in many different patients and can be applied in various clinical settings ,9,10,11.In this study, we assessed the immediate functional change in the RV of patients undergoing transcatheter closure of a secundum ASD using the VVI method of ICE, which is routinely performed during such procedures. To the best of our knowledge, this is the first such study on the use of this model. During two study years, 155 patients underwent transcatheter closure of an ASD at Severance Cardiovascular Hospital, Korea. All the patients were diagnosed with ASD based on the findings of transthoracic echocardiography prior to the procedure and considered suitable candidates for transcatheter device closure. Among these patients, those with other hemodynamically significant intracardiac lesions, moderate-to-severe pulmonary hypertension, or RV dysfunction were excluded. Conclusively, 74 patients who agreed to participate in this study were enrolled.All the patients underwent diagnostic cardiac catheterization to verify their hemodynamic state. Transcatheter closure of ASD was performed only when the ratio of pulmonary blood flow to systemic flow (Qp/Qs ratio) was >1.5. Device closure was performed under ICE and fluoroscopic guidance. ICE imaging was performed with the Sequoia ultrasound system . The ICE catheter used in the present study was the ACUSON AcuNav™ 8F Ultrasound Catheter , which has a side-viewing, 64-element, linear-phased array with four-way steering capability. The detailed ICE guidance protocol has been described in our previous study . In brieTo acquire sufficient information, the images were recorded at 60 frames per second. We captured images of a full cardiac cycle through the correlation of two consecutive QRS complexes on an electrocardiogram.® US Workplace . Image analysis was performed using recorded and separately stored raw data. The software used to analyze the data was Siemens SyngoThrough the analysis of data obtained on VVI, we obtained the peak systolic velocity, strain, strain rate (SR), and longitudinal displacement values. The “home view” RV image was divided into six different areas: right ventricular inlet, midinlet, apex-inlet, apex-outlet, midoutlet, and right ventricular outlet. The change in these parameters before and after the procedure was compared .To minimize inter- and intra- observer variation, images were obtained by a specialist interventionist (J.Y.C.), whereas the images were analyzed by another well-trained pediatric cardiologist (N.K.K) via the manual subendocardial border tracing method, a total of three times. The mean values were recorded for analysis in the present study. Statistical analysis was performed using SAS version 9.2  software. The D’Agostino–Pearson test was used to confirm a normal distribution among the continuous variables. All normally distributed continuous variables were reported as means and standard deviations, while their non-normally distributed counterparts were expressed as medians with ranges. Categorical variables were expressed as frequencies (percentages). Continuous variables before and after the procedure were compared using a chi-squared test, paired t-test, or Wilcoxon test, as suitable.p-values were two-sided, and a p-value of < 0.05 was considered statistically significant.A linear mixed model was used for the correction of variables such as age, sex, body surface area (BSA), RV pressure (RVP), and Qp/Qs. All the reported All the patients provided informed consent prior to the transcatheter closure of the ASD. The study was approved by the Institutional Review Board of the Yonsei University Health System (IRB No: 1-2011-0049).2. The mean systolic pulmonary artery pressure of the patients was 36.6 ± 10.8 mmHg and the mean Qp/Qs value was 2.2 ± 0.7. Baseline left ventricular ejection fraction (LVEF) was preserved as 67.0 % ± 5.2 %, and the median heart rate (HR) was 78  beats per minute. The procedure was successful in all the patients without any complications, and there was no significant change in LVEF  or HR  immediately after the procedure. Complete ASD closure was confirmed in all the patients within three months of device closure. During the follow-up assessment, none of the patients exhibited evidence of clinical or hemodynamic RV dysfunction.The demographic and hemodynamic data are presented in p = 0.0248, We found that the velocity decreased from the basal to apical segments of the RV. The average velocity of RV flow decreased after ASD device closure  before and after the procedure. As the “home view” is routinely imaged during transcatheter closure of ASD, no additional time or effort is required for intervention . As VVI uses the “border detecting algorithm,” analysis remains feasible, even though the image of the entire myocardial layer is not obtained. A degradation of image quality occurs after the implantation of an ASD device in some cases. However, these degraded images were of sufficient quality for VVI analysis. Therefore, VVI could serve as a useful assessment tool of right ventricular functional change before and after transcatheter closure. The data obtained in the present study, which showed that the velocity and longitudinal displacement decreased from the basal to apical segments of the RV, were similar to the findings of the previous study involving VVI in normal children , as wellThe main findings of this study are as follows: (1) the velocity of the RV myocardium decreased immediately after transcatheter closure, although the change in velocity at various regions differed; (2) the RV strain decreased, although the change in RV strain at various regions did not differ; (3) the RV SR decreased, irrespective of the regions assessed; and (4) longitudinal displacement decreased in the RV inlet and outlet, although the average value remained unchanged.In particular, we found that the RV myocardial velocity and strain decreased after transcatheter closure of the ASD. This was consistent with the findings from previous studies involving various modalities ,18. ThesLongitudinal displacement is a reliable measure of RV systolic function . In the The present study had several limitations. Although the trends in the VVI parameters were consistent with those in previous studies involving VVI in normal children , normal Both structural and hemodynamic changes occur immediately after ASD device closure. This study showed that the VVI methods could obtain a simple and accurate assessment of RV after ASD device closure. With the VVI technique, we could detect the regional differences of RV morphology and the subtle functional variations related to preload change occurring immediately after the transcatheter closure of the ASD. The RV inlet and outlet exhibited a decrease in velocity and strain, which suggests that the effect of RV volume reduction is marked in those areas. Moreover, RV longitudinal displacement was lower in the same areas, which may indicate the presence of subclinical RV systolic dysfunction. Further research is necessary to examine the relationship between changes in VVI measurement and anatomical characteristics of the RV to enhance our understanding of the physiological changes in RV function in congenital heart diseases.


