Long-term follow-up in outpatients with mildly elevated pulmonary artery systolic pressure on echocardiography: a single-centre retrospective cohort study in Shanghai, China.

OBJECTIVE: To investigate the correlation between mildly elevated pulmonary artery systolic pressure (PASP) on echocardiography and mortality, as well as long-term changes in PASP. DESIGN: Retrospective cohort study. SETTING: Shanghai, China, a single centre. PARTICIPANTS: A total of 910 patients were enrolled in this study. From January to June 2016, 1869 patients underwent echocardiography at the Zhongshan Hospital affiliated with Fudan University. Patients with malignant tumours, previous heart or other solid organ transplantation, previous or scheduled ventricular assist device implantation, severe kidney dysfunction (uraemia and patients on dialysis) and a life expectancy of less than 1 year for any medical condition were excluded. INTERVENTIONS: No interventions were done. PRIMARY AND SECONDARY OUTCOME MEASURES: The predictors of death in patients with mild echocardiographic pulmonary hypertension were analysed using univariate and multivariate Cox regression analyses. Paired t-tests were used to calculate changes in the PASP values at baseline and follow-up for different patient groups. RESULTS: The 5-year survival of patients was 93.2%. Patients were grouped according to whether they had combined organic heart disease (OHD). The PASP value was an independent predictor of all-cause mortality in patients with OHD, with each 1 mm Hg increase associated with an HR of 1.02 (95% CI: 1.01-1.03, p=0.038) but not in patients without OHD. Of the total, 46% (419/910) of the patients with 5-6 years of echocardiography were investigated for changes in the PASP value. We found significant PASP reduction in patients without OHD (42.8±2.4 mm Hg vs 39.3±8.2 mm Hg, p<0.001), but no significant change was observed for patients with OHD (42.8±2.5 mm Hg vs 42.4±8.8 mm Hg, p=0.339). CONCLUSIONS: The PASP was associated with all-cause mortality in patients with OHD and mildly elevated PASP compared with patients without OHD. After 5-6 years of follow-up, the PASP on echocardiography was not further elevated in patients without OHD.

Inhalable cardiac targeting peptide modified nanomedicine prevents pressure overload heart failure in male mice.

Heart failure causes considerable morbidity and mortality worldwide. Clinically applied drugs for the treatment of heart failure are still severely limited by poor delivery efficiency to the heart and off-target consumption. Inspired by the high heart delivery efficiency of inhaled drugs, we present an inhalable cardiac-targeting peptide (CTP)-modified calcium phosphate (CaP) nanoparticle for the delivery of TP-10, a selective inhibitor of PDE10A. The CTP modification significantly promotes cardiomyocyte and fibroblast targeting during the pathological state of heart failure in male mice. TP-10 is subsequently released from TP-10@CaP-CTP and effectively attenuates cardiac remodelling and improved cardiac function. In view of these results, a low dosage (2.5 mg/kg/2 days) of inhaled medication exerted good therapeutic effects without causing severe lung injury after long-term treatment. In addition, the mechanism underlying the amelioration of heart failure is investigated, and the results reveal that the therapeutic effects of this system on cardiomyocytes and cardiac fibroblasts are mainly mediated through the cAMP/AMPK and cGMP/PKG signalling pathways. By demonstrating the targeting capacity of CTP and verifying the biosafety of inhalable CaP nanoparticles in the lung, this work provides a perspective for exploring myocardium-targeted therapy and presents a promising clinical strategy for the long-term management of heart failure.

Global left ventricular myocardial work: A novel method to assess left ventricular myocardial function and predict major adverse cardiovascular events in maintenance hemodialysis patients.

