We evaluated if two-dimensional (2D) strain  were consecutively included in this single-center prospective longitudinal study. Echocardiographic evaluation included left atrial and left ventricular (LV) function on P = .02) and radial  ε, and LV torsion  were independent predictors of the primary end-point. Peak LV radial ε  was an independent predictor of CD progression.The primary end-point occurred in 91 patients after a follow-up of 6.5 ± 2.7 years. CD progression occurred in 26 out of 144 patients without cardiac form at baseline (2.88 cases/100 patient-years). Peak LV circumferential (HR 1.09, 95% CI 1.01–1.18, ε derived parameters can be useful for CD progression and mortality prediction.Therefore, 2D  We also evaluated if 2D-Doppler and 2D ε echocardiographic indexes were associated with CD progression from the indeterminate to the cardiac form.Chagas disease (CD) is still a major cause of death in endemic countries and an important cause of morbimortality among immigrant populations in non-endemic countries2The data that support the findings of this study are available from the corresponding author upon reasonable request.This is a single-center prospective longitudinal study. Patients with chronic CD aged between 18 and 80 years were consecutively recruited among those followed at Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil, and referred for echocardiograms between March 2010 and February 2014. CD diagnosis was based on positivity in two different serological tests (enzyme-linked immunosorbent assay and indirect immunofluorescence)From 557 recruited patients, 2 did not consent and 141 were excluded due to concomitant coronary artery disease (n = 14), valvular heart disease (n = 10), hypertensive heart disease (n = 26), congenital heart defect (n = 2), asthma (n = 10), cancer (n = 15), co-infections (n = 4), kidney transplant (n = 1), kidney failure (n = 9), lupus (n = 1), pregnancy (n = 1), inadequate acoustic window (n = 48), and 6 did not return after the index echocardiogram. The final studied population included 408 patients .This study was approved by the institutional review board under number 0059.0.009.000–09 and conformed to standards applied by the Brazilian National Committee for Research Ethics and Resolution 466/2012 of the National Health Council and to the ethical guidelines of the 1975 Declaration of Helsinki. All subjects gave written informed consent before their participation.Patients were classified according to the Brazilian CD consensusPrimary end-point was a composite of all-cause mortality and heart transplant. Patients were followed as previously describedhttp://www4.tjrj.jus.br/SEIDEWEB/default.aspx).Death was classified as sudden, due to stroke, HF, unrelated to CD, or unknown cause. Death was considered sudden when it occurred within 1 h after of symptoms onset, during sleep, or unwitnessed in a previously stable patientSecondary end-point was progression to cardiac form among patients with no evidence of cardiac form at baseline. Progression was defined by the occurrence of new changes in ECG used for diagnosis of CD cardiac formε analyses were performed with Echopac PC workstation software version 108.1.12 . All 2D clips analyzed were acquired at high frame rates (>60 frames/s).Echocardiograms were performed using a phased-array ultrasound system  equipped with M4S phased-array transducer. Cardiac dimensions and Doppler measurements were obtained as recommendedε was determined as previously describedε (LAScd), peak negative global LAε (LASct), and the sum of those previous values (LASr) were obtained.LA ε (LV-GRS), and LV torsion were calculated as previously describedLV-GLS, LV circumferential (LV-GCS), and radial 2.1P values were > 0.10. Data between groups were compared using one-way ANOVA followed by Student-Newman-Keuls post-hoc analysis or contingency tables, as appropriate. Separate multivariable Cox-proportional-hazards regression analyses were performed to test if 2D ε parameters were associated with the primary end-point and if any echocardiographic parameter was associated with CD progression. In case of the primary end-point, multivariable analyses were adjusted for parameters reported as independent mortality predictors in CD: ageContinuous variables were expressed as mean ± standard deviation and categorical variables as absolute and percentage values. Kolmogorov-Smirnov tests provided support that continuous variables were normal, as Receiver operating characteristic (ROC) curves were generated to define cut-off values with corresponding sensitivities and specificities for studied end-points prediction. The optimal cutoff obtained for a ROC curve corresponded to the maximum of the Youden index. Areas under the ROC curve (AUC) were compared by pairwise comparison as described by DeLong et alP < 0.05.Calculations were done using MedCalc version 12.5.0.0  and Stata version 13.0 . The null hypothesis was rejected at 3At baseline, 139 patients (34.1%) had the indeterminate form, 235 (57.6%) the cardiac form , 5 (1.2%) the digestive form, and 29 (7.1%) the cardiodigestive form . Patients with indeterminate and digestive forms were grouped together in a group named “without evidence of cardiac form” and patients with cardiodigestive form were grouped together with patients with cardiac form according to the stage of the cardiac form . The cliThere was a gradual increase in chamber size, decrease in LV and RV systolic function, worsening in LV diastolic function across patients with the cardiac form towards the stage D group, who presented severe LV systolic dysfunction . LA diamε analyses were feasible in all but three participants. Poor imaging quality was the reason to exclude 18 patients (4.4%) from LV-GLS analysis, 21 patients (5.1%) from LV-GCS and LV-GRS analyses, and 42 patients (10.3%) from LV torsion analysis.LA Regarding stain analysis, LA conduit (LAScd) and reservoir (LASr) function were depressed since the initial stages of the cardiac form and further depressed towards the stage D, while the LA contractile function (LASct) was depressed only in those stages with HF (stages C and D). Except for peak LV-GRS, ES LV-GRS, and torsion which were depressed since the stage A of the cardiac form, all other LV strain parameters were depressed since the stage B and further decreased towards stage D group .ε of our group, performed at same equipment and a subgroup of the same population, have already been publishedThe intra- and interobserver variabilities for LA and LV P = 0.63), stage A of the cardiac form , and stage B of the cardiac form .A total of 91 (22.3%) patients presented the primary end-point (89 deaths and 2 heart transplants) during a mean follow-up of 6.5 ± 2.7 years. Patients lost to follow-up  were censored from analysis. The mean LV EF at baseline inside each CD group were similar between patients who were lost or who were not lost to follow-up: without evidence of cardiac form , sudden death in 22 patients (24.7%), stroke in 3 patients (3.4%), unrelated to CD in 9 patients (10.1%), and unknown in 11 patients (12.3%). The unrelated to CD deaths were due to: septic shock (n = 3), breast cancer (n = 1), chronic obstructive pulmonary disease (n = 1), electric shock (n = 1), and gastrointestinal complications (n = 3).Multivariable Cox-proportional-hazards regression analyses models revealed that peak LV-GCS, ES LV-GCS, peak LV-GRS, ES LV-GRS, peak torsion and twist were independent predictors of the primary end-point . The fulThe implantation of cardiac devices may influence the mortality outcome by precluding or postponing cardiovascular death. During this study follow-up, 21 patients received a permanent pacemaker, 21 patients received an implantable cardioverter-defibrillator, and two patients received a cardiac resynchronization therapy device. Among these 44 patients, 20 subsequently presented the primary end-point.P < .0001), for ES LV-GRS was 15.9% , for peak LV-GCS was −15.7% , for ES LV-GCS was −10.3% , for LV twist was 8.10 , and for LV torsion was 1.030/cm . All these variables of interest presented similar AUC , while 2 patients progressed to stage B1, and 1 patient to stage C. The criteria for CD progression were new change in ECG , wall motion changes (n = 2), sustained VT (n = 1), and HF (n = 1). The patient who progressed to stage C also presented primary T wave changes on ECG and severe LV systolic dysfunction on echocardiogram. One patient with wall motion abnormality on echocardiogram also presented 16 months later a RBBB on ECG. One patient whose CD progression criteria was a RBBB, also presented wall motion abnormality 18 months later and finally progressed to HF 2.5 years after RBBB diagnosis.Multivariable Cox-proportional-hazards regression analyses revealed that peak systolic mitral annulus velocity (LV S’), E’ velocity, and peak LV-GRS were independent predictors of CD progression . The meaP = .03), for E’ velocity was 11.9 cm/s , and for peak LV-GRS was 41.78% . All these variables of interest presented similar AUC.Optimal cutoff values to predict the secondary end-point for LV S’ was 8.65 cm/s  and LV-GRS ≤ 41.8% In our study, LV-GLS was not an independent mortality predictor in multivariable analysis that included LV EF among the adjusting variables. LV-GLS evaluates the function of longitudinally orientated myofibers, which are located in the subendocardiumε parameters were impaired only since the stage B of CD cardiac form. Furthermore, others found a significant difference in ES LV-GRS between patients with the indeterminate form and controlsOn the other hand, LV-GCS, LV-GRS, and LV torsion were long-term independent mortality predictors in our study. Accordingly, others described in patients with HF that LV-GCSThe identification of CD progression predictors is still a challenge. The slow pace of CD progression makes necessary large long-term longitudinal studies, as the present study. The 95% confidence limits of the CD progression rate reported by us is within the reported incidence described by Mota et al (2.57/100 patient-years)4.1ε instead of a dedicated software for LA ε, use of the onset of the P wave as the reference frame set to zero LA ε, and lack of an external validation. Measurement of LA ε has other limitations as outlined elsewhereOur study limitations include the use of the same software to measure LV and LA Multicollinearity is a potential limitation in multivariable analyses, however the VIF results of the variables used to adjust the multivariable models were under 5, which indicates no evidence of a multicollinearity problemAnother possible limitation in survival studies is the incidence of events that preclude the occurrence of the studied end-point. These are considered competing risks4.2ε parameters predicted all-cause mortality or heart transplant in patients with CD independent of clinical and 2D-Doppler echocardiographic indexes. This finding allows the design of validation studies in order to further support the incorporation of such parameters in routine evaluation of patients with CD. Tissue Doppler and LV ε parameter predicted CD progression from the indeterminate to the cardiac form. The identification of patients with higher risk of CD progression is very important as those may benefit from treatment with trypanocide drugs.In conclusion, LV 510.13039/501100004586Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro, Brazil [grant numbers E-26/201.561/2014 and E-26/110.176/2014 to Dr Saraiva], and Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil .The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


