T1 and T2 maps and cine images, enabling a ∼3‐min scan.To introduce non‐rigid cardiac motion correction into a novel free‐running framework for the simultaneous acquisition of 3D whole‐heart myocardial T2‐preparation pulses. After correction for translational respiratory motion, non‐rigid cardiac‐motion‐corrected reconstruction with dictionary‐based low‐rank compression and patch‐based regularization enabled 3D whole‐heart T1 and T2 mapping at any given cardiac phase as well as whole‐heart cardiac cine imaging. The framework was validated and compared with established methods in 11 healthy subjects.Data were acquired using a free‐running 3D golden‐angle radial readout interleaved with inversion recovery and T1 and T2 maps and cine images were reconstructed for all subjects. Septal T1 values using the proposed approach (1200±50 ms) were higher than those from a 2D MOLLI sequence (1063±33 ms), which is known to underestimate T1, while T2 values from the proposed approach (51±4 ms) were in good agreement with those from a 2D GraSE sequence (51±2 ms).Good quality 3D T1 and T2 maps and cine images with isotropic spatial resolution in a single ∼3.3‐min scan.The proposed technique provides 3D  ADMMalternating direction method of multipliersCGconjugate gradientCMRcardiac magnetic resonanceECGelectrocardiogramEDVend‐diastolic volumeEFejection fractionESVend‐systolic volumeHD‐PROSThigh‐dimensionality undersampled patch‐based reconstructionIRinversion recoveryLGElate gadolinium enhancementLRIlow‐rank inversionLRMClow‐rank motion‐correctedLVleft ventricularMRFmagnetic resonance fingerprintingNUFFTnonuniform fast Fourier transform1T1 and T2 maps), measurements of cardiac function (cine), late gadolinium enhancement (LGE) images and perfusion images, among possible others. In this work, we consider an undersampled respiratory‐ and cardiac‐motion‐corrected simultaneous acquisition of 3D whole‐heart T1 and T2 maps and cine images at isotropic spatial resolution, pushing CMR closer toward the goal of a short and comprehensive CMR exam.Cardiac magnetic resonance (CMR) is an important imaging modality that allows for the noninvasive assessment of myocardial disease and cardiac function.T1 mapping) and GraSET2 mapping) use data acquired during breath hold and at a single cardiac phase via electrocardiogram (ECG) triggering. In these methods, parameter maps are generated independently by fitting a series of weighted images to exponential relaxation curves on a pixel‐ or voxel‐wise basis.Established gold standard sequences for 2D myocardial mapping such as MOLLIT1 and T2 myocardial maps in a single breath hold,T1 and T2 mapping in a single breath hold.Methods that jointly acquire both The reliance of each of these methods on ECG triggering generally means they are limited to providing maps at a set cardiac phase  and exhibit reduced scan efficiency relative to free‐running sequences.T1 mapping and cine imaging has been achieved through the use of continuous data acquisition and the retrospective sorting of the acquired data to cardiac phases.T1 mapping and cine imaging to include T2 mapping,Single‐breath‐hold simultaneous 2D Jaubert et al.T1 and T2 mapping across multiple cardiac phases, via the reconstruction of a low‐rank multidimensional image tensor that includes both respiratory‐ and cardiac‐motion dimensions.The novel multitasking framework≥ 8 mm. Hence, they do not provide isotropic whole‐heart coverage and may be subject to through‐plane motion artifacts.The studies considered thus far have mostly considered 2D slices, usually with slice thickness T1 and T2 methods,≥8 mm) and do not simultaneously provide cine images like their 2D counterparts.Various approaches for 3D myocardial mapping with whole‐heart coverage have been proposed,T1 and T2 maps and cine images with isotropic spatial resolution and whole‐heart coverage using LRI with HD‐PROST reconstruction. In that study, interleaved inversion recovery (IR) and T2‐preparation (T2‐prep) pulses were combined with a free‐running 3D golden‐angle radial acquisition and translational respiratory motion correction, and 3D T1 and T2 maps and cine images with 2‐mm isotropic spatial resolution were achieved. However, since the k‐space spokes were sorted into cardiac phases using ECG gating, only a fraction of the acquired data was used in the reconstruction of each phase, resulting in a relatively long scan time of ∼11 min to ensure sufficient image quality.Recently, Qi et al.T1 and T2 maps and cine images in ∼3.3 min.To significantly reduce the scan time, we propose to incorporate non‐rigid cardiac motion correction22.1T2‐prep pulses to provide sufficient T1 and T2 encoding, as introduced by Qi et al.T2‐prep pulse with an echo time of 30 or 60 ms.Data were acquired using a low‐flip‐angle spoiled gradient echo readout with a 3D golden‐angle radial trajectory, interleaved with IR and 2.2The proposed reconstruction framework consisted of three main steps: (1) translational respiratory motion correction; 2) estimation of non‐rigid cardiac motion from motion‐resolved low‐rank inversion (LRI) estimati2.2.1dth bin, a 3D translation vector Td=Txdx^+Tydŷ+Tzdz^ was estimated, representing the respiratory shift between that bin and the end‐expiration reference bin. A unique translation vector for each k‐space spoke was derived by linearly interpolating those vectors corresponding to the nearest bin centers on either side of the spoke's respiratory signal value. k‐Space spokes with a respiratory signal outside the minimum and maximum bin‐center values were assigned the translation vector of the nearest bin center. Finally, each k‐space spoke was corrected for translational respiratory motion by applying the phase shiftbjm is the uncorrected value of the k‐space sample at position j along the mth spoke, b^jm is the corrected value, kjm is the 3D position vector representing the k‐space location of that sample, and Tm is the translation vector for the mth spoke.Independent component analysis was applied to the k‐space center (acquired in every spoke) to extract a 1D respiratory signal.2.2.2Auxiliary cardiac‐motion‐resolved images were reconstructed using the LRI approach with HD‐PROST regularization to estimate 3D non‐rigid cardiac motion fields. These reconstructions are equivalent to those previously reported by Qi et al.,Alongside the respiratory‐motion‐corrected k‐space data, the LRI+HD‐PROST reconstruction required the input of a dictionary‐compression matrix, coil sensitivity maps, and sampling‐density compensation weights.Nt×ND dictionary D was created by simulating the signal evolution for ND different combinations of T1 and T2 values in the physiological range at Nt discrete time points corresponding to the spoke‐acquisition times in the sequence. An SVD of the dictionary yields D=USV∗, where U∈ℂNt×Nt and V∈ℂND×ND are unitary matrices, S∈ℝNt×ND is a diagonal matrix containing the singular values of D in descending order, and ∗ denotes the conjugate transpose. If Ur is defined as a sub‐matrix of U containing only the first r columns, then its conjugate transpose Ur∗ forms the dictionary‐compression matrix, which compresses the dictionary D such that each entry now contains the first r singular contrasts instead of every acquired contrast.The N voxels, Nc coils, r singular contrasts, and Kq k‐space samples at the qth cardiac phase, ρ∈ℂNr×1 is the multi‐singular‐contrast 3D image vector being solved for; kq∈ℂKqNc×1 is the vector of translational‐motion‐corrected multi‐coil k‐space data at the qth cardiac phase; Wq∈ℝKqNc×KqNc is a diagonal matrix of radial sampling‐density compensation weights; 𝒯p is the HD‐PROST tensor of patches similar to the patch centered at the pth voxel; Pp is a patch selection operator; Y is the augmented Lagrangian; λ and μ are penalty weightings; ∗ and F denote the nuclear and Frobenius norms, respectively; andS∈ℂNNcr×Nr, the estimated 3D coil sensitivity maps, Fq∈ℂKqNcr×NNcr, the nonuniform Fourier operator that transforms the 3D image of each coil and each singular contrast to a corresponding 3D radial k‐space with only those spokes acquired at the qth cardiac phase, and Urq∈ℝKqNc×KqNcr, which contains the dictionary‐compression weights that relate the singular contrasts to the T1 and T2 weighting of the contrast that each spoke (in the qth phase) was acquired with.LRI with HD‐PROST regularization was employed to reconstruct each cardiac phase by minimizing𝒯p, as described in detail by Bustin et al.Equation  was solvEq∗Eq, to be replaced with efficient 3D FFT operations on a grid with dimensions equal to twice the image size. The requisite initial evaluation of Eq∗Wqkq was achieved using NUFFTTo accelerate the iterative reconstruction, the Toeplitz approachT1 and T2 maps generated from the auxiliary cardiac‐motion‐resolved images via dictionary matching  k‐space data to be utilized in the reconstruction of each cardiac phase Figure , as in t2.2.4T1 and T2 maps were obtained from the output cardiac‐motion‐corrected multi‐singular‐contrast image at any given cardiac phase via voxel‐wise dictionary matching  were recruited with approval from the local institutional review board and written informed consent was given by all subjects prior to scanning.× 200 mm × 200 mm, spatial resolution = 2 mm × 2 mm × 2 mm, flip angle = 6°, spokes per shot = 195, shot interval = 2200 ms, TR= 10.3 ms, TE= 4.6 ms, Tgap= 9.5 ms (time between preparatory pulses and first readout), Tex= 182 ms (recovery time between last readout and next preparatory pulse).The proposed free‐running sequence was implemented for all subjects on a 1.5‐T scanner  using a 28‐channel cardiac coil and the following imaging parameters: FOV (with two‐fold readout oversampling) = 200 mm A “full” scan consisted of 300 shots and thus had an 11‐min scan time. Any subsequent undersampling was performed retrospectively by utilizing only the first shots acquired in the sequence.T1 maps) and 2D GrASE (T2 maps) scans at diastole and conventional 2D cine scans were performed, each in the mid‐short‐axis slice orientation.For comparison, 2D MOLLI  parameters were as follows: FOV = 288 mm × 288 mm, spatial resolution = 2 mm × 2 mm, slice thickness = 8 mm, flip angle = 90°, TR= 1 heartbeat, ΔTE= 8.8 ms, turbo spin‐echo factor = 9, echo‐planar‐imaging readout factor = 7, double IR black‐blood prepulse.The 2D GraSE parameters were as follows: FOV = 288 mm × 320 mm, spatial resolution = 0.95 mm × 0.95 mm, slice thickness = 8 mm, 12 slices, flip angle = 60°, TR= 3.0 ms, TE= 1.5 ms, 20 cardiac phases.Additionally, multi‐slice 2D cine scans were performed for five subjects with short‐axis slices covering the left ventricle. Parameters for these scans included: FOV = 320 mm 2.4r=3 singular contrasts were utilized and data were assigned to 16 cardiac phases.LRI (cardiac‐motion‐resolved) and LRMC (cardiac‐motion‐corrected) reconstructions at the diastolic phase were implemented for two subjects with and without HD‐PROST regularization and using four different amounts of data corresponding to different effective scan times: 100% of acquired data , 50% , 30% , and 20% . We note that LRI+HD‐PROST reconstructions at every phase were required for the estimation of the motion fields used in the LRMC+HD‐PROST reconstruction at diastole. For both reconstructions, Analysis of these results (reported below) led to the choice of 30% of the spokes as our proposed acceleration. Hence, for all subjects, LRI and LRMC reconstructions with HD‐PROST were implemented using 100% and 30% of the acquired data at all phases, allowing both diastolic parameter mapping and 3D cine imaging.L2 displacement norm), and 0.01 (Jacobian determinant). Parameters of the HD‐PROST regularization were as follows: patch size = 5 × 5 × 5, maximum number of similar patches = 20, search window size = 20 × 20 × 20, λ=750, μ=0.02. Parameters of the ADMM iteration were as follows: number of ADMM iterations = 4, number of CG iterations per ADMM iteration (LRI) = 9, number of CG iterations per ADMM iteration (LRMC) = 3.Parameters of the NiftyRegNt=385 discrete time points corresponding