T2*-weighted (T2*w) is deemed as a reference standard for post-infarction intramyocardial haemorrhage (IMH). However, high proportion of T2* images is affected by off-resonance artefacts hampering image interpretation. Diagnostic accuracy and precision of alternative techniques for IMH diagnosis and quantification have been seldomly investigated.p < 0.05 for both scores). For IMH quantification, hypocore on T2 map and T1 map strongly correlated  with IMH extent on T2*w and presented an overall excellent agreement on Bland-Altman analysis. By linear mixed model analysis, absolute hypocore size did not differ among T1-, T2 map, and T2*w. T2/T1 maps had the best intra- and inter-observer reproducibility among CMR techniques.Between April 2016 and May 2017, 50 ST-segment elevation myocardial infarction patients  and 15 healthy controls  were consecutively enrolled. Subjects underwent head-to-head comparison of single mid-infarct slice acquired on black-blood T2-weighted short-TI-inversion recovery (T2w-STIR), bright-blood T2prep-steady-state-free precession (T2prep-SSFP), and T2/T1 maps for IMH diagnosis and quantification against T2*w. All images were graded for quality  and diagnostic confidence . Reduced relaxation time/hypointense region (hypocore) embedded in infarct-related oedema on T2 map, T1 map, and T2w-STIR had the best overall diagnostic accuracy . By mixed-effects analysis, image quality, and diagnostic confidence were higher for T2 map and T1 maps than T2*w  contains supplementary material, which is available to authorized users. Moreover, multi-echo T2*w imaging does not allow for the concomitant detection and quantification of infarct-related oedema, which provides relevant complementary information in STEMI [Cardiovascular magnetic resonance (CMR) represents a valuable non-invasive modality for studying the ischemia/reperfusion (I/R) myocardial injury in patients with ST-segment elevation myocardial infarction (STEMI) . Intramyin STEMI . Black-bin STEMI –14. WithBased on these premises, we studied a cohort of STEMI patients and healthy control using T2w-STIR and T2prep-SSFP as well as T2/T1 maps and multi-echo T2*w imaging. We set T2*w imaging as the reference standard, and we hypothesised that, when compared with T2*w, CMR alternative techniques may (1) be associated with improved image quality, diagnostic confidence, and non-inferior diagnostic accuracy for IMH detection; (2) provide reliable surrogate estimates of IMH (for mapping techniques); and (3) offer better intra- and inter-observer reproducibility.Between April 2016 and May 2017, 61 STEMI patients were consecutively evaluated for study inclusion at the Lausanne University Hospital. Inclusion and exclusion criteria are provided in the All subjects underwent CMR at 1.5-T scanner  after a mean period of 3 ± 2 days from index primary percutaneous coronary intervention (PCI) as described in detail in the A side-by-side visual comparison between LGE target slice and multi-echo T2* was used to localise the infarct region on the corresponding T2* images. Intramyocardial haemorrhage was defined as sub-endocardial to mid-wall hypointense signal within the infarct region on the multi-echo T2*w image with the longest echo time (i.e. 16.22 ms) (T2*w) . HypointAn experienced CMR technician (G.B) blinded to patients’ clinical history and CMR results anonymised patients’ and healthy controls’ DICOM target slices and uploaded them in a dedicated workstation with a random order using vendors’ independent software . The same operator (PGM) analysed all studies. Target-slice assessment started with a 4-grade image quality score: (1) extensive artefacts not allowing image interpretation; (2) moderate artefacts not hampering image interpretation; 3) mild artefacts with overall good image quality; and (4) absence of artefacts with excellent image quality. Only target slices graded ≥ 2 were then analysed. The operator’s confidence for binary assignment of IMH was graded according to 5-point Likert scale  . The sam mild artp < 0.05 was considered statistically significant. Detailed statistical methods are provided in the Differences in qualitative features across CMR techniques were evaluated by multilevel mixed-effects ordered logistic regression. CMR technique diagnostic accuracy was measured on a per-subject and a per-segment basis using the T2*w as the reference standard (“true diagnosis”). We estimated sensitivity, specificity, false and negative rates, and positive (PPV) and negative (NPV) values . Receive. All study patients were treated according to the current guidelines for STEMI [p = 0.706) and gender distribution  compared with STEMI patients  and 6 20%) patients were excluded because of poor T2*w image quality (grade 1) and previous MI/coronary revascularisation, respectively  and 63 images of T2-STIR and T2prep-SSFP were included in the analysis. The mean image quality and diagnostic confidence based on Likert’s scale are reported in Table p = 0.047) and T2 map (p = 0.001). In terms of diagnostic confidence, T2 map was not inferior to T2*w (p = 0.676). In contrast, all other imaging techniques had lower diagnostic confidence than T2*w (p < 0.001)  to excellent (grade 4) in 21 (32%) and 43 (66%) subjects, respectively . The diagnostic confidence for T2*w was good (grade 4) to excellent (grade 5) in 17 (26%) and 44 (68%) subjects, respectively (mean score: 4.6 ± 0.7). All T2 maps and T1 maps were judged good or excellent (grade 3 or 4), whereas T2-STIR and T2prep-SSFP were scored very poor quality (grade 1) in 2 (4%) cases. Accordingly, all parametric images (p < 0.05) (Table p < 0.05) among all alternative techniques to T2*w.On T2*w target slice, 19 of 50 evaluable STEMI patients (38%) showed IMH whereas none of the healthy controls was positive for IMH. Per-subject basis, T2 map, T1 map, and T2w-STIR showed the best overall