Cumulative blood pressure (BP) exposure is a known risk factor for cardiovascular disease. This study sought to investigate the association between cumulative BP from early adulthood to middle age and right ventricular (RV) structure and function in middle age.We included 2844 participants from the CARDIA study (Coronary Artery Risk Development in Young Adults). Cumulative BP over the 30‐years follow‐up was defined as the sum of the product of mean BP for each pair of consecutive examinations and the time interval between these two consecutive examinations in years. RV structure and function were assessed by echocardiography. The main analyses utilized logistic and linear regression models.In fully adjusted models, higher cumulative systolic BP was independently associated with lower tricuspid annular plane systolic excursion (TAPSE), right ventricular peak systolic velocity (RVS′), right ventricular early diastolic velocity (RVe′), and higher pulmonary arterial systolic pressure. Higher cumulative diastolic BP was independently associated with smaller RV basal diameter, lower TAPSE, RVS′, and RVe′. For categorical analyses of RV dysfunction, cumulative systolic BP was not related to systolic dysfunction. Per 1‐SD increase in cumulative systolic BP was associated with a higher risk of diastolic dysfunction, while an increase in cumulative diastolic BP was associated with a higher risk of systolic dysfunction and diastolic dysfunction.Cumulative exposure to increased BP from early adulthood to middle age was associated with incipient RV systolic and diastolic dysfunction in middle age. Exposure to higher diastolic BP levels from early adulthood to middle age was associated with a smaller RV basal diameter in middle age. Detailed descriptions of the design, recruitment, and protocol for examinations have been described previously.The present study included participants who had BP measurements on three or more visits between baseline and Year 30, and who underwent comprehensive echocardiography at Year 30. Among 5115 participants, 2271 participants were excluded: 1756 did not attend the year‐30 examination, 502 did not undergo echocardiography at Year 30 and 13 did not have BP measurement data for three or more visits. The final analytic cohort was composed of 2844 participants.3BP was measured at each CARDIA visit and reported as the average of second and third readings taken by trained personnel using a Hawksley random‐zero sphygmomanometer  or a digital BP monitor . A calibration study was performed and standardized to the sphygmomanometer measure to remove any potential machine bias. Cumulative systolic BP was calculated for each participant as the sum of the product of mean systolic BP for each pair of consecutive examinations and the time interval between these two consecutive examinations over 30 years of follow‐up. Cumulative diastolic BP was calculated in an analogous manner.4Comprehensive echocardiography, including two‐dimensional (2D), M‐mode, Doppler, and tissue Doppler, was performed at the year‐30 examination conforming to American Society of Echocardiography guidelines.e′) at the septal and lateral walls. Pulsed Doppler‐derived E‐wave from mitral inflow was used to derive the E/e′ ratio, a surrogate for LV filling pressures. LV end‐diastolic volume and LV ejection fraction were measured by biplane Simpson's method to assess LV systolic function. The latest American Society of Echocardiography guidelines recommended cut‐off values for defining RV systolic and diastolic dysfunctions as follows: RVS’ < 9.5 cm/s or TAPSE < 17 mm/s and RVe′ < 7.8 cm/s.Right ventricular basal diastolic dimension was acquired from a 2D four‐chamber view. Tricuspid annular plane systolic excursion (TAPSE) was measured as the peak excursion of the lateral tricuspid annulus in the apical four‐chamber view using an M‐mode cursor. Tissue doppler imaging was used to assess tricuspid annular peak systolic velocity (right ventricular peak systolic velocity [RVS′]), tricuspid annular early diastolic velocity (right ventricular early diastolic velocity [RVe′]), and tricuspid annular late diastolic velocity (right ventricular late diastolic velocity [RVa′]). The tricuspid regurgitant (TR) jet velocity was measured in triplicate using continuous‐wave Doppler echocardiography. Pulmonary arterial systolic pressure (PASP) was determined from the TR jet velocity using the modified Bernoulli equation, and combining this value with an assumed right atrial pressure of 10 mm Hg (PASP = 4[TR jet velocity]2 + 10 mm Hg). The higher the RVS′ or TAPSE, the better the RV systolic function. The higher the RVe′, the better the RV diastolic function. Left ventricular (LV) diastolic function was assessed by tissue Doppler‐derived mitral annular velocity  was calculated as weight (kg) divided by height in meters squared. Lung function measurements included FVC  and FEV1 (forced expiratory volume in one second).6χ2 test for categorical data, and the independent Student t test and Mann–Whitney U were used for normally and nonnormally distributed continuous variables, respectively. Multivariable linear regression models were used to assess the association between cumulative BP over 30 years and echocardiographic parameters measured at Year 30 . Multivariable models were adjusted for the following traditional cardiovascular disease risk factors. Model 1 is unadjusted; Model 2 included age, race, gender, BMI, current smoking status, educational level, antihypertensive medications, total cholesterol, high‐density lipoprotein, fasting glucose, physical activity, FVC, and FEV1 at Year 30; Model 3 included the variables in Model 2 and left ventricular ejection fraction, E/e′ septal, E/e′ lateral, left ventricular mass and left ventricular end‐diastolic volume as LV function. In addition, restricted cubic spline analysis with four knots was used to explore the nonlinear dose–response relationship between cumulative BP over 30 years and echocardiographic parameters measured at Year 30.Normally distributed continuous variables were presented as mean (SD), while non‐normal data were presented as the median and interquartile range. Categorical variables were presented as counts (percentages). Differences between groups were tested by the For categorical analyses of clinically significant RV dysfunction, binary logistic regression models were performed to estimate the association between cumulative BP over 30 years and clinically relevant RV dysfunction at Year 30. In multivariate logistic regressions, we adjusted for similar covariates, reporting odds ratios (ORs) and 95% confidence intervals (CIs). Potential effect modification by race and sex was assessed.p < .05 was considered as statistically significant.All analyses were performed using R 3.6.2 software and a 7Overall, the study cohort included a total of 2844 participants . Table β = −.21, p < .05), RVS′ , RVe′  and higher PASP . Higher cumulative diastolic BP was independently associated with smaller RV basal diameter , lower TAPSE , RVS′ , RVe′ , and higher PASP .Table p = .396). Per 1 SD increase in cumulative systolic BP was associated with a higher risk of diastolic dysfunction , while an increase in cumulative diastolic BP was associated with a higher risk of systolic dysfunction  and diastolic dysfunction .Results from the binary logistic regression models to examine the association between cumulative BP exposure and RV dysfunction are summarized in Table p for nonlinearity = .398 and .640, respectively). Linear association was detected between cumulative DBP and TAPSE, RVS′, and RVe′ (p for nonlinearity > .05). There was no evidence of effect modification by sex and race for the cumulative BP‐RV structure and function associations , except for the cumulative BP‐RV basal diameter association which was influenced by sex (p interaction = .004 for cumulative SBP and .029 for cumulative DBP).Figure 8E/e′ septal, E/e′ lateral, left ventricular mass and left ventricular end‐diastolic volume).In this large population‐based study of generally healthy young adults followed over 30 years, several important findings were observed. First, higher cumulative BP exposure from early adulthood was associated with RV dysfunction in middle age. Second, cumulative diastolic BP was more strongly associated with worse RV function parameters compared with cumulative systolic BP. Third, cumulative diastolic BP was associated with smaller RV basal diameter in middle age. Finally, these associations were independent of several confounders, including anthropometric relationships, demographic and clinical variables, as well as the corresponding LV parameters  were not available for CARDIA patients at Year 30. However, TAPSE, RVS′, and RVe′ are easy to perform, with very low inter‐ and intraobserver variability. Finally, few patients had RV systolic dysfunction. Thus, overadjustment might have been a problem in the multivariable logistic regression.This study also has some limitations. First, baseline measures of echocardiographic RV structure and function are not available. Thus, we cannot rule out the possibility of reverse causation. However, the youth and good health of our study population at baseline make it less likely to be related to subclinical dysfunction in baseline cardiac function. Second, echocardiographic data were available in only approximately 50% of the CARDIA participants. Thus there is a potential for selection bias in the observed associations. Third, this study used M‐mode‐derived TAPSE and tissue Doppler‐derived RVS′ as measures of RV systolic function and tissue Doppler‐derived RVe′ as measures of RV diastolic function. Other commonly traditional parameters such as RV Fractional area change, Tei index, speckle tracking echocardiography, and RV 10Cumulative exposure to higher systolic and diastolic BP over 30 years from early adulthood to middle age is associated with incipient RV systolic and diastolic dysfunction in middle age. Exposure to higher diastolic BP levels from young adulthood to midlife is associated with a smaller RV basal diameter in midlife.The authors declare that there are no conflict of interests.


