Strain parameters before and after PVR were compared using paired t-tests. One-way ANOVA with Tukey post-hoc analysis was used for comparisons between the before and after PVR groups and the control group. There were no differences in strain parameters before and after PVR. The GPSmax before PVR was lower than that in the control group (P = 0.002). Before and after PVR, GCSs were higher and GLSs were lower than those in the control group . RV strains from radially reconstructed short-axis cine images revealed unchanged myocardial motion after PVR. When compared to the control group, changes in GCS and GLS in TOF patients before and after PVR might be due to RV remodeling.We measured right ventricular (RV) strain by applying a novel postprocessing technique to conventional short-axis cine magnetic resonance imaging in the repaired tetralogy of Fallot (TOF) and investigated whether pulmonary valve replacement (PVR) changes the RV strain. Twenty-four patients with repaired TOF who underwent PVR and 16 healthy controls were enrolled. Global maximum and minimum principal strains (GPS These sequelae are believed to be in part related to chronic pulmonary regurgitation caused by efforts to relieve pulmonary valve stenosis with the initial repair. PVR is performed to improve pulmonary regurgitation or valvular stenosis and improve long-term outcomes5 in adult patients with repaired TOF. However, cardiovascular magnetic resonance (CMR) feature tracking showed that ventricular strain was unchanged, even after PVR6.Patients with surgically repaired TOF experience significant morbidity and mortality related to biventricular dysfunction and arrhythmia in their adult years9, especially in the RV, because the image quality of echocardiography is sometimes inadequate11. Generally, the RV strain is evaluated using circumferential strain (CS) or longitudinal strain (LS) from the motion of the endocardium in one plane of the ventricular short- or long-axis, respectively. However, the motion of the heart is three-dimensional. Accordingly, such predefined directions of change may not reliably describe deformation in the dominant direction of tissue movement established by engaged myocardial fibers. On the other hand, three-dimensional image acquisition for myocardial strain is technically difficult and time-consuming, if possible. Recently, the feasibility of three-dimensional image analysis using routine cine CMR images for the estimation of principal strain (PS), a geometry-independent measure established from the dominant direction of local tissue deformation, has been reported12. Therefore, we measured RV PS of three-dimensional “real” strain in repaired TOF by applying this novel postprocessing technique to conventional two-dimensional cine imaging. In the present study, we investigated whether PVR changes the RV PS. We also investigated the clinical impact of the relationship between strain parameters and clinical and hemodynamic measurements.Peak strain is a helpful marker for quantifying myocardial tissue deformationTable max before PVR was lower than that in the control group (P = 0.002). GCSs before and after PVR were higher than those in the control groups (P = 0.002 for both). GLSs before and after PVR were lower than those in the controls (P < 0.0001 and P = 0.0003). The rS  indicated significant correlations between the GPSmin and RVP/ LVP  and between the GPSmin and the RV-PA pressure gradient   . Excellent intra-observer and inter-observer reproducibility were observed for RV strain measurements using radial long-axis reconstructed cine images 13. Furthermore, in RV pressure overload, it is mainly the middle myocardial layer that hypertrophies15. The RV in patients with adapted remodeling is similar to the normal left ventricle, which has a well-developed middle circumferential layer16. Thus, the increase in the circumferential fiber mass may also contribute to the predominant circumferential RV free-wall shortening. According to our results, increased GCS and decreased GLS in the TOF group relative to the control group were consistent with these reports. Furthermore, our results suggest that even if the RV volume is reduced by PVR, there is no reverse remodeling of myocardial motion 1 year after the surgery. Earlier surgical intervention might be preferable to prevent myocardial remodeling.According to our investigation, there were no differences in global PS values before and after PVR in adult patients with surgically repaired TOF. Furthermore, GCS and GLS were unchanged before and after PVR. Our results are in line with those of previous researchmin and GPSmax were significantly correlated. The advantage of CMR with respect to cardiac catheterization is its accurate volume measurement and low invasiveness. However, its weakness is an inability to measure the pressure in the cardiac cavity or blood vessels. Surgical indications for PVR include volumetric parameters  and pressure parameters . The estimation of pressure-derived parameters using our method has the potential to overcome CMR’s weakness. Because our strain analysis requires only short-axis cine CMR, a well-established method without the need for additional imaging, a wider range of applications could be expected.In clinical situations, pressure parameters derived from cardiac catheterization are important indicators for PVR. We found that CMR-derived GPS18, no software has been established for RV PS for CMR. We considered that the values of PS, GCS, and GLS were clinically reasonable and reliable in the study populations. Furthermore, the reproducibility of the strain measurements with radially reconstructed long-axis images was compared with CMR-derived strain measurements using feature tracking20. However, a future validation study by comparing the commercially available software with echocardiography would be required. Additionally, it will be necessary to verify the technique by applying the analysis to different right heart diseases and investigating their relationship with other clinical indicators and prognoses.We acknowledge that our strain analysis with radially reconstructed long-axis cine CMR was based on the original in-house algorithm. Although measurements of RV PS with echocardiography using commercial software have been reportedIn this cohort, the three-dimensional PS revealed unchanged RV myocardial motion after PVR. In TOF patients before and after PVR, changes in GCS and GLS with respect to the control group might be due to RV remodeling. PS values reconstructed by short-axis CMR images were correlated with the parameters of pressure overloading with cardiac catheterization.This retrospective observational study was approved by the institutional review board of Kyushu University and conducted in accordance with the 1964 Declaration of Helsinki. Written informed consent was obtained from each patient. Twenty-four patients with surgically repaired TOF who underwent PVR were enrolled in the study, and datasets derived between October 2012 and March 2018 were analyzed. All patients were older than 18 years and underwent CMR assessment and cardiac catheterization of the right and left heart before PVR. In addition, CMR control data were obtained from 16 age- and sex-matched healthy subjects.All patients with repaired TOF underwent left and right heart catheterization before PVR. Cardiac catheterization provided pressure parameters of the left ventricular, right ventricular, and pulmonary arteries.21 using a 3.0T clinical scanner  with a dStream Torso coil using electrocardiographic gating. Steady-state free precession images were obtained using multi-breath holding with retrospective electrocardiogram gating in the axial and short-axis views covering the entire right ventricle with 20 phases per cardiac cycle. The axial cine imaging parameters were as follows: repetition time = 2.4 ms, echo time = 1.18 ms, SENSE factor = 2.0, flip angle = 35°, slice thickness = 8 mm, slice gap = 0 mm, field of view = 380 × 380 mm, acquisition matrix 176 × 245, and reconstruction matrix 448 × 448. The short-axis cine imaging parameters were as follows: repetition time = 2.7 ms, echo time = 1.37 ms, SENSE factor = 2.0, flip angle = 45°, slice thickness = 8 mm, slice gap = 0 mm, field of view = 380 × 435 mm, acquisition matrix 176 × 142, and reconstruction matrix 512 × 512. RV volume analysis was performed semi-automatically with subsequent manual correction using a workstation . RV volumes were measured using axial images, as previously reported22. End-diastolic volume (EDV) and end-systolic volume (ESV) were indexed to the body surface area. The ejection fraction (EF) was calculated using EDV and ESV. Stroke volume index (SVi) was calculated as the difference between indexed EDV and ESV values . The cardiac index was the product of the SVi and the heart rate (HR).Cine CMR was performed following a previous researchε), the percentages at each point, were calculated from the orthogonal lengths of circumferential, longitudinal, and radial directions at end-systole with respect to the lengths at end-diastole . Strain values were calculated from the three-dimensional coordinates of the RV endocardial point using standard short-axis cine CMR images. First, the point of the RV center was manually determined on the mid-heart short-axis slice during systole Fig. a. The imole Fig.  using Eqole Fig. :1\docume12. In the present study, the GPSmax and GPSmin were determined as the mean values of maximum and minimum PS of all RV endocardial points, respectively. The GCS and GLS were the means of the strains in the circumferential and longitudinal directions for all RV endocardial points, respectively.Further, the maximum and minimum PS were calculated from the three orthogonal regional strains, as per the previous researchP < 0.05. The Shapiro–Wilk test was used to evaluate the normality of the data distribution, and the mean and standard deviations were calculated. All strain parameters before and after PVR were compared using paired t-tests. One-way ANOVA with Tukey post-hoc analysis, was used for the comparisons between patient groups before and after PVR and the control group. Spearman correlation coefficients (rS) between the GPSmin and the right ventricular to left ventricular pressure (RVP/ LVP) ratio and between the GPSmin and RV to pulmonary artery (PA) pressure gradient were calculated. Similarly, the rS for GPSmax were also calculated.All statistical analyses were performed using GraphPad Prism version 8.1.2. . Differences were considered statistically significant at 23. A single observer performed all analyses for 10 randomly selected patients and then blindly repeated the analyses at least 1 month later. Inter-observer reproducibility was evaluated based on the same 10 patients and performed by a second observer who was blinded to the clinical and experimental data. Pearson’s correlation coefficients of intra- and inter-observer strain parameters were calculated. The intra-observer and inter-observer reproducibility of the strain measurements was evaluated using Bland–Altman analyses and intraclass correlation coefficients (ICC) with one-way or two-way random single measures . The ICC values were defined as excellent (≥ 0.75), good (0.60–0.74), moderate (0.40–0.59), or poor (≤ 0.39).The intra-observer reproducibility of the image analysis for strain calculations was evaluated following a previous research