diagnostic accuracy with very good or excellent sensitivity and specificity resulting in balanced negative and positive predictive values for IMH diagnosis (Table p < 0.001). T2 and T1 relaxation times of the oedematous myocardium were higher than those of the remote myocardium (p < 0.001), while T2 and T1 relaxation times of the hypocore were comparable with those of the remote tissue (p > 0.05). T2* relaxation time of IMH moderately correlated with hypocore T2 relaxation time , whereas no correlation was found with hypocore T1 relaxation time . By general linear mixed model analysis, no evidence of difference in absolute hypocore size was found between T2*w and either T1 map (p = 0.854) or T2 map (p = 0.856) (Table p < 0.001 for both). Hypocore size measured on T2 map was comparable with that on T1 map (p = 0.669)  Table . However9) Table .Table 3Qp < 0.001) with slight attenuation in the relationship with T1 map hypocore  (Supplementary Table p < 0.001 for both). Hypocore extent of 1% and 0.5% on T2 map and T1 map had a sensitivity of 95%, 89%, and 93% and specificity of 87%, 83%, and 88% for IMH diagnosis, respectively.There was a strong correlation between IMH extent on T2*w and hypocore size on T2 map .In the total population, T2 map showed the highest intra- and inter-observer reproducibility among comparators of T2*w for IMH diagnosis based on Cohen’s kappa statistic and intra-class correlation coefficients Table .Table 4I compared with T1 mapping (mean bias = − 0.66) and T2*w (mean bias = − 1.1) Fig.  . As a result, it was not possible to investigate whether the alternative techniques were able to visualise hypointense or hypo-T2/T1 regions within the infarcted myocardium not otherwise detected by T2* imaging. Histological validation was not possible in the current study and therefore, we were unable to investigate the contribution of diverse pathophysiological components of I/R injury on the relaxivity properties of the myocardium. Several studies adopted a T2* relaxation time < 20 ms as the gold standard for post-infarction IMH detection and quantification , 28, 31., in reperfused STEMI patients, the hypocore on T2 map or T1 map is an accurate and precise surrogate metric of IMH overcoming the limitations inherent to T2* imaging.In conclusionESM 1(DOCX 200 kb)


To investigate cardiac involvement in patients with sporadic inclusion body myositis (IBM) by cardiac magnetic resonance tomography (CMR).A case series of 20 patients with IBM underwent basic cardiac assessment and CMR including functional imaging, native and contrast-enhanced T1-weighted, and late gadolinium enhancement (LGE) imaging.All IBM patients reported no cardiac symptoms. Echocardiography was normal in 16/17 IBM patients. In CMR, IBM patients had normal ejection fractions (mean LVEF 63 ± 7%) and ventricular mass. They had reduced left (mean 55 versus 88 ml) and right ventricular stroke volumes (mean 54 versus 86 ml) and increased early myocardial enhancement , as compared to age- and gender-matched controls. Since arterial hypertension was more often observed in IBM patients, hypertensive heart disease can also be causative for these changes. Late gadolinium enhancement did not differ statistically from healthy controls. There was no apparent association between elevated biomarkers, echocardiography and CMR.CMR revealed subtle changes in cardiac geometry and tissue characterization in IBM patients when compared to a gender- and age-matched control group. Findings in CMR indicated a higher extent of diffuse myocardial fibrosis as well as smaller left ventricular stroke volumes. These alterations may be due to a higher prevalence of arterial hypertension in the IBM cohort. Sporadic inclusion body myositis (IBM) is the most common and disabling inflammatory myopathy among persons > 50 years of age , 2. InclEpidemiologic studies found no significant increase of cardiovascular disease in IBM patients since cardiac abnormalities would also be expected in healthy controls of this age group , 14. In Cardiac magnetic resonance (CMR) imaging has been shown to be a valuable tool in the diagnostic work-up of inflammatory myocarditis , 16 and Patients with histologically proven inclusion body myositis  were scrMedical charts were reviewed for clinical and laboratory data. Exclusion criteria were contraindication for CMR, gadolinium-based contrast agent, pregnancy, or no secured contraception. All included patients gave informed written consent. The study was approved by the local ethics committee (reference no. 13/10).Blood levels of creatine kinase (CK), myocardial creatine kinase (CK-MB), troponin I and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) were analyzed for each patient .As controls, a cohort of age- and gender-matched patients from the ongoing multicenter study for the assessment of age- and gender-specific reference values for cardiac imaging markers (USAGE) was implemented. Within this study, healthy subjects lacking any cardiac comorbidity underwent a comprehensive CMR examination.Transthoracic echocardiography (2D and Doppler) was performed using a CX 50 Ultrasound . Left ventricular (LV) cavity dimensions, mass and wall thickness, and diastolic dysfunction were assessed in accordance with the recommendations of the European Association of Echocardiography .An abnormal echocardiography was defined by a left ventricular end-diastolic diameter (LVEDD) > 56 mm, an interventricular septum (IVS) > 11 mm and a left ventricular end-systolic diameter > 40 mm. The ejection fraction was visually evaluated. Additionally, echocardiography was used to assess valve disease and fractional shortening.All patients were examined in a 1.5 T whole-body scanner  using a 32-channel phased-array cardiac surface coil. Steady-state free precession cine sequences were acquired in contiguous short axis orientation covering the