to the 195 spoke‐acquisition times in each of the three shots. A total of 138 T1 values (between 200 and 3000) and 303 T2 values (between 10 and 200) were considered, resulting in ND=41 814 total entries.Dictionary entries were calculated at the Coil sensitivity maps were estimated for each cardiac phase using Walsh's method.2.52.5.1The mean and standard deviation of septal parameter values in a given map were determined by manually segmenting the septum in mid‐short‐axis slices and considering the values of pixels located in that region.Further analysis of the 3D parameter maps was performed via the manual segmentation of the left ventricular (LV) wall into the 16 segments of the American Heart Association (AHA) standard.2.5.2End‐diastolic volume (EDV), end‐systolic volume (ESV), and ejection fraction (EF) measurements were used to compare the 3D cine images from different amounts of acquired data and the multi‐slice 2D cine images (where those scans were available).EDV and ESV values were determined via a manual slice‐by‐slice segmentation of the left ventricle at diastole and systole, respectively. The EF was then calculated as3T1 maps and T2 maps, respectively, for one representative subject, produced using the LRI (cardiac‐motion‐resolved) and LRMC (cardiac‐motion‐corrected) reconstruction schemes both with and without HD‐PROST regularization and with varying percentages of the total acquired data. In all cases, the reconstructions without HD‐PROST exhibit noise‐like artifacts that tend to increase in severity with increased undersampling. Comparing the images and maps achieved with HD‐PROST at each data percentage visually, the motion‐corrected reconstructions appear to have sharper features, notably around the septum and papillary muscles. As the number of spokes incorporated in the reconstruction is reduced from 100% to 20%, the quality of the LRI images and maps significantly decreases and blurring becomes evident, whereas the LRMC reconstruction appears to be more robust.Figures T1 and T2 map  and 68 ms (20%). Additionally, the mean septum T1 values increase to values in the range of 1200–1400 ms for both LRI reconstructions at low data percentages, whereas the means recorded with the LRMC reconstructions remain in the 1100–1250 ms range.The standard deviation of the T2 maps, and although the LRI+HD‐PROST reconstructions here appear more robust to undersampling, they are still outperformed by LRMC+HD‐PROST. The standard deviation of the T2 septum values increases from 13.2 to 27.8 ms with decreasing acquired data for the LRI reconstructions without HD‐PROST and is in the range of 7–9 ms for all LRMC reconstructions without HD‐PROST. Comparatively, the standard deviation of ∼3 ms recorded for both LRI+HD‐PROST and LRMC+HD‐PROST reconstructions using 100% of the acquired data is maintained down to 20% of the data.Similar trends are evident in the Singular‐contrast images and parameter maps for a second subject are presented in Supporting Information Figures Balancing the desire to minimize the amount of acquired data, and hence the effective scan time, with the consequent reduction in image quality, we select an undersampling to 30% of the acquired spokes  as our proposed acceleration for further evaluation of the LRMC method. Note that HD‐PROST is utilized in all the results that follow.3.1T1 and T2 maps for two representative subjects reconstructed using the proposed technique and 30% of the acquired data are presented alongside the 2D maps at mid‐short‐axis produced using the conventional methods MOLLI and GraSE in Figure Diastolic T1 and T2 values in the septum are plotted in Figure T1 value for MOLLI (1063±33 ms) is lower than that achieved using the previous LRI+HD‐PROST method with 100% of the acquired data (1237±45 ms) or the proposed LRMC+HD‐PROST method with 30% of the data (1200±50 ms). The Bland–Altman plot in Figure T1 values.T1 values in each septum region is slightly higher with the 3D approaches  than with MOLLI (62±15 ms).For a quantitative comparison between the proposed and existing methods, the mean and standard deviation of the T2values  and the 2D GraSE sequence (51±2ms), and a difference of 0 ms is seen to be within the 95% confidence interval on the Bland–Altman plot in Figure 4.5±1.0 ms) slightly more precise than the LRMC+HD‐PROST technique with 30% of data (5.5±1.4ms).The equivalent plots for the  Figure  indicatT1 and T2 values in the maps reconstructed using the proposed LRMC+HD‐PROST approach are presented in Figure T1 and T2 segment values over all 11 subjects, for all of the 3D reconstructions considered (LRI+HD‐PROST and LRMC+HD‐PROST with 30% and 100% of the acquired data). The T1 standard deviation across all segments and subjects for 30% LRMC+HD‐PROST was 84±24 ms, which compares to 105±32 ms for 30% LRI+HD‐PROST. For T2, the standard deviation across all segments and subjects was similar for all four methods: 5.5±2.1 for 100% LRI+HD‐PROST, 5.5±2.0 ms for 30% LRI+HD‐PROST, 5.9±2.7 ms for 100% LRMC+HD‐PROST, and 5.4±1.7 ms for the proposed 30% LRMC+HD‐PROST.Bullseye plots of the myocardial 3.2Frames from the mid‐short‐axis slice of the 3D cine images for two subjects, reconstructed using the proposed approach with 30% of the acquired data, are presented alongside frames from the conventional 2D cine images acquired for those subjects in Figure 50.6±2.4% and 53.7±3.5%, respectively) is lower than that from the multi‐slice 2D cines (60.6±5.2%) or LRI+HD‐PROST with 30% or 100% of acquired data . We note that the higher EF values obtained with 30% LRI+HD‐PROST compared with 30% LRMC+HD‐PROST are despite the poorer quality images and maps produced by this method, as seen in Figures −8.9% relative to multi‐slice 2D.Quantitative indicators of cardiac function are presented in Figure 4T1 and T2 mapping and cine imaging with isotropic spatial resolution in a single ∼3‐min scan via the incorporation of non‐rigid cardiac motion correction alongside low‐rank dictionary compression and patch‐based regularization. The scan is easy to plan, free‐breathing, achieves 100% scan efficiency due to its continuous acquisition scheme, and represents a significant step toward an easy‐to‐use and comprehensive whole‐heart CMR exam. The proposed reconstruction method was successfully applied for 11 subjects and compared to the results of conventional 2D mapping sequences and cine images and the previously proposed cardiac‐motion‐resolved methodWe have presented a framework that allows joint 3D whole‐heart myocardial T2 values achieved using the proposed technique and the 2D GraSE scans. Higher T1 values were observed than with the conventional MOLLI T1‐mapping sequence; however, the latter is known to underestimate T1. For both T1 and T2 parameter maps, the standard deviations recorded within the septum . Since the 2D multi‐slice cine consists of 8‐mm‐thick slices, its ESV and EDV measurements are based on more‐discretized volume segmentations, and in some cases, the most apical or basal slice may not be acquired. A more direct comparison between the 3D and 2D cine images can be performed by estimating ESV and EDV from the 3D reconstructions using only those slices that match the slices in the multi‐slice cine, that is, every fourth 2‐mm‐thick slice. Using this measurement, the 100% LRI+HD‐PROST EF bias is reduced from −2.3% to −0.7% and the EF bias of the proposed 30% LRMC+HD‐PROST method is reduced from −8.9% to −6.9%. Bland–Altman plots comparing EF measurements using this “matched slice” approach are included in supporting information Figure However, motion field quality is not entirely sufficient to explain the bias in cardiac function measurements. Relative to multi‐slice 2D cine, the 100% motion‐resolved LRI+HD‐PROST reconstructions record a mean EF bias of Future work will consider whether the current motion field quality limitations can be overcome by the implementation of more‐advanced motion estimation methods. For example, several deep learning‐based techniques have recently been proposedAnother limitation of the cine comparison is that the conventional cine images were acquired with only 16 frames (single slice) or 20 frames (multi‐slice), in order to match the 16 frames used in the 3D approach. To compare cardiac function evaluation more accurately, a fuller comparison between the 3D approach and a standard 2D cine with more frames is needed in future studies.T1 and T2 mapping techniques at a single cardiac phase,The 3.3‐min scan time of the proposed method compares favorably not only to the 11‐min time of the previous motion‐resolved reconstructionAdditionally, while the results are pre‐contrast, the framework also has the potential to be applied post‐contrast and used in the generation of synthetic LGE images.∼8 h, with an additional ∼2 h required for the LRMC+HD‐PROST reconstruction of each cardiac phase. Future improvements including code optimization, GPU‐based implementations, and the use of deep‐learning networks to replace certain steps could provide the necessary acceleration for clinical feasibility.A limitation of the proposed framework is the current long computational time. Using 30% of the acquired data, the LRI+HD‐PROST reconstruction at all 16 cardiac phases took Currently, the proposed technique has only been validated in a small and healthy sample size (11 subjects). A larger study including patients with myocardial disease is thus warranted.5T1 and T2 myocardial maps and cine images with isotropic spatial resolution, enabling the acceleration of the scan time from 11 to 3.3 min. Three‐dimensional T1 and T2 maps and cine images with good image quality were generated for 11 healthy subjects. The proposed 3D radial sequence and LRMC+HD‐PROST reconstruction is thus a promising step toward a quick, simple, and comprehensive whole‐heart CMR exam.In this study, non‐rigid cardiac motion correction was incorporated into a free‐running framework for the simultaneous acquisition of 3D whole‐heart The authors acknowledge financial support from the BHF PG/18/59/33955, EPSRC EP/V044087/1, EP/P001009/, EP/P032311/1, and EPSRC EP/P007619, Wellcome EPSRC Centre for Medical Engineering (NS/A000049/1), Fondecyt 1210637 and 1210638, Millennium Institute for Intelligent Healthcare Engineering iHEALTH ICN2021_004.Figure S1. Mid‐ventricular short‐axis slices of the 3D second‐singular‐contrast images produced by different reconstruction methods and utilizing different amounts of k‐space data for a second representative subject.Figure S2. Mid‐ventricular short‐axis slices of the 3D T1 maps produced by different reconstruction methods and utilizing different amounts of k‐space data for a second representative subject. The mean and standard deviation of the T1 value in the septum region are given in the corner of each panel.Figure S3. Mid‐ventricular short‐axis slices of the 3D T2 maps produced by different reconstruction methods and utilizing different amounts of k‐space data for a second representative subject. The mean and standard deviation of the T2 value in the septum region are given in the corner of each panel.Figure S4. Bland–Altman plots comparing the ejection fraction (EF) measured from the 3D LRMC+HD‐PROST and LRI+HD‐PROST reconstructions with that measured from the conventional multi‐slice 2D cine. (A–C) The 3D‐reconstruction EF is measured via the manual segmentation of every 2‐mm‐thick slice covering the left ventricle. (D–F) Every fourth 2‐mm‐thick slice  is used.Figure S5. Bland–Altman plots comparing end‐systolic volume (ESV), end‐diastolic volume (EDV), and ejection fraction (EF) measured from LRMC+HD‐PROST reconstructions using 30% of the acquired data, 100% of the acquired data, or a mixed reconstruction utilizing 30% of the acquired data but the motion fields estimated from the LRI+HD‐PROST reconstruction with 100% of the acquired data (11 subjects).Click here for additional data file.Video S1. Video of the mid‐short‐axis 2D cine and the 3D cine at three slices for each of three slice orientations for one representative subject.Click here for additional data file.