BACKGROUND: The application value of myocardial work (MW) in evaluating myocardial function and predicting major adverse cardiovascular events (MACE) in maintenance hemodialysis (MHD) patients has not been fully explored. PURPOSE: Comparing noninvasive MW parameters between MHD patients and healthy controls, and further determining its value in predicting MACE in MHD patients. METHODS: A prospective single-institution study included 92 MHD patients without prior cardiovascular disease and 40 age- and sex-matched healthy controls. Conventional echocardiographic data, global longitudinal strain (GLS), and MW parameters (global work index [GWI], global constructive work [GCW], global work efficiency [GWE], global wasted work [GWW]) were derived and compared between MHD and the control. Logistic regression was used to determine the predictive value of these parameters for MACE. The receiver operating characteristic curve was utilized to compare the predictive differences of MACE between GWE and GLS. RESULTS: Compared with healthy individuals, MHD patients had significantly reduced GWE, GLS and elevated LVMI, GWW (all p < 0.001), while there was no significant difference in left ventricular ejection fraction. Twenty eight (30%) MHD patients experienced MACE. Two nested models adding GWE and GLS, respectively, showed that age (p < 0.005), GWE (p = 0.034), and GLS (p = 0.014) were independent predictors of MACE. The AUC derived from GWE for predicting MACE was significantly higher than that derived from GLS (0.836 vs. 0.743, p = 0.039). CONCLUSIONS: Myocardial work is a novel tool for assessing left ventricular myocardial performance in MHD patients. GWE is an independent predictor of MACE.

2-year results and myocardial impact of transapical mitral valve repair in patients with primary mitral regurgitation: an echocardiographic study.

BACKGROUND: There is limited data on the 2-year outcomes of transapical transcatheter edge-to-edge repair (TA-TEER) using the ValveClamp in patients with severe primary mitral regurgitation (MR) and its impact on myocardial deformation. METHODS: From July 2018 to March 2021, 53 patients with symptomatic severe primary MR underwent TA-TEER were enrolled. The endpoint was the composite of all-cause mortality, recurrent 3 + or 4 + MR, or need for mitral surgery. RESULTS: Among the 53 patients who had successfully ValveClamp implantation, 8(15.1%) reached the composite endpoint. Significant improvement in left ventricular (LV) end-diastolic volume, pulmonary artery systolic pressure, NYHA functional class, and MR severity were observed (P < 0.05 for all). Univariate Cox's regression analysis revealed that LV end-diastolic volume index, LV end-systolic volume index, left atrial volume index, and pulmonary artery systolic pressure were associated with adverse events (P < 0.05 for all). On multivariate Cox regression analysis, left atrial volume index was independently associated with the endpoint (hazard ratio, 1.049; 95% CI, 1.009-1.091; P < 0.001) after adjustment for above echocardiographic parameters. LV global longitudinal strain and apical longitudinal strain in global and regional segments decreased at 30 days, but showed a recovery at 2 years with no significant difference compared to the baseline. CONCLUSION: TA-TEER using the ValveClamp presented favorable safety and efficacy at 2-year. Myocardial deformation impairment was observed at 30 days post-procedure, but did not persist at 2 years.

The recommendation of re-classification of variants of uncertain significance (VUS) in adult genetic disorders patients.

Since variants of uncertain significance (VUS) reported in genetic testing cannot be acted upon clinically, this classification may delay or prohibit precise diagnosis and genetic counseling in adult genetic disorders patients. Large-scale analyses about qualitatively distinct lines of evidence used for VUS can make them re-classification more accurately. We analyzed 458 Chinese adult patients WES data, within 15 pathogenic evidence PS1, PS2, PM1, PM6 and PP4 were not used for VUS pathogenic classification, meanwhile the PP3, BP4, PP2 were used much more frequently. The PM2_Supporting was used most widely for all reported variants. There were also 31 null variants (nonsense, frameshift, canonical ±1 or 2 splice sites) which were probably the disease-causing variants of the patients were classified as VUS. By analyzed the evidence used for all VUS we recommend that appropriate genetic counseling, reliable releasing of in-house data, allele frequency comparison between case and control, expanded verification in patient family, co-segregation analysis and functional assays were urgent need to gather more evidence to reclassify VUS. We also found adult patients with nervous system disease were reported the most phenotype-associated VUS and the lower the phenotypic specificity, the more reported VUS. This result emphasized the importance of pretest genetic counseling which would make less reporting of VUS. Our result revealed the characteristics of the pathogenic classification evidence used for VUS in adult genetic disorders patients for the first time, recommend a rules-based process to evaluate the pathogenicity of VUS which could provide a strong basis for accurately evaluating the pathogenicity and clinical grade information of VUS. Meanwhile, we further expanded the genetic spectrum and improve the diagnostic rate of adult genetic disorders.