To explore whether multiparametric approach including blood oxygenation level-dependent MRI (BOLD-MRI) and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) can be applied in the assessment of renal function in children with chronic kidney disease (CKD).Dt, Dp, and fp values on BOLD and DWI images. Appropriate statistical methods were applied for comparing MRI-derived parameters among the three groups and calculating the correlation coefficients between MRI-derived parameters and clinical data. Receiver operating characteristic (ROC) curves were used to assess the diagnostic performance of MRI-derived parameters.This prospective study included 74 children  for renal MRI examinations including coronal T2WI, axial T1WI and T2WI, BOLD-MRI, and DWI sequences. We measured the renal cortex and medulla T2*, ADC, Dt, fp and medulla T2*, ADC, Dt among the three groups. Cortex T2*, ADC, Dt, fp and medulla T2*, ADC, Dt had a trend: CKD stage 4–5 < CKD stage 1–3 < healthy volunteers. Cortex and medulla T2*, ADC, Dt were significantly correlated with eGFR, serum creatinine (Scr), cystatin C. In addition, cortex T2* and eGFR showed the highest correlation coefficient . Cortex Dt and medulla T2* were optimal parameters for differentiating healthy volunteers and CKD stage 1–3 or CKD stage 4–5 and CKD stage 1–3, respectively.There were significant differences in cortex T2*, ADC, BOLD-MRI and IVIM-DWI might be used as a feasible method for noninvasive assessment of renal function in children with CKD. Cortex T2*, ADC, Dt, fp and medulla T2*, ADC, Dt had a trend: CKD stage 4–5 < CKD stage 1–3 < healthy volunteers.Cortex and medulla T2*, ADC, Dt were all significantly correlated with eGFR, serum creatinine, cystatin C.Cortex Dt and medulla T2* were optimal parameters for differentiating healthy volunteers and CKD stage 1–3 or CKD stage 4–5 and CKD stage 1–3, respectively.BOLD-MRI and IVIM-DWI might be used as a feasible method for noninvasive assessment of renal function in children with CKD.Chronic kidney disease (CKD) is recognized as a common disease globally. The worldwide prevalence of CKD is estimated to be 13.4%, and patients with end-stage renal disease (ESRD) requiring renal replacement therapy are estimated between 4.902 and 7.083 million , S0 represents the signal intensity when b = 0 s/mm2, Sb represents the signal intensity at a specific b value, Dt indicates the true diffusion coefficient, Dp indicates the pseudo-diffusion coefficient, and fp indicates the perfusion fraction. Specifically, ADC values were calculated based on a monoexponential fit using two specific b values  according to the equation: Sb/S0 = e−bADCmon. Figures IVIM-DWI. We used the post processing software offline provided by MR Body Diffusion Toolbox v1.4.0  to obtain IVIM-DWI parameters. Freehand cortex and medulla ROIs were delineated bilaterally on renal hilar slice to calculate the mean values of IVIM-DWI parameters. Cortical ROIs 5–10 cm were del−1.154 × Age−0.203 × 0.742  × 1.233 (if Chinese) [For all patients, venous blood samples were collected within 10 days before the MRI examination. We measured serum creatinine (Scr) levels, albumin/creatinine ratio (ACR), serum albumin and cystatin C and calculated the eGFR by using the modification of diet in renal disease (MDRD) equation. eGFR = 186 × ScrChinese) . CKD1: eAll patients underwent ultrasound-guided kidney biopsies and performed by two renal pathologists within 1–2 days after completing the MR examination in our research. We selected the lower pole of the right kidney as the biopsy position and fewer than 8 glomeruli were not included to the study which was similar to the method used by previous study . All renp < 0.05 were considered significantly different in statistics. We used the Shapiro–Wilk test  to assess the normality. Quantitative data was shown as means ± standard deviations. We employed ANOVA to compare the differences of various clinical values and parameters among the three groups. The least-significant difference (LSD) test was applied to find differences between the further two relevant groups. Pearson product-moment correlation coefficient was performed to study the relationship between clinical data and imaging parameters. We calculated the intraclass correlation coefficients (ICCs) to assess the interobserver agreements .SPSS  was used for statistical analysis and the values of p = 0.449 and p = 0.051, respectively). The values of eGFR, Scr, ACR and cystatin C showed significant differences among the three groups . The Scr, ACR and cystatin C increased with the decrease of eGFR. Serum albumin showed no significant difference between CKD stage 1–3 and CKD stage 4–5 (p = 0.641). Underlying disease types included henoch–schonlein purpura nephritis, lupus nephritis, IgA nephropathy, chronic glomerulonephritis, primary nephrotic syndrome, vesicoureteral reflux, unknow. Table Sixty-three patients with CKD and 11 healthy volunteers were included in the statistical analysis . There were no significant differences in sex and age among the three groups . Therefore, a measurement result was randomly selected from two radiologists for the statistical analysis. The ICC values for different MRI-derived parameters were present in Table Dt, fp and medulla T2*, ADC, Dt among the three groups. Cortex Dp and medulla Dp, fp were not significantly different among the three groups. The values of cortex T2*, ADC, Dt, fp and medulla T2*, ADC, Dt were in the order of healthy volunteers > CKD stage 1–3 > CKD stage 4–5. The results of comparisons were shown in Fig. There were significant differences in cortex T2*, ADC, Dt were all significantly correlated with eGFR, serum creatinine, cystatin C. In addition, cortex T2* and eGFR showed the highest correlation coefficient . The correlations between the clinical data and MRI-derived parameters were presented in Fig. Cortex and medulla T2*, ADC, Dt generated the highest area under the curve  for differentiating CKD stage 1–3 from healthy volunteers with sensitivity of 60.78%, specificity of 100%, and a cut-off value of 1.697 × 10−3mm2/s. Medulla T2* showed the highest AUC  for differentiating CKD stage 1–3 from CKD stage 4–5 with sensitivity of 92.16%, specificity of 83.33%, and a cut-off value of 22.9 ms.To compare the capacity of MRI-derived parameters to differentiate CKD stage 1–3 from healthy volunteers or CKD stage 4–5, ROC curve analysis was performed Fig. , Table 6Dt were significantly related to eGFR, Cystatin C and Scr and enable to assess kidney function in children with CKD. Furthermore, the cortical and medullary parameters obtained from MRI had favorable inter-observer consistency.In this research, we focused on the potential diagnostic performance of T2* relaxation time, ADC, and IVIM MRI-derived parameters in children with CKD. The results of this research showed that T2*, ADC and BOLD-MRI, which is based on the paramagnetic properties of deoxyhemoglobin and does not need for the introduction of contrast agents, can non-invasively assess the oxygenation of the human kidney tissue . PreviouDWI is a promising MRI technology applied to investigate the diffusion and movement of water molecules, reflecting the changes in the microstructure of biological tissues . PreviouDt (the true diffusion coefficient), Dp (the pseudo-diffusion coefficient), and fp (the perfusion fraction). Previous study showed that IVIM-DWI can separate the influence of Fp from true diffusion and improve the evaluation of chronic changes in renal tissue [IVIM-DWI, which uses multiple b-values to perform biexponential fitting on DWI, is a more advanced MRI technology compared with the ADC obtained from the monoexponential fitting from DWI and can provide more information about water molecule. IVIM-DWI is able to differentiate between diffusion in extra- and intravascular space: l tissue .Dt also showed significantly positively correlated with cystatin C, eGFR and serum creatinine . However, its correlations were not as obvious as ADC values and this result was not consistent with previous research results [Dt were in the order of healthy volunteers > CKD stage 1–3 > CKD stage 4–5.In our study, cortex and medulla  results . However results . The conDp, fp. These perfusion-related parameters may have important clinical significance because hemodynamic changes occurred during the process of renal interstitial fibrosis formation, such as decreased blood flow of capillaries around renal tubules and changes in vascular endothelial growth factor [fp showed significant differences between healthy volunteers, CKD stage 1–3 and CKD stage 4–5 among these perfusion-related parameters. Previous study showed similar results with our study and demonstrated that fp had a significant negative correlation with the area of fibrosis, whereas Dp did not show a significant relationship [Dt and ADC were positively correlated with contrast-enhanced MRI GFR. In a previous research of CKD patients by Mao et al. [fp and Dp were significantly negatively correlated with eGFR and the histopathological fibrosis score. Therefore, this indicates that the perfusion-related parameters from IVIM-DWI may be related to the progression of renal fibrosis, but they are currently not robust enough to be used in the clinical setting. The following factors may have contributed to the discrepancies between studies: the different number and size of b-values, and the contrary research groups.We can further investigate the perfusion-related parameters by IVIM MRI, such h factor , 31. In tionship . Bane ettionship  also shoo et al. , both fpThere were several limitations of our study. First of all, this was a single-center research, and the numbers of CKD stage 4–5 were relatively small, which may influence the clinical application of the conclusion. Second, the ROI technique used in this research was the most commonly used clinically but relatively old method. When the kidney function was in good condition, the ROI is easy to place. For patients with ESRD, it was difficult to place ROI due to the lack of visually distinguishable distinction between the renal cortex and medulla. The twelve-layer concentric objects (TLCO) method is currently the most commonly recommended method . Third, Dt values, might be feasible for noninvasive assessment of renal function in children with CKD.In conclusion, multiparametric MRI including BOLD MRI and IVIM-MRI, especially T2* relaxation time, ADC and


