Chronic heart failure (CHF) patients often present with heterogeneous patterns of cardiac dyssynchrony. Although QRS prolongation (>150 ms) and left bundle branch block (LBBB) are classical markers of electrical dyssynchrony, their direct association with mechanical dyssynchrony remains controversial. This study aimed to identify key determinants of left ventricular (LV) synchrony using machine learning and explainable artificial intelligence techniques. A cohort of 412 CHF patients was stratified using integrated echocardiographic and electrocardiographic criteria: synchronous group (SG, n = 239) with standard deviation of time to peak longitudinal strain in 18 LV segments (SD18STE) ≤ 33 ms, QRS duration ≤ 120 ms, and left ventricular end-diastolic volume (LVEDV) ≤ 150 mL; asynchronous group (AG, n = 173) with SD18STE > 33 gt; 33 ms typically accompanied by QRS duration > 120 gt; 120 ms and/or LVEDV > 150 gt; 150 mL. All patients underwent speckle tracking echocardiography (STE) to assess LV and left atrial function, along with electrocardiographic evaluation of QRS duration. Key parameters included electrical dyssynchrony markers (QRS duration, LBBB status) and mechanical dyssynchrony markers (LV ejection fraction [EF], end-diastolic volume [EDV], end-systolic volume [ESV], and segmental strain timing). A random forest model was used to identify predictors of mechanical dyssynchrony, and SHapley Additive exPlanations (SHAP) analysis was employed to quantify feature contributions. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1-score. Compared with the SG group, AG patients had significantly higher QRS duration (132 vs. 116 ms, p < 0.001), B-type natriuretic peptide (BNP) levels (2,520 vs. 1,820 pg/mL, p = 0.034), EDV (211 vs. 142 mL, p < 0.001), and ESV (171 vs. 97 mL, p < 0.001), as well as lower EF (21% vs. 34%, p < 0.001). Machine learning identified EF, ESV, and posterior wall segments as the primary predictors of dyssynchrony. SHAP analysis revealed that EF < 40% and ESV > 100 gt; 100 mL increased the probability of dyssynchrony. Posterior wall delays were strongly associated with dyssynchrony. LBBB presence increased the likelihood of dyssynchrony 3-fold. The model demonstrated excellent performance (AUC = 0.925, accuracy = 85.5%, F1-score = 0.878), outperforming traditional dyssynchrony indices. Mechanical dyssynchrony indicators such as EF, ESV, and EDV are superior to electrical markers in predicting LV synchrony. Dysfunction in posterior wall segments significantly contributes to mechanical asynchrony. These findings provide new insights into CHF pathophysiology and support the use of personalized criteria for cardiac resynchronization therapy candidate selection.

Coronary microvascular dysfunction (CMD) exhibits a high prevalence and is associated with adverse clinical outcomes, underscoring the critical importance of early detection. Early identification of CMD can significantly improve patient prognosis. This study aims to provide a novel strategy for the precise diagnosis of CMD during its early inflammatory phase. Focusing on this key inflammatory stage in the pathological progression, we sought to identify stage-specific molecular biomarkers. Through proteomic screening, we identified Nerve Injury-Induced Protein 1 (Ninj1). During the inflammatory response, Ninj1 promotes leukocyte migration and macrophage transendothelial migration, thereby influencing the trafficking and distribution of inflammatory cells. IR780 is a novel near-infrared (NIR) fluorescent agent characterized by excellent photostability and low toxicity. Loading IR780 onto nanoparticles enhances its in vivo biocompatibility and photostability while prolonging its circulation time. This project proposes a dual-modal molecular imaging probe targeting Ninj1 and loaded with IR780, which integrates NIR fluorescence and ultrasound imaging capabilities. This probe is designed to enable the early screening of CMD.

IntroductionThis study investigated the changes in left atrial (LA) structure and function in patients with severe aortic stenosis (AS) by comparing those with preserved left ventricular ejection fraction (LVEF) to those with reduced LVEF.MethodsPatients with severe AS were classified into two groups: preserved LVEF (≥ 50%) and reduced LVEF (< 50%). Healthy controls were also enrolled. Transthoracic echocardiography and two-dimensional speckle-tracking echocardiography (2D-STE) were employed to measure LA structural parameters and evaluate LA function. Restricted cubic splines (RCS) analyses were used to explore the nonlinear relationship between LVEF and LA parameters.ResultsPatients with an LVEF < 50% had larger LA volumes [LA maximal volume (LAVmax), LA minimal volume (LAVmin), LA pre-systolic volume (LAVpre), and LA volume index (LAVI)] and higher left atrioventricular coupling index (LACI) and LA stiffness index (LASI) than those with an LVEF ≥ 50% (P < 0.05). LA functional parameters [including LA total emptying fraction (LATEF), LA active emptying fraction (LAVaEF), LA passive emptying fraction (LAVpEF), LA expansion index (LAEI)] and the absolute values of LA strain were significantly impaired in severe AS patients with an LVEF < 50% compared with those with an LVEF ≥ 50% (P < 0.05). Furthermore, the LVEF inflection points for trend changes in LA structure and function were approximately 46% and 59%, respectively.ConclusionsIn patients with severe AS, LA structural and functional impairments are evident even when LVEF ≥ 50%, and become more pronounced in those with an LVEF < 50%.