Echocardiographic Measurements in Normal Chinese Adults (EMINCA) II focusing on left ventricular and left atrial size and function by three-dimensional echocardiography.

Current guidelines encourage large studies in a diverse population to establish normal reference ranges for three-dimensional (3D) echocardiography for different ethnic groups. This study was designed to establish the normal values of 3D-left ventricular (LV) and left atrial (LA) volume and function in a nationwide, population-based cohort of healthy Han Chinese adults. A total of 1117 healthy volunteers aged 18-89 years were enrolled from 28 collaborating laboratories in China. Two sets of 3D echocardiographic instruments were used, and full-volume echocardiographic images were recorded and transmitted to a core laboratory for image analysis with a vendor-independent off-line workstation. Finally, 866 volunteers (mean age of 48.4 years, 402 men) were qualified for final analysis. Most parameters exhibited substantial differences between different sex and age groups, even after indexation by body surface area. The normal ranges of 3D-LV and 3D-LA volume and function differed from those recommended by the American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines, presented by the World Alliance Societies of Echocardiography (WASE) study, and from the 2D values in the EMINCA study. The normal reference values of 3D echocardiography-derived LV and LA volume and function were established for the first time in healthy Han Chinese adults. Normal ranges of 3D-LV and 3D-LA echocardiographic measurements stratified with sex, age, and race should be recommended for clinical applications.

Right ventricular volume and function by three-dimensional echocardiography: results of the echocardiographic measurements in normal Chinese adults (EMINCA) II.

Three-dimensional (3D) echocardiography is an emerging technique for assessing right ventricular (RV) volume and function, but 3D-RV normal values from a large Chinese population are still lacking. The aim of the present study was to establish normal values of 3D-RV volume and function in healthy Chinese volunteers. A total of 1117 Han Chinese volunteers from 28 laboratories in 20 provinces of China were enrolled, and 3D-RV images of 747 volunteers with optimal image quality were ultimately analyzed by a core laboratory. Both vendor-dependent and vendor-independent software platforms were used to analyze the 3D-RV images. We found that men had larger RV volumes than women did in the whole population, even after indexing to body surface area, and older individuals had smaller RV volumes. The normal RV volume was significantly smaller than that recommended by the American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines in both sexes. There were significant differences in 3D-RV measurements between the two vendor ultrasound systems and the different software platforms. The echocardiographic measurements in normal Chinese adults II study revealed normal 3D-RV volume and function in a large Chinese population, and there were significant differences between the sexes, ages, races, and vendor groups. Thus, normal 3D-RV values should be stratified by sex, age, race, and vendor.

Left atrial reservoir longitudinal strain and its incremental value to the left ventricular global longitudinal strain in predicting anthracycline-induced cardiotoxicity.