We present a case of a 62-year-old male who was admitted to the hospital with out-of-hospital ventricular fibrillation (VF) arrest. He had a VF arrest in 2011 and was admitted to another hospital. He had several investigations excluding cardiac magnetic resonance imaging, all of which were normal. He was playing tennis on both occasions when he experienced the VF arrest. His electrocardiogram on admission showed AF with partial right bundle branch block, inverted T waves in V1-V2, low voltage QRS complexes, ventricular ectopic in lead V1-V2, and prolonged QTc. His echocardiogram showed normal left ventricular function and a dilated right ventricle. Cardiac magnetic resonance imaging showed a dilated RV cavity size with impaired systolic function and dyskinetic region in the mid-ventricular free wall proximal to the insertion of the moderator band and late gadolinium enhancement in both right and left ventricles insertion points and mid-wall late gadolinium enhancement in the basal inferolateral wall suggestive of arrhythmogenic right ventricular cardiomyopathy. He had a single chamber VVI implantable cardioverter-defibrillator fitted for primary prevention and was discharged home. He had outpatient follow-up and showed good improvement and his implantable cardioverter-defibrillator checks were satisfactory and did not experience any shocks. Arrhythmogenic right ventricular cardiomyopathy (ARVC) was first described by Frank and Fontain in 1978 based on findings in six patients presenting with ventricular tachycardia . This reA 62-year-old man had sudden-onset ventricular fibrillation (VF) induced cardiac arrest whilst he was playing tennis. He had bystander cardiopulmonary resuscitation (CPR) for 10 minutes later and was given three shocks by the London ambulance services team (LAS) for ventricular fibrillation. The patient had a return of spontaneous circulation (ROSC) and was admitted to the intensive care unit (ITU) following intubation in the emergency department. He had a similar VF cardiac arrest 10 years ago while playing tennis and was admitted to another hospital, however, we did not have access to his medical records from that admission. Based on the patient information, he had several investigations including normal echocardiography and coronary angiogram, and the cause for his VF arrest was not identified. He however did not have cardiac magnetic resonance imaging (CMR). According to the patient, an implantable cardioverter-defibrillator was not offered to him during his previous admission in view of no ischaemic cause for the VF arrest.His current admission electrocardiogram (ECG) showed AF with good rate control, partial or incomplete right bundle branch block (RBBB), and prolonged QTc of 473 milliseconds Figure , and parHis lab tests results are shown below in Table He underwent an emergency coronary angiogram which showed normal coronary arteries. He had a computerised tomographic pulmonary angiogram (CTPA) that showed enlarged right ventricle, bi-basal consolidation, and broken anterior ribs likely due to cardiopulmonary resuscitation (CPR) Figure .Following this, he had a repeat echocardiogram two weeks later that showed good LV function of about 60%, bi-atrial dilatation, dilated RV, and moderate tricuspid regurgitation (TR). He had a ventilation/perfusion scan in view of his enlarged right ventricle that did not show any pulmonary embolism (PE). He had CMR following this to assess for ARVC which showed dilated and impaired RV with dyskinesia of the mid-ventricular segment of the RV free wall Figures -4. The LHe remained in permanent AF and was anticoagulated. He attended outpatient follow-up and ICD check that was satisfactory and has made a good recovery since.Hypertrophic heart disease is followed by ARVC as the second-most common cause of death in young patients and it can also present in middle-aged patients. As the disease is more common in young adults and adolescents who may present with palpitations, fatigue, or syncope episode, it is important for paediatricians to be aware of this condition as young patients can face sudden unexpected death from the disease. Marcus et al. in 1982 described the disease as ARVD as they believed the disease to be caused by congenital weakness in the development of the right ventricle . Thiene The true incidence of ARVC is unknown; however, the prevalence amongst the general population is approximately 0.02-0.1% . The preSeveral case reports of ARVC causing sudden death in young patients have been published over the last two decades and most of these patients were diagnosed on post-mortem biopsies. Choung et al. (2017) reported a case of a 26-year-old east African professional athlete who was 36-37 weeks pregnant, suffering a cardiac arrest in a restaurant, and had a history of previous cardiac arrest. She had been diagnosed with right ventricular outflow tract-induced ventricular tachycardia in the past which was associated with her previous cardiac arrest and underwent ablation. She had unsuccessful resuscitation and autopsy findings showed a focal area of myocardial thinning at the right ventricular apex, and histology of the cardiac biopsy confirmed ARVC findings such as myocardial cell degeneration and replacement by adipose tissue . Low et Wu et al. (2021) published a case report of a 43-year-old patient with three syncopal episodes during exercise and was found to be in VT in the emergency department and was administered intravenous propafenone to terminate his VT . His repARVC should be always be considered as the most likely diagnosis in patients with ECG and overt structural changes. It has four particular phases consisting of concealed phase, apparent electric disorder, right ventricular failure, and the advanced phase with severe diffuse bi-ventricular failure resembling dilated cardiomyopathy . The conThere is a lack of gold-standard tests or pathognomonic criteria for making a definitive diagnosis of ARVC. The revised 2020 Task Force Criteria for diagnosis of ARVC is based on the presence of major criteria and minor criteria (Table Each major criteria is scored two points and each minor criteria is scored one; at least two major criteria or one major and two minor criteria, or four minor criteria should be present to give a score of four to make a diagnosis of ARVC. The diagnosis of ARVC is considered to be borderline in patients with a score of three points . The 201In summary, our case involved a 62-year-old male patient who had two out-of-hospital ventricular fibrillation cardiac arrests and was successfully resuscitated both times. The results of his coronary angiogram were normal and cardiac magnetic resonance imaging features were suggestive of the diagnosis of arrhythmogenic right ventricular cardiomyopathy and his cardiac biopsy revealed subendocardial fibrosis. He had an implantable cardioverter-defibrillator implanted to minimize the risk of future sudden cardiac death.Arrhythmogenic right ventricular cardiomyopathy is a rare inherited cardiac muscle disease and should be considered as a possible cause in young patients presenting with ventricular tachyarrhythmias as they are at risk of sudden death if not appropriately managed. It is important for physicians to be aware of the possibility of arrhythmogenic right ventricular cardiomyopathy in young adults who may present with palpitations, fatigue, and syncope or exercise-induced cardiac arrest. Making a diagnosis of arrhythmogenic right ventricular cardiomyopathy can be difficult and patients with ARVC should be offered implantable cardioverter-defibrillator for primary prevention to prevent sudden death. These patients may have right ventricular dilatation alone or biventricular dilatation.


The transforming growth factor β1 (TGFβ1), whose level may depend onthe polymorphism of the TGFB1 gene, is involved in the formation of myocardialfibrosis. Myocardial fibrosis in a cardiac allograft may lead to aheart’s structural and functional remodeling and subsequent dysfunction.The frequency of occurrence of alleles and genotypes of the TGFB1 genepolymorphic regions rs1800469, rs1800470, and rs1800471 in heart transplantrecipients and their association with graft myocardial fibrosis were analyzed.Carriers of the CC genotype ,and more often the G allele of rs1800471 , were found among heart transplant recipients less frequentlythan among healthy individuals. In patients with ischemic heart disease (IHD),the GG genotype was less common , while the A allele of rs1800469 was found more frequently than in patients with dilatedcardiomyopathy (DCM). In heart transplant recipients with the AA genotype ofrs1800470, myocardial fibrosis, verified by endomyocardial biopsy, was detectedmore often than in carriers of the G allele . The revealed differences suggest a relationshipbetween TGFB1 gene polymorphism and graft myocardial fibrosis. Studies on alarger group of patients would make it possible to characterize the influenceof genetic factors on the formation of myocardial fibrosis in heart transplantrecipients. The number of patients with heart failure is constantly on the rise as the meanlife expectancy increases, while mortality due to acute medical conditions inyoung and middle-aged individuals declines. Heart transplantation is anefficient method for treating end-stage heart failure that improves theprognosis and quality of life of patients. The recently observed increase inthe longevity of heart transplant recipients has been achieved mainly thanks toa reduction in the mortality rate during the early posttransplant period.Myocardial fibrosis, whose development is accompanied by structural andfunctional remodeling of the cardiac graft, is among the factors with anunfavorable impact on the long-term outcome of heart transplantation .Graft myocardial fibrosis is a multifactorial process, with a number ofcellular and molecular factors predisposing one to it . Recent The finding that the TGFβ1 level in the peripheral blood is geneticallydetermined is now a fact. Some genetic polymorphisms of the TGFB1 gene wereshown to be associated with the severity of coronary artery atherosclerosis andgenetic predisposition to myocardial infarction; this association varies fordifferent ethnic groups , 5.The TGFβ1 protein is encoded by the TGFB1 gene residing on chromosome 19.Eight single nucleotide polymorphisms and a deletion/insertion polymorphismaffecting the expression and activity of TGFβ1 have been identified thusfar . ResearcThis study aims at uncovering any association between the rs1800469, rs1800470,and rs1800471 polymorphisms of the TGFB1 gene and myocardial fibrosis incardiac allograft in heart transplant recipients.A total of 110 randomly selected heart transplant recipients who had undergonecardiac allograft transplantation at the Shumakov National Medical ResearchCenter of Transplantology and Artificial Organs in 2017–2019 wereenrolled in the study. All study participants were ethnic Russians; of those,99 (84%) patients were males: the recipients’ mean age was 44 ± 14(range: 16–70) years. The reason for the development of the end-stageheart failure responsible for the indications to transplantation was dilatedcardiomyopathy (DCM) in 57 patients and ischemic heart disease (IHD) in 53patients. The duration of the follow-up period after heart transplantationextended up to 4 (2.3 ± 1.3) years.The patients were examined and treated in compliance with the clinicalguidelines of the Russian Transplant Society. Endomyocardial biopsy for hearttransplant recipients was performed according to the protocol during scheduledclinical laboratory examination or if there were respective indications.Endomyocardial biopsy specimens were assessed based on the histological andimmunohistochemical data. Thin sections of endomyocardial tissue were subjectedto Masson’s trichrome staining to confirm fibrosis in a cardiac allograft.