Hong Ran

Myocardial ischemia-reperfusion (MI/R) injury significantly limits the clinical benefits of coronary reperfusion therapy. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has been implicated in myocardial ischemia-reperfusion (I/R) injury. Liproxstatin-1 (Lip-1) is a potent ferroptosis inhibitor, but its dynamic, dose-dependent effects on key molecular pathways and pathological hallmarks in the heart remain incompletely characterized. To systematically investigate the dose- and time-dependent cardioprotective effects of Lip-1 against myocardial I/R injury, with a focus on the NRF2/GPX4 pathway, iron deposition, and lysosomal integrity. Ninety Wistar rats were randomly allocated to 15 experimental groups (n = 6 per group): Normal (no surgery), Sham (thoracotomy without ischemia), I/R model, and I/R + Lip-1 treatment groups. Lip-1 was administered intravenously at doses of 1, 3, or 5 mg/kg at 0, 24, 48, and 72 h post-reperfusion initiation, with myocardial tissue and blood samples harvested 6 h after each injection. Cardiac function was assessed by echocardiography. Myocardial infarct size was determined by Evans Blue/TTC double staining. Serum levels of CK-MB and LDH were measured as markers of myocardial injury. Analyses included Western blot for NRF2 and GPX4 expression, Prussian blue staining for iron deposition quantification, and immunofluorescence for LAMP1 localization and intensity. Statistical analysis was performed using two-way ANOVA with Tukey’s post hoc test for Lip-1 treatment groups, and t-tests or one-way ANOVA for model validation comparisons. Compared to Sham, I/R injury significantly decreased LVEF, increased infarct size, and elevated CK-MB and LDH levels (all P < 0.0001), confirming successful model establishment. It also downregulated GPX4 expression, induced severe iron deposition, and reduced LAMP1 levels, while triggering an adaptive upregulation of NRF2. Lip-1 treatment produced dose- and time-dependent protection across all measured endpoints. It improved cardiac function, reduced infarct size, and attenuated CK-MB and LDH release, with significant dose×time interactions for infarct size (F(6,60) = 8.338, P < 0.0001), CK-MB (F(6,60) = 6.467, P < 0.0001), and LDH (F(6,60) = 9.021, P < 0.0001). It dynamically modulated the NRF2/GPX4 axis, with peak GPX4 expression observed following the 48-hour administration (sampled at 54 h post-reperfusion). Lip-1 progressively reduced iron deposition, with maximal effect observed after the 72-hour administration (sampled at 78 h post-reperfusion), and rescued LAMP1 downregulation in later sampling points. Statistical analysis revealed significant dose×time interactions for NRF2 (F(6,60) = 200.8, p < 0.0001), GPX4 (F(6,60) = 34.84, p < 0.0001), and iron deposition. High-dose Lip-1 (5 mg/kg) demonstrated superior and sustained efficacy across all parameters. Lip-1 confers multi-faceted cardioprotection against I/R injury through sequential mechanisms involving early potentiation of the NRF2/GPX4 antioxidant defense, progressive attenuation of pathological iron accumulation, and restoration of lysosomal membrane integrity. The strict dose and temporal dependency of these effects provide critical insights for optimizing ferroptosis-targeted therapeutic strategies in ischemic heart disease.