Background: Cardiovascular disease starts early in the course of chronic kidney disease (CKD) and is the leading cause of death in patients with end-stage renal disease. Since high-sensitivity cardiac troponin T (hs-cTnT) can detect much lower levels of myocardial injury than conventional assays, it may be useful for studying the earliest stages of heart disease in patients with CKD.Objective: To evaluate the association of circulating hs-cTnT with LV structural and functional abnormalities detected by echocardiography among dialysis dependent and non-dialysis dependent CKD patients.Methods: This study was conducted on 107 subjects divided into three groups.n = 42), Group II: hemodialysis patients (n = 42), Group III: control group: age and sex matched healthy volunteers (n = 23). All subjects were subjected to clinical examination, biochemical evaluation including estimation of hs-cTnT and Echo-Doppler study of cardiac structure and function.Group I consisted of CKD patients on conservative treatment (p < 0.01), LVM (p < 0.01) in both patient groups compared to the control group. Mitral annular plane systolic excursion (MAPSE) was significantly decreased in both patient groups compared to the control group  and in group I compared to group II (p < 0.05) with a significant decrease in S velocity in group I compared to groups II and III (p < 0.01). There was a significant decrease in Vp (p < 0.01) with a significant increase in AEF (p < 0.01) in both patients’ groups compared to the control group and AEF was significantly increased in group II compared to group I (p < 0.01). Ea velocity and Ea/Aa decreased significantly (p < 0.01) with significant increase in Aa velocity , E/Ea (p < 0.01) and E/Vp (p < 0.05) in both patient groups compared to the control group.Results: There was a significant increase in LAV (P < 0.01). We found a positive correlation between hs-cTnT levels and LAV , IVST , PWT , LVM , A wave velocity , E/Ea , PCWP  and a negative correlation between hs-cTnT and MAPSE , S wave velocity , Ea , Ea/Aa .There was a significant increase in hs-cTnT levels in both patient groups compared to the control group (P < 0.01) for discrimination of Group I vs control group and 76.2% sensitivity and 95.7% specificity with AUC 0.796 and accuracy 71.84% (P < 0.01) for discrimination of group II vs control group.Troponin at the cut-off value of >5 ng/L, revealed 100% sensitivity and 95% specificity with areas under curve (AUC) of 0.998 and accuracy of 95.65% (Conclusion: Structural and functional cardiac abnormalities are common in CKD patients. Serum hs-cTnT levels increased in CKD patients and was associated with LVH, LAV and some of the echocardiographic parameters of LV systolic and diastolic dysfunction.Our research suggests that hs-cTnT levels may be important for early screening of cardiac structure and function in CKD patients to provide evidence for early intervention. Left ventricular hypertrophy (LVH), left ventricular (LV) dilatation, and cardiac systolic or diastolic dysfunction are present in most CKD patients starting dialysis, predisposing them to an increased risk of ischemic heart disease (IHD), heart failure, or cardiac death2.The major cause of death in patients with end-stage renal disease (ESRD) is cardiovascular disease (CVD), which begins early in the course of chronic kidney disease (CKD)3. Doppler imaging can provide indirect information about LV relaxation and diastolic function. The assessment of LV function has been improved by the use of tissue Doppler imaging (TDI)4.Echocardiographic studies may play a critical role in evaluating cardiac structure and function. Two-dimensional (2D) and M-mode echocardiographic images are capable of assessing LV geometry, quantifying LV mass and systolic function5. Therefore, it is important to investigate serum biomarkers for early assessment of cardiac structure and function in CKD patients, to provide evidence for early intervention.Many traditional cardiac risk factors, as well as non-traditional risk factors specifically associated with renal disease , can be modified by aggressive therapy. In addition, detecting cardiac disease at an early stage would facilitate aggressive treatment of patients at increased risk6.Cardiac troponin T (cTnT) and troponin I (cTnI) are integral parts of cardiac muscle infrastructure and play a major role in excitation-contraction coupling7.Cardiac myocyte membrane damage leads to the release of cardiac troponins into circulation, which can be detected by specific immunoassays developed for these proteins (TnT and cTnI)8. Previous studies reported that the level of serum hscTnT was higher in CKD patients than in non-CKD patients9. Some studies have suggested that hscTnT can be used to evaluate cardiac structure and function abnormalities in CKD patients9–13. However, these studies are sparse and have led to different conclusions.New high-sensitivity cardiac troponin (hscTnT) assays have been developed with detection limits 10–100 times lower than those detected by traditional methodsTherefore, we carried out the following research to evaluate the association of circulating hs-cTnT with LV structural and functional abnormalities, as detected by echocardiography, among dialysis-dependent and non-dialysis-dependent CKD patients.This study was conducted on 107 subjects . The subjects were divided into three groups: •n = 42).Group I: Patients with CKD on conservative treatment ( •n = 42), 3x per week in 4-hour sessions for more than 6 months.Group II: Patients with CKD on regular hemodialysis (HD) ( •n = 23).Group III: control group .Written informed consent was obtained from all patients. The study protocol was in accordance with the declaration of Helsinki 1975 as modified in 2012, and approved by the institutional review board of TBRI before enrolling participants.Routine laboratory investigations including kidney function tests, serum electrolyte and lipid profiles were assayed with a Beckman Coulter AU 480 autoanalyzer . A complete blood picture was assayed with Swelab Alpha Plus .High-sensitivity cardiac troponin T was determined using the cTnT 4th-generation electrochemiluminescent immunoassay “ECLIA” on Cobas e411 immunoassay autoanalyzer according to the instructions of the manufacturer . The analytical measurement range was 3 to 10.000 pg/mL.In the hemodialysis group (II), blood samples were taken before the dialysis session.14,15 by two members of the study team using a high resolution (x11-15305) Sonata Plus ultrasound scanner.Echo-Doppler was performed on all subjects according to ASE/EACVI recommendations• Measurements of the dimensions of the left ventricle and its walls were performed in the parasternal long-axis view at or immediately below the level of the mitral valve leaflet tips. LV mass was calculated using the Devereux formula:3 − [LVID]3 + 0.616.LV mass(g) = 0.8  × 1.04  × [LVIDd + PWTd + IVSd]Where LVIDd is the left ventricular end-diastolic dimension, PWTd is the end diastolic posterior wall thickness, IVSd is the end diastolic interventricular septal thickness. •LV volumes were measured in the apical four- and two-chamber views using the biplane method of disks (modified Simpson’s rule) summation and LV ejection fraction was estimated. •π 2.Mitral annular diameter was measured from apical four chamber view and mitral orifice area was calculated assuming that it is circular. Mitral orifice area=  •Left atrial dimensions were measured. Measurement of left atrial volume was done from apical 4-chamber and apical 2-chamber views at ventricular end-systole using biplane method of disks (modified Simpson’s rule). •Mitral annular plane systolic excursion (MAPSE) was measured in an apical four chamber view from the lowest point to the highest point during systole using M-mode echocardiography. MAPSE was measured from the septal and lateral mitral annulus and measurements were averaged. •17: “Stroke Volume = LVOT VTI  × Cross Sectional Area of LVOT”.  The Left Ventricular Outflow Tract was used to estimate stroke volume and cardiac output (COP) from the following equation –COP = stroke volume ×  heart rate. –18. “Cross Sectional Area of LVOT = π (LVOT diameter/2)2.”LVOT VTI was calculated by placing the pulsed Doppler sample volume in the outflow tract below the aortic valve and recording the velocity (cm/s) in the apical four-chamber. LVOT diameter measurement was made just below the aortic valve plane in mid-systole in the parasternal long-axis view –Pulsed Doppler was used to record transmitral flow in the apical four chamber view. The sample volume was placed at the tip of the mitral valve. From the mitral valve inflow velocity curve, we measured: peak E wave velocity (cm/s), peak A wave velocity (cm/s), E/A ratio and deceleration time . Isovolumic relaxation time  which represents the time interval from aortic valve closure to mitral valve opening, was measured using a continuous wave Doppler signal, which intersects both the left ventricular outflow and the mitral valve motion. –Tissue Doppler velocities were measured at the lateral and medial sites of the mitral annulus and measurements were averaged. We measured peak early diastolic mitral annular velocities  and peak late diastolic mitral annular velocities  and Ea/Aa was calculated. –Flow propagation velocity (Vp) (cm/s) was measured from color M mode in the apical four chamber view by measuring the slope of the early diastolic color m-mode wave. –19,20.LV filling pressure was estimated from E:Ea and E:Vp ratios –21.Pulmonary capillary wedge pressure (PCWP) was calculated according to the formula: “PCWP = 1.55 + 1.47(E/Ea)” –We measured the mitral peak systolic annular velocity (Sa) at the two annular sites and measurements were averaged. –2 in kdynes22.LA ejection force was calculated as 0.5 x 1.06 x mitral annular area x (peak A velocity) –15. The ASE/EACVI recommended four variables for identification of left ventricular diastolic dysfunction (LVDD) and their abnormal cut-off values in subjects with normal LVEF: annular e’ velocity , average E/e’ > 14, LA volume index > 34 mL/m2, and peak TR velocity > 2.8 m/s. Left ventricular diastolic function was normal when less than half of the available variables met the cut-off values for identifying abnormal function. LVDD was positive when more than half of the available variables met these cut-off values, but was indeterminate when only half met these values. Patients were graded in three groups .Identification of diastolic dysfunction was performed according to ASE/EACVI