™ amplification system . The probesfluorescently labeled using VIC /FAM  channels weredetected at each amplification cycle. The resulting data were analyzed usingthe BioRad CFX manager 3.0 software.Genomic DNA was isolated from peripheral blood in accordance with the protocol,using a commercial QIAamp DNA Blood Mini Kit on a QIAcube™ automatedanalyzer . The rs1800469, rs1800470, and rs1800471polymorphisms of the TGFB1 gene were analyzed by real-time polymerase chainreaction using TaqMan probes  on aCFX96The statistical analysis was carried out using the suite of applied softwarefor research and engineering computations IBM SPSS STATISTICS 20 . In order to prove an independent distribution of alleles in theanalyzed polymorphisms, their compliance to the Hardy–WeinbergEquilibrium was tested . ThefreGenomic typing of the rs1800469, rs1800470, and rs1800471 polymorphisms of theTGFB1 gene in heart transplant recipients was conducted. No deviations in thedistribution of the alleles and genotypes from the Hardy–WeinbergEquilibrium were revealed in the sex- and age-matched control group, consistingof healthy individuals (43). Compliance with the Hardy–WeinbergEquilibrium was detected in none of the heart transplant recipients for allthree polymorphisms .The deviation from the Hardy–Weinberg Equilibrium in the heart transplantrecipient group can be associated with a cardiovascular pathology, although theeffect of a small sample size should not be ruled out; so, a larger sample isneeded for testing.A comparative analysis of the distribution of the genotypes and alleles of thers1800469 and rs1800470 polymorphisms of the TGFB1 gene detected no differencesbetween healthy individuals and heart transplant recipients. However, somedifferences in the distribution of the alleles and genotypes of the rs1800471polymorphism of the TGFB1 gene were found.Carriers of the CC genotype of the rs1800471 polymorphism of the TGFB1 genewere found among heart transplant recipients less frequently than among healthyindividuals , while carriers ofthe G allele were found more often (within the GG and GC genotypes) .An analysis of the association between the frequencies of distribution of thestudied polymorphisms and the demographic and clinical characteristics of theheart transplant recipients revealed statistically significant associationswith sex, diagnosis, and myocardial fibrosis in a cardiac allograft.The distribution of the alleles and genotypes of the rs1800470 polymorphism ofthe TGFB1 gene differed significantly among male and female heart transplantrecipients .Male heart transplant recipients were less likely to carry the GG genotype thanfemales (p ≤ 0.05). A comparison of the frequencies of individual allelesshowed that the frequency of the A rs1800470 allele of the TGFB1 gene is higherin males . No differences inthe distribution of the genotypes and alleles of the rs1800469 and rs1800471polymorphisms of the TGFB1 gene among males and females were revealed.A comparison analysis of the frequencies of the alleles and genotypes of thepolymorphisms in the TGFB1 gene depending on the disease responsible for theheart failure and subsequent cardiac allograft transplantation revealed thatpatients with DCM carried the GG genotype of rs1800469 more frequently thanpatients with IHD did .The frequency of the A allele among patients with IHD was higher than thatamong patients with DCM .Examination of the endomyocardial biopsy specimens showed that myocardialinterstitial fibrosis in cardiac allografts was verified in 49 out of 110transplant recipients. Staining made it possible to clearly discern theconnective tissue, which was colored in various shades of blue (depending onits maturation state) and differed from other cardiac muscle tissues. Allfibrosis types  were taken into accountduring the analysis.A comparative analysis of the frequency and genotype distribution revealeddifferences in the frequency of the AA genotype of the rs1800470 polymorphismof the TGFB1 gene in heart transplant recipients with and without myocardialfibrosis .Heart transplant recipients carrying the AA genotype of the rs1800470polymorphism of the TGFB1 gene were more likely to have fibrosis than thosecarrying the G allele .This study has analyzed the distribution of the alleles and genotypes of threefunctionally significant polymorphisms of the TGFB1 gene in heart transplantrecipients. In heart transplant recipients, differences in the frequency ofoccurrence of genotypes and alleles of the rs1800471 polymorphism of the TGFB1gene were found in comparison with healthy individuals. A number of studieshave shown that the G allele of the rs1800471 polymorphism is associated with ahigher level of gene expression and elevated blood level of TGFβ1.Dysregulation of the TGFβ1 signaling pathway caused by a mutation can beassociated with an increased risk of cardiovascular diseases , 13.When analyzing the genetic predisposition to the primary disease that had beenresponsible for the end-stage heart failure and had made it necessary toperform heart transplantation, we observed a significant association betweenischemic heart disease and the rs1800469 single nucleotide polymorphism.Similar data were obtained by Barsova et al. . Liu et Having analyzed the genetic predisposition to myocardial fibrosis in hearttransplant recipients, we found significant associations between this trait andthe rs1800470 polymorphism. The A allele of this polymorphism is known to beassociated with a high level of TGFβ1 in peripheral blood. TGFβ1 is apotent stimulator of extracellular matrix production; its hyperproduction isassociated with fibrotic disorders and the development of myocardial fibrosis.Leask  showed tThis study has revealed the differences in occurrence of the alleles andgenotypes of the TGFB1 gene: the rs1800471 polymorphism in heart transplantrecipients and healthy individuals, the rs1800469 polymorphism in patients withDCM and IHD, and the rs1800470 polymorphism in patients with and withoutmyocardial fibrosis in a cardiac allograft. The findings give grounds forassuming that the TGFB1 gene and its polymorphic variants are involved in theformation of genetic predisposition to myocardial fibrosis in heart transplantrecipients. Further studies using a larger cohort of patients would providemore specific characteristics of the impact of single nucleotide polymorphismson the development of fibrosis in a cardiac allograft.


Objectives: To investigate the correlation of cardiac magnetic resonance (CMR) feature-tracking with conventional CMR parameters in patients with a first anterior ST-segment elevation myocardial infarction (STEMI).Methods: This sub-analysis of OCTAMI  registry included 129 patients who finished a CMR examination 1 month after a first anterior STEMI. Cine images were applied to calculate both global and segmental left ventricular peak strain parameters. The patients were divided into two groups by left ventricular ejection fraction (LVEF) and compared with 42 healthy controls. Segmental late gadolinium enhancement (LGE) was graded according to LGE transmurality as follows: (1) >0 to ≤ 25%; (2) >25 to ≤ 50%; (3) >50 to ≤ 75%; (4) >75%. Left ventricle was divided into infarcted, adjacent, and remote regions to assess regional function.Results: Compared with controls, global radial , circumferential , and longitudinal  strains were impaired in STEMI patients with normal LVEF (≥55%). Strain parameters were strongly associated with LGE . A significant and stepwise impairment of global strains was observed in groups divided by LGE tertiles. Furthermore, segmental strain was different in various degrees of LGE transmurality especially for radial and circumferential strain. Strains of adjacent region were better than infarcted region in radial and circumferential directions and worse than remote region in all three directions.Conclusion: Global and regional strain could stratify different extent and transmurality of LGE, respectively. Although without LGE, adjacent region had impaired strains comparing with remote region. Left verization .Moreover, myocardial deformation can be evaluated by CMR. Recently, strain analysis by CMR feature-tracking, using routinely acquired cine images, has been increasingly conducted to detect subtle and regional myocardial dysfunction in a variety of cardiovascular diseases including myocardial infarction , 7. UnliTherefore, we aimed to investigate whether strain analysis by CMR feature-tracking could provide complementary evaluation value in STEMI patients on top of conventional CMR parameters including LVEF and LGE. We hypothesized that myocardial strain assessed by CMR feature-tracking could be more sensitive to detect early decline in left ventricular (LV) function with preserved LVEF, quantify regional dysfunction, and discriminate different degrees of myocardial infarction assessed by LGE.The present retrospective study was a sub-analysis from OCTAMI  registry , which continuously enrolled a prospective cohort of STEMI patients for evaluating culprit lesions by optical coherence tomography. The major inclusion criteria for OCTAMI were as follows: (1) age ≥18 years; (2) presented with persistent chest pain lasting more than 30 min with ST-segment elevation >0.1 mV in at least two contiguous leads or new left bundle-branch block on the 18-lead electrocardiogram and elevated troponin I level  with a phased-array cardiovascular coil, using electrocardiographic and respiratory gating. The protocol mainly consisted of cine imaging and LGE imaging for analysis. Cine images were acquired in three long-axis views  and short-axis views encompassing the entire LV using balanced steady-state free precession sequence (b-SSFP). Typical imaging parameters were field of view = 320 × 320 mm, matrix = 224 × 192, repetition time (TR) = 3.3 ms, echo time (TE) = 1.7 ms, flip angle = 50°, temporal resolution = 46–60 ms, slice thickness = 8 mm, and slice gap = 2 mm. LGE images were acquired 10–15 min after intravenous administration of gadolinium-DTPA  at a dose of 0.2 mmol/kg, using a segmented phase-sensitive inversion recovery sequence at the same views as cine images in end diastole. Typical imaging parameters were field of view = 360 × 360 mm, matrix = 224 × 192, TR = 6.0 ms, TE = 2.8 ms, flip angle = 25°, slice thickness = 8 mm, slice gap = 2 mm, and TI = 300 ms.All the analyses were conducted using commercial software CVI42  by investigators with more than 3 years' experience. Endocardial and epicardial contours of LV myocardium were manually traced on short-axis cine at end diastole and end systole, respectively, and cardiac functional parameters were computed automatically. Papillary muscles were assigned to the LV volume. For quantification of contrast enhancement, outline of left ventricular myocardium was manually depicted and LGE was detected by +5 SDs over the signal intensity of normal myocardium , 9. LGE t-test or Mann–Whitney U test was applied to compare two groups; one-way ANOVA with post hoc LSD tests or Kruskal–Wallis H test was performed for comparisons of three groups. Categorical variables were reported as exact numbers with percentages and χ2 test or Fisher exact test was conducted for comparison. Linear regression analyses were performed to determine the association between strain parameters and LGE. Receiver operating characteristics analysis was used to define the optimal cut-off values by the Youden Index and to quantify discriminative power. Inter- and intra-observer analyses were conducted by intraclass correlation coefficient. Statistical analyses were performed using IBM SPSS Statistics 23.0  and MedCalc 16.8.4 . A two-tailed p-value <0.05 was considered statistically significant.Continuous variables were expressed as mean ± SD or median values with interquartile range (IQR) depending on normality variables. Correspondingly, A total of 129 STEMI patients  and 42 healthy controls  were included in the study . Table 1p < 0.001). Conventional cardiac function parameters (except cardiac output) were similar between patients with LVEF ≥55% and controls , but GRS, GCS, and GLS were impaired in patients with LVEF ≥55% (p < 0.001). Furthermore, all strain parameters of STEMI patients with LVEF <55% were much worse than LVEF ≥55% group (p < 0.001). It is worth noting that the percentage of LGE in LVEF <55% group was significantly more than LVEF ≥55% group (p < 0.001). Therefore, the correlation of myocardial strain and extent of LGE was investigated further.CMR examinations were conducted 33  days after index events. The STEMI patients were divided into two groups by LVEF (55%) and compared with healthy subjects. An overview of assessed CMR parameters is presented in r = 0.65, β = −0.41, p < 0.001; GCS: r = 0.69, β = 0.21, p < 0.001; GLS: r = 0.61, β = 0.15, p < 0.001). When dividing the patients by LGE tertiles, the increase in LGE extent was correlated to a significant and stepwise impairment of global strains  and circumferential  directions (p > 0.05) but both significantly worse than remote region .The strain of remote region, adjacent region, and infarcted region presented a significant and stepwise impairment in radial  compared with healthy controls, CMR feature-tracking detected impaired global strains in STEMI patients with normal LVEF; (2) strain was closely associated with infarcted myocardium detected by LGE, and