(1) Background: Our aim was to evaluate left atrial (LA) volumes and function in patients with newly diagnosed, treatment-naive type 2 diabetes mellitus (T2DM) using Four-Dimensional Automated Left Atrial Quantificative (four-dimensional auto LAQ) analysis and to explore the independent factors influencing left atrial function in diabetic patients. (2) Method: A total of 62 treatment-naive, newly diagnosed T2DM patients without hypertension or obesity and 50 healthy controls were prospectively enrolled in the study. All participants underwent laboratory analyses, routine echocardiography and 4D LAQ assessment. The parameters were compared between the two groups, and independent factors influencing left atrial function in diabetic patients were investigated through univariate and multivariate linear regression analyses. (3) Results: Despite no significant difference in LA end-systolic anteroposterior diameter between groups, LA volume parameters (LAVmax, LAVmin, LAVpreA, and LAVmaxI) were significantly increased in T2DM patients (all p < 0.05). Regarding LA strain, reservoir and conduit function were significantly impaired in T2DM patients, as reflected by lower LASr, LAScd, LASr-c, and LAScd-c (all p < 0.05). Conversely, circumferential contractile strain (LASct-c) was significantly higher in the T2DM group (p = 0.029), while longitudinal contractile strain (LASct) did not differ significantly between groups (p = 0.146). Multivariate analysis revealed that HbA1c and E/e’ ratio were independently associated with multiple LA strain parameters (all p < 0.05). (4) Conclusion: Newly diagnosed, treatment-naive patients with T2DM exhibited increased LA volumes, decreased left atrial ejection fraction (LAEF), and impaired reservoir and conduit functions, accompanied by a compensatory increase in contractile function. Furthermore, HbA1c and E/e’ demonstrated an independent correlation with 4D strain parameters. 4D Auto LAQ echocardiography may serve as a sensitive tool for early detection of diabetic atrial myopathy.

Background: Pneumopericardium is the presence of air within the pericardial cavity. We report a case of iatrogenic pneumopericardium following pericardiocentesis in a patient with primary cardiac angiosarcoma. Additionally, we provide a systematic review of pericardiocentesis-associated pneumopericardium to offer a comprehensive overview and evaluate the role of echocardiography in its diagnosis. Methods: The PubMed database was searched from inception until January 2025 to perform a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to evaluate articles on iatrogenic pneumopericardium following pericardiocentesis published in the English language. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports was used to appraise the included case reports. Results: Of the 108 search results obtained, after screening and a backward citation search, 37 articles were selected for inclusion in this review, accounting for a total of 37 patients. According to the JBI Critical Appraisal Checklist for Case Reports, 7 case reports were of high quality and 12 of low quality. The overall evidence of quality of the case reports was moderate, and 51.6% of patients developed hemodynamic compromise or showed signs of cardiac tamponade. The main underlying cause for the development of pneumopericardium was issues relating to the catheter drainage system; 64.9% of cases required decompressive therapy. Conclusions: Pneumopericardium can occur as a complication after pericardiocentesis and must therefore be considered in symptomatic patients. While detection by transthoracic echocardiography is difficult and relies on non-validated signs, chest X-ray and computed tomography can provide a definitive diagnosis.

Objective: Noninvasive measurement of myocardial work (MW) incorporates left ventricular (LV) pressure, and, therefore, allows correction of global longitudinal strain for changing afterload conditions. We sought to investigate MW as a tool to detect early signs of LV dysfunction in primary systemic hypertension patients, particularly with different predictive indices. Methods and Results: None left ventricular hypertrophy (NLVH) and left ventricular hypertrophy (LVH) patients established were all primary systemic hypertension with preserved ejection fraction. Forty in NLVH and forty in LVH according to left ventricular end-diastolic mass index (LVEDmassI) were prospectively enrolled. The following indices of MW were assessed: global work index, global constructive work, global wasted work (GWW), and global work efficiency (GWE). Both global work index (P=0.348) and global constructive work (P=0.225) were increased in NLVH and decreased in LVH, and GWW (PP0.85). Conclusion: GWW and GWE derived from MW are more accurate, sensitive, and reproducible predictors to detect early LV dysfunction in primary systemic hypertension patients, especially in distinguishing the potential functional abnormality of NLVH and LVH, even though the ejection fraction is preserved.