Sodium-glucose cotransporter 2 (SGLT2) inhibition reduces cardiovascular events in type 2 diabetes (T2DM) and is associated with a reduction in left ventricular (LV) mass index. However, the impact on right ventricular (RV) remodeling is unknown. Accordingly, the objective of this study was to assess the impact of SGLT2 inhibition on RV parameters and function in T2DM and coronary artery disease (CAD).In EMPA-HEART CardioLink-6, 97 patients with T2DM and CAD were randomly assigned to empagliflozin 10 mg (n = 49) once daily or placebo (n = 48). Cardiac magnetic resonance imaging was performed at baseline and after 6 months. RV mass index (RVMi), RV end-diastolic and end-systolic volume index  and RV ejection fraction (RVEF) were assessed in blinded fashion.2), RVEF (53.5 ± 4.8%), RVEDVi (64.3 ± 13.2 mL/m2) and RVESVi (29.9 ± 6.9 mL/m2) were within normal limits and were similar between the empagliflozin and placebo groups. Over 6 months, there were no significant differences in RVMi , RVEF , RVEDVi  and RVESVi  in the empaglifozin group as compared with the placebo group. In both groups, there was no significant correlation between RVMi and LVMi changes from baseline to 6 months.At baseline, mean RVMi (± SD) (11.8 ± 2.4 g/mIn this post-hoc analysis, SGLT2 inhibition with empagliflozin had no impact on RVMi and RV volumes in patients with T2DM and CAD. The potentially differential effect of empagliflozin on the LV and RV warrants further investigation.Clinical Trial Registration: URL: https://www.clinicaltrials.gov/ct2/show/NCT02998970?cond=NCT02998970&draw=2&rank=1. Unique identifier: NCT02998970. The sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin reduces cardiovascular (CV) mortality, all-cause mortality and heart failure (HF) hospitalization in patients with type 2 diabetes (T2DM) and established atherosclerotic CV disease (ASCVD) . Other SThe mechanism of these benefits, particularly on reducing HF hospitalizations and CV death, remains unclear. In diabetic kidney disease, canagliflozin was associated with attenuated or decreased levels of biomarkers that suggest an effect on molecular processes related to inflammation, the extracellular matrix and fibrosis . Other pThe EMPA-HEART CardioLink-6 trial demonstrated that compared with placebo, the addition of empagliflozin to antihyperglycemic treatment in individuals with T2DM and coronary artery disease was associated with a significant reduction in left ventricular (LV) mass index (LVMi) as measured by cardiac magnetic resonance imaging (cMRI). Treatment with empagliflozin was also associated with a significant lowering of ambulatory systolic blood pressure with no impact on the circulating levels of NT-pro B-type natriuretic peptide (NT-pro-BNP) .cMRI provides the reference standard assessment of right ventricular (RV) structure and function , which aThe primary objective of this post-hoc analysis of the EMPA-HEART CardioLink-6 was to assess using cMRI whether empagliflozin alters RV parameters, function and remodeling among patients with T2DM and established coronary artery disease. The secondary objective was to examine the relationships of RV remodeling with LV remodeling, blood pressure and select cardiac biomarkers.2 and previous myocardial infarction or coronary revascularization. At baseline, participants underwent clinical and laboratory assessment, and were evaluated with 24-h ambulatory blood pressure monitoring as well as cMRI. Recruited patients were randomized in a 1:1 ratio to 6 months of empagliflozin 10 mg daily or placebo in addition to standard of care. Clinical visits were performed three times over the 6-month follow-up period. Standard transthoracic echocardiography was performed at baseline and 6 months. Right ventricular systolic pressure (RVSP), tricuspid regurgitation peak velocity, tricuspid annular plane systolic excursion (TAPSE) and RV S’ were assessed. The final visit included a repeat cMRI and 24-h ambulatory blood pressure monitoring.This study is a post-hoc analysis of the EMPA-HEART (Effects of Empagliflozin on Cardiac Structure in Patients with Type 2 Diabetes) CardioLink-6 trial (Unique identifier: NCT02998970), the details of which have been described . In shorcMRI scans were performed using a standardized protocol at baseline and 6 months using a clinical 3T MRI scanner . A steady-state free-precession sequence was used for standard cine imaging covering the entire LV and RV, typically with 8–12 contiguous short-axis images without interslice gap. Images were acquired in the supine position and at end–expiration.3) to calculate the RV mass (RVM). RV trabeculations were considered part of the blood pool and not as a part of the RVM. RV end-diastolic and end-systolic volumes (RVEDV and RVESV) were determined by summing the volume across slices without geometric assumptions, and RV ejection fraction (RVEF) was calculated as (RVEDV-RVESV)/RVEDV × 100%).Image post-processing was performed offline using CVi 42  and was blinded to clinical data as well as the timing of image acquisition. Contouring was performed by a single cardiovascular imaging fellow (BS), over read by two level 3 cMRI readers (ATY and KAC). Endocardial borders at end–diastole and at end–systole in contiguous short-axis images were manually traced Fig. . The epiIn this substudy, the primary outcome measure was the change in RVM from baseline to 6 months indexed to the body surface area at baseline (RVMi). Secondary outcomes included the baseline to 6-month changes in RVEDV and RVESV indexed to body surface area , and RV ejection fraction (RVEF).2 test. Continuous variables are presented as either mean (standard deviation) and compared with the Student’s t-test, or as median (interquartile range) and compared with the Kruskal–Wallis test. Spearman’s (nonparametric) correlation was used to assess the relationships between RV parameters and LV parameters, blood pressure, NT-pro-BNP and high sensitivity troponin I. Analysis of covariance (ANCOVA) was used to compare primary and secondary outcomes between the two randomized arms, adjusting for the baseline measurements. Intra-observer variability in the measurement of RV parameters was assessed by intraclass correlation coefficient for absolute agreement using 20 randomly selected studies. Analysis was performed using SPSS 25 (IBM) and statistical significance was set at a two-sided p value < 0.05.All analyses followed an intent-to-treat approach. Categorical variables were presented using counts and percentages and were compared using the χOf the 97 participants enrolled, 49 were assigned to empagliflozin 10 mg/day and 48 to placebo. Among those randomized, 6-month outcome data were unavailable for 7 (5 in the treatment group and 2 in the placebo group). Of these, 3 patients refused and 2 did not undergo follow-up cMRI. Two other patients were lost to follow-up. Accordingly, both baseline and 6-month cMRI were available for 44 participants in the empagliflozin group and 46 in the placebo arm.2 and 58.0 (7.5)% in the empagliflozin group, and 62.2 (12.8)g/m2 and 55.5 (8.7)% in the placebo group, respectively. The change in LVMi from baseline to 6 months was − 2.6 (7.8)g/m2 for the empagliflozin group and − 0.01 (5.7)g/m2 for the placebo group . There was no significant change in LV end-systolic or end-diastolic indices or LVEF from baseline to 6 months.The demographics and baseline characteristics of those randomized were previously published  and are 2 and 12.8 (2.37)g/m2 in the empagliflozin and placebo groups, respectively , RVEF , RVEDVi  and RVESVi  in the empaglifozin group as compared with the placebo group by ANCOVA adjusting for baseline values. Intraclass correlation coefficient values for absolute agreement in the measurement of RV parameters were > 0.95 for RVMi, RVEDVi, RVESVi and 0.86 for RVEF. Adjusted between group differences  using ANCOVA are displayed in Table Mean (SD) baseline RVMi was 11.5 2.35)g/m.35g/m2 aMean (SD) baseline RVSP and tricuspid regurgitation peak velocity were 22.8 (6.5) mmHg and 2.2 (0.38) m/s in 14 patients in the empagliflozin group, and 20.7 (4.4) mmHg and 2.1 (0.27) m/s in 17 patients in the placebo group, respectively. The remaining subjects had missing data due to an insufficient tricuspid regurgitation spectral Doppler profile. Echocardiographic parameters that assess RV function were normal at baseline and unchanged at 6 months: − 0.099  for TAPSE and − 0.32  for RV S’.The relationships between RV parameters and LV parameters, blood pressure and biomarkers were evaluated. In both groups, there was no significant correlation between RVMi and LVMi changes from baseline to 6-month follow up Table . HoweverIn this post-hoc analysis of the EMPA-HEART CardioLink-6 trial, the addition of empagliflozin to stable antihyperglycemic therapy in patients with T2DM and established coronary artery disease without HF did not result in significant changes in RVMi, RV volumes or RVEF over 6 months, as measured by cMRI. To our knowledge, this is the first cMRI study to assess changes in RV parameters and function in a randomized controlled trial of an SGLT2 inhibitor.There has been considerable work conducted to delineate how SGLT2 inhibition affects the LV , 25. TheThe RV is considerably different from the LV with respect to its structure, function, loading conditions and adaptation in states of disease . ImportaThe clinical relevance of RVMi in left-sided HF is not well established, and our current understanding is largely derived from other patient populations that included those with pulmonary hypertension . In the In the Multi-Ethnic Study of Atherosclerosis, RVM by cMRI was positively associated with systolic blood pressure in 4204 individuals who were free of CV disease . In a cMIt remains unknown whether SGLT2 inhibition may have an effect on the RV in left-sided HF with combined pre- and post-capillary pulmonary hypertension. Animal models provide some insight with regard to pulmonary artery hypertension. In one study, empagliflozin significantly improved survival in rats with monocrotaline-induced pulmonary artery hypertension while reducing mean pulmonary artery pressure; this was accompanied by reduced RV hypertrophy and fibrosis . The EMBOur cohort likely had a low prevalence of group 2 pulmonary hypertension since RVSP and tricuspid regurgitation peak velocity values were not elevated . MoreoveRV volumes and RVEF in the EMPA-HEART cohort were in the normal range, as were LV volumes and LVEF. Moreover, NT-pro-BNP values were normal. Indeed, in the SUGAR-DM-HF trial, which enrolled patients with T2DM, LVEF < 40%, and NYHA class II-IV symptoms, empagliflozin reduced LV end-diastolic and end-systolic volume index as measured by cMRI . RV paraOur study has a number of limitations. First, the sample size was small and most of the participants were men, which may be relevant since the relationship between RV volumes and T2DM may differ between sexes . AlthougThere are also important strengths. First, to the best of our knowledge, this is the first substudy of a randomized placebo-controlled trial utilizing cMRI to assess the effect of SGLT2 inhibition on RV parameters and function. Second, cMRI is the gold standard assessment of the RV and is independent of geometric assumption. Image analysis was performed with blinding and good intra-observer variability, and all RV measurements were made independent of LV measurements.In this post-hoc analysis of the EMPA-HEART CardioLink-6 trial, in contrast to the LV, SGLT2 inhibition with empagliflozin had no impact on RVMi in patients with T2DM, coronary artery disease and normal LVEF. The potentially differential effect of empagliflozin on the LV and RV warrants further investigation.