left and right ventricle for volumetric and functional analysis of both ventricles  as previously reported .A non-breath-hold T1-weighted fast spin-echo sequence was performed in three axial slices using the body coil . This sequence was acquired before and 30 s after intravenous application of 0.1 mmol gadolinium-based contrast agent . After acquisition of T1-weighted images, a second bolus of 0.1 mmol contrast agent was injected . Ten minCMR images were anonymized and transferred as DICOM images to a dedicated workstation. Two blinded and experienced readers evaluated all images in consensus using commercially available software . End-diastolic and end-systolic endocardial contours of the left and right ventricle were drawn manually for evaluation of end-diastolic and end-systolic volumes. Ejection fractions were calculated, and end-diastolic left-ventricular epicardial contours were drawn for assessment of left ventricular myocardial mass. Stroke volumes and myocardial mass were also reported as indexes (relation to body surface area as a matter of body weight).Regions of interest covering the left ventricular myocardium were drawn in the pre-contrast T1-weighted images and copied to the postcontrast images. Early myocardial enhancement was calculated in accordance to the Lake Louis Criteria as increase of signal intensity in percent . For T1 The inversion-recovery gradient-echo sequence was evaluated for presence of hyperenhancement consistent with myocardial fibrosis. LGE volume was quantified as percentage of left ventricular myocardial using a cutoff signal intensity increase of more than five standard deviations of remote myocardium .U test was used for non-normal distributed variables. A p value ≤ 0.05 was regarded to be statistically significant.All data are reported as median value and interquartile range  in case of normal distributed values with mean and standard deviation. Mann–Whitney Results from all tests were considered exploratory, in keeping with the study design and therefore, no adjustment for multiple testing was done.The study group consisted of 20 patients with histologically proven IBM. 14 patients were scored as clinico-pathologically defined diagnosis and 6 patients as clinically defined IBM. Thirteen patients were treated with immunoglobulins (IVIG) every 6–8 weeks during the CMR acquisition, one of the patients was on therapy with corticosteroids and mycophenolate mofetil during the 3 months before CMR. All patients fulfilled the diagnostic ENMC criteria  at the tEchocardiography revealed normal diameters of the ventricles in all patients. The systolic function was not diminished in the visual evaluation with normal values of fractional shortening in 16/17 patients. Slight insufficiencies of the valves were reported in several patients. No pericardial effusions were reported. All other documented values were in the normal range despite an increase of left atrium diameter in 4/17 patients Table .Table 2RN = 11 at time of MRI). NT-proBNP  was abnormal in 3/15 patients, indicating myocardial insufficiency.Creatine kinase was elevated in 18/20 patients  and CKMB in 11/20 . Troponin I was normal in all patients tested  were in the normal range Table , but myoPatients with and without LGE did not differ significantly for all other variables.Patients with increased early myocardial enhancement or LGE did not show any statistical correlation with any reported laboratory value, echocardiographic parameters or any of the reported CMR analyses.Pericardial effusion without a hemodynamic restriction were detected in the same frequency as in healthy controls. The detected pericardial effusions in the CMR were not visible in the echocardiography.To the best of our knowledge, the current study is the first report of an IBM patient cohort using CMR for the detection of potential myocardial involvement. No significant abnormalities in the routine cardiac assessment with echocardiography could be found except slight valve insufficiencies in a majority of the patients.Cardiac evaluation of 20 IBM patients with CMR revealed reduced stroke volumes, while ejection fractions and left ventricular heart mass were normal. Since the heart scales with the size of the body and therefore with height and weight, we used the index of ventricular mass and volume as a ratio of body surface area (BSA) for comparison with controls (Index = mass/BSA or volume/BSA) . IndexesA confounding factor for this difference could be the treatment (most of cases with IVIG) in the IBM cohort compared to controls. The LGE prevalence did not relate to IVIG treatment.Though there are seven case reports with different cardiac abnormalities in IBM patients in the literature, there is only one cohort study with a systematic cardiac evaluation in 51 patients  and an eFor arterial hypertension, left ventricular hypertrophy and reduced stroke volumes due to afterload increase are well known –27.LGE may be attributed to unrecognized cardiac events  and hypertension , 29. SinIn summary, we therefore conclude that the apparent differences we found in heart ventricles and the detection of myocardial fibrosis are probably due to increased amount of arterial hypertension in our IBM cohort and not due to primary heart muscle inflammation.n = 65) [n = 18) reported arterial hypertension in 72% [It remains unclear if arterial hypertension is generally more common in IBM compared to healthy controls or if this is just a bias of the cohort sample size. In a survey on idiopathic inflammatory myositis and their comorbidities in Australia, the IBM subgroup also showed arterial hypertension in 65% (n = 65) . A Brazin in 72% .Any form of cardiac inflammation as reported in other inflammatory muscle diseases could be ruled out in IBM. This is well in accordance to the assumption that IBM differs from primary inflammatory muscle diseases.