Objective Echocardiography is a time and cost-effective imaging modality, providing evidence of myocardial ischemia by detecting the regional wall motion abnormalities (RWMA). However, quite a few coronary heart disease (CHD) patients do not present RWMA. The left atrium (LA) plays an irreplaceable role in determining the prognosis and risk stratification of cardiovascular disease including CHD. In this present study, we intend to explore the myocardial mechanics changes of LA mainly using four-dimensional (4D) LA quantitative volume-strain in CHD patients without RWMA at rest but were confirmed by coronary angiography (CAG) and to figure out several variables of the LA that could contribute to the identification of those patients. Methods We prospectively enrolled 76 patients who underwent two-dimensional echocardiography (2DE), four-dimensional echocardiography (4DE), and CAG for suspected CHD but without echocardiographic visible RWMA at rest. Patients diagnosed with CHD by CAG were furtherly divided into three groups according to the extent of coronary stenosis accessed by Gensini score (GS) as the mild, moderate, and severe CHD group. Twenty-four subjects with negative CAG results served as the control group. LA end-systolic anteroposterior diameter (LAAPD) and biplane LV ejection fraction (Biplane LVEF) were measured by 2DE; LA maximum volume (LAVmax), LA minimum volume (LAVmin), LA volume at the onset of atrial contraction (LAVpreA), LAVmax index (LAVmaxI), LA ejection volume (LAEV), LA ejection fraction (LAEF) accompanied by LA longitudinal strain during reservoir phase (LASr), conduit phase (LAScd), contraction phase (LASct) and LA circumferential strain during reservoir phase (LASr_c), conduit phase (LAScd_c), contraction phase (LASct_c) were measured by 4DE automatically. We compared these parameters between groups, explored how they change and whether they are related to the CHD severity. Results LAEF, LASr_c, and LASct_c was lower in CHD group compared with the control group (p = .031, .002, .004, respectively). Pearson correlation analysis showed that LASr, LASct, LASr_c, and LASct_c negatively correlated with the GS. Additionally, LASr of patients in the severe CHD group decreased significantly compared with those in the mild CHD group, moderate CHD group, and control group, demonstrating the highest area under the receiver operating characteristic (ROC) curve (AUC) (AUC = .736 [p = .003, 95% CI .589-.884], sensitivity 67.8%, specificity 70.6%) with the cut-off value of 17.5% for predicting severe CHD patients. Conclusion Four-dimensional LA strain may provide new insight into identification and management for CHD patients and correlate with CHD severity. LASr showed good sensitivity (67.8%) and specificity (70.6%) for diagnosing severe CHD individuals.

Objective: The objective of this study was to describe the different components of left atrial (LA) dysfunction predictors in nonobstructive and occult obstructive hypertrophy cardiomyopathy (HCM) patients especially with preserved left ventricular (LV) ejection fraction, particularly using LA 4-dimensional (D) longitudinal and circumferential strains. Methods: Twenty-eight nonobstructive HCM patients and 30 occult obstructive HCM patients according to LV outflow tract gradient at rest and after exercise were prospectively enrolled. 4D echocardiographic evaluation was performed in 58 HCM patients, both nonobstructive and occult obstructive, and 38 control subjects. LA reservoir, conduit, contractile functions were performed by 4D volume-strain with volumes and longitudinal, circumferential strains. Results: Optimal correlation coefficients obtained between LV 4D mass (index) and LA 4D longitudinal/circumferential strain (r=−0.860 to 0.518, all PPPP0.75 and >0.85, respectively. Conclusions: LA volumes were significantly increased and LA reservoir, conduit, and contractile functions were significantly impaired in HCM patients. Furthermore, different performances of LA functional analyses in nonobstruction and occult obstruction patients with 4D volume-strain echocardiography may facilitate the recognition of subtle LA dysfunctional differentiation in HCM patients.