global and regional strain could stratify different extent and transmurality of myocardial infarction respectively; (3) although without LGE, adjacent region had impaired strains comparing with remote region—deformation reduced successively from remote region to adjacent region and infarcted region.Recently, myocardial strain analysis is considered as a powerful tool to quantify subtle and regional myocardial dysfunction over ejection fraction , 12. Sper ranged from 0.32 to 0.64) and provided prediction of prognosis . Moreover, the present study investigated the correlation of myocardial strain and LGE in detail. Our study showed that regional and global strain could discriminate different transmurality and extent of LGE, and segmental strains were good discriminators for LGE >50% (AUC: 0.763–0.903). A previous study reported that segments with >50% LGE extent were hard to recover despite successful revascularization . Moreover, prognostic results were not reported in the present study since the event rate was low. Therefore, the prognostic association between strain and LGE could not be investigated. Further prospective study with large numbers of patients might be warranted.There were several limitations in the present study. First, sample size was relatively small. Second, the study only focused on patients with first anterior STEMI so that it limited the ability to extrapolate the findings in a general acute coronary syndrome or STEMI population. Third, CMR parameters were retrospectively analyzed from a prospective cohort with LGE 1 month after percutaneous coronary intervention as study endpoint—T2/T2Global and regional strain could stratify different extent and transmurality of LGE, respectively. Although without LGE, adjacent region had impaired strains comparing with remote region.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by The Review Board of Fuwai Hospital. The patients/participants provided their written informed consent to participate in this study.SY conception and design of study, analyzed images, and drafted the article. JZ conception and design of study, acquired clinical data, and drafted the article. KY, YZ, JS, and KJ analyzed images and critically revised the article. XC, HY, and SZ conception and design of study and critically reviewed the article. KZ performed statistical analysis and critically reviewed the article. PZ acquired clinical data and critically reviewed the article. All authors read and approved the final article for publication.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.


BackgroundMyocardial clefts (MCs) are rare anomalies with debatable clinical significance. Increased use of cardiac magnetic resonance (CMR) has led to the appreciation of subtle left ventricular (LV) wall structural defects, and studies showed varying clinical significance, ranging from asymptomatic incidental findings to being considered a novel imaging marker of hypertrophic cardiomyopathy. Sparse data are available about the utility of two-dimensional echocardiography (2DE) to visualize these anomalies. We describe our institutional experience categorizing MCs using 2DE.MethodsThe echocardiography database was retrospectively queried for diagnosing MCs using Synapse® Cardiovascular Picture Archiving and Communication System (PACS) . Identified patients were admitted to Detroit Medical Center (DMC) between January 2012 and May 2019. MCs were defined as recesses filled with luminal blood, obliterate during systole, and have U, wedge, and tunnel shapes. Images were interpreted by a cardiologist blinded to the data. Baseline demographics and clinical characteristics were documented. The study was descriptive; no intervention was done.ResultsSixteen patients with a mean age of 62.43 were included; 68.75% were women, and 81.25% were African American. The prevalence of cardiac comorbidities was primary hypertension 12 (75%), coronary artery disease 5 (31.25%), heart failure with reduced ejection fraction (HFrEF) 4 (25.0%), valvular heart disease 4 (25.0%), arrhythmia/heart block 4 (25.0%), and heart failure with preserved ejection fraction (HFpEF) 2 (12.5%). The indications for 2DE evaluation were heart failure/cardiogenic shock 2 (12.5%), acute coronary syndrome 2 (12.5%), syncope/presyncope 2 (12.5%), atypical chest pain 2 (12.5%), and others 8 (50.0%). Twenty-one MCs were visualized in eight segments of LV walls and septum as follows: basal inferior 7, mid inferoseptal 6, mid inferior 3, mid anteroseptal 2, mid inferolateral 1, mid anterolateral 1, basal inferoseptal 1, apical inferoseptal 1, and apical septal 1. Morphology was classified as tunnel in 66.66%, wedge in 23.8%, and U in 9.5%.ConclusionIn various LV and septal walls, MCs detected on 2DE were benign and incidental findings without significant implications for preclinical hypertrophic cardiomyopathy (HCM). Myocardial clefts (MCs) are narrow, deep invaginations within the myocardium, localized predominantly in the basal inferior septum and left ventricular (LV) free walls . The terEchocardiography was used earlier for imaging of myocardial structural defects. However, its accuracy can be challenging, particularly if the defect's location does not coincide with standard acquisition planes ,4. Although clefts or crypts may be significant findings in the context of a high pretest probability of HCM ,6, theirPatient selection and baseline characteristicsUsing the Synapse® Cardiovascular Picture Arching and Communication System (PACS)  search option, our echocardiography database was retrospectively queried by the following keywords: clefts, crypts, fissures, or crevices. Seventeen patients were identified. For this report, myocardial clefts (MCs) were used synonymously with crypts, fissures, and cervices. Patients included in the analysis were admitted to Detroit Medical Center/Wayne State University  between January 2012 and May 2019 and had two-dimensional echocardiography (2DE) for various indications  was done in six subjects , and biplane echocardiography was performed on three subjects , which aided in the diagnosis. A variety of views were obtained for resting imaging, including but not limited to the parasternal long-axis, parasternal short-axis (at multiple levels), apical two-chamber, apical three-chamber, and apical five-chamber views.Image analysis and definition of cleftsAll routine 2DE images were processed using commercially available PACS. MCs were defined as structural abnormalities composed of narrow, deep blood-filled invaginations that penetrate the adjoining myocardium during diastole and obliterate during systole. Due to the inconsistency in MCs classification and the lack of good spatial resolution as seen with CMR, we included any depth of myocardial thickness penetration. The overall appearance of the MCs was divided into three groups: triangular (wedge-shaped), a width half the height (tunnel-shaped), or little difference in width and height (U-shaped). Their locations were reported based upon the 17-segment heart model recommended by the American Heart Association. To minimize interobserver variability, the images were reviewed by two experts blinded to the patient’s data.Further echocardiographic parameters were measured and included interventricular septal thickness in diastole and posterior wall thickness (PWT). Ejection fraction (EF) was assessed visually. Geometrical assessment of LV was conducted by calculating LV relative wall thickness (RWT) and LV mass. A formula (2 × PWT)/ was used for RWT calculation, and a cutoff of 0.42 mm was used for the upper limit of normal for both genders. Using the linear method, LV mass was then calculated by Cube formula, and the following reference values were utilized (67-162 g for women and 88-224 g for men) [Patients' characteristicsSixteen patients with a mean age of 62.4 (±20.2) were included; 68.8% were women, and 81.3% were African American. Prevalence of cardiovascular comorbidity was primary hypertension 12 (75.0%), coronary artery disease 5 (31.25%), heart failure with reduced ejection fraction (HFrEF) 4 (25.0%), valvular heart disease 4 (25.00%), arrhythmia/heart block 4 (25.0%), and heart failure with preserved ejection fraction (HFpEF) 2 (12.5%). Indications for evaluation whether outpatient visit or in-hospital admission were heart failure/cardiogenic shock 2 (12.5%), acute coronary syndrome 2 (12.5%), syncope/presyncope 2 (12.5%), atypical chest pain 2 (12.5%), and others 8 (50.0%). Table Myocardial clefts characteristicsA total of 21 MCs were identified in all patients, with a minimum of one and a maximum of three. MCs visualized in eight American Heart Association (AHA) myocardial segments all confined to the LV wall and septum as follows: basal inferior 7, mid inferoseptal 6, mid inferior 3, mid anteroseptal 2, mid inferolateral 1, mid anterolateral 1, basal inferoseptal 1, apical inferoseptal 1, and apical septal 1. Morphology was classified as tunnel shape in 66.7%, wedge shape in 23.8%, while 9.5% had U shape. Table Using the reference values for LV geometry measurements from the American Society of Echocardiography and the European Association of Cardiovascular Imaging , concentCardiovascular imagingThis study addresses the role of 2DE in describing MCs. Contrast echocardiography was employed in six subjects (37.5%), while biplane imaging was conducted in only three subjects (18.75%). The diagnostic yield of these techniques had not been thoroughly evaluated in the literature.Most of our information about echocardiography is based upon individual case reports -10. ThesOn the other side, multiplanar CMR has high spatial resolution and increased contrast between blood and endocardial border surface and has led to the appreciation of subtle LV wall structural features, not seen or neglected by 2DE . Most stClinical significance and comparison to other studiesOur study findings remain in keeping with previously published data in healthy volunteers and other cardiac diseases including primary hypertension ,3,11 andThe most common comorbid condition in our cohort of patients was primary hypertension followed by coronary artery disease. An earlier study by Johansson et al. described 27 basal inferior and 24 septal clefts among 399 CMR cases studied retrospectively. In that study, MCs were found in 15.6% of healthy volunteers (13/120), 5.5% of HCM patients (5/19), and 11.4% of hypertensive patients (5/44) [On the other side, two other studies with different designs utilizing CMR suggested the use of MCs as a novel cardiovascular imaging marker for HCM that can potentially identify HCM family members who should be offered genetic testing ,6. One oOther myocardial structural anomaliesMyocardial clefts or crypts must be differentiated from diverticula, aneurysms, and pseudoaneurysms. Morphologically and histologically, clefts and muscular diverticula are very similar in that both have all three layers , have a narrow neck and a thick myocardial wall, and exhibit myocardial contractility during systole; however, diverticula extend beyond the myocardial wall into the epicardium . TherefoStudy limitationsOur study was retrospective, single-center, and has a small sample size, and thus observations might not be generalizable to a large cohort of the population. In addition, with the lack of sharp contrast between endocardial border and blood with the use of CMR, the cleft definition was not accurately assessed. Left ventricular geometry measurements with 2DE are not as accurate as 3D echo and CMR - both techniques were not used in our study. We suggest a multicenter prospective registry with a large number of patients imaged by both CMR and 2DE to investigate the utility and accuracy of echocardiogram in the diagnosis.In conclusion, MCs are generally benign and incidental findings and can be detected in a variety of patients without significant implications for preclinical HCM.