Furthermore, z scores >2 were identified in 45%, 13%, 40%, 13%, and 70% of the GLS, LVMI, IVSd, LVPWd, and aortic diameter, respectively. The most severe GLS was observed in those with MPS VI, followed by in those with MPS II and MPS I. The GLS z score was positively correlated with the LVMI z score (p < 0.01). Moreover, diastolic dysfunction  ventricular filling velocity (E/A ratio < 1)) was identified in 12 patients (23%). Ejection and shortening fractions were abnormal in four (8%) and seven (13%) patients, respectively. Mitral regurgitation (MR) (92%) was the most common valvular heart disease, followed by aortic regurgitation (AR) (57%), mitral stenosis (MS) (21%), and aortic stenosis (AS) (15%). The z scores of the GLS and LVMI and severity scores of the MS, MR, AS, and AR were all positively correlated with increasing age (p < 0.05). Twenty patients (38%) had a left ventricular remodeling pattern. Conclusions: The most significant left ventricular myocardial deformation, hypertrophy and valvular heart disease were observed in the patients with MPS VI, II, and I, followed by those with MPS IV; in contrast, patients with MPS III had the mildest manifestations. Cardiac abnormalities in patients with MPS worsened with increasing age in accordance with the progressive nature of this disease.Background: Mucopolysaccharidoses (MPSs) are a group of rare inherited metabolic disorders that can damage various organs, including the heart. Cardiac abnormalities have been observed in patients with all MPS types, with the most documented abnormalities being cardiac valvular regurgitation and stenosis, valvular thickening, and hypertrophic cardiomyopathy. Methods: Cardiac features of 53 Taiwanese patients with MPS  were evaluated using two-dimensional speckle-tracking echocardiography and conventional echocardiography. Results: The mean  Mucopolysaccharidoses  are a group of rare inherited metabolic disorders resulting from a specific lysosomal enzyme deficiency associated with glycosaminoglycan (GAG) accumulation in various cells and tissues, leading to a progressive multiple organ dysfunction. The development of patients with MPS is usually unaffected at birth; however, multiple clinical manifestations may subsequently appear including coarse facial features, corneal clouding, hearing impairment, skeletal abnormalities, profound growth retardation, poor joint range of motion, hepatosplenomegaly, cardiac hypertrophy, and valvular heart disease. Seven major types of MPS disorders  consisting of 11 diverse enzyme deficiencies have been identified. All MPS disorders are inherited with an autosomal recessive pattern, except for MPS II, which is an X-linked trait that mainly affects men. Patients with various types of MPS generally have a wide clinical heterogeneity, ranging from attenuated to severe forms in MPS I , and Scheie syndromes), MPS II, and MPS VI .Patients with all MPS types suffer from cardiac abnormalities, including cardiac hypertrophy, cardiac valve thickening, and valvular regurgitation and stenosis. The deformed valves with mitral or aortic leaflet thickening and calcification may lead to valvular stenosis or regurgitation ,13,14,15Assessing myocardial strain using two-dimensional speckle-tracking echocardiography (2D STE) has been reported to be a reliable tool for identifying nascent myocardial injury, which is imperative in the early detection of subclinical cardiac dysfunction and prognosis of several cardiac diseases ,22. Long®, Genzyme Corporation, Cambridge, MA, USA), those with MPS II received 0.5 mg/kg/week intravenous idursulfase , those with MPS IVA received 2.0 mg/kg/week intravenous elosulfase alfa , and those with MPS VI received 1.0 mg/kg/week intravenous galsulfase . Written informed consent for cardiac evaluations was obtained from a parent if the patient was aged <18 years. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation  and with the Declaration of Helsinki of 1975, as revised in the year 2000. The Institutional Review Board of MacKay Memorial Hospital approved this study , and written informed consent was obtained from all of the patients or their parents who were included in the studyCardiac features of 53 patients with MPS  were evaluated using 2D STE and conventional echocardiography from December 2013 to December 2018 at MacKay Memorial Hospital. The diagnosis of MPS was confirmed by measuring the enzymatic activities of particular lysosomal hydrolases in leukocytes or skin fibroblasts using two-dimensional electrophoresis of the urinary GAGs and/or through mutational analysis ,30. PatiWe performed LV deformational imaging using baseline 2D STE from three LV apical views for longitudinal strain , as described in our previous work . We manu2 and a mean gradient < 30 mmHg; moderate AS = a valve area of 1.0–1.5 cm2 and a mean gradient of 30–50 mmHg; severe AS = a valve area < 1.0 cm2 and a mean gradient > 50 mmHg; mild mitral stenosis (MS) = a valve area > 1.5 cm2 and a mean gradient < 5 mmHg; moderate MS = a valve area between 1.0–1.5 cm2 and a mean gradient between 5–10 mmHg; and severe MS = a valve area < 1.0 cm2 and a mean gradient >10 mmHg. Because the frequency of physiological tricuspid regurgitation is high in the general population, we did not include tricuspid regurgitation as a pathological finding in this study.Echocardiography was performed using a Vividi system  equipped with a 2- to 4-MHz transducer (3S-RS) during the recruitment period of this study. Data were digitally stored and analyzed by one experienced cardiologist (CLH) to minimize any potential interobserver variations as described in our previous study . The lefz score >2 and RWT <= 0.42), and concentric hypertrophy (LVMI z score >2 and RWT >0.42) [z score