BACKGROUND: Left ventricular global longitudinal strain (LVGLS) has been recommended by current guidelines for diagnosing anthracycline-induced cardiotoxicity. However, little is known about the early changes in left atrial (LA) morphology and function in this population. Our study aimed to evaluate the potential usefulness of LA indices and their incremental value to LVGLS with three-dimensional echocardiography (3DE) in the early detection of subclinical cardiotoxicity in patients with lymphoma receiving anthracycline. METHODS: A total of 80 patients with diffuse large B-cell lymphoma who received six cycles of anthracycline-based treatment were enrolled. Echocardiography was performed at baseline (T0), after four cycles (T1), and after the completion of six cycles of chemotherapy (T2). Left ventricular ejection fraction (LVEF), LVGLS, LA volumes, LA emptying fraction (LAEF), LA active emptying fraction (LAAEF), and LA reservoir longitudinal strain (LASr) were quantified with 3DE. Left atrioventricular global longitudinal strain (LAVGLS) was calculated as the sum of peak LASr and the absolute value of peak LVGLS (LAVGLS = LASr+|LVGLS|). LV cardiotoxicity was defined as a new LVEF reduction by ≥10 percentage points to an LVEF of ≤50%. RESULTS: Fourteen (17.5%) patients developed LV cardiotoxicity at T2. LA volumes, LAEF, and LAAEF remained stable over time. Impairment of LASr (28.35 ± 5.03 vs. 25.04 ± 4.10, p < .001), LVGLS (-22.77 ± 2.45 vs. -20.44 ± 2.62, p < .001), and LAVGLS (51.12 ± 5.63 vs. 45.61 ± 5.22, p < .001) was observed by the end of the fourth cycle of chemotherapy (T1). Statistically significant declines in LVEF (61.30 ± 4.73 vs. 57.08 ± 5.83, p < .001) were only observed at T2. The relative decrease in LASr (ΔLASr), LVGLS (ΔLVGLS), and LAVGLS (ΔLAVGLS) from T0 to T1 were predictors of LV cardiotoxicity. A ΔLASr of >19.75% (sensitivity, 71.4%; specificity, 87.9%; area under the curve (AUC), .842; p < .001), a ΔLVGLS of >13.19% (sensitivity, 78.6%; specificity, 74.2%; AUC, .763; p < .001), and a ΔLAVGLS of >16.80% (sensitivity, 78.6%; specificity, 93.9%; AUC, .905; p < .001) predicted subsequent LV cardiotoxicity at T2, with the AUC of ΔLAVGLS significantly larger than that of ΔLVGLS (.905 vs. .763, p = .027). Compared to ΔLVGLS, ΔLAVGLS showed improved specificity (93.9% vs. 74.2%, p = .002) and maintained sensitivity in predicting LV cardiotoxicity. CONCLUSIONS: LASr could predict anthracycline-induced LV cardiotoxicity with excellent diagnostic performance. Incorporating LASr into LVGLS (LAVGLS) led to a significantly improved specificity and maintained sensitivity in predicting LV cardiotoxicity.

Step-by-step transesophageal echocardiographic guidance for transjugular transcatheter tricuspid valve replacement with a radial force-independent bioprosthesis.

The prohibitive risk of isolated tricuspid valve (TV) surgery encouraged rapid development of a transcatheter solution for tricuspid regurgitation (TR). The favorable results of these devices informed recent guidelines to recommend considering transcatheter treatment of symptomatic secondary severe TR in inoperable patients. Transcatheter TV repair systems usually reduce TR through leaflet approximation and direct annuloplasty. Orthotopic transcatheter TV replacement (TTVR) devices generally rely on radial force and tricuspid leaflet engagement for implantation and stability. The LuX-Valve is a novel radial force-independent orthotopic TTVR device that is operated through the trans-atrial approach. Its radial force-independency is achieved through an interventricular septal anchor tab (septal insertion) and two leaflet graspers (leaflet engagement). Such a unique design makes the intraprocedural imaging different from that of other currently available TTVR systems. The latest generation of this device, the LuX-Valve Plus, comes with a newly designed delivery system through the transjugular approach, which makes the intraprocedural monitoring and adjustment of the device even more complex for successful implantation. However, its unique imaging needs for intra-procedural guidance and post-operative evaluation have not been described before. Therefore, we aimed to elaborate the key steps of transesophageal echocardiography (TEE) to guide this novel procedure. Herein, the primary 2-dimensional (2D) and 3-dimensional (3D) echocardiographic work planes are proposed and the critical steps are emphasized for better communication between imagers and interventionists. The suitability of 2D and 3D echocardiography to guide this procedure is also discussed to increase the flexibility of choice during the implantation.

In vitro and clinical validation of different correction algorithms for the two-dimensional proximal isovelocity surface area method in a low-velocity flow field for quantifying tricuspid regurgitation.