SYNTAX score (SS) was shown to positively correlate with postprocedural myocardial injury in patients after elective coronary artery intervention, but evidence about the association of SS with myocardial salvage in ST-segment elevation myocardial infarction (STEMI) patients is still needed. This study aimed to evaluate the prognostic value of SS for myocardial injury and salvage assessed by cardiac magnetic resonance (CMR) after primary percutaneous coronary intervention (PCI) in STEMI patients.This single-center retrospective study consecutively enrolled STEMI patients who had undergone primary PCI within 12 h from symptom onset. Both angiography and CMR were performed during hospitalization, and patients were divided into low SS (SS ≤ 22), mediate-high SS (SS > 22) groups. Correlation and multivariable analyses were performed.p < 0.001, Spearman r = 0.292) between SS and infarct size (IS), and a negative correlation  between SS and myocardial salvage index (MSI). In the multivariable model, SS  was significantly associated with high IS (≥ mean 35.43). The areas under the receiver operating characteristic (ROC) curves of SS for high IS and low MSI (≤ median 28.01) were 0.664 and 0.610.A total of 149 STEMI patients  were included. In terms of myocardial injury parameters, there was a positive correlation (In STEMI patients undergoing primary PCI, SYNTAX score positively correlated with infarct size and negatively with myocardial salvage, indicating an independent predictive value of the myocardial injury. Recovery from reperfused myocardial infarction (MI) is burdened by the occurrence of dynamic tissue changes, such as edema, inflammation, microvascular obstruction and hemorrhage , 2. MicrEarly assessment of myocardial salvage is the most important during the intense care phase. Cardiac magnetic resonance (CMR) is the gold-standard technique for noninvasive myocardial tissue characterization. It is increasingly used for improved long-term risk stratification of post-MI patients or initial evaluation preceding percutaneous coronary intervention (PCI) . TypicalThe anatomical Synergy between PCI with Taxus and Cardiac Surgery  is an important angiographic scoring system that can help clinicians establish the optimum revascularization approach in patients with CAD –16. PrevBased on the above, the study aimed to evaluate the prognostic value of SS for myocardial injury and salvage assessed by CMR in STEMI patients after primary PCI.This single-center retrospective observational study enrolled STEMI patients who underwent primary PCI at Cangzhou central hospital  between October 2018 and September 2020. Inclusion criteria were as follows: (1) electrocardiography (ECG) features consistent with acute STEMI in accordance to Fourth Universal Definition of Myocardial Infarction [Primary PCI was performed based on current guidelines . Patienthttp://www.syntaxscore.com). Based on the previous reports [The SS for each patient was calculated retrospectively, based on scoring for all coronary lesions with diameter stenosis > 50%, and vessels with diameter > 1.5 mm, using the SS algorithm, as recommended , 16. The reports , 23 SS wBlood samples were taken immediately after hospitalization, and echocardiography was performed on 5 (3–7) days from symptom onset. CMR was performed on 7.15 5.26–8.24) days from symptom onset using a 3.0-T scanner  with electrocardiographic-gated image acquisition, as described in previous studies  days fro. MRI parAnalysis was performed using dedicated software . Images were anonymized, batched, and analyzed in a blinded fashion by two experienced operators. The AAR was defined as a high-signal myocardial edema mass/LV mass ratio. The IS was defined as the hyperenhanced myocardium on the LGE images and is expressed as the infarcted LV mass/LV mass ratio. MVO was defined as dark areas surrounded by hyperenhanced myocardium on the LGE images. The presence of IMH was defined as hypointense areas within the brighter edematous zone on T2-STIR images. The papillary muscles were included in the LV cavity volume. The regions of interest for the volumes of AAR, IMH, IS, and MVO were created by manually drawing the lesion contours. In contrast, the LV volume was calculated by the semiautomated drawing of endocardial and epicardial contours on each slice for the whole LV myocardium. Myocardial edema was described as areas with a signal intensity > 5 standard deviations (SD) that of remote normal myocardium. The IS was calculated using the > 5 SD method. Discordant cases were reviewed and reconciled with superior imaging specialists. The myocardial salvage index (MSI) was defined as (AAR − IS)/AAR × 100.For echocardiographic evaluation, Xcelera R4.1  was used. Echocardiographic morphological and functional parameters were measured according to the definitions and recommendations from the available American Society of Echocardiography guidelines .p < 0.05) in the univariable logistic regression model. Receiver operating characteristic (ROC) curves were generated to determine the usefulness of SS to discriminate high IS and low MSI. All statistical analyses were performed using SPSS version 20  and graphs were generated using GraphPad Prism version 8.0 . P-value of < 0.05 was regarded as statistically significant.Categorical data are presented as numbers and percentages, and continuous data are presented as the mean (standard deviation) or median (interquartile range). The Shapiro–Wilk test was applied to assess for data normality. Continuous variables with normal distributions were compared using the t-test. Continuous parameters that were not normally distributed were compared using the Mann–Whitney test. Categorical variables were compared using the chi-squared test . Spearman’s correlation coefficient was used to analyze associations between SS and CMR or echocardiographic parameters. Independent predictors of high IS and low MSI were determined in a multivariable binary logistic regression model using the backward stepwise method adjusted for all baseline variables found significant (p = 0.011), and had a lower BMI . The prevalence of multivessel disease (p < 0.001), initial TIMI thrombus grade 4/5 (p = 0.002), initial TIMI flow grade 0/1 (p = 0.008), and APOB (p = 0.038) were higher but creatinine clearance rate (p = 0.016) was lower in the mediate-high SS group. There were no differences between groups concerning medical history, culprit lesion, mode of reperfusion, and medications after surgery .A total of 215 AMI patients who underwent primary PCI within 12 h from symptom onset were retrospectively included. Out of the 39 with no CMR data, 24 with old myocardial infarction, and three with poor image quality were excluded. Finally, 149 patients  were enrolled for analysis , MSI  and higher left ventricular end-systolic volume , and IS  in mediate-high SS group patients when compared with those in low SS group. There was no significant difference between the two groups in terms of MVO, IMH and AAR (Table All transthoracic echocardiography (TTE) parameters were comparable between the two groups Table . Whereas(30.3019.3–45.41 vp < 0.001) and CK  showed relative stronger correlation with IS (%LV) than other variables. Also, SS  and initial TIMI flow  were more correlated with MSI. Therefore, SS had a positive correlation with IS (%LV) and a negative correlation with MSI  and CMR parameters by Spearman correlation analysis are presented in Table p < 0.05) were significantly associated with an increased risk of high IS (≥ mean 35.43), including initial heart rate, pro-BNP, CK, CKMB, LVEF-TTE, left ventricular end-diastolic diameter (LVEDD), infarct-related artery LAD, SS > 22  and SS (as a continuous variable); LVEF-TTE, baseline TIMI flow 0/1 and SS  were significant predictors for risk of low MSI (≤ median 28.01) (Table p = 0.001) and SS > 22  were significant for high IS in model 1; in model 2, LVEF-TTE  and SS (as continuous variable)  were also the independent predictors of high IS; for low MSI in model 3, only LVEF-TTE  was the independent predictor. Among the three models, the SS had higher odd ratio than LVEF-TTE , 0.610 , respectively. At the optimal cutoff point of SS , the sensitivity and specificity were similar for high IS diagnosis  and for low MSI .The ROC analysis results of SS predicting high IS (≥ mean 35.43) and low MSI (≤ median 28.01) are shown in Fig. Although the SYNTAX score was shown to positively correlate with postprocedural myocardial injury in patients after elective coronary artery intervention, quality evidence about the association of SS with myocardial salvage in STEMI patients is still needed. This study evaluated the prognostic value of SS for myocardial injury and salvage assessed by CMR after primary PCI in STEMI patients. To the best of our knowledge, the present study is the first report on the relationship between SS and myocardial injury in STEMI patients undergoing primary PCI within 12 h from symptom onset. We identified three major findings: (1) a significant positive correlation between SS and IS and a negative correlation between SS and MSI. (2) compared to the low SS group, the mediate-high group had lower LVEF as assessed by CMR and higher LVESV, but LVEDV was comparable between groups. (3) according to the univariable and multivariable logistic models, SS  was the independent predictor of high IS after adjustment for confounders.p = 0.021) than those treated with immediate CR. Interestingly, staged approach patients also had larger IS (%LV)  and lower MSI  compared with immediate CR. However, no direct relationship among them was found. In several studies [In the CvLPRIT study , patient studies , 28, 29, studies . These fp = 0.070), however, LVEF-CMR in the low SS group was significantly higher than that in the mediate-high group . In addition, among our study population, LVEF-CMR was lower than LVEF-TTE, in line with findings reported by another recent multicenter study [In our study, the LVEF-TTE in the low SS group was comparable with that in the mediate-high SS group  in our population was too small to allow conclusions in all three groups. Consequently, tests of interaction were underpowered, especially when adjusted for covariables. Secondly, although all patients were enrolled consecutively, part of them declined CMR for personal reasons or unstable clinical station, for example, severe heart failure; on the other hand, only patients presented in hospital undergone primary PCI within 12 h from symptom onset were included in our study population. Thus, we should be very cautious about interpreting the conclusions in specific patients. Thirdly, considering the “shrinkage” of the infarcted region after the acute infarction phase [In STEMI patients who had undergone primary PCI, SYNTAX score positively correlated with infarct size and negatively with myocardial salvage. SYNTAX score had an independent predictive value of the myocardial injury.