with normal values according to the report by Foster et al. [We recorded data on left ventricular mass index (LVMI), interventricular septal end-diastolic dimension (IVSd), left ventricular posterior wall end-diastolic dimension (LVPWd), left ventricular end-diastolic dimension (LVIDd), and aortic diameter obtained by echocardiographic evaluations. The relative wall thickness (RWT) was calculated as (2×LVPWd)/LVIDd. Three patterns of LV remodeling were determined based on measurements of the LVMI and RWT, namely, concentric remodeling , eccentric hypertrophy (LVMI T >0.42) . Measurer et al. . These vr et al. .z score derived by subtracting the mean reference value from an individual observed value, then dividing the difference by the standard deviation from the reference value. A z score value between −2 and +2 was considered normal.All echocardiographic parameters were transformed into a r), and the significance was determined using the Fisher’s r–z transformations to obtain two-tailed p-values. All statistical analyses were conducted using SPSS version 11.5 , and any differences with a p < 0.05 were considered statistically significant.Sex, MPS type, age, height, weight, and the duration of receiving ERT at the time of echocardiographic assessments were recorded for each patient. Descriptive statistics, including the mean and standard deviation, of all echocardiographic parameters were calculated. The relationships between the age and various echocardiographic parameters were established using a Pearson’s correlation coefficient   (h MPS II . The GLS < 0.01) . Diastol < 0.01) . The z s < 0.05) . Twenty  < 0.05) .z score of >2 was observed in 45% of these patients. The findings of a GLS z score of >2 in the absence of LV ejection and shortening fraction abnormalities suggests that 2D STE is an early marker for LV dysfunction in patients with MPS. We demonstrated early stage systolic dysfunction using the more sensitive LV deformation parameter, GLS z score, which preceded global LV systolic dysfunction as traditionally assessed using LV ejection and shortening fractions. Additionally, we observed that the GLS z score as a measure of myocardial deformation was significantly associated with the LVMI z score and age. In addition, diastolic dysfunction (E/A ratio < 1) was identified in 12 patients (23%). MPS was related to myocardial deformation and more impaired diastolic function and a decline in the global LV systolic mechanics, despite globally preserved LV ejection and shortening fractions. These results were consistent with those of previous studies [To the best of our knowledge, this is the first study to delineate the cardiac structure and function of Asian patients with various MPS types in a single population using 2D STE and conventional echocardiography and compare the results with normal values, including young adults, based on the reports of Marcus et al.  and Kamp studies ,27,28.Conventional two-dimensional echocardiography is a clinically useful tool, however its use in determining the early stages of myocardial dysfunction is limited. In recent years, 2D STE imaging has been used to independently identify early stage LV dysfunction before conventional echo parameters become abnormal. Conventional echocardiography can detect overt global systolic dysfunction with regard to the reduced LV ejection fraction in patients with MPS; however, it is not sufficiently sensitive to identify early stage LV dysfunction. Diastolic function parameters may be useful; however, they are only indirect measures of LV contractile function and are considerably affected by hemodynamic load conditions. Accordingly, STE may help in the identification of early stage LV systolic dysfunction in patients with MPS before the development of obvious heart failure and is more reliable and practicable .z score of >2, whereas only 13% had an LVMI z score of >2. IVSd is related to the LVMI, and the clinical significance of an isolated increase in IVSd may be caused by a LV remodeling pattern in these patients. Our results revealed that the most significant LV myocardial deformation, hypertrophy, and valvular heart disease were observed in patients with MPS VI, II, and I, followed by those with MPS IV, and that patients with MPS III had the mildest manifestations. Deformed mitral or aortic valves with varying degrees of severity were commonly noted (92%) in our patients with MPS. In this cohort, mitral valve abnormalities (92%) were more prevalent than aortic valve abnormalities (57%), and valvular regurgitation (92%) was more common than valvular stenosis (28%), which is consistent with previous studies [All patients with MPS in the present study had cardiac abnormalities. Overall, 40% of these patients had an IVSd malities 7%, and v studies ,7,8. Thely noted 2% in our studies ,15,41.z score >2 in 70% of patients with all MPS types and 93% of those with MPS IVA). Routine screening for this potentially critical observation should be integrated into the multidisciplinary care of patients with MPS.Aortic root dilatation classically evolves through cystic medial degeneration and migration of the smooth muscle cells from the tunica media to the tunica intima with age . BolourcVentricular remodeling leads to alterations in the ventricular architecture with associated increases in volume and altered chamber configuration, thereby causing myocyte hypertrophy and apoptosis, myofibroblast proliferation, and interstitial fibrosis . Few repThe ERT for some MPS disorders appears to be effective in stabilizing or reducing cardiac hypertrophy, and better results may be associated with initiating the ERT at a younger age. There is currently no definitive evidence of the effects of ERT on valvulopathy ,13,14. HIn