Background: The 2-dimensional proximal isovelocity surface area (2D PISA) method underestimates tricuspid regurgitation (TR) severity. Previously proposed correction algorithms should be further scrutinized. Methods: Two correction algorithms were tested. One approach involves dividing the 2D PISA effective regurgitant orifice area by a constant of 0.7 (EROA0.7). Another approach involves multiplying the unadjusted EROA by Vorifice/(Vorifice - Valiasing), where Vorifice denotes the TR jet velocity, and Valiasing represents the color aliasing velocity (EROAVo-Va). In vitro validation was performed on a commercially available multifunctional valve tester with different size orifices and peak pressure gradients. A true EROA was derived through the regurgitant volume (RVol) calculated from the tester. For clinical validation, RVol was calculated as the difference between the overall stroke volume and the forward stroke volume of the right ventricle. Volumetric EROA was derived by dividing the RVol by the TR velocity-time integral (VTI). The vena contracta area (VCA) was obtained through direct planimetry with 3D echocardiography. The mean of volumetric EROA and VCA served as the reference in clinical validation. Results: Excellent correlation between the calculated EROAs and the true EROA was observed in vitro (r=0.98, r=0.97, and r=0.98 for uncorrected EROA, EROAVo-Va, and EROA0.7, respectively; all P values <0.0001). EROAVo-Va underestimated the true EROA and averaged 33% (P=0.3163), while EROA0.7 overestimated the true EROA and averaged 8% (P=0.0032). Clinically, these methods consistently exhibited a notable underestimation that varied with the reference EROA. This systematic underestimation was mitigated by both algorithms when either the VCA (biases of 19.6, 15.1, and 11.8 mm2 for uncorrected EROA, EROAVo-Va, and EROA0.7, respectively) or the volumetric EROA (biases of 10.1, 5.6, and 2.3 mm2 for uncorrected EROA, EROAVo-Va, and EROA0.7, respectively) served as the reference. Their ability to distinguish severe TR was similar, with area under the curve values of 0.905, 0.903, and 0.893 for uncorrected EROA, EROAVo-Va, and EROA0.7, respectively. No statistically significant differences were observed for diagnostic accuracy (all P values >0.05). Conclusions: Using a correction factor of 0.7 in quantifying TR provides similar accuracy when compared to other techniques. This represents a valuable clinical tool for quickly correcting the underestimation of the 2D PISA method in TR. This simple method may increase the frequency of applying the correction and earlier recognition of patients with severe TR.

Cardiac magnetic resonance-based layer-specific strain in immune checkpoint inhibitor-associated myocarditis.

AIMS: To assess the different imaging characteristics between corticosteroid-sensitive (CS) and corticosteroid-refractory (CR) immune checkpoint inhibitor-associated myocarditis (ICIaM) with cardiac magnetic resonance (CMR) and the potential CMR parameters in the early detection of CR ICIaM. METHODS AND RESULTS: Thirty-five patients diagnosed with ICIaM and 30 age and gender-matched cancer patients without a history of ICI treatment were enrolled. CMR with contrast was performed within 2 days of clinical suspicion. Left ventricular ejection fraction (LVEF) and late gadolinium enhancement (LGE) were assessed by CMR. LV sub-endocardial (GLSendo) and sub-epicardial (GLSepi) global longitudinal strains were quantified by offline feature tracking analysis. CS and CR ICIaM were defined based on the trend of Troponin I and clinical course during corticosteroid treatment. All 35 patients presented with non-fulminant symptoms upon initial assessment. Twenty patients (57.14%) were sensitive, and 15 (42.86%) were refractory to corticosteroids. Compared with controls, 22 patients (62.86%) with ICIaM developed LGE. LVEF decreased in CR ICIaM compared with the CS group and controls. GLSendo (-14.61 ± 2.67 vs. -18.50 ± 2.53, P < 0.001) and GLSepi (-14.75 ± 2.53 vs. -16.68 ± 2.05, P < 0.001) significantly increased in patients with CR ICIaM compared with the CS ICIaM. In patients with CS ICIaM, although GLSepi (-16.68 ± 2.05 vs. -19.31 ± 1.80, P < 0.001) was impaired compared with the controls, GLSendo was preserved. There was no difference in CMR parameters between LGE-positive and negative groups. LVEF, GLSendo, and GLSepi were predictors of CR ICIaM. When LVEF, GLSendo, and GLSepi were included in multivariate analysis, only GLSendo remained an independent predictor of CR ICIaM (OR: 2.170, 95% CI: 1.189-3.962, P = 0.012). A GLSendo of ≥-17.10% (sensitivity, 86.7%; specificity, 80.0%; AUC, 0.860; P < 0.001) could predict CR ICIaM in the ICIaM cohort. Kaplan-Meier analysis showed that in patients with impaired GLSendo of ≥-17.10%, cardiovascular adverse events (CAEs) occurred much earlier than in patients with preserved GLSendo of <-17.10% (Log-rank test P = 0.017). CONCLUSIONS: CR and CS ICIaM demonstrated different functional and morphological characteristics in different myocardial layers. An impaired GLSendo could be a helpful parameter in early identifying corticosteroid-refractory individuals in the ICIaM population.