In patients hospitalized for corona virus infectious disease 19 (COVID-19) it is currently unknown whether myocardial function changes after recovery and whether this is related to elevated cardiac biomarkers. In this single center, prospective cohort study we consecutively enrolled hospitalized COVID-19 patients between 1 April and 12 May 2020. All patients underwent transthoracic echocardiography (TTE) evaluation during hospitalization and at a median of 131 days  follow-up. Of the 51 patients included at baseline, 40 , 78% male) were available for follow-up TTE. At baseline, 68% of the patients had a normal TTE, regarding left ventricular (LV) and right ventricular (RV) volumes and function, compared to 83% at follow-up (p = 0.07). Median LV ejection fraction  and tricuspid annular plane systolic excursion  were comparable between hospitalization and follow-up, but a significantly lower RV diameter  and trend towards better global longitudinal strain (GLS)  was found at follow-up. Subgroup analysis showed no relation between patients with and without elevated TroponinT and/or NT-proBNP during hospitalization and myocardial function at follow-up. Although there were no significant differences in individual myocardial function parameters at 4 months follow-up compared to hospitalisation for COVID-19, there was an overall trend towards normalization in myocardial function, predominantly due to a higher rate of normal GLS at follow-up.The online version contains supplementary material available at 10.1007/s10554-021-02346-5. In recovered COVID-19 patients there is a trend towards better global longitudinal strain and the combination of echocardiographic parameters for LV and RV volumes and function 4 months after hospitalization.Elevated TroponinT and/or NT-proBNP during hospitalization was not associated with myocardial function at follow-up.Most recovered COVID-19 patients have normal myocardial function on echocardiography at 4 months follow-up (83%).Corona virus infectious disease 19 (COVID-19) has a huge impact on the global healthcare system. A substantial percentage of COVID-19 patients requires hospitalization for supplemental oxygen or invasive ventilation , 3, venoIn this single center prospective cohort study, we recruited non-selected, previously hospitalized COVID-19 patients . In shor2, Indexed LV end diastolic diameter ≤ 31 mm and RV basal diameter ≤ 42 mm [All patients underwent a first clinical transthoracic echocardiogram (TTE) at the COVID-19 nursing ward, in supine position, and a second follow-up TTE  afterwards at the outpatient clinic. TTE was focused on LV- and RV systolic function, LV diastolic function and global longitudinal strain (GLS). We did not extensively assess valvular function. All TTE’s were performed by experienced sonographers using one single ultrasound system  in hospitalized patients, and another single ultrasound system  at the outpatient clinic. Offline analysis was performed by one single investigator (EACVI TTE certified) using dedicated software . Detailed information about echocardiographic assessment was described previously  and/or EHigh-sensitive TroponinT and NT-proBNP concentrations  were measured during hospitalization, within 48 h of the TTE. Elevation in TroponinT levels were defined as a value > 14 ng/L (i.e. 99th percentile of upper reference limit) and elevated NT-proBNP was defined as a value > 300 pg/mL.Categorical variables are summarized with counts and percentages, continuous variables with median and interquartile range . All statistical analyses were performed using IBM SPSS statistics version 25 . A p-value of < 0.05 will be considered significant. The Wilcoxon signed-rank test was used for comparing echocardiographic parameters  across timepoints. For categorical variables a McNemar test for paired data is used. Subgroup analyses of echocardiographic parameters at follow-up were performed using the Mann–Whitney U test. The following subgroups were defined: intensive care unit (ICU) admission, pulmonary embolism diagnosed during hospitalization, elevated TroponinT, elevated NT-proBNP and persistent self-reported symptoms.2   were available for follow-up: 5 were excluded because of no consent to participate, 3 because of palliative oncology care, 1 because of large travel distance,1 because of hospitalization elsewhere and 1 deceased during index hospitalizing. Of the remaining 40 patients, median age was 62 years , 78% was male, and the median body mass index was 27 kg/m2, p = 0.04) were higher in patients during hospitalization for COVID-19 compared to follow-up. RV S’  was different between both TTE’s although the absolute value of RV S’ at follow-up was in all but 1 patient (3%) within the normal range. During hospitalization, 13% had abnormal LVEF, 38% abnormal GLS, 5% abnormal TAPSE, 6% abnormal RV S’ and 10% abnormal RV basal diameter. At follow-up and compared to hospitalization, 5% had abnormal LVEF (p = 0.25), 18% abnormal GLS (p = 0.13), 0% abnormal TAPSE (p = 0.50), 3% abnormal RV S’ (p = 0.50) and 3% abnormal RV basal diameter (p = 0.50). With regard to a combination of LV and RV volumes and function parameters 67.5% of patients had a normal TTE during hospitalization for COVID-19 and 82.5% at follow-up, with a trend towards statistical significance (P = 0.07). Median LVEF, GLS, TAPSE and RV S’ during hospitalization and at follow-up are shown in Fig. All echocardiographic parameters are summarized in Table At least one TroponinT value was available in 92.5% of all patients, and 47.5% had elevated TroponinT during hospitalization. NT-proBNP was measured in 95% of all patients, of whom 50% had elevated NT-proBNP during hospitalization. All laboratory values are shown in Table 2 (7.5%). Follow-up after discharge was available in all patients, with a median duration of 200 days  after the first TTE. After discharge, 2 (5%) patients had a pulmonary embolism diagnosed on a chest CT which was performed for other reasons and 1 patient (3%) developed de novo atrial fibrillation  followed by atrial fibrillation (7.5%), acute heart failure (7.5%), and acute kidney failure with a glomerular filtration rate below 30 mL/min/1.73 mon Table .To the best of our knowledge, this is the first study evaluating longitudinal changes in myocardial function in patients with COVID-19 from hospitalization to 4 months after discharge. In this non-selected and consecutively enrolled patient cohort, there was an overall trend towards normalization in myocardial function, predominantly due to a higher rate of normal GLS at follow-up compared to hospitalization. There were no significant changes in LVEF, LV diastolic function and TAPSE over time, but there was a decrease in RV basal diameter. Our findings regarding LV and RV volumes and function during hospitalization for COVID-19 are similar to other echocardiography studies , 12, 13 Because COVID-19 predominantly affects the respiratory system, theoretically RV function parameters would be expected to show the largest differences between hospitalization and follow-up. The decrease in RV basal diameter at follow-up could hypothetically be due to a decrease or normalization in pulmonary artery pressure after pulmonary recovery, however, pulmonary pressures have not been assessed in the current study. RV S’ was significantly lower at follow-up compared to hospitalization. We considered the change of RV S’ over time as not clinically relevant because the absolute value of RV S’ at follow-up remained within the normal range for all but one patient. The most remarkable difference in functional parameters is seen in GLS. GLS during hospitalization is associated with elevated inflammatory markers and hypoxia suggesting that abnormal GLS could be secondary to systemic inflammation . Three mIn large international registries, it is estimated that 27.8% of hospitalized COVID-19 patients require ICU admission , 6.6% haIn conclusion, 4 months after hospitalization for COVID-19, patients had more often a normal TTE than during hospitalization, predominantly related to an increased number of patients with normal GLS at follow-up. There was no association between elevated cardiac biomarkers during hospitalization and myocardial function at follow-up, nor between symptomatology and echocardiographic functional parameters at follow-up.Our study has limitations. First, the relatively small sample size, and therefore sub-analyses should be carefully interpreted. We tried to include as many patients as possible during the first wave in the Netherlands but due to a drop of hospitalizations in May 2020, we stopped including. Second, since written informed consent was required, the frailest patients could not be enrolled. Third, TTE’s were performed on different ultrasound systems, however, both machines were from the same vendor and analyses were performed using the same software. Fourth, biomarkers were not available at follow-up. Last, we only have follow-up in 40 of the initial 51 patients (78%)  which coSupplementary file1 (DOCX 173 kb)Below is the link to the electronic supplementary material.