P < 0.01). Compared with the LGE(−) group, the global and regional RS, CS, LS and the subendocardial, subepicardial LS of the LGE(+) group were significantly diminished (P < 0.05). In the ILVNC group, the basal–apical CS and LS gradient, and the subendocardial-subepicardial LS gradient were significantly lower than those in the control group (P < 0.01). There were significant differences in myocardial strain between patients with and without ILVNC. ILVNC revealed a specific pattern in terms of strain change. The myocardial strain of the cardiac apex and endocardium was significantly lower than that of the cardiac base and epicardium, respectively. Myocardial strain reduction was more significant in ILVNC patients with focal myocardial fibrosis.We used cardiac magnetic resonance tissue tracking (CMR-TT) to quantitatively analyze the global, regional and layer-specific strain of isolated left ventricular noncompaction (ILVNC). Combined with late gadolinium enhancement (LGE), we initially explored the effect of focal myocardial fibrosis on myocardial strain. CMR was performed in 63 patients with ILVNC and 52 patients without ILVNC . The ILVNC group was divided into an LGE(+) group (29 patients) and an LGE(−) group (34 patients) according to the presence or absence of late gadalinum enhancement (LGE). CVI42 software was used to measure global and regional  radial strain (RS), circumferential strain (CS), longitudinal strain (LS), subendocardial LS and subepicardial LS. The basal–apical strain gradient was defined as the apical mean strain minus the basal mean strain. We then compared differences between these strain parameters. The subendocardial-subepicardial LS gradient was defined as the maximum subendocardial LS minus the subepicardial LS. Compared with the control group, the global and regional RS, CS, LS and the subendocardial, subepicardial LS of the ILVNC group were significantly diminished ( We have observed that some patients with ILVNC will show LGE(+). It often represents myocardial fibrosis, so we explored whether myocardial fibrosis affects strain. Cardiovascular magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE) has been used to detect myocardial fibrosis, and it is currently the most commonly used method for detecting focal myocardial fibrosis. LGE is used in diagnosis, differential diagnosis, and judgment of disease prognosis and risk stratification. LGE is frequently present in ILVNC patients, and previous studies have associated LGE with systolic dysfunction and major adverse cardiovascular events5. The accurate assessment of cardiac function can help to better assess pathogenic conditions and guide effective treatment.Isolated left ventricular noncompaction (ILVNC) is a congenital left ventricular myocardial structural abnormality with a complex pathogenesis and pathophysiological background. The clinical manifestations are nonspecific and the prognosis varies6. Therefore, myocardial strain can more accurately evaluate changes in cardiac function than LVEF. Correlation between CMR tissue tracking (CMR-TT) and speckle tracking echocardiograph (STE) was modest and agreement was not optimal due to systematic bias regarding GLS and GCS. Consequently, CMR-TT and STE should not be used interchangeably for myocardial strain evaluation7. This article focuses on CMR strain analysis and no longer compares them.The evaluation of cardiac function usually uses the left ventricular ejection fraction (LVEF). However, LVEF can only evaluate global myocardial function. Myocardial strain can be used to evaluate changes in local myocardial motion. Previous studies have shown that patients with cardiomyopathy, including ILVNC, have reduced systolic function and strain when LVEF is normalCardiac magnetic resonance tissue tracking (CMR-TT), which is based on the conventional cine sequence, has become a commonly used technique to assess myocardial strain. Clinically, accurate assessment of heart function helps to better assess the severity of the disease and guide effective treatment. Strain evaluates cardiac function more accurately than EF. The myocardial strain characteristics of patients with ILVNC is still unclear. Therefore, the main purpose of this article is to analyze the global, regional and layer-specific strains of the ILVNC group and the control group to obtain the myocardial strain pattern of ILVNC patients, so as to assess changes in cardiac function more accurately. Myocardial fibrosis often affects cardiac function, so we hypothesis that the myocardial strain of ILVNC patients with LGE(+) decreased more significantly than that of LGE(−), which will be verified in the text. The relationship between LGE(+) and myocardial strain in ILVNC patients will be analyzed.10: (1) the left ventricular wall showed a bilayer appearance of compacted myocardium (C) and noncompacted myocardium (NC), (2) a noncompacted myocardium was evident with an obvious trabecular meshwork and deep intertrabecular recesses, (3) the end-diastolic ratio of noncompacted to compacted myocardium (NC/C ratio) was > 2.3 involving at least three segments8, (4) no other cardiac abnormalities were present. Once successfully enrolled, patients with ILVNC were categorized into LGE(+) and LGE(−) groups. Fifty-two age- and sex-matched healthy individuals were enrolled in the control group. The inclusion criteria for controls were as follows: (1) no history of cardiovascular disease, (2) chest radiograph, electrocardiogram and echocardiography findings were normal, (3) CMR showed normal cardiac function.A retrospective study was conducted of 63 patients with ILVNC diagnosed in the Second Xiangya Hospital of Central South University from August 2016 to January 2020. The inclusion criteria were as followsThis study was approved by ethics committee of the Second Xiangya Hospital of Central South University, and informed consent was signed by all participants. All methods were carried out in accordance with relevant guidelines and regulations.A cine balanced steady-state free processing (bSSFP) sequence with segmented acquisitions, which collected left ventricular two-chamber, four-chamber, and short-axis images at the end of inspiration, with 25 retrospectively calculated phases per cardiac cycle. The scanning parameters were as follows: repetition time, 3.2 ms; echo time, 1.43 ms; flip angle, 44°; temporal resolution, 40 ms; field of view, 320 mm × 400 mm; acquisition matrix, 126 × 224; slice thickness, 8 mm with no slice gap.LGE with gadopentetate dimeglumine as the contrast agent at a dose of 0.2 mmol per kilogram of body weight. After the contrast agent had been injected, 20 ml of normal saline was injected. All patients in the ILVNC group and control group were injected with the contrast agent. Images were taken 10 minutes after the injection of contrast agent. Scan parameters were as follows: repetition time: 2.8 ms; echo time: 1.3 ms; flip angle: 40°; field of view: 320 mm × 400 mm; acquisition matrix: 125 × 256.Scanning were performed on a 3 T scanner  with 18-channel body coil scan protocols. The scanning sequence was carried out as follows:All conventional cardiac function parameters were obtained using CVI42 post-processing software . The parameters included LVEF, left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), left ventricular stroke volume index (LVSVI), and left ventricular myocardial mass index (LVMMI). Index mean parameters were indexed to body surface areas.According to the 17-segment method for left ventricular myocardium established by the American Heart Association, we measured the thickness of the compacted (C) layer, the thickness of the noncompacted (NC) layer, and the NC/C ratio on the end-diastolic short-axis cine sequence image of 1–16 segments. Because the measurement error in section 17 is relatively large, quantitative measurements do not include this section. Segments with an NC/C ratio greater than 2.3 were defined as noncompacted segments. We calculated mean values for C, NC, and NC/C in the noncompacted segments. The LGE images were visually inspected for the presence or absence of LGE by two experienced radiologists. If the results were inconsistent, a third radiologist was introduced and asked to judge the results in a blinded manner. Each radiologist studied CMR for more than 3 years.All strain parameters were obtained using CVI42 post-processing software. In the tissue tracking module, we introduced the left ventricle short-axis, two-chamber, and four-chamber long-axis cine images. The subendocardium and subepicardium were delineated at the end of diastole and end-systolic period, and the left and right ventricle demarcation points were marked manually Fig. . Myocardt-test. The Mann–Whitney U test was used to compare two variables that did not conform to a normal distribution. The Spearman method was used to test the correlation between strain parameters and LVEF or LVEDVI. Logistic regression models and receiver operating characteristic (ROC) curves were used to evaluate the efficacy of myocardial strain parameters in predicting LGE. Bland–Altman plots were used to evaluate intra- and interobserver reproducibility. A P-value less than 0.05 was considered to be statistically significant.Statistical analysis was performed using IBM SPSS Statistics . Data were tested for normality using the Kolmogorov–Smirnov method. Continuous data are expressed as the means ± standard deviations (SDs). Comparisons of two normally distributed variables were performed using an independent sample student The ILVNC group (63 patients) comprised 44 men (69.8%) and 19 women (30.2%), and the mean age was 44.44 years ± 14.4 SD. The control group (52 patients) comprised 36 men (69.2%) and 16 women (30.8%), with a mean age of 44.10 years ± 15.7 SD.Compared with the control group, LVEF and LVSVI in the ILVNC group were significantly lower P < 0.01), whereas LVEDVI, LVESVI, and LVMMI were significantly higher (P < 0.01). Compared