Effect of left bundle branch pacing on right ventricular function: A 3-dimensional echocardiography study.

BACKGROUND: The effect of left bundle branch pacing (LBBP) on right ventricular (RV) function is not well known, and there is conflicting evidence regarding whether cardiac resynchronization therapy improves RV function. OBJECTIVES: The study aimed to investigate the effect of LBBP on RV function and to evaluate the response of RV dysfunction (RVD) to LBBP. METHODS: Sixty-five LBBP candidates were prospectively included in the study and underwent echocardiography at baseline and 6-month follow-up. LBBP response was left ventricular (LV) reverse remodeling, defined as a reduction in LV end-systolic volume of ≥15% at follow-up. RESULTS: Patients were assigned to 2 subgroups on the basis of 3-dimensional echocardiography-derived RV ejection fraction (EF) before LBBP implantation: 30 patients (46%) in the no RVD group and 35 patients (54%) in the RVD group. The RVD group was characterized by higher N-terminal pro-brain natriuretic peptide levels, New York Heart Association functional class, and larger LV/RV size. LBBP induced a significant reduction in QRS duration, LV size, and improvement in LVEF and mechanical dyssynchrony in both the no RVD and RVD groups, and a significant improvement in RV volumes and RVEF in the RVD group (all P<.01). LBBP resulted in a similar percentage reduction in QRS duration, LV dimensions, LV volumes, and percentage improvement in LVEF in RVD and no RVD groups (all P＞.05). LV reverse remodeling (29 of 35 patients vs 27 of 30 patients; P = .323) in the RVD group was similar to that in the no RVD group after LBBP. CONCLUSION: LBBP induces excellent electrical and mechanical resynchronization, with a significant improvement in RV volumes and function. RVD did not diminish the beneficial effects on LV reverse remodeling after LBBP.

Three-dimensional echocardiography reveals early mitral valve alterations in hypertrophic cardiomyopathy genetic mutation carriers.

BACKGROUND: The mitral valve undergoes structural modifications in response to cardiac functional changes, often predating cardiac decompensation and overt clinical signs. Our study assessed the potential of mitral valve morphological changes as early indicators for detecting carriers of hypertrophic cardiomyopathy (HCM)-associated gene mutations. METHODS: We studied 505 participants: 189 without the pathogenic gene mutations and left ventricular hypertrophy (G-/LVH-), 149 carriers without LV hypertrophy (G+/LVH-), and 167 manifest HCM patients (G+/LVH+). We juxtaposed the mitral valve morphology and associated metrics across these groups, emphasizing those carrying MYH7 and MYBPC3 mutations. RESULTS: We discerned pronounced disparities in the mitral annulus and leaflet structures across the groups. The mitral valve apparatus in mutation carriers exhibited a tendency towards a flattened profile. Detailed analysis spotlighted MYBPC3 mutation carriers, whose mitral valves were notably flatter (with notably lower AHCWR values than non-carriers); this contrast was not evident in MYH7 mutation carriers. This mitral valve flattening, manifest in the mutation carriers, suggests it might be an adaptive response to incipient cardiac dysfunction in HCM's nascent stages. CONCLUSIONS: Three-dimensional echocardiography illuminates the initial mitral valve structural changes in HCM patients bearing pathogenic gene mutations. These morphological signatures hold promise as sensitive imaging markers, especially for asymptomatic carriers of the MYBPC3 mutation.

Application of myocardial work in predicting adverse events among patients with resistant hypertension.