A SIM pediátrica (SIM-P) já foi bem definida pela Organização Mundial da Saúde (OMS) e é caracterizada por hiperinflamação com tempestade de citocinas e níveis elevados de marcadores de lesão do miocárdio, com envolvimento de um ou mais órgãos dos sistemas cardíaco, renal, respiratório, gastrointestinal ou neurológico.2 Há evidências crescentes sobre o envolvimento cardiovascular na COVID-19 e na SIM-P.4A combinação do momento de ocorrência da SIM-P com sorologia positiva e PCR negativo na maioria dos pacientes sugere que a SIM-P seja mais uma complicação pós-infecciosa (até seis semanas após o insulto), mediada pelo sistema imune, que uma complicação da infecção aguda. Acredita-se que a fisiopatologia da SIM-P seja devido a uma resposta imune exacerbada em uma criança geneticamente susceptível. Os sintomas de SIM-P podem se sobrepor aos sintomas de doença de Kawasaki, síndrome do choque tóxico, síndrome de ativação macrofágica, sepse bacteriana, e síndrome de liberação de citocinas (“tempestade de citocinas”). A tempestade de citocinas é caracterizada por febre persistente, com níveis elevados de marcadores inflamatórios e citocinas pró-inflamatórias, tais como a interleucina.5 demonstraram manifestações cardiovasculares agudas em 286 crianças com idade média de 8,4 anos , cujas complicações mais frequentes foram choque, arritmia cardíaca, efusão pericárdica, dilatação da artéria coronária, e elevação da troponina em 93% dos casos. Foi registrada uma morte por arritmia ventricular e havia um paciente na lista de transplante cardíaco.5 Em outro estudo com 186 pacientes com SIM-P em 26 estados americanos, comprometimento cardíaco foi observado em 80% dos pacientes, e 33% desses apresentaram fração de ejeção ventricular esquerda (FEVE) menor que 55%, e 5% apresentaram FEVE menor que 30%. Níveis aumentados de troponina e peptídeo natriurético tipo-B (BNP) foram observados em 50% e 73% dos pacientes, respectivamente, efusão pericárdica em 26%, arritmia cardíaca em 12%, e envolvimento cardíaco em 8%.6 Um estudo conduzido na América Latina, com participação de centros brasileiros, mostrou que crianças com COVID-19 e envolvimento cardiovascular tiveram apresentação clínica mais grave, com maiores alterações laboratoriais, instabilidade hemodinâmica, necessidade de drogas vasoativas e maior número de internação em unidade de terapia intensiva.7Em um recente estudo multicêntrico europeu, Valverde et al.8 até outros fatores tais como microtrombose, disfunção microvascular, estado hiperinflamatório, hipoxemia, aumento da demanda metabólica e hipotensão.9Os mecanismos potenciais de lesão miocárdica na COVID-19 variam desde cardiotoxicidade viral direta, conforme relatado pelo grupo do Instituto da Criança do HCFMUSP-São Paulo-Brasil em uma criança de 11 anos de idade com SIM-P que desenvolveu taquicardia ventricular indo a óbito dentro de 28 horas da admissão, e teve partículas virais detectadas no tecido cardíaco,2 Vários parâmetros são avaliados pela ecocardiografia, tais como função sistólica e diastólica, efusão pericárdica, alterações valvares, comprometimento da artéria coronária incluindo hiperecogenicidade, irregularidades da parede, dilatação e aneurismas avaliados com as medidas dos diâmetros das artérias coronárias e analisados pelos z-scores. Em várias séries publicadas durante a pandemia, o envolvimento da artéria coronária em pacientes com SIM-P foi observado entre 8 e 36%, provavelmente devido à disfunção endotelial associada com tempestade de citocinas causada pelo SARS-CoV-2.2A ecocardiografia tem se destacado como um método robusto tanto para o diagnóstico como para o seguimento de pacientes pediátricos com COVID-19 e já foi indexada nas diretrizes clínicas para SIM-P.10 os autores avaliaram retrospectivamente 48 pacientes pediátricos, 73% com doenças pré-existentes e 41,7% com SIM-P. Foram realizadas avaliações ecocardiográficas padronizadas, com adequadas variabilidades intraobservador e entre observadores. Anormalidades ecocardiográficas foram significativamente associadas com SIM-P, internação e maior permanência na unidade de terapia intensiva pediátrica, disfunção de múltiplos órgãos, suporte ventilatório/vasoativo e morte. Observou-se uma interessante correlação estatisticamente significativa dos achados ecocardiográficos com alterações nos marcadores inflamatórios e lesão miocárdica. Pacientes com disfunção do ventrículo esquerdo apresentaram níveis mais elevados de D-dímero, proteína C reativa, ferritina e troponina, aqueles com disfunção ventricular direita apresentaram níveis mais elevados de D-dímero e proteína C-reativa e aqueles com anormalidades na artéria coronária apresentaram níveis mais elevados de D-dímero somente. Devido a esses achados, os autores destacam a importância da imunotrombose na SIM-P e levantam a hipótese de se bloquear a cascata de coagulação para diminuir a resposta inflamatória, enfatizando as propriedades não anticoagulantes da heparina, tais como inibição da quimiotaxia de neutrófilos e migração de leucócitos, com consequente diminuição dos biomarcadores inflamatórios. O uso da heparina, além da sua função antitrombótica, melhoraria a terapia anti-inflamatória juntamente com a imunomodulação realizada pela imunoglobulina humana endovenosa, corticoides e agentes imunobiológicos em pacientes com SIM-P. 11No estudo intitulado “O Coração de Pacientes Pediátricos com COVID-19: Novos Insights a Partir de um Estudo Ecocardiográfico Sistemático em um Hospital Terciário no Brasil”,strain) avaliada pela técnica de speckle tracking em pacientes pediátricos com SIM-P tanto na fase aguda como no acompanhamento .Outra importante ferramenta que agrega valor à ecocardiografia é o uso da deformação miocárdica  may occur in 0.6% of the cases. MIS in children (MIS-C), already well defined by the World Health Organization (WHO), is characterized by hyperinflammation with cytokine storm and high levels of myocardial injury markers, with involvement of one or more organs of the cardiac, renal, respiratory, gastrointestinal or neurological systems.2 There increasing evidence on cardiovascular involvement in COVID-19 and MIS-C.4The combination of the timing of MIS-C cases with positive serology and negative PCR in most patients suggests that MIS-C is a post-infectious (up to six weeks after the insult), immune-mediated complication rather than of the acute infection. The pathophysiology of MIS-C is thought to be due to a hyperimmune response to the virus in a genetically susceptible child. The symptoms of MIS-C can overlap with those of Kawasaki disease, toxic shock syndrome, macrophage activation syndrome, bacterial sepsis, and cytokine release syndrome (“cytokine storm”). Cytokine storm is characterized by persistent fever, and markedly elevated inflammatory markers and pro-inflammatory cytokines such as interleukin.5 demonstrated acute cardiovascular manifestations in 286 children with an average age of 8.4 years (3.8 to 12.4 years), whose most common complications were shock, cardiac arrhythmia, pericardial effusion, coronary dilation, and troponin elevation in 93% of the cases. There were one death due to ventricular arrhythmia and one patient listed for heart transplantation.5 In another study with 186 patients with MIS-C in 26 American states, cardiovascular involvement was observed in 80% of patients, and 33% of these had left ventricular ejection fraction (LVEF) less than 55% and 5% had LVEF less than 30%. Increased troponin and B-type natriuretic peptide (BNP) e levels were found in 50% and 73% of patients, respectively, pericardial effusion in 26%, cardiac arrhythmia in 12%, and coronary involvement in 8%.6 A Latin American study7 that also included the participation of Brazilian centers showed that children with COVID-19 with cardiovascular involvement had more severe clinical presentation, more laboratory abnormalities, greater hemodynamic instability and the greater need for vasoactive drugs and intensive care unit admission, when compared to those without cardiovascular involvement.7In a recent European multicenter study, Valverde et al.8 to several other factors such as microthrombosis, microvascular dysfunction, endothelial injury, hyperinflammatory state, hypoxemia, increased metabolic demand and hypotension.9The potential mechanisms of myocardial injury in COVID-19 range from direct viral cardiotoxicity, as first reported by the group of the Instituto da Criança of HCFMUSP - São Paulo - Brazil, about a case of an 11-year-old child affected by MIS-C, who developed ventricular tachycardia and died within 28 hours of admission, and had viral particles detected in the cardiac tissue,2 Several parameters are evaluated by echocardiography, such as left ventricular systolic and diastolic function, pericardial effusion, valvular alterations, coronary involvement such as increased hyperechogenicity, parietal irregularities, dilation, and aneurysms by measurement of the of coronary artery diameter and analysis using z-score. In several series published during the pandemic, coronary involvement in MIS-C occurred from 8 to 36%, probably due to endothelial dysfunction associated with cytokine storm caused by SARS-CoV-2.2Echocardiography has emerged as a robust tool both in diagnosis and in clinical follow-up in the pediatric population with COVID-19 and has already been indexed in the clinical guideline for MIS-C.10 the authors retrospectively evaluated 48 pediatric patients, 73% with pre-existing diseases and 41.7% with MIS-C. Standardized echocardiographic assessments were performed with adequate intraobserver and interobserver variability. Echocardiographic abnormalities were significantly associated with MIS-C, admission and longer stay in the pediatric intensive care unit, multiple organ dysfunction, ventilatory/vasoactive support, and death. There was an interesting, statistically significant correlation of echocardiographic findings with changes in inflammatory markers and myocardial injury. Patients with left ventricular dysfunction had higher levels of D-dimer, C-reactive protein, ferritin and troponin; those with right ventricular dysfunction had higher levels of D-dimer and C-reactive protein; and those with coronary abnormalities had higher levels of D-dimer only. Due to these findings, the authors highlight the importance of immunothrombosis in MIS-C and raise the hypothesis of blocking the coagulation cascade to decrease the inflammatory response, emphasizing the non-anticoagulant properties of heparin, such as the inhibition of neutrophil chemotaxis and migration of leukocytes, with a consequent decrease in inflammatory biomarkers. The use of heparin, in addition to its antithrombotic function, would enhance the anti-inflammatory therapy together with the immunomodulation performed by intravenous human immunoglobulin, corticosteroids and immunobiological agents in patients with MIS-C.11In the study “The Heart of Pediatric Patients with COVID-19: New Insights from a Systematic Echocardiographic Study in a Tertiary Hospital in Brazil”,12 demonstrated that systolic and diastolic cardiac dysfunctions might occur frequently, probably due to the presence of a state similar to myocarditis. Even in patients with preserved ejection fraction, subtle changes in myocardial deformation were detected, suggesting subclinical myocardial dysfunction. In addition, these authors demonstrated that even patients whose ejection fraction was normalized, remained with ventricular diastolic changes in the echocardiographic assessment by speckle tracking over time, reinforcing the need for the follow-up of patients with MIS-C with complementary exams .Another important tool that has added value to echocardiography is the use of the strain assessed by the speckle tracking technique in pediatric patients with SIM-P both in the acute phase and in the follow-up . MatsubaThe cardiovascular manifestations of COVID-19 are frequent in patients with MIS-C and can lead to high morbidity and consequent deaths. The understanding of the SARS-CoV-2-related syndrome in the pediatric population is growing. All knowledge gained to date reflects the current evidence available together with expert opinion. There is a lot to learn about MIS-C in COVID-19, towards better diagnosis, treatment and follow-up of these patients.