recommendations –Echocardiographic studies of the patients on dialysis were performed before dialysis.P ≤ 0.05 was considered statistically significant, and p ≤ 0.01 was considered highly significant.Data analysis was performed using Microsoft Excel 2016 and Statistical Package for Social Science (SPSS) Statistics for Windows, version 26 . Data was expressed as the mean ± SD. Pearson correlation coefficient was calculated to get the association between hs-cTnT and different variables.The diagnostic performance of Troponin, LA volume, IVST, LVPWT, LV mass, MAPSE, A, Ea avg, Ea/Aa avg, E/Ea avg, PCWP, and S avg was assessed by receiver operating characteristic (ROC) curves. The area under the ROC (AUC) was calculated as an accuracy index for prognostic performance of selected tests. The cutoff for the diagnosis of a group of the study was taken from the point of maximum combined sensitivity and specificity.The demographic data of the patient groups (1 & 2) and the control group (3) revealed mean ages (54.90 ± 11.13), (50 ± 13.73) (51.55 ± 8.71) years, respectively. In group I, 19 were males (45.24%) and 23 were females, in group II, 22 were males (52.38%) and 20 were females (47.62%). In the control group, 10 were males (43.48%) and 13 (56.52%) were females .There was no significant difference between the patient groups and control regarding age & gender.Laboratory data of the studied groups are shown in P < 0.01, P < 0.01), LVM (P < 0.01) in both patient groups compared to the control group. SV was significantly increased in group II compared to group I and III (P < 0.01) and in group I compared to group III (P < 0.05). COP was significantly higher in both patients’ groups compared to the control group and in group II compared to group I (P < 0.01). MAPSE was significantly decreased in both patients’ groups compared to the control group  and in group I compared to group II (P < 0.05) with a significant decrease in S velocity in group I compared to group II and III (P < 0.01). There was a significant decrease in Vp (P < 0.01) with a significant increase in AEF (P < 0.01) in both patients’ groups compared to the control group and AEF was significantly increased in group II compared to group I (P < 0.01). Ea velocity and Ea/Aa were decreased significantly (P < 0.01) with significant increase in Aa velocity , E/Ea (P < 0.01) and E/Vp (P < 0.05) in both patients’ groups compared to the control group.The echocardiographic findings , show a P < 0.01, P < 0.01) (There was a significant increase in hs-cTnT levels in both patient groups compared to control group ( < 0.01) .r = 0.291, p < 0.03), IVST , PWT , LVM , A-wave velocity , E/Ea , PCWP  and a negative correlation between hs-cTnT and MAPSE , S-wave velocity , Ea , Ea/Aa  (We found a positive correlation between hs-cTnT level and LAV (  0.0001) .We found a positive correlation between hs-cTnT level and serum urea and creatinine in addition to a negative correlation between hs-cTnT and glomerular filtration rate (GFR) .Receiver Operating Curves (ROC) were established to show the diagnostic performances of LA volume, IVST, LVPWT, LV mass, MAPSE, A, Ea average, Ea/Aa average, E/Ea average, PCWP, and S average m in comparison with Troponin regarding the studied groups.In reference to  •P < 0.01).Troponin at the cut-off value of >5 ng/L, revealed 100% sensitivity and 95% specificity with areas under curve (AUC) 0.998 and accuracy 95.65% ( •P < 0.01).LA volume at the cut-off value of >44 mL, revealed 66.67% sensitivity and 78.26% specificity with AUC 0.754 and accuracy 44.93% ( •P < 0.01).IVST and LVPWT at the cut-off values of >1.1, revealed 52.38% sensitivity and 91.30% specificity with AUC 0.786 & 0.777 respectively and accuracy 43.69% ( •P < 0.01).LV mass at the cut-off value of >213.88 gm revealed 71.34% sensitivity and 91.30% specificity with AUC 0.798 and accuracy 62.73% ( •P < 0.01).MAPSE at the cut-off value of ≤13 mm revealed 66.67% sensitivity and 95.65% specificity with AUC 0.844 and accuracy 62.32% ( •P < 0.01).A velocity at the cut-off value of >57.46 cm/s revealed 85.71% sensitivity and 86.96% specificity of with AUC 0.876 and accuracy 72.67%. ( •P < 0.01).Ea (average) at the cut-off value of ≤11.45 cm/s revealed 95.24% sensitivity and 95.65% specificity with AUC 0.986 and accuracy 90.89% ( •P < 0.01).Ea/Aa (average) at the cut-off value of ≤0.97 revealed sensitivity of 85.71% and specificity of 100% with AUC 0.963 and accuracy 85.71% ( •p > 0.01).E/Ea (average) at cut-off value of >5.76 revealed 80.95% sensitivity and 95.65% specificity with AUC 0.874 and accuracy 76.60% ( •P < 0.01).PCWP at cut-off value of >10.01 revealed 80.95% sensitivity and 95.65% specificity with AUC 0.874 and accuracy 76.60% (With reference to  •P < 0.01).It was found that, Troponin at the cut-off value of >5 ng/L, revealed 76.2% sensitivity and 95.7% specificity with AUC 0.796 and accuracy 71.84% ( •P < 0.01).LA volume at the cut-off value of >46 mL, revealed 61.90% sensitivity and 86.96% specificity with AUC 0.789 and accuracy 48.86% ( •P < 0.01).IVST at the cut-off value of >1.1, revealed 47.62% sensitivity and 91.30% specificity with AUC 0.758 and accuracy 38.92% ( •P < 0.01).LVPWT at the cut-off value of >1 revealed 80.95% sensitivity and 65.22% specificity with AUC 0.792 and accuracy 46.17% ( •P < 0.01).LV mass at the cut-off value of >213.88 gm revealed 61.90% sensitivity and 91.30% specificity with AUC 0.777 and accuracy 53.21% ( •P < 0.05).MAPSE at the cut-off value of ≤15 mm revealed 61.90% sensitivity and 69.57% specificity with AUC 0.682 and accuracy 31.47% ( •P < 0.01).A velocity at the cut-off value of >57.46 cm/s revealed 85.71% sensitivity and 86.96% specificity of with AUC 0.907 and accuracy 72.67%. ( •P < 0.001).Ea (average) at the cut-off value of ≤11.15 cm/s revealed 90.48% sensitivity and 95.65% specificity with AUC 0.934 and accuracy 86.13% ( •P < 0.01).Ea/Aa (average) at the cut-off value of ≤1.1 revealed sensitivity of 95.24% and 100% specificity with AUC 0.977 and accuracy 95.24% ( •P < 0.01).E/Ea (average) at cut-off value of >5.76 revealed 80.95% sensitivity and 95.65% specificity with AUC 0.810 and accuracy 76.60% ( •P < 0.01).PCWP at cut-off value of >10.01 revealed 80.95% sensitivity and 95.65% specificity with AUC 0.810 and accuracy 76.60% .Average S-wave velocity at the cut-off value of >9.11 cm/s revealed 86.96% sensitivity and 57.14 specificity with AUC 0.719 and accuracy 44.10% ( •P < 0.05).MAPSE at the cut-off value of >13 mm revealed 78.26% sensitivity and 66.67 specificity with AUC 0.668 and accuracy 44.93%  but the difference in troponin level between patients with intermediate and patients with normal diastolic function is statistically insignificant.The mean troponin level was 52.63 ± 23.36 ng/L in patients with positive diastolic function, 32.66 ± 22.52 ng/L in patients with intermediate or inconclusive diastolic function and 31.53 ± 14.93 ng/L in patients with normal diastolic function . The difIn group II, diastolic dysfunction was present in 38.10%, normal in 38.10% and inconclusive or intermediate in 23.80% of patients . The meaP = 0.25). Also, the difference in troponin level between patients with intermediate and patients with normal diastolic function is statistically insignificant (P = 0.23). The difference in troponin levels was statistically significant in comparison between patients with positive diastolic dysfunction and patients with normal diastolic function (P < 0.05)  .This study investigated the association of circulating hs-cTnT with LV structural and functional abnormalities as detected by echocardiography among dialysis dependent and non-dialysis dependent CKD patients.23,24. de Simone reported that concentric LV hypertrophy is a natural pattern in end-stage renal disease (ESRD), and it identifies more severe impairment of the cardiovascular system25.We demonstrate significant increase in left ventricular mass in both patients’ groups compared to the control group. This is in agreement with previous reports that estimated the prevalence of left ventricular hypertrophy (LVH) in CKD patients to range from 40% to 78%, to reach 75% at the time of initiation of dialysis26.We found a significant increase in aortic root diameter (ARD) in both patient groups compared to the control group. Our results are in agreement with the results of Mulé et al., who found significantly increased ARD in hypertensive subjects with CKD when compared to those with normal renal function, in addition to significant and inverse association of GFR with ARD as assessed by transthoracic echocardiography (TTE)27. Aortic root dilatation may play a role in the increased cardiovascular risk associated with renal insufficiency. Cuspidi et al., concluded that LVH and ARD dilatation is a stronger predictor of cardiovascular events than LVH alone in general population28.In addition to the remodelling of the aortic root as a result of increased stress on the aortic wall due to hypertension, the cause of aortic root dilatation in CKD seems to be due to mechanisms similar to those responsible for decreased large artery elasticity in CKD patients, such as endothelial dysfunction, renin-angiotensin-aldosterone system and endothelin system activation, inflammation, oxidative stress and lipid peroxidation29.Our study revealed a significant increase of left ventricular internal diameter at end diastole (LVIDd) in the dialysis-dependent group II compared to the control. The increased LVIDd can be due to anemia, high-flow arteriovenous shunts, sodium, or water retentionStroke volume (SV) was significantly increased in the dialysis-dependent group compared to other groups. COP was higher in both patient groups compared to the control group. It was also higher in the dialysis-dependent group compared to the non-dialysis dependent CKD patients.30.The increased SV and COP in CKD patients is a consequence of anemia that leads to hemodynamic changes that act to raise COP including: decreased systemic vascular resistance, increased stroke volume, decreased blood viscosity, increased venous return and activation of the sympathetic nervous system. Also, the creation of arteriovenous shunts for hemodialysis access is partly responsible for high output states in dialysis dependent patientsRegarding systolic function, although we found no statistically significant differences in ejection fraction (FF%) and fraction shortening (FS) between groups, mitral annular plane systolic excursion (MAPSE) was significantly decreased in both patient groups compared to the