BACKGROUND: Hypertension is the most common chronic disease and the leading risk factor for disability and premature deaths worldwide. Approximately 10-20% of all patients with hypertension and 15-18% of the general population who are treated for hypertension have resistant hypertension (RH). Patients with RH have a higher risk of end-organ damage, such as carotid intima-media thickening, retinopathy, left ventricular hypertrophy and heart failure, myocardial infarction, stroke, impaired renal function, and death than those with controlled blood pressure. In the present study, we applied echocardiography to patients with RH to evaluate myocardial work (MW) and determine whether it is predictive for the occurrence of adverse events within 3 years. METHODS: We included 283 outpatients and inpatients aged ≥ 18 years who met the clinical criteria for RH, without arrhythmia and severe aortic valve stenosis, between July 2018 and June 2019. The patients were followed up for 3 years from starting enrollment, and any adverse event that occurred during the period was used as the observation end point. Each enrolled patient underwent a complete transthoracic echocardiogram examination, blood pressure was measured and recorded, and MW was then analyzed. RESULTS: Eighty-two (28.98%) patients with RH had adverse events, such as myocardial infarction (n = 29, 35.36%), heart failure (n = 4, 0.05%), renal insufficiency (n = 40, 48.78%), renal failure (n = 2, 0.02%), cerebral infarction (n = 5, 0.06%), and cerebral hemorrhage (n = 2, 0.02%), and no death events occurred. In patients with RH and adverse events, global longitudinal strain (GLS) (- 16% vs. - 18%), the global work index (2079 mmHg% vs. 2327 mmHg%), global constructive work (2321 mmHg% vs. 2610 mmHg%), and global work efficiency (93% vs. 94%) were lower than those in patients without adverse events. However, global wasted work (GWW) was higher in patients with RH and adverse events than in those without adverse events (161 mmHg% vs. 127 mmHg%). GLS and GWW were the most significant in predicting adverse events. CONCLUSIONS: MW, especially GLS and GWW, is a good method to predict 3-year adverse events in patients with RH.

Left ventricular myocardial work for the prediction of postoperative outcomes in patients with bicuspid aortic stenosis.

Chronic elevation of left ventricular (LV) afterload contributes to adverse LV remodeling and myocardial impairment in bicuspid aortic valve (BAV) patients with severe aortic stenosis (AS). Incorporating LV afterload into global longitudinal strain (GLS) analysis, myocardial work facilitates early detection of LV dysfunction. The present study was to evaluate myocardial work in BAV patients with severe AS undergoing surgical aortic valve replacement (SAVR) and to evaluate its prognostic impact on early postoperative outcomes. Between January 2021 and March 2022, BAV patients with severe AS scheduled for SAVR were included and underwent comprehensive transthoracic echocardiography. Quantification of LV myocardial work was performed to obtain LV global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). Clinical outcome was defined as a composite of major cardiovascular events including mortality, myocardial infarction, stroke, acute kidney injury, low cardiac output syndrome and vascular complications during hospitalization or within 30 days after operation. Among 103 BAV patients with severe AS undergoing SAVR (mean age of 65 ± 9 years, 57.3% male), 22 experienced postoperative major cardiovascular events. BAV patients with major cardiovascular events demonstrated lower LV GWI (P < 0.001) and GCW (P = 0.002) along with elder age (P = 0.030), decreased LVGLS (P = 0.026) and right ventricular longitudinal strain (P = 0.019), and higher prevalence of abnormal average E/e' ratio (P = 0.029) than those without major events. Decreased LV GWI and GCW was independently associated with the occurrence of major cardiovascular events (P < 0.01 for adjusted OR). Multivariable logistic regression model including LV GWI demonstrated superior power than the model including LVGLS and yielded best discrimination for BAV patients with and without major cardiovascular events during early postoperative period. Echocardiography-based LV myocardial work overcomes the limitations of LVGLS and presents as a promising novel index for the early detection of functional myocardial damage and the optimization of intervention timing among BAV patients with severe AS.

ESCRT-III Component CHMP4C Attenuates Cardiac Hypertrophy by Targeting the Endo-Lysosomal Degradation of EGFR.