Objective: Myocardial work (MW) is a novel non-invasive method that uses speckle tracking echocardiography (STE) to assess left ventricular (LV) function. MW incorporates the global longitudinal strain and afterload conditions. Here we aimed to use MW to assess the LV function of patients with coronary artery disease (CAD) with or without heart failure (HF).Methods: We enrolled a total of 150 individuals (50 each) with CAD and a normal LV ejection fraction (LVEF), CAD with HF, and healthy controls. Patients were divided into the hypertension (HTN) and normal blood pressure (no HTN) subgroups. MW was determined from the pressure-strain loop using STE. The relationships between MW indices and conventional echocardiographic parameters were evaluated, and the MW indices were compared among groups.Results: Univariate and multivariate analyses showed that MW indices were strongly correlated with LVEF. The global work index (GWI) was increased in the CAD with normal LVEF subgroup with HTN vs. controls  and decreased in CAD patients with HF . Global waste work was increased in all CAD subgroups vs. controls. Global constructive work had the same tendency as GWI in patients with CAD. Global MW efficiency was decreased in all patients with CAD.Conclusion: MW using STE accurately quantifies LV function in patients with CAD. It offers additional information about LV function with respect to disease progression, particularly in CAD patients with a normal LVEF. An accurate assessment of left ventricular (LV) function is crucial in clinical decision-making regarding cardiovascular diseases. This remains a major challenge during disease development. In addition to echocardiography, cardiac magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) are used to assess heart function. However, MRI and SPECT are severely limited by their high operational cost, need for expensive and high-maintenance equipment, and radioactivity. In addition to these advantages, echocardiography can provide diagnostic results faster than MRI and SPECT. The conventional echocardiographic parameter, LV ejection fraction (LVEF), is currently recognized as the standard assessment of LV function. However, LVEF is based on movement of the endocardial border, which is less sensitive in the early stage of ischemia. Tissue Doppler imaging (TDI) was used to evaluate heart function before speckle tracking echocardiography (STE) emerged. However, TDI has the disadvantage of its angle dependence leading to inaccurate results. Global longitudinal strain (GLS), which is derived from speckle tracking imaging, is a more sensitive measure of myocardial impairment and ischemia-induced LV function damage and has gradually been used in clinical practice . HoweverRecent studies reported that MW showed distinct patterns in different afterload conditions and settings –8. LVEF This study enrolled all individuals treated at Beijing Hospital between September 2018 and December 2019. The study protocol complied with the guidelines of the Declaration of Helsinki. All participants provided written informed consent. This study was approved by the Beijing Hospital Ethics Committee. The participants were divided into three groups of 50 each: controls, CAD with normal LVEF, and CAD with heart failure (HF). The control group included healthy individuals from the healthcare management center who had no cardiopulmonary symptoms, had normal electrocardiography findings, and received no medication. Patients with symptoms and diagnosed as HF were assigned to the HF group. The HF group included patients with a mid-range or reduced ejection fraction . The incAngiography was performed after echocardiography by an experienced cardiologist. Stenosis ≥50% in at least one major coronary artery or its main branch was identified as CAD. Echocardiography was performed using a Vivid E95  according to the guidelines of the American Society of Echocardiography . All imaGLS and MW were measured using 2D STE. The indices were obtained from four-, two-, and three-chamber views at 45–75 frames/s. The offline analysis was performed using an EchoPAC V203 (GE Vingmed Ultrasound). The MW parameters were obtained using a pressure-strain loop (PSL) area module that was constructed using LV pressure values on the vertical axis and strain on the horizontal axis. Based on previous studies, the peak systolic LV pressure was assumed to be equal to the brachial SBP  represents the total work within the area of the LV-PSL from mitral valve closure to mitral valve opening . Global 2 test for categorical variables and analysis of variance for continuous variables in relation to the control group. Correlation analysis was performed using Pearson's or Spearman's correlation coefficients. Multivariable linear regression analyses were performed to evaluate the independent correlations between the MW indices and other parameters. Two-sided values of p < 0.05 were considered statistically significant. All analyses were performed using SPSS v25.0 .Continuous variables are represented as mean ± standard deviation. The normality of the distribution was tested using the Kolmogorov–Smirnov test. Categorical variables are presented as numbers and percentages. Individual characteristics were compared across subgroups using the χp < 0.05) (p < 0.05) in the CAD patients with a normal LVEF. The SBP was significantly higher in the HTN subgroup (p < 0.05). The DBP was significantly higher in patients in the CAD and normal LVEF with HTN subgroup and lower in patients with CAD and HF without HTN subgroup (p < 0.05). The SBP and DBP values differed significantly between the CAD subgroups (p < 0.05).Patients in the CAD groups were significantly older than those in the control group ( < 0.05) . The bodp < 0.05) (p < 0.05) in the CAD subgroup except in HF patients with HTN. The E/A ratio was decreased (p < 0.05) in the CAD subgroups except in HF patients with HTN. GLS was significantly impaired (P < 0.05) in both HF subgroups. However, no significant differences in GLS were observed in CAD patients with a normal LVEF. The E/e′ was increased (P < 0.05) in all patients with CAD.Patients in the HF subgroup had significantly thicker interventricular septal thickness than the controls ( < 0.05) . The PWdGWI was strongly correlated with the LVEF and LVDd, moderately correlated with SBP, E wave, and E/e′, and weakly correlated with IVSd ; Table 3p < 0.05) but not in those without HTN. In the HF group, the GWI was significantly reduced in both subgroups . It also significantly increased in both HF subgroups  but not in those with a normal LVEF and no HTN. In the HF group, GCW significantly decreased in all patients  and HF subgroups  study, which demonstrated strong correlations between GWI and GLS and LVEF . In the MW may provide additional information about dyssynchronous contractions, segmental MW, and myocardial contractility . GLS hasOur study described various patterns of MW in CAD patients with different heart functions. However, the baseline patient ages varied among groups. No study to date demonstrated any effect of age on MW; however, this requires further investigation. Some CAD patients in this study had a history of diabetes and HTN, and it is unclear whether either condition affects MW. Poor image quality limits the assessment and application of MW. In this study, we used only one product . Possible variations in speckle tracking strain findings among products have not been investigated. And finally, this was a small-sample single-center study; thus, larger studies are required to confirm our results.MW manifested special patterns in the subgroups of CAD patients with different heart functions under different afterload conditions. Our findings suggest that MW enables an accurate and subtle assessment of ventricular function in CAD patients.The data supporting the conclusions of this article will be made available by the authors upon request.The studies involving human participants were reviewed and approved by Beijing Hospital Ethics Committee. The patients/participants provided their written informed consent to participate in this study.HZ and YG contributed to the study planning and conduct, and the article writing. XW, CY, YL, and XM contributed to the patient enrolment process. ZP and RZ contributed to the data analysis and echocardiography examinations. YZ and FW contributed to the study design and take responsibility for the overall content as guarantors. All authors contributed to the article and approved the submitted version.FW was supported by a grant from the Project of the Ministry of Science and Technology (No. 2020YFC2008106) and the 13th Five-Year National Science and Technology Major Project (2017ZX09304026). YG was supported by a grant from the Beijing Hospital Research Project (No. BJ-2019-133).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.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.


Despite marked advances in therapeutics, HIV infection remains a leading cause of morbidity and mortality worldwide. HIV infection is associated with cardiovascular complications including myocardial dysfunction. The description of HIV-associated cardiomyopathy (HIVAC) has evolved over time from a predominantly dilated cardiomyopathy with systolic dysfunction to one of subclinical diastolic dysfunction. Multimodality cardiovascular imaging plays an integral role in our understanding of the etiology and pathogenesis of HIVAC. Such imaging is also essential in the evaluation of individuals with chronic HIV disease who present with cardiac symptoms, especially of heart failure. In the present review, we will highlight current evidence for the role of multimodality imaging in establishing the diagnosis, etiology and pathophysiology of HIVAC as well as guiding treatment and assessing prognosis. Human immunodeficiency virus (HIV) infection remains a leading cause of morbidity and mortality worldwide . Of the HIV infection is associated with various cardiovascular manifestations. In settings where ART is readily accessible, PWH are living longer but continue to have chronic low-grade inflammation despite immunosuppression . In addiThe presentation of myocardial disease in PWH ranges from incidental asymptomatic findings on autopsy or cardiovascular imaging to symptomatic heart failure. Decades after its recognition, the etiology and pathophysiology of HIV-associated cardiomyopathy (HIVAC) remains a topic of intense speculation with no consensus criteria for its definition. Nevertheless, its description has evolved from the pre-HAART era, when HIVAC was characterized by a dilated cardiomyopathy with systolic dysfunction associated with end-stage HIV disease and a poor prognosis. Morbidity and mortality occurred largely in the context of myocarditis, opportunistic infections, toxicity from medications, nutritional disorders, autoimmune mechanisms and inflammation. In more recent times, subclinical diastolic dysfunction has become the hallmark of HIVAC in individuals with treated HIV infection .Cardiac imaging plays an integral role in the assessment of PWH who present with cardiac symptoms and signs especially those of heart failure. In the current review, we will highlight evidence for the role of multimodality imaging in establishing the diagnosis, etiology, and pathophysiology of HIVAC as well as guiding treatment and assessing prognosis.The epidemiology of HIVAC has changed over the course of time from its initial description characterized by left ventricular (LV) systolic dysfunction to its current description of varying levels of diastolic dysfunction. Data on the prevalence of HIVAC is largely from studies conducted in the United States and Europe despite the fact that more than two-thirds of PWH are found in Sub-Saharan Africa . With thThe pathogenesis of HIVAC is unclear but is likely multifactorial. Prior to the widespread implementation of ART, systolic dysfunction was thought to be mainly due to direct viral invasion of the myocardium, with or without myocarditis by the HIV virus or secondary to opportunistic infections such as toxoplasmosis and cryptococcosis . HoweverEchocardiography remains the first line imaging modality in assessing myocardial function. It is readily available, cost effective and robust in detecting both systolic and diastolic dysfunction. Prior to HAART, HIVAC was recognized on transthoracic echocardiography (TTE) as systolic LV dysfunction with varying degrees of LV dilatation. However, with the onset of HAART, HIVAC is largely recognized on TTE as subclinical diastolic dysfunction.3 in these patients. The HIV-HEART study assessed the prevalence of abnormalities in cardiac structure and function in 803 PWH in the era of ART  had a dilated cardiomyopathy, 33 (22%) had LV dysfunction and 9 (6%) had isolated right ventricular (RV) dysfunction . These ra of ART . The autEchocardiography has been shown to be instrumental in early detection of cardiovascular disease and has also been helpful for researchers to diagnose differences between heart disease in PWH and in people without HIV. One study analyzed 1,195 participants from the Multicenter AIDS Cohort (MACS) study who underwent TTE exams demonstrating that men with HIV had a larger LV mass index and right ventricular size compared to controls . In addiOther studies evaluated LV systolic function by tissue Doppler strain echocardiography in PWH and participants without HIV. One study demonstrated that while LVEF in PWH was slightly lower than in patients who were uninfected, the LVEF values were still within normal limits. However, PWH had subtle cardiac dysfunction, as evidenced by reduced LV strain . SubclinRight ventricular (RV) dysfunction is relatively common in PWH occurring largely in the setting of dilated cardiomyopathy or with varying degrees of HIV associated pulmonary hypertension (PH) . IsolateThe evidence highlights the value of echocardiography in the evaluation of myocardial function in PWH. Studies from the pre-HAART era demonstrate the pivotal role that echocardiography played in diagnosing systolic dysfunction in symptomatic patients often with advanced HIV disease. The same remains true today, and echocardiography remains an essential first line modality for assessing cardiac structure and function in PWH who present with heart failure symptoms. This non-invasive approach is important in characterizing biventricular function and cardiac structure as well as excluding other non-myocardial causes of symptoms. In the case of LV systolic dysfunction, evidence-based goal directed medical therapy should be considered per guideline recommendations . AlthougCardiac magnetic resonance (CMR) has been used to detect subtle and subclinical myocardial abnormalities, contributing to the current understanding of the pathogenesis of HIVAC. Untreated HIV infection is characterized by an immunodeficient state. In contrast, patients with well-treated HIV infection are in a state of immune activation. Several studies have shown a correlation between elevated inflammatory biomarkers and cardiovascular events in PWH . This obCMR is a useful tool in assessing the role of inflammation and fibrosis in myocardial dysfunction in PWH. CMR can detect several components of inflammation, which include edema and fibrosis depending on the extent of cardiac involvement and stage of disease. p < 0.001)  . A more < 0.001) . CMR has< 0.001) . HoweverCMR plays an important role in the evaluation of HIV associated myocarditis. Before the introduction of ART, an early autopsy study demonstrated myocarditis in 52% of patients who died of AIDS . HoweverMeasures of tissue characterization using CMR also have prognostic value for PWH. In a recent study, CMR was used to quantify ECV, reflective of myocardial inflammation or fibrosis, and showed that PWH have significantly higher ECV fraction when compared to people without HIV. The higher ECV value corresponded to more diffuse fibrosis, and studies have also shown a link between higher ECV values and increased adverse cardiovascular events. A prospective observational study evaluated the prognostic association between CMR measures and cardiovascular outcomes including heart failure in PWH on HAART. It was found that patients with diffuse myocardial fibrosis on CMR had a higher rate of cardiovascular events .Lastly, novel non-contrast CMR techniques have been developed that may help in the work up of PWH who are prone to developing early vascular disease and microvascular dysfunction that may contribute to the pathogenesis of cardiomyopathy . ImpaireCardiac computed tomography (CT) and coronary CT Angiography (CCTA) have emerged as important imaging tools for evaluating both clinical and subclinical CAD in PWH. An analysis of the MACS cohort, a large cohort of HIV infected and matched uninfected men showed that after adjusting for known CVD risk factors, HIV infected men had an increased prevalence of non-calcified and mixed plaques compared to HIV uninfected men using CCTA . CCTA waCoronary artery calcification (CAC) is a highly specific marker of coronary atherosclerosis and is frequently employed to screen for CAD and assess risk for cardiovascular events . The MACPWH may present with symptomatic heart failure secondary to ischemic heart disease. In this setting CCTA is useful in the diagnostic workup of CAD. The utility of CT to establish the diagnosis of CAD as well as its value as a gatekeeper for invasive coronary angiography in patients with heart failure and LV systolic dysfunction was shown in a study of 93 patients with newly diagnosed heart failure of unknown etiology . If the Nuclear medicine-based techniques have the ability to identify vascular inflammation and can permit the early detection of vascular disease in PWH . The degA summary of multimodality cardiovascular imaging techniques used for HIV-related heart disease is shown in The introduction of HAART has led to a paradigm shift in the presentation of cardiovascular disease in PWH including that of HIVAC. Although the etiopathogenesis of HIVAC remains unclear, multimodality imaging has played a role in defining various putative mechanisms including inflammation and myocardial fibrosis. Multimodality imaging is also crucial in establishing a diagnosis of HIVAC in symptomatic patients. Although many studies have established prognosis in HIV patients with cardiomyopathy and systolic dysfunction, the prognostic significance as well as progression of diastolic dysfunction in HIVAC remains largely unknown and further long-term studies are needed. In addition, the mechanism and significance of right ventricular dysfunction especially in the absence of PH and LV dysfunction should be explored further. In summary, an approach tailored to the clinical presentation of the patient should be used to guide the use of cardiovascular imaging to identify myocardial dysfunction, investigate the possible underlying causes and facilitate appropriate preventive and evidence-based treatment for this condition.EG, RR, and AH drafted the manuscript. MM, GS, EG, SB, SS, and BC reviewed and edited the manuscript. All authors contributed to the article and approved the submitted version.EG and AH received support from the Women as One Foundation. Further support was received from the National Institute of Health (R01HL147660) and the Johns Hopkins Center for AIDS Research (P30AI094189), Ruth L. Kirschstein Institutional National Research Service Award; T32HL007227-Pathophysiology of Myocardial Disease, the National Institute of Health.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.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.


RV + Qbest LV1 + Qbest LV2). The best “pseudo MPP”  and best BVp (QRV + Qbest LV) were also calculated. A theoretical longevity was estimated for each configuration at the threshold without a safety margin. Results: A total of 235 configurations were tested in 15 consecutive patients. “Pseudo-MPP” was feasible in 80% of patients with 3.1 ± 2.6 vectors available per-patient and LVproximal-LVdistal (most distant electrodes) vectors were available in 47% of patients. Each MPP pacing spike electrical charge was comparable to “pseudo-MPP” . Theoretical longevity was 6.2 years for MPP, 5.6 years for “pseudo-MPP” and 13.7 years for BVp. Conclusions: “Pseudo MPP” using intentional anodal capture with a quadripolar left ventricular lead, mimicking conventional multisite pacing, is feasible in most of CRT patients, with comparable energy consumption. Further studies on their potential clinical impact are needed.Background: Up to 40% of patients are CRT non-responders. Multisite pacing, using a unique quadripolar lead, also called multipoint/multipole pacing (MPP), is a potential alternative. We sought to determine the feasibility of intentional anodal capture using a single LV quadripolar lead, to reproduce MPP without the need of a specific algorithm . Methods: Consecutive patients implanted with a commercially available CRT device and a quadripolar LV lead in our department were prospectively included. The electric charge  of RV and LV pacing spikes were calculated for all available LV pacing configurations at the threshold. The best MPP was defined as the configuration with the lowest consumption (Q Cardiac resynchronization therapy (CRT) in heart failure showed a diminution of mortality and morbidity ,3,4,5,6.The initial concept of LV multisite pacing (MSp) emerged in this context and showed that pacing using 2 LV leads was associated with improved LV reverse remodeling, as compared with standard biventricular pacing (BVp) , especiaAnodal capture results, during bipolar pacing, from a high density current from the cathode allows for the capturing of the myocardium near the anode. Depolarization arises from both the anode and the cathode of the used electrical bipole. Intentional anodal capture during bipolar pacing by the LV quadripolar lead, so-called “pseudo-MPP” , may havWe sought to determine the feasibility of the intentional anodal capture using a single LV quadripolar lead, to reproduce MPP without the need for a specific algorithm.® , Boston Scientific®  and Medtronic®  were used.Consecutive patients implanted with a CRT device and a quadripolar LV lead in our department were prospectively included. Commercially available MPP-capable CRT device from AbbottEnrolled patients provided oral informed consent and data were collected in accordance with institutional guidelines on ethics.Electrical and ECG tests were performed after implantation. Threshold and impedance were manually measured in each programmable LV configuration. The pacing duration was 0.4 milliseconds. “Pseudo-MPP” stimulation was identified by a QRS morphology resulting from the fusion of the unipolar-cathode paced QRS complex and the unipolar-anode paced QRS complex. Its threshold was identified using an LV true bipolar vector decremental threshold test . VectorsRV + Qbest LV1 + Qbest LV2). The best “pseudo MPP”  and best BVp (QRV + Qbest LV) were also calculated. A theoretical longevity was estimated for best BVp, best MPP and best “pseudo-MPP” configurations in order to compare the battery drain. We considered permanent (100%) RV and LV pacing at 60 beats per minute in the VVI mode without atrial pacing, without any electrical shock, at the threshold without a safety margin, with a pacing duration of 0.4 ms, and a usable capacity of 1000 mAh.Using the data of the threshold tests, the electric charge  of the RV and LV pacing spikes were calculated for all available LV-pacing configurations at the threshold at 0.4 ms (without any safety margin). The first LV vector for MPP was named LV1, the second was named LV2. The best MPP was defined as the configuration with the lowest consumption . Qualitative variables are described using counts and percentages and continuous quantitative variables as mean ± standard deviation. Comparisons between MPP, pseudo-MPP and BVp were performed using non-parametric tests. Statistical significance was assumed at p < 0.05. All statistical analyses were performed using JMP®, 5 with a Boston® and 5 with a Medtronic® device).A total of 235 configurations were tested in 15 consecutive patients  vectors was available in 47% of patients . The mean “pseudo-MPP” threshold was 5.2 ± 0.9 V. Only two vectors with PNS during the “pseudo-MPP” test were excluded.Pacing characteristics are described in p = 0.15). The theoretical longevity was 6.2 years for MPP, 5.6 years for “pseudo-MPP” and 13.7 years for BVp  “pseudo-MPP” is feasible in 80% of patients, in almost half of the patients when using the most distant electrodes; (2) “pseudo-MPP” and MPP energy consumptions are comparable.Dell’Era et al. enrolled 30 CRT patients and tested, during the implantation procedure, the anodal capture on quadripolar leads from the three main manufacturers, using a Medtronic pacing-sensing analyzer .Conversely, we evaluated the feasibility of “pseudo-MPP” after implantation using the implanted CRT devices algorithms. They found an anodal capture in 93% of the patients, with a maximum pacing impulsion of 10 V at 0.5 ms, a much higher value than the one programmable in “real life”, explaining the lower 80% rate in our study. The mean anodal capture threshold was 3.9 ± 2.4 V at 0.5 ms (5.2 ± 0.9 V at 0.4 ms in our study) and the mean cathodal capture threshold was 1.9 ± 1.6 V at 0.5 ms (2.2 ± 0.8 V at 0.4 ms in our study), which was found to be comparable in both studies.“Pseudo MPP” has several advantages. It allows for MPP in MPP incompatible devices. Anodal capture is also associated with absence of intraventricular delay (0 ms), which could be useful in devices with a minimum programmable delay (5 ms for Abbott and 10 ms for Medtronic for example), and may achieve a better resynchronization .We do not provide data on any hemodynamics improvement. Morishima et al. showed an acute improvement on dP/dT max during “pseudo-MPP” comparable to MPP . The benefits of MPP and more so of “pseudo-MPP” remain unclear, and acute hemodynamics improvement does not predict the long-term response and/or clinical outcomes.Anodal capture is time consuming, necessitating a 12-lead electrocardiogram and a manual threshold test, which may be difficult to perform routinely. Very limited changes in the QRS morphology during “pseudo-MPP” threshold tests were observed in a few cases, with a difficult determination of the true “pseudo-MPP” threshold and probably limited effects on the depolarization wavefront and resynchronization.“Pseudo-MPP” and MPP are associated with rapid battery depletion as compared with conventional BVp. Indeed, the battery drain was about twice the difference versus BVp. A prospective study of the selected patients would be interesting in order to detect potential clinical impact. However, high battery drain would be associated with frequent generator changes and associated risks (infectious for example). In our opinion, only non-responder patients to CRT could ethically be included by comparing the best BVp versus MPP and “pseudo-MPP”. “Pseudo MPP”, using intentional anodal capture with a quadripolar left ventricular lead, mimicking conventional multisite pacing, is feasible in most CRT patients, with a comparable energy consumption. Further studies on the potential clinical impact are needed.