this study, there was no healthy control group to compare the echocardiographic parameters with those of our patients. Further, not all patients in our study cohort had echocardiographic data before the ERT. Consequently, we used reference values from a Caucasian population due to the lack of data from an Asian population, under the recognition that longitudinal strain values from single four-chamber may be highly consistent from those averaged from three planes based on the systemic review ,50. The Our results showed that a substantial proportion of patients with MPS had myocardial deformation, cardiac hypertrophy, aortic dilatation, and valvular heart disease. Assessing the LV function using 2D STE to evaluate myocardial deformation may help to stratify the risk of MPS. STE was more sensitive than global LV ejection fraction and fractional shortening, and its derived parameter, GLS, may prove especially useful in patients with subclinical LV dysfunction prior to the development of obvious systolic dysfunction. Cardiac abnormalities in our patients worsened with increasing age in accordance with the progressive nature of this disease. The most significant LV myocardial deformation, hypertrophy and valvular heart disease, were observed in patients with MPS VI, II, and I, followed by those with MPS IV, whereas those with the MPS III had the mildest manifestations. Despite the globally preserved LV ejection and shortening fractions, MPS was associated with myocardial deformation, more impaired diastolic function, and decline in the global LV systolic mechanics.


Myocardial native T1 and T2 relaxation time mapping are sensitive to pathological increase of myocardial water content . However, the influence of physiological hydration changes as a possible confounder of relaxation time assessment has not been studied. The purpose of this study was to evaluate, whether changes in myocardial water content due to dehydration and hydration might alter myocardial relaxation times in healthy subjects.A total of 36 cardiovascular magnetic resonance (CMR) scans were performed in 12 healthy subjects . Subjects underwent three successive CMR scans: (1) baseline scan, (2) dehydration scan after 12 h of fasting (no food or water), (3) hydration scan after hydration. CMR scans were performed for the assessment of myocardial native T1 and T2 relaxation times and cardiac function. For multiple comparisons, repeated measures ANOVA or the Friedman test was used.P > 0.05, respectively). T1 relaxation times were significantly reduced with dehydration . Similar results were observed for T2 relaxation times .There was no change in systolic blood pressure or left ventricular ejection fraction between CMR scans (Dehydration may lead to significant alterations in relaxation times and thereby may influence precise, repeatable and comparable assessment of native T1 and T2 relaxation times. Hydration status should be recognized as new potential confounder of native T1 and T2 relaxation time assessment in clinical routine. Myocardial native T1 and T2 mapping allow for a non-invasive quantification of myocardial tissue alterations across a broad range of myocardial diseases in patients eligible for cardiovascular magnetic resonance (CMR) imaging , 4. Aparnormal scan) was performed during the morning hours. Participants were allowed to have normal breakfast at home, but coffee intake was restricted. Also, they were told not to ingest significant amounts of water prior to the baseline scan. After 12 h of fasting (no access to food or water) another scan was performed (dehydration scan). The last scan was performed after adequate hydration (hydration scan). After the end of fasting each participant was offered a standardized small cheese sandwich. For hydration, the participants were instructed to drink 1.5 l of still water within 15 min. Drinking was supervised by a study team member. The hydration scan was started 15 min after fluid intake to allow water absorption. For all participants the scans were performed at 1 day. Blood pressure measurements and laboratory markers were obtained directly prior to every scan. Blood samples were promptly transported to the central laboratory and were immediately analyzed. A visualized description of the study protocol is presented in Fig. The institutional review board approved this prospective study and all subjects gave written informed consent. The study population consisted of healthy subjects without known cardiovascular disease and without cardiovascular disease risk factors. All subjects had an unremarkable past medical history of cardiovascular disease. Electrocardiographic results prior to CMR were unremarkable. All control participants had normal CMR results without structural abnormalities or wall motion abnormalities. To assess possible influences of hydration status on native T1 and T2 relaxation time measurements, three separate CMR scans were performed in each participant: The baseline scan . A 32-channel torso coil with digital interface was used for signal reception. For functional and myocardial strain analysis, electrocardiographic-gated balanced steady-state free precession cine images were obtained in short-axis, four-chamber, and two-chamber views. Scan parameters for short-axis cine imagines were: time of repetition 2.8 ms, time of echo 1.38 ms, flip angle 60°, parallel imaging factor 3, acquired voxel size 1.79 × 2 × 8 mm, reconstructed voxel size 0.99 × 0.99 × 8 mm, scan duration/breath hold 13.0 s, cardiac phases per RR interval 40. Native T1 and T2 mapping were performed in end-diastole in short-axis views. For myocardial T1 and T2 mapping, one midventricular section was acquired. For myocardial T1 mapping, an optimized native 5(3 s)3 