control group. Additionally, we found a significant decrease in the peak systolic wave velocity (Sa) of the mitral annulus in the non-dialysis dependent CKD patients compared to the dialysis dependent group and the control group.31. Kai Hu et al., concluded that MAPSE is a sensitive echocardiographic parameter to assess global longitudinal LV function and seems to be more sensitive than EF for detecting early systolic dysfunction32.Although LVEF has been widely used to define systolic function, it gives limited insight into direction-based myocardial systolic function. MAPSE and S-wave velocity assess LV longitudinal function. Reduced LV longitudinal function is indicative of subclinical impairment of the systolic function33,34.Subclinical systolic dysfunction can be observed in patients with CKD despite normal LVEF. Impairment of LV longitudinal function reflects early CKD-related myocardial changes such as myocardial ischemia and interstitial fibrosis because sub-endocardial longitudinal myocardial fibers are more vulnerable to ischemia and increased wall stress35 and Luszczak et al.,36 highlight the sensitivity of MAPSE to early changes in LV systolic function and concluded that MAPSE can be used as a sensitive tool to detect early longitudinal LV systolic dysfunction and in the absence of global longitudinal strain (GLS) by speckle-tracking echocardiography (STE).The results of the studies of Israa et al.,35.The use of MAPSE by M- mode echocardiography and/or peak systolic velocity (Sa) of the mitral annulus by pulsed-wave Doppler tissue imaging (DTI) can be a reliable alternative for quantification of LV longitudinal function37 showed that GLS deteriorated along with the decline of renal function among CKD patients. In agreement with our study, Ravera et al.,38 reported that renal disease is associated with early and subclinical impairment of LV systolic function in spite of normal standard EF, regardless of the degree of renal function. Our finding of more impairment of LV longitudinal function in the non-dialysis dependent CKD patients compared to the dialysis dependent patients is consistent with the study of Lui et al., who reported better GLS in ESRD patients on dialysis than in those with CKD not on dialysis yet37.Lui et al.,Concerning left atrial (LA) function and diastolic function, our study showed a significant increase in left atrial volume (LAV) in both patients’ groups compared to the control group. The increased LAV may reflect both volume expansion and diastolic dysfunction in CKD patients. Additionally, there was a significant decrease in velocity of flow propagation (Vp) with a significant increase in atrial ejection force (AEF) in both patient groups compared to the control group. AEF is also significantly increased in the dialysis-dependent patients compared to the non-dialysis dependent CKD patients.39,40. AEF is the force exerted by the LA during atrial systole to push blood into the LV41 and it can be a useful index in assessing the atrial contribution to diastolic performance42. The rise in Left AEF in both patients’ groups may reflect the increase in the vigor of LA contraction with rising left ventricular end diastolic pressure (LVEDP).Vp is inversely related to the time constant of LV relaxation and is a preload independent index of LV diastolic performance43. Our results are in agreement with the results of Kadappu et al. 44 who demonstrated increased LAV and impaired LA strain in CKD patients. Similar findings have been reported by Tripepi et al. 45 who found increased LAV index in patients with ESRD. El-Sherbeny and El=hefnawy46 also reported LA dysfunction and enlargement in patients with early CKD and they found that the alteration in LA function (systolic strain) precede the changes in LV function (EF).Increased LA systolic force, was found to be associated with a significant increase in cardiovascular eventsWe found a significant increase in A-wave velocity with a significant decrease in E/A ratio in patient groups compared to the control group. DTI at the mitral annulus revealed significantly decreased Ea velocity and Ea/Aa ratio with a significant increase in Aa velocity, E/Ea, E/Vp and mean pulmonary capillary wedge pressure (PCWP) in both patient groups compared to the control group.47. Also, the study of Matuso et al. on Japanese patients with ESRD showed that almost all patients had some degree of abnormal LV filling pattern48. A previous study demonstrated that the presence and severity of CKD is associated with the progression of LV diastolic dysfunction independently of age, sex, hypertension, coronary disease, and ejection fraction49.Our results show that left ventricular diastolic dysfunction is present in dialysis-dependent and non-dialysis dependent CKD patients. In agreement with our study, the study of Farshid et al. who concluded that some degree of diastolic dysfunction was present in 86% of patients on hemodialysis50.The study of Sidmal et al. on patients with early and ESRD with or without dialysis showed that left ventricular diastolic dysfunction is present in all patients with CKD, including those with an early stage of CKD and they found that diastolic dysfunction got worsened in parallel with the severity of kidney dysfunction. They concluded that Doppler indices can detect subtle changes of diastolic function caused by CKD51. We found a positive correlation between hs-cTnT level and LAV, IVST, PWT, LVM, A wave velocity, E/Ea ratio, PCWP and a negative correlation between hs-cTnT and MAPSE, S wave velocity, Ea, Ea/Aa ratio. Similar findings have been reported by Sun et al.,52 who found higher levels of hs-cTnT in non-dialysis CKD patients than in normal population and that the progressively higher hs-cTnT quartiles were associated with greater LVM index and higher prevalence of LV diastolic dysfunction.Regarding hs-cTnT levels, our study revealed significant increase in hs-cTnT levels in both patient groups compared to the control group. In agreement with our findings, deFilippi et al., reported that patients with CKD have persistently elevated hs-cTnT levels compared with those with normal renal functionIn contrast to our study, Sun et al., found that hs-cTnT is associated with LVEF. We found no correlation between hs-cTnT level and EF but we found a negative correlation between hs-cTnT and MAPSE & Sa wave velocity of the mitral annulus, which measures LV longitudinal function.53 found that asymptomatic ESRD patients with normal EF who have high hs-cTnT levels had more severe cardiac systolic dysfunction as determined by GLS than those with low hs-cTnT level. Other previous studies revealed that hemodialysis patients with increased hs-cTnT levels have more impaired LV systolic function, higher LV filling pressure (estimated from E:Ea and E:Vp) and higher LV mass index54,55.In agreement with our findings, Liu et al. 56 reported that in CKD patients, hs-cTnT is strongly associated with left ventricular hypertrophy and diastolic dysfunction  for both estimated glomerular filtration rate categories (≥60 or <60 mL/min per 1.73 m2) but was not associated with systolic dysfunction (EF < 50%).Kang et al., in the Korean Cohort Study for Outcome in Patients with Chronic Kidney Disease57. Kitagawa et al., found that hs-cTnT and E/Ea were significantly increased and that Ea was significantly decreased with increasing CKD stage in non-diabetic CKD patients. They suggested that hs- cTnT may be a useful biomarker of left ventricular diastolic dysfunction in non-diabetic CKD patients58.The study of Stein et al., on mild to moderate CKD patients in the Chronic Renal Insufficiency Cohort (CRIC), revealed that hs-cTnT was strongly associated with measures of left ventricular structure and function as well as left atrial structure and concluded that hs-cTnT is associated with echocardiographic measurements of subclinical cardiovascular disease5. Studies have demonstrated that adequate control of cardiovascular risk factors associated with CKD  appears to benefit the cardiovascular system. Lifestyle modifications to establish a healthier way of life are the first steps to slow the progression, and even enhance the regression, of CKD and reduce the risk of cardiovascular complications at the same time59.In patients with CKD, detecting cardiac disease at an early stage would facilitate aggressive pharmacological and non-pharmacological treatment to reduce cardiovascular complications. Earlier intervention may be the best way to reduce the burden of CKD on the cardiovascular system60. Strategies to reduce CVD risk should be tailored to the individual and should be specific to their particular CKD stage61.Modulating cardiovascular risk factors specific to people with CKD , hyperphosphatemia, sodium and water excess and electrolyte imbalance) could be important in decreasing cardiovascular complicationsA limitation of our study is that patients with CKD had significantly higher systolic and diastolic blood pressures compared to the control arm, which may be one of the mechanisms by which CKD causes myocyte necrosis. This raises the possibility that our findings may be attributed to hypertension rather than CKD disease per se.62.Other mechanisms by which CKD causes myocyte necrosis may include stable CAD, subendocardial ischemia, clinically silent micro-MI, direct myocardial toxicity from uremic toxins, hemodynamic overload, and hemodialysis-related stress. LVH, which is initially a compensatory adaptive response, can lead to cardio-myocyte damage with continual LV overload63.Elevated cTn in CKD patients, likely due to kidney disease-related subclinical cardiac damage, may be exacerbated by reduced renal clearance of cTnDialysis-dependent and non-dialysis dependent CKD patients have structural and functional (systolic & diastolic) cardiac abnormalities that can be assessed by echocardiography.MAPSE and Sa wave velocity of the mitral annulus may be impaired despite normal EF and FS in CKD patients and may be used to detect early longitudinal LV systolic dysfunction.Levels of hs-cTnT are increased in CKD patients and is associated with LVH, LAV and some of the echocardiographic parameters of LV systolic and diastolic dysfunction.Our research suggests that serum hs-cTnT assay may be an important, simple, and possibly cost-effective test for the early screening of cardiac structure and function in CKD patients to provide evidence for early intervention.The authors declare no conflicts of interest.The authors received no specific funding for this research.