Background: Influence of right ventricular diastolic function on the hemodynamics of heart failure (HF). We aimed to clarify the hemodynamic features of deep Y descent in the right atrial pressure waveform in patients with HF and preserved left ventricular systolic function.Methods: In total, 114 consecutive inpatients with HF who had preserved left ventricular systolic function (left ventricular ejection fraction ≥ 50%) and right heart catheterization were retrospectively enrolled in this study. The patients were divided into two groups according to right atrial pressure waveform, and those with Y descent deeper than X descent in the right atrial pressure waveform were assigned to the deep Y descent group. We enrolled another seven patients  with HF and preserved ejection fraction, and implanted a pacemaker to validate the results of this study.Results: The patients with deep Y descent had a higher rate of atrial fibrillation, higher right atrial pressure and mean pulmonary arterial pressure, and lower stroke volume and cardiac index than those with normal Y descent . Multiple linear regression revealed a negative correlation between stroke volume index and pulmonary vascular resistance index (wood unit*m2) only in the patients with deep Y descent . A positive correlation was also observed between cardiac index and heart rate in this group . In the other seven patients, increasing the heart rate  significantly reduced the level of BNP .Conclusions: The hemodynamics of patients with HF with deep Y descent and preserved left ventricular systolic function resembled right ventricular restrictive physiology. Optimizing the heart rate may improve hemodynamics in these patients. Right ventricular (RV) function affects the severity of heart failure independently of left ventricular (LV) systolic function . The rigIn this study, after receiving approval from the Human Subject Review Committee of our institute, all data from the RHC database and medical records were retrospectively obtained. Between April 2011 and March 2020, 216 consecutive inpatients with heart failure who underwent RHC to assess their hemodynamics were enrolled . PatientEchocardiography with Vivid 7  was performed using standard methods , 9, 10. Right heart catheterization (RHC) was performed by experienced cardiologists using a standard method . ElectroThe phases of diastole are isovolumic relaxation and filling. The filling phase is divided into the early rapid filling, slow filling period, and atrial contraction. In the filling phases, heart rate influences mainly the duration of the slow filling period and atrial contraction . In rest = –.To validate the results of this study, we examined whether sustained increases in heart rate for 3 months improved clinical indices.t-test or Mann–Whitney U test was performed to compare parametric data between the groups. The chi-square test or Fisher's exact test was performed to compare non-parametric data between the groups. Repeated measures ANOVA or the Friedman test was performed to compare the change in three measurements taken from the same individual. The relationship between X and Y was calculated using univariate linear regression. Parameters with a p-value <0.1 in the univariate linear regression were included in the multivariate analysis. Statistical analysis variance inflation factor was used to check for multicollinearity. Significance was established at p < 0.05. All the statistical analyses were carried out using EZR   or mean ± SD. Student's , Japan) .Patient characteristics are shown in The results of hemodynamics assessed by RHC are shown in The results of single and multiple linear regression are shown in Clinical features in the other seven patients and the effectiveness of increasing the heart rate with a pacemaker on clinical characteristics are shown in This study revealed that the resting hemodynamics of Y descent was deeper than that of X descent in the right atrial pressure waveform. Lower SVI and CI were observed in patients with deep Y descent. The hemodynamics of deep Y descent and preserved LV systolic function resembled RV restrictive physiology. Increasing the heart rate using a pacemaker improved the clinical condition of patients with HFpEF.Regarding the hemodynamic features of deep Y descent and preserved LV systolic function, a negative correlation was observed between SVI and PVRI, and right heart system pressures were high; a positive correlation was observed between CI and heart rate, and low CI was accompanied by low SVI. Unique hemodynamics was observed in patients with deep Y descent and preserved LV systolic function. The SVI in these patients significantly depended on PVRI, but this relationship was not observed in patients with normal Y descent. This suggested that RV preload reserve in patients with deep Y descent and preserved LV systolic function is limited by increased RV afterload or failure of the Frank-Staring mechanism . From thThis study revealed that deep Y descent was a functional marker for RV diastolic function rather than a specific disease marker. Therefore, assessment of RV diastolic function, the cause of deep Y descent, and selection of therapeutic strategies suitable for less-distensible right ventricle are of importance in patients with heart failure and preserved LV systolic function, because the complication of less-distensible right ventricle deteriorates the hemodynamics.Nowadays, echocardiography is an important non-invasive tool for quantitative assessment of cardiac function, but in comparison with LV diastolic function, there is a lack of guidance for the assessment and quantification of RV diastolic function . TherefoAs the essential hemodynamic feature of a less-distensible right ventricle was lower CI in this study, the cause of deep Y descent should be examined. Although constrictive pericarditis is the representative disease of the less-distensible right ventricle and preserved systolic function, the rate of AF was higher in patients with deep Y descent than in those with normal Y descent, which should be paid attention to. Previous studies have revealed that AF is associated with deep Y descent in the right atrial pressure or jugular venous pressure waveform , 8. Thervia pacemaker can improve clinical features, such as BUN/Cre ratio, renal function, BNP, mitral E/e', and SPAP, in patients with HFpEF and less-distensible right ventricle. Therefore, to maintain an appropriate heart rate to support CI, a pacemaker may be needed, as in this study, in order to improve the poorer outcomes of patients with HFpEF and RV afterload mismatch.Heart failure and preserved ejection fraction (HFpEF), representative heart failure with preserved LV systolic function, has multifaceted pathophysiology contributing to poor outcomes of the disease. Compared with heart failure with reduced LVEF, the therapeutic strategies of HFpEF have not been fully established yet, which remains an open issue in the world. We recently reported that less-distensible right ventricle is a clinical factor associated with phenotype, increase in posterior probabilities of developing cardiac events, and poorer outcomes of HFpEF –29. TherSome limitations must be considered. This is a retrospective study conducted in a single center, and a retrospective study has limitations. Echocardiography and blood sample testing of all the patients were performed within 5 days before and after RHC but not simultaneously. RHC was performed on patients without discontinuation of their medicine. The heterogeneity of cardiac disease also influenced hemodynamics. Therefore, our results may have been affected. Our study was only performed at rest. Exercise and drug loading examinations were not performed. Marked hemodynamic change occurs during exercise; therefore, the right atrial pressure waveform may change because the assessment of RV distensibility judged by the right atrial pressure waveform is influenced by RV systolic function, relaxation ability, and RV preload and afterload . As LV pThe hemodynamics of patients with heart failure with deep Y descent and preserved LV systolic function resembled RV restrictive physiology. Optimizing the heart rate may improve hemodynamics in these patients.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Imizu Municipal Hospital Ethics/Clinical Trial Review Committee. The patients/participants provided their written informed consent to participate in this study.DH and HA worked on the conception, methodology, and formal analysis. Data collection were performed by DH, TN, and JT. DH wrote the manuscript. All authors approved the final version of the manuscript.HA declares that this study received funding from Sun Medical Technology Research Corp., Sumitomo Riko Company Limited., Century Medical, Inc., Teijin Pharma Limited., Nipro Corporation., and Medtronic Japan Co, Ltd. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.HA declares that this study received funding from Sun Medical Technology Research Corp., Sumitomo Riko Company Limited., Century Medical, Inc., Teijin Pharma Limited., Nipro Corporation., and Medtronic Japan Co., Ltd. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. 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.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.