Background: We try to investigate whether the values of three‐dimensional principal longitudinal strain present differently between the left and right ventricles in patients with long‐time follow‐ups after heart transplantation (HTx).Methods and results: Transthoracic echocardiography with three‐dimensional speckle tracking was performed at one‐, five‐ and ten‐year follow‐ups in 62 “healthy” HTx patients together with routine echocardiographic evaluation in 32 control group (CG) individuals. Longitudinal strain was applied in all subjects assessing without myocardium wall motion abnormality. Firstly, left ventricular ejection fraction preserved in HTx and had no significant difference in comparison with the controls (p > .05). 3D measurement showed obvious reduction in global (%: CG: −20.5 ± 3.5 vs. HT1y: −13.7 ± 4.6, HT5y: −14.4 ± 4.5, HT10y: −14.6 ± 4.7. p < .01) and horizontal segmental (basal, mid, apical, CG vs. HTx: all p < .01) strain values of the left compared HTx with control subjects. Secondly, tissue Doppler imaging s' velocity and tricuspid annular plane systolic excursion reduced in HTx as compared to the controls in right ventricle (p < .01). Longitudinal strain presented a more distinctive reduction in global (%: CG: −24.5 ± 4.6 vs. HT1y:‐14.8 ± 7.5, HT5y: −15.5 ± 6.4, HT10y: −15.9 ± 6.8. p < .01) and horizontal segmental (basal, mid, apical, CG vs. HTx: all p < .01) average values of the right compared HTx with control subjects. Thirdly, there weren't any significant changes between one‐, five‐ and ten‐year of all the values with HTx inter‐group comparison in both the left and right ventricles (p > .05). Fourthly, the global and segmental strain of the right ventricle decreased more than that of the left ventricle in all HTx groups, with the global decreased differentiation rates of 7%, 7%, 6%, respectively.Conclusions: Compared HTx with control subjects in both ventricles, conventional evaluation showed preserved or decreased functions in the left and right separately. Myocardial function evaluating by 3D longitudinal strain reduced after HTx, but the deformation of the right ventricle reduced more than those of the left ventricle. Additionally, 3D strain values almost remained with stable decreased differentiation rates during the long‐time follow‐ups.

Objective: The purpose of this study was to evaluate the different components of left atrial (LA) dysfunction predictors in asymptomatic primary systemic hypertension patients with preserved left ventricular (LV) ejection fraction, particularly using LA 4-dimensional (4D) longitudinal and circumferential strain values. Methods and Results: Patients with no left ventricular hypertrophy (NLVH) and left ventricular hypertrophy (LVH) are all asymptomatic regarding primary blood hypertension. Thirty NLVH patients and 30 LVH patients according to LV mass index and 40 controls analyzed by 4D echocardiography were prospectively enrolled. LA volumes and longitudinal and circumferential strains were measured using 4D volume-strain echocardiography with a Vivid E95 Version 203 instrument. Correlation analysis indicated a significant relation between LV 4D mass index and LA 4D longitudinal/circumferential strain (r = –0.446 to 0.381, p = 0.000–0.042). LVH patients had a reduced LA emptying fraction compared with NLVH patients and control subjects (p < 0.01). NLVH patients had an impaired LA conduit function and increased contractile function compared with the control group (p < 0.01). LVH patients had increased LA volumes and significantly decreased reservoir, conduit and contractile functions compared with the controls (p < 0.01). LVH patients had increased LA volumes and decreased reservoir and contractile functions compared with NLVH patients (p < 0.01). The clinical utility of LA 4D volume-strain measurement was verified by receiver-operating characteristic curve analysis showing larger net benefits as evaluated with NLVH, LVH and control group comparisons. Interclass correlation coefficients of interobserver and intraobserver assessments in the LV and LA 4D value evaluations were >0.75 and >0.85, respectively. Conclusions: LVH patients showed increased LA volumes and decreased LA emptying fractions. LA reservoir, conduit and contractile functions were significantly impaired in LVH patients. Decreased LA conduit function and increased contractile function were revealed in NLVH patients. LA volumetric and functional analyses with 4D volume-strain echocardiography may facilitate the recognition of subtle LA and LV dysfunctions in asymptomatic systemic hypertension patients.