Congenital complete atrioventricular block (CCAVB) is usually due to failure of atrioventricular nodal conduction with preservation of the His‐Purkinje system. Most patients with CCAVB ultimately require pacemaker therapy to restore physiologic heart rates, dealing with the detrimental effects of chronic right ventricular (RV) pacing on cardiac structure and function. The ideal stimulation pattern aims to mimic the normal conduction to restore electromechanical coupling, preventing the harmful effects of lack of atrioventricular and inter‐intraventricular synchrony. This can be done through conduction system pacing. Using His bundle pacing (HBP) for cardiac resynchronization therapy in two complete congenital atrioventricular block patients, we have reported better exercise tolerance and echocardiographic improvements related to reversible left ventricular dysfunction that can be corrected by restoration of the normal activation pathway via the His‐Purkinje network. The 12‐lead ECG showed sinus rhythm with complete atrioventricular block and a ventricular‐paced QRS  associated with evident septal dyskinesia .In this perspective, key questions in CCAVB are yet unanswered owing to the impossibility to run methodologically correct studies in this pediatric population. The timing to consider pacing is individually based. The choice of the pacing site and mode has been mostly debated in literature (Cabrera Ortega et al., A first pacemaker implant or replacement after early childhood or in adolescence is a different setting, because key decisions are taken for long‐term cardiac pacing in a view to restore—possibly—all the 3 electrophysiologic determinants of cardiac function. A mild LV systolic dysfunction, especially when associated with functional mitral or tricuspid regurgitation and initial left atrial enlargement, is a clinical hint of the RV pacing detrimental effect and may promote upgrading the system to restore cardiac synchronicity. CRT is well known to improve cardiac function in RV pacing‐induced heart failure/LV dysfunction (Höijer et al., A single case of cardiac resynchronization via direct HBP in a CCAVB patient with RV pacing‐associated cardiomyopathy has been reported to date (Rehwinkel et al., The ongoing development of dedicated tools and the improved skillfulness in HBP implantation have now set the ground for the expansion of this pacing modality to CCAVB patients.3.1The observations about these two patients need to be confirmed in a large series of CCAVB patients. Moreover, some caveats are to be considered, such as persistence of conduction in the His‐Purkinje network at long term; minimization of intravascular leads that dwell lifelong in young patients; device longevity when a moderate‐to‐high HBP threshold dictates a high current drain; and lead revision in the event of loss of capture, as the number of pocket surgeries is a main predisposing factor to infection. Technical aspects like the amount of lead slack need to accommodate for patients’ growth are better addressed in late rather than in early childhood.4Taken these points as a habit at innovation, we believe that HBP should be explored as the first‐choice strategy in CCAVB undergoing pacemaker implantation in childhood, and in CCAVB candidates to upgrading because of RV pacing–associated LV dysfunction. A challenge may be represented by the possible increase in chronic pacing threshold, as also reported by Dandamudi et al. (Dandamudi et al., Mauro Biffi has held educational activity and received honoraria as speaker's bureau for Biotronik, Boston Scientific, and Medtronic. Matteo Ziacchi has held educational activity and received honoraria as speaker's bureau for Biotronik, Boston Scientific Abbott and Medtronic. All other authors declare that they have no conflict of interests.5This study was conducted in accordance with Helsinki Declaration as revised in 2013. Statements of written informed consent from legally authorized representatives/parents are available. All figures and tables are sourced from authors’ clinical cases at IRCCS Azienda Ospedaliero‐Universitaria Sant’Orsola‐Malpighi di Bologna.6Dr Biffi and Dr Ziacchi performed devices implantation. Dr Piemontese, Dr Biffi, Dr Ziacchi wrote the manuscript. All the authors equally contributed to the data collection and analysis at the implant and during the patients' follow‐up. Dr Massaro was the language reviewer.


Myocarditis is an umbrella term for non-ischemic myocardial inflammation andremains a leading cause of sudden cardiac death in active individuals andathletes. Accurate diagnosing is challenging and diseases could often remainundetected. In the majority of cases, acute myocarditis resolves favourably.However, a relevant proportion of patients may have an increased risk ofprognostically relevant cardiac arrhythmias and/or the development andprogression of maladaptive myocardial remodelling (dilated cardiomyopathy). Thisreview provides current knowledge on myocarditis and sports with special regardto the COVID-19 pandemic. Possible causes, common symptoms and proposeddiagnostics are summarized. The relevance of temporary avoidance of intensivesports activities for both the prevention and therapy of acute myocarditis isdiscussed. Risk stratification, specific return-to-play recommendations andproposed follow-up diagnostics  arepresented. Myocarditis (MC) is the third most frequent cause of sudden cardiac death (SCD)during physical activity in young sportsmen and women ≤35 years) in Germany5 years iMC is an umbrella term for non-ischaemic myocardial inflammation, which can varywidely regarding symptoms, course, and prognosisUp to 20% of patients develop dilated cardiomyopathy (DCM) over the long-termcourse, sometimes taking years to become clinically evidentThe causes of MC are manifoldinfectious toxic  andautoimmune .In Europe and North America, MC is chiefly attributable to viral pathogens, suchas a cold, influenza, or gastroenteritisIn young patients and/or patients with sporting ambitions, it is alsoconceivable that drugs or doping agents are involved. Likewise, geneticpredispositions can promote development of the diseaseDiagnosing MC is complex owing to its often heterogeneous course. Othercardiovascular diseases, such as coronary artery disease (CAD) or valvularvitia, must be excluded using differential diagnostics. The fact that sometimes(particularly in women) symptoms are only mild/modified should also betaken into accountmedical history/symptomselectrocardiography (ECG)transthoracic echocardiography (TTE)biomarkers and/or inflammatory markerscardiovascular magnetic resonance imaging (CMR)endomyocardial biopsy (EMB).Possible symptoms of MC can vary considerably in their manifestation. Degreesof severity range from a complete lack of symptoms to cardiacdecompensation, cardiogenic shock or SCDFrequently, chest pain and/or classic symptoms of heart failure or arrhythmias  are initially describedAthletic patients additionally report restricted physical performance,increased muscle soreness, as well as a slightly elevated heart rate both atrest and during exercise (approx. 5–10 bpm). However, in adifferential diagnosis these symptoms can also point to“overtraining syndrome”, and this needs to be excludedIf the MC has an autoimmune cause, extra-cardiac symptoms can also occur(e. g. in conjunction with sarcoidosis or systemic sclerosis) andprovide an indication of the underlying diseaseIn 42% of patients with suspected MC (96% in the ITAMY study)the resting ECG was conspicuousventricular and supraventricular arrhythmiasST-segment deviationsT-wave inversionsconduction disorderslow voltage.In many patients, however, no special changes are discovered in the restingECG. In elite endurance athletes, interpretation of the ECG signal can alsoprove difficult since similar ECG changes can occur as typical andnon-pathological adaptations of the “athlete’sheart”. If available, the findings should therefore be compared toprevious examinations in order to verify any changes. A 24-hour Holter ECGcan be considered. The monitored time period should then also include aregular workoutImaging with TTE is a standard diagnostic procedure. The following phenomenacan provide indications of MCpericardial effusionleft ventricular dilatation with thin myocardial wallsincrease in myocardial wall thickness global or regional altered systolic function and wall motionabnormalitiesdiastolic dysfunction.Left ventricular ejection fraction (LVEF) can be slightly or considerablyreduced at rest, but not necessarilyIn case of suspected MC, the following laboratory values are relevantcardiac troponin T/IC-reactive protein (CRP)creatine kinase (CK), creatine kinase-MB (CK-MB) andleukocytes.These laboratory values are not specific MC markers, so that correspondingconcentration increases can also occur with other diseases ornon-pathological states. Nevertheless, the troponin T/I value inparticular has proved helpful. In approx. 63% of all cases ofsuspected MC (100% in the ITAMY study), increased troponin valuescan be foundIn athletes it should be taken into account that corresponding biomarkers canalso be physiologically increased following intense physical exercise and,at least temporarily, be beyond the threshold range. However, the increasein troponin caused by exercise is not quite as high and usually normalisesagain within 48 h. A sports anamnesis and repeat tests can providethe necessary informationCMR has become established in the last few years as one of the primarynon-invasive diagnostic tools for patients with suspected MCThe updated Lake Louise Criteria cite as the main criteria for radiologicalproof of MCmyocardial oedema  and/ormyocardial injury .Secondary criteria focus on pericardial effusion and left ventriculardysfunctionIn the current discussion, the valency and sensitivity of CMR in the chronicphase of MC are controversial. For example, LGE is unable to differentiateclearly whether the inflammation/scar is fresh, ongoing or alreadyhealed. Estimating a patient’s sporting capability using thisparameter is therefore difficult. However, studies show the prognosticsignificance of positive LGE for a major adverse cardiac event (MACE)EMB is the gold standard among diagnostic examinations for acute MC, and yetit is not used routinely owing to its invasive natureThe risk of contracting MC can be reduced by protectionfrom/minimisation of pathogen triggering . The use of suitable protective clothing and anadequate level of vaccination appropriate to the country of residence isrecommendedExposure to pathogens is not always avoidable. It is therefore crucial thatthe body’s own immune system is functioning. With regard tointensive sports activities, the following two problems arise in conjunctionwith the emergence of MCan assumed higher susceptibility to infection following intensiveexercising (“open window effect”)a stronger MC development following intensive exercising inconjunction with an already existing infection.It is generally assumed that regular moderate physical training inducesmulti-layer protective health effects and is concomitant with a strongerimmune systemIn professional athletes, the negative impact on the