modified Look-Locker inversion recovery (MOLLI) acquisition scheme was used . FollowiImage analysis was performed by two radiologists experienced in CMR (J.A.L. (reader 1) and D.T. (reader 2)). Readers were blinded to the scan and personal data. CMR analyses were performed offline by using dedicated software . Myocardial native T1 and T2 relaxation maps were reconstructed offline by using a software-implemented motion-correction algorithm (fast elastic image registration). Myocardial contours were drawn throughout the T1 and T2 maps to investigate the entire midventricular myocardium, and mean midventricular T1 and T2 relaxation times were calculated. For intra- and inter-reader reproducibility measurements all relaxation time measurements were performed by reader 1 and 2 and were repeated by reader 1. Inter-study reproducibility measurements were performed by reader 1.t test. For multiple comparisons, repeated measures one-way analysis of variance (ANOVA) followed by Tukey’s multiple comparison test or the nonparametric equivalent (Friedman test followed by Dunn’s multiple comparisons test) were used where appropriate. Intra- and inter-rater reproducibility of T1 and T2 mapping measurements was assessed using intraclass correlation coefficient (ICC) estimates. ICC estimates and their 95% confident intervals (CI) were based on a single measurement, absolute-agreement, 2-way mixed-effects model. Single measure coefficients are reported. Bland Altman analysis was also used to assess agreement and bias among T1 and T2 mapping measurements. The level of statistical significance was set to P < 0.05.Prism  and SPSS Statistics  were used for statistical analysis. Subject characteristics are presented as mean ± standard deviation or as absolute frequency. Kolmogorov-Smirnov test was used for the assessment of normality. Continuous variables between two groups were compared by using Student P = 0.063). Mean body mass index was 22.9 ± 3.5 kg/m2 . All participants completed the study protocol. Structural CMR results were normal for all participants.A total of 12 healthy subjects were enrolled . Mean age was 25.8 ± 3.2 years , red blood cell count , and platelet count  in dehydration. Hematocrit levels were significantly elevated during the dehydration scan . Also, magnesium electrolyte level was increased in dehydration . All other laboratory results are given in the Table As a sign of the lack of water intake, we found significantly increased levels of white blood cell count . Native T1 relaxation times were significantly reduced in dehydration . Similar results were observed for T2 relaxation times   of native T1 and T2 mapping measurements revealed good or excellent results: T1 (intra): 0.969, 95% CI: 0.940–0.984; T2 (intra): 0.808, 95% CI: 0.657–0.897; T1 (inter): 0.962 95%, CI: 0.926 to 0.980; T2 (inter): 0.924 95%, CI: 0.856 to 0.961. Bland Altman analysis showed a low bias for T1 (intra-observer: − 0.2 ± 7.1 ms (95% limits of agreement: − 14.1 - 13.7 ms); inter-observer: − 1.1 ± 8.0 ms (95% limits of agreement: − 16.7 - 14.6 ms)) and T2 measurements (intra-observer: 0.1 ± 1.2 ms (95% limits of agreement: − 2.3 - 2.6 ms); inter-observer: 0.0 ± 0.84 ms (95% limits of agreement: − 1.6 - 1.7 ms)) . Bland Altman analysis showed low bias for inter-study reproducibility (T1: 1.0 ± 6.6 ms (95% limits of agreement: − 11.9 - 13.8 ms); T2: − 0.6 ± 0.5 ms (95% limits of agreement: − 1.6 – 0.4 ms)).In this prospective study, we evaluated whether differences in hydration status in healthy subjects could influence the assessment of myocardial native T1 and T2 relaxation times. The main finding of this study is that myocardial native T1 and T2 values were significantly reduced in dehydration, indicating an influence of hydration status on relaxation time assessment. Therefore, hydration status might be a confounder of native T1 and T2 mapping.Dehydration (deficit of body water) is a general physiological condition that can have profound effects on human health . Mild deAlthough different tissues with similar water content have been shown to have significantly different native T1 and T2 relaxation time , to someAlthough differences in myocardial native T1 relaxation times after dehydration compared to baseline were rather small (mean difference: 19 ± 19 ms), the mean difference was higher than the 95% of agreement of inter- and intra-observer and the inter-study reproducibility measurements, indicating a potential important effect when evaluating relaxation times in a clinical setting. However, the influence of dehydration in a clinical context has not been evaluated yet. According to a consensus statement about the clinical use of CMR mapping, local reference ranges for myocardial mapping should be obtained from healthy subjects and only values below or above two standard deviations should be considered as pathological . HoweverBecause of the explorative study design, our study has several limitations. Our study population consisted of healthy young subjects with a low to normal body mass index. Therefore, our results may not be directly transferable to patient cohorts. Although the applied 53 s)3 MOLLI sequence has a reduced sensitivity to heart rate compared to the original MOLLI scheme  s3 MOLLI. BetweenHydration status may influence myocardial native T1 and T2 relaxation time. In our study, dehydration led to significant alterations in relaxation times and therefore may influence precise or repeatable assessment of native T1 and T2 relaxation times. Hydration status should be recognized as new potential confounder of T1 and T2 relaxation time assessment in clinical routine. Future studies should assess the influence of dehydration on CMR relaxation time measurements in a clinical setting.