Objective We try to investigate whether the values of longitudinal strain present differences between the left and right ventricles in long‐time follow‐ups after heart transplantation (HTx) with dynamic changes in function. Methods and Results Follow‐up transthoracic echocardiography was performed in 1‐ and 3‐month and 1‐ and 5‐year follow‐ups in 50 “healthy” HTx patients and compared with 26 control subjects. The left ventricle with preserved ejection fraction evaluated by biplane Simpson (control group [CG] vs HT; P > .05) had an obvious reduction in global (CG: −20.49 ± 2.38 vs heart transplant 1 month [HT1m]: −13.06 ± 2.86, heart transplant 3 month [HT3m]: −13.61 ± 2.61, heart transplant 1 year [HT1y]: −13.69 ± 4.56, heart transplant 5 year [HT5y]: −14.41 ± 4.54; P < .001) and horizontal segmental (basal, mid, apical) (P < .001) together with chamber segmental (apical 4‐chamber, apical 3‐chamber, apical 2‐chamber) (P < .001) average strain values. The right ventricle with reduced ventricular function measured by tissue Doppler imaging S’ and tricuspid annular plane systolic excursion had a more distinctive reduction in global (CG: −24.53 ± 4.20 vs HT1m: −12.94 ± 5.03, HT3m: −13.68 ± 4.35, HT1y: −14.95 ± 7.50, HT5y: −15.20 ± 6.15; P < .001) with segmental lateral (P < .001) strain values. There were not any significant changes between 1‐ and 3‐month follow‐ups of all the values (P > .05). But it could be seen that values increased in 1‐ and 5‐year follow‐ups compared with the baseline of 1‐ and 3‐month follow‐ups (P < .05). The global and segmental strain of the right ventricle decreased more than that of the left ventricle in all HTx groups, and the strain values were decreased in the HTx groups compared with the CG, with the global decreased change rates being 11%, 10%, 6%, and 8%, respectively. Conclusions The strain values decreased after HTx and almost remained stable in the long‐time follow‐ups. Compared with the CG in both ventricles, they were with preserved or reduced functions. In addition, the deformation values of the right ventricle decreased more than those of the left.

Objectives Our study investigated left ventricular dyssynchrony (LVD) in coronary artery disease (CAD) patients without regional wall-motion abnormality (RWMA) by three-dimensional echocardiography (3-DE) and explored the relationship between LVD and severity of CAD as assessed by the Gensini score (GS). Methods Sixty-one patients with a confirmed diagnosis of CAD by coronary angiography (CAG) were enrolled. We quantified LVD parameters, including the left ventricular segments (16, 12, and 6) standard deviation of the time to minimum systolic volume (TmsvSD-16, TmsvSD-12, and TmsvSD-6) and the systolic dyssynchrony index in regions 16, 12, and 6 (16R-SDI, 12R-SDI, 6R-SDI) using 3-DE. The severity of coronary atherosclerotic lesions was evaluated by the GS system on the basis of CAG findings. We further divided all patients into three groups according to the tertiles of GS: low-GS ≤20, mid-GS >20 and ≤48, and high-GS >48. The differences of LVD values among the three groups were compared, and the associations between LVD parameters and GS were analyzed. Results Coronary artery disease patients demonstrated increased LVD parameters compared with healthy controls. TmsvSD12, 16R-SDI, and 6R-SDI were prolonged in the high-GS group compared with the low- and mid-GS groups. 16R-SDI was positively correlated with the GS, and multivariate regression analysis showed that 16R-SDI was an independent predictor of the GS. 16R-SDI above 10.7% had a sensitivity of 84.21% and a specificity of 92.86% for identifying high-GS. Conclusion Three-dimensional echocardiography is a noninvasive technique to detect LVD in non-RWMA CAD patients, and the parameter 16R-SDI was significantly correlated with CAD severity.