immune system ofadditive factors should not be underestimated, e. g. increasedtravelling, time differences, lack of sleep, extreme ambient conditions,depression or an insufficient time for regenerationIt is also assumed – in cases where an infection already exists– that intensive physical training units can negatively impact theemergence and course of MC. In animal experiments it could be proven thatintensive exertion in mice infected with Coxsackie B3 led to a significantlyincreased mortality and more frequent pathological cardiac findings compared to animals withoutsuch physical training unitsThe question of whether and when a preventive training break is necessary canbe difficult to answer in individual casesSport and competitive sport must be completely abandoned if the symptoms arebelow the neck or if systemic complaints occur, such asdyspnoeahigh temperaturejoint painsswollen lymph nodesgastrointestinal symptoms (e. g. diarrhoea)increased heart rate at restsevere cough.The relevance of this training break should be made sufficiently clear toathletes since a high degree of motivation or a pressure to perform couldtempt them to maintain or prematurely resume their training programme.Especially in the early days of the disease, the risk of pathophysiologicalchanges is higherAccording to the current literature, a SARS-CoV-2 (COVID-19) infection can alsobe concomitant with myocardial involvementDifferent societies and authors have been fast to publish recommendationsregarding when and with which precautionary measures it is viable to restarttraining and competitive sport after a COVID-19 infectionThere is still no consensus among the societies regarding about whichcardiological diagnostics are necessary prior to return-to-play (RTP). Acompromise must be found between cost and benefit since the potential numberof positively tested athletes would considerably exceed screening capacityRTP should be introduced with gradually increasing intensity. As a rule ofthumb, 2–3 days of graduated return can be planned per training unitcancelled due to illness. This period should also serve to sufficientlyregenerate the non-cardiac systems Since mid-2021 there have been a growing number of reports that MC courseshave been more frequently observed following a COVID-19 mRNA vaccinationThere are currently no generally recognised restrictions regarding theinterval between a COVID-19 vaccination and a return to sporting activity.It does appear reasonable, however, to refrain from exertion in the firstfew days, to await potential side-effects and to rest the body. The Ministryof Health in Singapore recommends refraining from exertive sport for atleast 2 weeks following a COVID-19 vaccinationIn most cases, acute MC resolves favourably within a few weekstreatment of heart failure in accordance with the guidelines, andtreatment of arrhythmias in accordance with the guidelines.In the case of acute symptoms, hospital admission and monitoring are necessaryFor the treatment of advanced heart failure, the temporary use of mechanicalcirculatory support systems as a “bridge to recovery” can benecessary in a small percentage of patientsIn patients with arrhythmias, the danger of SCD can be minimised through thetemporary use of a wearable cardioverter defibrillator (WCD). A permanentdefibrillator system is implanted only later should symptoms persistFor patients with supposed or proven MC, the cardiological societiesrecommend a break from training and competitions of at least 3–6monthsPrior to RTP, a comprehensive cardiological diagnosis is necessary for riskstratification. It includes the following examinationsmedical history/symptomsbiomarkers and/or inflammatory markersTTE24-hour Holter ECGstress TTE and/or cardiopulmonary exercise testing (CPET)CMR (recommended).MC patients are at permanent increased risk of malign arrhythmias due topossible myocardial scarringFor risk stratification, evaluation of the LVEF and increasingly also thechange of a possible positive LGE finding are used. In asymptomatic patientswith an uncomplicated disease course, preserved systolic function and anegative LGE finding, the prognosis is very goodAn isolated reduced LVEF was accompanied by a poorer prognosis . The highest annual event rates wereobserved in patients with restricted LVEF (<40%) andpositive LGE finding The isolated interpretation and weighting of a positive LGE finding iscurrently still being intensively researched and discussedThe precise scheduling of permitted resumption of sporting activity has to bedecided from case to case and in discussion with the patientAccording to the current recommendations, a release for intensive sportingactivities and competitions can be issued 3–6 months after the acutedisease phase, provided that the following criteria are observedventricular systolic function within normal rangecardiac and inflammatory biomarkers within normal rangelack of clinically relevant arrhythmias in daily routines (24-hour HolterECG) and in stress situations (e. g. CPET).The importance of re-assessments should be pointed out once againTwo recent overviews provide additional pointers for a more differentiatedevaluationIf during the acute phase of MC, in contrast, there was a restricted LVEFand/or positive LGE indication of LGE, intensive physical exertion(e. g. HIIT) and competitive sport should be avoided for at least 6months, even if the systolic function has recovered in the meantimeIn MC patients with restored systolic function after 6 months yet stilldisplaying a positive  LGE indication, there is atheoretically an increased risk of ventricular arrhythmias linked to potentialSCD. In such cases, a release to sport can be granted only after thoroughlyinforming the patientA release to intensive sports and competitions cannot be granted if a loweredLVEF or other indications of incomplete myocardial recovery are still presentafter 6 monthsIn cases where there is no improvement, not even in the long term, a decisionmust be reached for the individual patient and together with that patient. Thedecision process should include the nature of the envisaged sport with regard toits cardiovascular impact , as well as therisks involved in losing consciousness (e. g. during motor sports ordiving)In the training design a difference is made between healing and healed MC2) (RPE:<10–12)2(RPE: 12–14) can be performed over the courseThe training design following healed MC draws upon many years of experiencewith heart failure patients, as well as the results of the individualsymptom-limited exercise testA moderate dynamic resistance training should start with low exertion(30–50% of the 1 repetition maximum (1-RM), RPE:12–13), with the intensity increasing gradually over the courseAdequate education of patients and their coaches or training partners is acrucial aspect for reliable training design. Experience has shown that ideasabout moderate/regenerative training plans can diverge considerably,and that consistent compliance is unfortunately not a given in all casesWith regard to emergency prophylaxis, it is vital to instruct and educatethose with direct access to the patient/athlete since first aid iscrucial if a haemodynamically relevant arrhythmia should occur. Training ingroups, knowledge about adequate first aid measures, and the rapidavailability of an automated external defibrillator (AED) have all provenfavourable for the prognosistraining range and intensity during the first post-MC phasepossible consequences if ignoredsymptoms of possible complicationsfirst aid measuresrelevance of regular check-upsprevention of renewed MC.Another significant point for RTP is the mental health of the patient: forambitious amateur or professional athletes, an uncertain long-term medicalprognosis, long training breaks, a lack of competitions and/or thecancellation of sponsoring/prize money can represent a hugepsychological burden and tempt athletes to resume intensive physicalactivities too soon. Potential anxieties can also restrict RTP followingresolved MC. The early integration of a psychological carer should thereforebe considered in relevant constellationsMC is a frequent cause of malignant arrhythmias and SCD in young, active, physicallyfit persons with no further pre-existing conditions.In most cases, acute MC resolves. Depending on the disease course, however, somepatients have a long-term increased risk of prognostically relevant arrhythmiasand/or progressive maladaptive remodelling up to DCM.In the future, multi-centre registry studies in combination with the latestdiagnostic options are desirable


The importance of right heart failure (RHF) treatment is magnified over the years due to the increased risk of mortality. Additionally, the multifactorial origin and pathophysiological mechanisms of RHF render this clinical condition and the choices for appropriate therapeutic target strategies remain to be complex. The recent change in the United Network for Organ Sharing (UNOS) allocation criteria of heart transplant may have impacted for the number of left ventricular assist devices (LVADs), but LVADs still have been widely used to treat advanced heart failure, and 4.1 to 7.4% of LVAD patients require a right ventricular assist device (RVAD). In addition, patients admitted with primary left ventricular failure often need right ventricular support. Thus, there is unmet need for temporary or long-term support RVAD implantation exists. In RHF treatment with mechanical circulatory support (MCS) devices, the timing of the intervention and prediction of duration of the support play a major role in successful treatment and outcomes. In this review, we attempt to describe the prevalence and pathophysiological mechanisms of RHF origin, and provide an overview of existing treatment options, strategy and device choices for MCS treatment for RHF. The number of heart failure (HF) patients reached more than 6 million in the U.S. in 2018 and is expected to rise to 8 million by 2030 . The samCurrently, the indication for mechanical circulatory support (MCS) treatment for RHF is for patients who are refractory to medical or surgical therapy , howeverThe pathogenesis of RHF can be divided into three major categories: isolated RV injury, pulmonary etiology, and the one secondary to LV failure . Addition = 69) documented the long-term mortality among patients with RV MI after the first year was at an additional 2/year to 3%/year through 10th year  are representative of isolated RV injury. Acute inferior MI patients with high-grade proximal occlusion of the right coronary artery tend to show severe RV ischemic dysfunction, which may result in higher in-hospital mortality . However0th year .Pulmonary pathogenesis, which caused by increased RV afterload inducing RV pressure overload and hypoxia, is a broad category. The representatives of this pathogenesis are pulmonary hypertension (PH) and acute pulmonary embolism (PE). Regarding PH, the world health organization (WHO) classification for PH and the European Society of Cardiology and European Respiratory Society guidelines for PH may help organize the topic , 13. In Group 1: pulmonary arterial hypertension (PAH) ;Group 2: left heart disease ;Group 3: lung disease ;Group 4: chronic thromboembolic disease ;Group 5: miscellaneous .n = 2,635) showed a survival rate among PAH patients, which was 85 ± 1%, 68 ± 1%, 57 ± 1%, and 49 ± 1% at 1, 3, 5, and 7 years from diagnosis, respectively (n = 679) described that estimated survival at 1, 2, and 3 years was 93% , 91% , and 89%  in operated patients (n = 404), and only 88% , 79% , and 70%  in not-operated patients (n = 275).It should be noted here that the most prevalent group is group 2 (68%), which is the group of PH due to left heart disease, such as systolic and diastolic dysfunction of LV . Therefoectively . The morAs noted earlier, the RV function has a close interactive relationship with the LV function. As a result, the cause of the RHF in this pathogenesis could be decreased RV contractility and/or RV pressure overload. Cases are equally distributed in a wide variety of causes, such as myocarditis, LVAD support, ischemic disease, and mitral/aortic valvular heart disease; however, as long as this pathogenesis is secondary, the MCS for RHF is considered after or while receiving the LV treatment. Also noted earlier, this pathogenesis will include the patients with group 2 PH. Particular attention should be paid to the HF with preserved ejection fraction (HFpEF). The initial step should be made to treat RHF due to HFpEF after or while receiving the LV treatment; however, the treatment for HFpEF is still limited. Several efforts are undergoing in both medical and device-based treatment –18. Regaet al., the treatment mechanism of MCS devices for acute RHF can be divided into two categories; direct RV bypass and indirect RV bypass  is a U.S. FDA-approved, 22 Fr micro axial pump mounted on an 11 Fr catheter  and post-cardiotomy or post-MI patients with RHF (n = 29). The primary endpoint was survival at 30 days, hospital discharge post-device explant, or transition to the subsequent therapy, and was achieved in 73.3% of the study population. The total duration of device support in this study was ~ 3 days. The major adverse events at 30 days were major bleeding (60%) and hemolysis (13%). PA perforation occurred in one patient, which led to hemothorax, and was likely caused by the guidewire used during the device positioning. No PE was reported.The efficacy of the Impella RP was investigated in a prospective study, the RECOVER RIGHT study, in 2015 –25. The ® systems  and Impella RP (n = 20) reported that in-hospital mortality was 50% , formerly called TandemHeart, is an extracorporeal continuous-flow (CF) centrifugal flow pump with a magnetic pivot bearing , the LifeSPARC Pump is often used with the ProtekDuo cannula percutaneously via the right internal jugular vein  who went through the implantation with this system, during the mean length of support of 10.5 ± 6.5 days, 23% of patients were successfully weaned, 35% required conversion to either a surgical temporary extracorporeal RVAD (sRVAD) or durable implantable RVAD, and 41% did not survive . Another® system  is developed to permit extracorporeal life support circuit to be wearable, and the system consists of LifeSPARC pump, ProtekDuo® cannula, VoyagerVest®, and TandemLung® , Rotaflow II® , CAPIOX® , and MERA® Centrifugal Blood Pump   . Due to , Japan) , 38. Ant, Japan) . The adv, Japan) . The sysThe clinical outcome data of using VA-ECMO to isolate RV failure pathogenesis is limited to small cases studies –41; howe® (HVAD) from the global market in 2021; therefore, HeartMate 3® (HM3)  is the only U.S. Food and Drug Administration-(FDA) approved LVAD in 2022. HM3 is a CF centrifugal pump with full maglev bearing, displacing volume of 80 ml. For the anatomical limitation, the placement of the right pump may be a concern  announced that it was withdrawing the HeartWare Ventricular Assist Device concern . In one  concern . The pum concern . As a re concern , 45, 46. concern .In the same study of 14 patients who received dual HM3 implantation , five pa®  Soft Tissue Patch and placed in the right pleural space. Graft downsizing was done in three cases, and pump thrombosis was observed in three patients . The RVAD was implanted to the RA using the spacer and was wrapped with a Gore-Texpatients . The relThe authors also suggested that the extremely low thrombosis risk of the HM3 as an LVAD may explain this phenomenon . The maj®  is a paracorporeal pneumatic-drive pulsatile device with a lineup of different pump sizes that cover pediatric to adult  with different valves . For the variety of the pump sizes, dual Excor has been used as a BVAD, especially in the pediatric population  is a pneumatically driven pulsatile TAH with independent ventricles that are capable of providing a flow of more than 9 L/min  . Additio® TAH  is a pulsatile TAH that is electro-hydraulically driven  study showed that three out of four PAH patients who underwent bridge to recovery therapy successfully survived to VA-ECMO decannulation   . In addi 7 days) –69. Besi 7 days) ; howeverAcute PE and some of PH may need to be treated as acute RVF. For example, a post-operative period in CTEPH (group 4), and acute respiratory distress syndrome (ARDS) (group 3). The most suitable treatment option is indirect RV bypass with VA-ECMO. The 2019 European Society of Cardiology guidelines for the management of acute PE defined high-risk PE patients as having hemodynamic instability, PE severity index class III-V or simplified PE severity index ≥ 1, RV dysfunction on transthoracic echocardiogram or computed tomography pulmonary angiography, and elevated cardiac troponin levels. Furthermore, the guidelines suggest VA-ECMO therapy as class IIb, evidence level of C, in combination with surgical embolectomy or catheter-directed treatment and use of rapid short-term support , 72. OneConversely, a group from China reported in its subgroup analysis that the earlier ECMO treatment was associated with lower in-hospital mortality and significant overall survival . In casen = 39) reported that patients who received percutaneous RVAD with ECMO therapy had significantly lower in-hospital and 30-day mortality than patients treated with invasive mechanical ventilation only  were all reported as predictors for the RHF requiring RVAD , destination therapy (OR: 1.69), INTERMACS profiles 1–2 (OR: 1.60), and estimated glomerular filtration rate > 10 mL/min/1.73 ming RVAD .The RV MCS device selection during long-term LV support may largely depend on the duration of the RV support. Unplanned temporary RVAD use was reported with successful RVAD weaning rates of over 60% with a median support duration of 13–17 days , 94–96. As for long-term biventricular support, as discussed, the situation is rare, but it does exist. The options are limited due to the lack of durable MCS devices designed explicitly for RVAD. Currently, these options are: the off-label implantation of CF LVAD as an RVAD ; a paracorporeal pulsatile ventricular assist device as a biventricular support configuration ; and TAH (SynCardia TAH or Aeson TAH). For the timing of RVAD intervention, severe late RHF, which is defined by the requirement for an RVAD at months 3–12, is very rare . HoweverAs for the predictors for RHF, several research efforts are ongoing. The PA pulsatility index predicted the early RHF with a cutoff value of 2.0  . The RV There seems to be major three work fields that should have explored. First, the development of specifically designed, durable RVAD may be required. The specifically designed ventricular assist device that is able to operate on both sides of the heart, such as the Cleveland Clinic Universal Ventricular Assist Device UVAD, , is seenSecond, mobility of percutaneous RVAD must be improved. Currently, Impella RP is inserted from femoral vein because of the inlet of the cannula is designed to place in IVC and 11 Fr sheath (15 Fr outer diameter) stays at cannulation site, therefore, not suitable for rehabilitation. As for ProtekDuo cannula, 29 Fr cannula is inserted from right jugular vein; however, the large-bore cannula may still limit patients' outcome.® system is applicable for this category.Third, the oxygenation support with RVAD may be interesting field to explore. RVAD circuit connecting to membrane oxygenator, known as Oxy-RVAD configuration, has been reported for use in the patient waiting for lung transplant . TandemLWith an increasing incidence of RHF in the last decade, the therapeutic and device options for this pathology remain unmet. While previously underestimated, the RV has triggered interest with the scope of better understanding of the underlying disease pathogenesis in order to provide potential therapeutic options and device solutions. With ongoing effort amongst multiple engineering and clinical groups, there has been a substantial spike in research interest and development of unique device-based target therapies.The device selection for the shorter support duration seemed to have progressed to less invasive. To provide less invasive MCS therapy for RHF, the prediction for the support duration increases its importance. In the LV failure pathogenesis, more than 98% of patients received their LVAD therapy with centrifugal pumps in 2020, and more than 83% of patients were implanted HM3 . This trp = 0.01)  , howeverp = 0.93)  . AdditioFor long-term RVAD support, the currently available option is mainly limited to HM3 off-label use. The most concerning issue with this treatment is RVAD pump thrombosis. Regarding the necessity of outflow graft downsizing, one study operated the HM3 RVAD with a mean RVAD speed of 4,991 rpm and mean RVAD flow of 4.3 L/min . It was Moreover, in this review, we discussed about one-to-one correspondence treatment strategy for each pathogenesis; however, in the real clinical world, the most of the patients are expected to have multiple pathogenesis. For example, the patient in acute exacerbation of American College of Cardiology/American Heart Association stage C heart failure with comorbidity of severe chronic obstructive pulmonary disease, may not be a rare case. Therefore, there may be a situation that LV is not bad as receiving LVAD therapy but RV requires MCS device, to overcome the acute decompensation. For these patients, applying the algorithm for RV MCS device us may be helpful .Lastly, we did not include the RHF after HT because of the complexity of the mechanism and pathogenesis; however, the importance of MCS therapy for RHF is increasing. Moreover, since the first successful human HT was reported in 1967 in South Africa, more than 120,000 patients have received HT therapy , and theTK: manuscript preparation. CM: critical manuscript review. KF: critical revision of article. JK: critical revision of article, approval of article. All authors contributed to the article and approved the submitted version.The Universal Ventricular Assist Device Program is supported by federal funding from the National Heart, Lung, and Blood Institute under grant 5R21HL133871 (to KF).Author KF is a co-inventor of Universal Assist Device. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer MS declared a past co-authorship with one of the authors CM, KF, and JK to the handling Editor.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.