BACKGROUND: Cardiac hypertrophy and subsequent heart failure impose a considerable burden on public health worldwide. Impaired protein degradation, especially endo-lysosome-mediated degradation of membrane proteins, is associated with cardiac hypertrophy progression. CHMP4C (charged multivesicular body protein 4C), a critical constituent of multivesicular bodies, is involved in cellular trafficking and signaling. However, the specific role of CHMP4C in the progression of cardiac hypertrophy remains largely unknown. METHODS: Mouse models with CHMP4C knockout or cardiadc-specific overexpression were subjected to transverse aortic constriction surgery for 4 weeks. Cardiac morphology and function were assessed through histological staining and echocardiography. Confocal imaging and coimmunoprecipitation assays were performed to identify the direct target of CHMP4C. An EGFR (epidermal growth factor receptor) inhibitor was administrated to determine whether effects of CHMP4C on cardiac hypertrophy were EGFR dependent. RESULTS: CHMP4C was significantly upregulated in both pressure-overloaded mice and spontaneously hypertensive rats. Compared with wild-type mice, CHMP4C deficiency exacerbated transverse aortic constriction-induced cardiac hypertrophy, whereas CHMP4C overexpression in cardiomyocytes attenuated cardiac dysfunction. Mechanistically, the effect of CHMP4C on cardiac hypertrophy relied on the EGFR signaling pathway. Fluorescent staining and coimmunoprecipitation assays confirmed that CHMP4C interacts directly with EGFR and promotes lysosome-mediated degradation of activated EGFR, thus attenuating cardiac hypertrophy. Notably, an EGFR inhibitor canertinib counteracted the exacerbation of cardiac hypertrophy induced by CHMP4C knockdown in vitro and in vivo. CONCLUSIONS: CHMP4C represses cardiac hypertrophy by modulating lysosomal degradation of EGFR and is a potential therapeutic candidate for cardiac hypertrophy.

Layer-specific strain in patients with cardiac amyloidosis using tissue tracking MR.

Background: Cardiac infiltration is the major predictor of poor prognosis in patients with systemic amyloidosis, thus it becomes of great importance to evaluate cardiac involvement. Purpose: We aimed to evaluate left ventricular myocardial deformation alteration in patients with cardiac amyloidosis (CA) using layer-specific tissue tracking MR. Material and Methods: Thirty-nine patients with CA were enrolled. Thirty-nine normal controls were also recruited. Layer-specific tissue tracking analysis was done based on cine MR images. Results: Compared with the control group, a significant reduction in LV whole layer strain values (GLS, GCS, and GRS) and layer-specific strain values was found in patients with CA (all P < 0.01). In addition, GRS and GLS, as well as subendocardial and subepicardial GLS, GRS, and GCS, were all diminished in patients with CA and reduced LVEF, when compared to those with preserved or mid-range LVEF (all P < 0.05). GCS showed the largest AUC (0.9952, P = 0.0001) with a sensitivity of 93.1% and specificity of 90% to predict reduced LVEF (<40%). Moreover, GCS was the only independent predictor of LV systolic dysfunction (Odds Ratio: 3.30, 95% CI:1.341-8.12, and P = 0.009). Conclusion: Layer-specific tissue tracking MR could be a useful method to assess left ventricular myocardial deformation in patients with CA.

Echocardiographic parameters recommended for assessing the severity of tricuspid regurgitation: concordance and discordance.

Background: Current guidelines recommend integrating several echocardiographic indices to evaluate the severity of tricuspid regurgitation (TR). Discordance of indices, including qualitative and quantitative methods, commonly exists in practice. The discordance among these parameters has not yet been fully elucidated. Methods: A total of 127 patients with recognizable TR jets without pulmonary regurgitation or intracardiac shunt were prospectively enrolled. We evaluated 8 parameters by 2-dimensional (2D) echocardiography: proximal iso-velocity surface area (PISA)-derived regurgitant volume (RVol), PISA-derived effective regurgitant orifice area (EROA), PISA radius, vena contracta width (VCW), color Doppler jet area, tricuspid valve annular diameter, inferior vena cava (IVC) diameter, and peak E wave. According to current guidelines, each echocardiographic parameter was determined to represent either severe or non-severe TR. A concordance score was calculated as the number of concordant parameters divided by 8, with a higher score reflecting better concordance. Data were further categorized into 3 subgroups: complete concordance (0 discordant parameters), high concordance (1-2 discordant parameters), and low concordance (3-4 discordant parameters). Results: The mean concordance score was 81%±17% for the entire cohort. There were 48 (38%) patients with complete concordance, including 6 patients with severe TR. In contrast, the low concordance group (n=43, 34%) mostly comprised severe TR patients (36 patients). When considering only EROA, RVol, and VCW, concordance improved, with 98 patients (77%) in complete agreement. Conclusions: Concordance seems limited when using echocardiographic parameters to assess TR severity. Applying only EROA, RVol, and VCW results in better concordance, as recommended by the current guidelines.