with the LGE(−) group, LVEF and LVSVI in the LGE(+) group were significantly lower (P < 0.01), whereas LVEDVI, LVESVI, and LVMMI were higher (P < 0.05). Baseline characteristics and conventional CMR function parameters are shown in Table , whereasA total of 29 patients (46.0%) in the ILVNC group presented with LGE. Mid-myocardial LGE was found in 25 patients (86.2%), the most common of which was in the ventricular septum. Subendocardium LGE was found in two patients (6.9%), transmural LGE was found in two patients (6.9%) Fig. . Figure P = 0.895).There were 257 noncompacted segments (NC/C > 2.3) in the ILVNC group, of which the basal, middle, and apical parts accounted for 10.1%, 27.6%, and 62.3%, respectively. There was no significant difference of NC/C between the LGE(+) and LGE(−) groups . Compared to the LGE(−) group, the LGE(+) group had diminished global and regional RS, CS and LS (P < 0.05) as well as diminished subendocardial, subepicardial LS (P < 0.01)  Table .Table 2GP < 0.01). LVEDVI was also correlated with global RS, CS, and LS .LVEF was correlated with global RS, CS, and LS . In the ILVNC group, CS and LS did not tend to increase from the base to the apex (P > 0.05)  Fig. .Figure 4P < 0.01)  Table .Table 3MP < 0.05), although there was no difference between the subendocardial and subepicardial LS in the ILVNC group (P > 0.05)   Fig. . The sub1) Table .The global RS, CS, LS of the ILVNC and control groups were measured within intra- and interobservers. We used the Bland–Altman plots to evaluate the intra- and interobserver reproducibility. The intraobserver and interobserver reproducibility were high for global RS, CS, and LS in the ILVNC Fig.  and contLGE-positive were used as the dependent variable (Y), the Logistic regression model was used to conduct single-factor ROC analysis on LVEF, global RS, CS, LS, subendocardial LS and subepicardial LS. LVEF, (area under the curve [AUC] = 0.767), RS (AUC = 0.802), CS (AUC = 0.759), LS (AUC = 0.690), subendocardial LS (AUC = 0.766) and subepicardial LS AUC = 0.747) showed predictive value for LGE. , the basal–apical CS and LS gradient and the subendocardial-subepicardial LS gradient were significantly lower than those in the control group (P < 0.01). The correlation between myocardial fibrosis and myocardial strain was also analyzed. We find that the global and regional RS, CS, LS, and the subendocardial and subepicardial LS of the LGE(+) group were significantly diminished compared with the LGE(−) group (P < 0.05). We obtained more about the myocardial strain change pattern of ILVNC patients from these analyses.Studies have suggested that CMR deformation indices including GLS, GCS and strain rate parameters were reduced in patients with LVNC especially in affected midventricular and apical slices and correlated well with parameters of the non-compacted myocardium1. The dilated subtype is the most common, and studies have shown that patients with dilated ILVNC have a worse prognosis than those without dilated ILVNC12. In the current study, the LVEDVI of the ILVNC group was significantly higher than that of the control group, and there was a correlation between LVEDVI and the global strain. This finding suggests that the expansion of left ventricular volume is associated with myocardial dysfunction in ILVNC patients.According to the morphologic and functional characteristics of the heart, ILVNC can be divided into different subtypes, including dilated ILVNC, hypertrophic ILVNC, restrictive ILVNC, and hypertrophic dilated ILVNC13. Therefore, the apical part is more severely affected than the basal part. In the current study, the apical segments of all patients with ILVNC were involved, and the compacted layer of the myocardium was significantly thinned. Analysis of regional strain found that in the control group, the apical CS and LS were significantly higher than that of the basal part; the reason for this is not clear but might be related to the geometry of the heart14.In the early stages of embryo development, the myocardium gradually undergoes compaction from the subepicardium to the subendocardium, from the base to the apex. Failure of this process leads to abnormally large, disordered trabeculae and deep trabecular crypts, resulting in myocardial noncompaction15 and Haland et al.16, who used tissue Doppler imaging and ultrasound speckle tracking to identify unique strain change patterns in ILVNC. The authors postulated that this was related to the compaction process of the embryonic myocardium from the base to the apex.The longitudinal and circumferential myocardial fibers integrate at the apex. During systole, the radius of curvature of the ventricular wall gradually decreases from the base to the apex, and the stress of the ventricular wall gradually decreases toward the apex. However, in the ILVNC group, there was no statistical difference between the basal and apical CS and LS. To evaluate the trend and extent of strain changes from the base to the apex, we defined the basal–apical strain gradient. The basal–apical CS and LS gradient in the ILVNC group was significantly lower than that in the control group; myocardial function decreased from the base to the apex in a non-homogeneous manner. This finding is consistent with those of Niemann et al.18. We compared the subendocardial and subepicardial LS in the control group, observing that the subendocardial LS was higher. The presence of this gradient may be related to differences in the focal curvature between the subepicardial and subsubendocardial myocardium19. However, in patients with ILVNC, no statistical difference was found between the subendocardial and subepicardial LS. Then we defined the basal–apical strain gradient. The current study results showed that the subendocardial-subepicardial LS gradient of the patients with ILVNC was significantly lower than that of the control group. That is, the degree of subendocardial myocardial involvement was relatively more severe. The subendocardial compacted myocardium was replaced by noncompacted myocardium, and the myocardium was grossly disordered. Therefore, in patients with ILVNC, subendocardial myocardial dysfunction is more pronounced than in the subepicardial myocardium.CMR-TT can obtain subendocardial and subepicardial strain. The myocardium of the left ventricle is divided into three layers: the subendocardial myocardium, the middle myocardium, and the subepicardial myocardium. The subendocardial and subepicardial myocardium are mainly longitudinally arranged and thereby related to the longitudinal movement of the heart20. Furthermore, we performed ROC analysis on myocardial strains in the LGE(+) and LGE(−) groups and concluded that global RS, CS, and LS, subendocardial LS, and subepicardial LS have a predictive value for LGE. That is to say, when these strain parameters are reduced to a threshold in patients with ILVNC, we can predict the possibility of focal myocardial fibrosis in that patient. The variation of these strain parameters suggested that the quality and efficiency of ILVNC myocardial movement in all directions were significantly reduced in patients with LGE.In the current study, the global and regional RS, CS, and LS of the LGE(+) group decreased compared to those of the LGE(−) group, demonstrating that myocardial fibrosis can cause limited myocardial movement in different directions. Further layer-specific studies of LS revealed that in patients with ILVNC with LGE  group), subendocardial and subepicardial LS was also lower than in patients without LGE  group), indicating that the myocardial layer-specific strain is a sensitive parameter. Quantitative analysis of subendocardium and subepicardium LS provides useful non-invasive information for the layer-specific localization of fibrosisThere are some limitations that need to be considered. Firstly, the sample size is small, and other forms of cardiomyopathy, including dilated cardiomyopathy and valvular cardiomyopathy, can also be manifested as left ventricular enlargement and excessive trabeculation, requiring further comparative analysis. Secondly, LGE could not evaluate diffuse myocardial fibrosis; this requires further study using native T1 and extracellular volume fraction. Thirdly, most patients with ILVNC had a moderate to severe reduction in LVEF. It was not possible to analyze the strain change pattern in patients with preserved LVEF.CMR-TT enables the comprehensive evaluation of regional and layer-specific strain. ILVNC is a heterogeneous cardiomyopathy with the most severe apical and subendocardial involvement. Patients with LGE and ILVNC had a higher degree of myocardial strain reduction than those without LGE and ILVNC. CMR-TT can provide more comprehensive information for assessing cardiac function in patients with ILVNC.


To the editorLeft atrial remodeling is receiving great concern as a great contributor to the heart failure progression in addition to the biventricular function.The primary concern is the variability of this index. In general, left atrial size is variable depending on hemodynamic status. Data on which timings  were the index measured would strengthen their findings. If the index is variable, the next concern is the possibility of intervention on this index to improve clinical outcomes. For example, heart rate modulation, preload unloading by using diuretics, and afterload reduction by using vasodilators might improve the index and clinical outcomes.The second concern is the mechanism of worsening heart failure in patients with higher sphericity index: whether the index is a marker of poor background and/or a contributor to the worsening heart failure. Detailed hemodynamic assessment using invasive right heart catheterization, histopathological assessment of endomyocardium, and measurement of peripheral inflammatory markers would further approach the mechanism.As minor concerns, their hypothesis might be expanded into those with cardiac diastolic dysfunction.