Objective:This study aimed to evaluate the myocardial mechanical properties of the left atrium, left ventricle, and left atrioventricular coupling using ultrasound in patients with isolated basal septal hypertrophy (IBSH) caused by primary hypertension. Methods:This retrospective study enrolled 210 participants [140 hypertensive patients subdivided into IBSH and left ventricular hypertrophy (LVH) groups (n = 70 each) and 70 controls]. Speckle-tracking echocardiography was used to analyze left atrium (LA)/left ventricle (LV) strain parameters and atrioventricular coupling. Results:(1) The IBSH group demonstrated higher adherence to antihypertensive medication than the LVH group (P < 0.05). (2) Both the IBSH and LVH groups showed reduced global longitudinal strain (GLS) and global circumferential strain (GCS) (more severe in LVH) but increased global radial strain (GRS) (more prominent in IBSH) (P < 0.05). The 18-segment LV strain analysis revealed significantly reduced strain in the basal anterior and inferior septum (P < 0.05), while compensatory increased strain in all apical segments (P < 0.05) in the IBSH group. (3) Left atrioventricular coupling index (LACI) increased in both groups (P < 0.01), while left atrial reservoir strain (LASR) and left atrial conduit strain (LASCD) decreased (more in LVH), yet left atrial contraction strain (LASCT) markedly rose in IBSH (P < 0.01). (4) Correlation analysis in the IBSH group showed the following results: Left ventricular mass index (LVMI) negatively correlated with left ventricular ejection fraction (LVEF), GRS, and GCS (P < 0.05); LACI positively correlated with left atrial volume index(LAVI) (r = 0.73); LASR positively correlated with GLS and E/A but negatively with E/e' (all P < 0.05). Conclusion:This study elucidates the potential association between regular antihypertensive medication use and cardiac remodeling in patients with IBSH. Through a comprehensive analysis of global and regional left atrioventricular myocardial function, we identified the basal septal segment as the most significantly impaired myocardial region. Furthermore, the study demonstrated the existence of a compensatory redistribution mechanism in myocardial mechanics.

Background ST segment depression (STD) on electrocardiogram (ECG) is the most frequently used examination to detect myocardial ischemia and myocardial contrast echocardiography (MCE) is considered as a reliable technique to assess myocardial purfusion. However, association between two examinations and the underlying clinical implication in hypertrophic cardiomyopathy (HCM) patients is not fully illustrated. Objective To investigate the correlation between ECG and MCE findings in HCM patients and elucidating the underlying clinical implications. Methods Thirty-two patients diagnosed with HCM comprising the HCM cohort and 28 healthy individuals were enrolled as controls. The amplitude of ST segment depression (STD) was assessed, and the following MCE parameters: peak intensity (PI), area under the curve (AUC), rising slope (RS) and time to peak (TTP) were recorded and compared between the two groups, and correlation between MCE parameters and the extent of STD was calculated. Furthermore, HCM patients were categorized into three subgroups according to the severity of STD: ST1 group (0 < STD <= 0.1 mV); ST2 group (0.1 mV < STD <= 0.2 mV); ST3 group (0.2 mV < STD <= 0.3 mV), and data was compared among the four groups. Results ECG showed that all patients in the HCM group present STD (t = 8.294, P < 0.001). MCE showed that the values of PI, RS, and AUC were significantly reduced in the HCM group as compared to the control group (P < 0.001). Results of correlation analysis show no linear correlation between the PI values and the extent of STD (r = -0.348, P = 0.051). Of note, a significant difference in PI values between ST1 and ST3 (P = 0.01), ST2 and ST3 (P = 0.023) was observed. Conclusion Our findings reveal that STD greater than 0.2 mV strongly indicates myocardial perfusion impairment in HCM patients, and can serve as a reliable index for stratifying patients and identifying those at high risk.

This study develops a clinically applicable, explainability-enhanced AI model, CMVD_MDAS, to improve the diagnosis of coronary microvascular Dysfunction (CMVD) by integrating deep learning and multimodal machine learning. The model was trained and internally validated on 592 myocardial segments and externally validated on 352 clinical patient segments. The architecture includes automated myocardial segmentation, convolutional neural network-based feature extraction, and multimodal diagnostic modeling with SHAP-based feature ranking to enhance explainability. The CMVD_MDAS demonstrated excellent internal performance (AUC: 0.999) and robust external performance (AUC: 0.79), surpassing physician assessments and commercial software. This explainability-enhanced AI solution significantly improves the accuracy and efficiency of CMVD assessment, reducing diagnostic time by approximately 90% and offering a potential diagnostic tool for clinical practice.

Rationale: Myocardial contrast echocardiography (MCE) plays an important role in diagnosis of myocardial infarction (MI). However, its accuracy is limited by image quality because microbubble-based MCE produces negative contrast enhancement in the infarcted myocardial tissue. This study aimed to develop nanoscale gas vesicles (GVs) from Halobacteria NRC-1 (hGVs) and GV-expressing genetically engineered E. coli (eGVs) and compare their imaging performance with commercial Sonovue in MI rats. Methods: We developed nanoscale gas vesicles (GVs) from Halobacteria NRC-1 (hGVs) and GV-expressing genetically engineered E. coli (eGVs) and compared their imaging performance with Sonovue in MI rats. Unlike SF₆-filled Sonovue, GVs are air-filled protein nanobubbles with unique shapes. We used immunofluorescence and TEM to examine GVs' distribution in myocardial tissue and analyzed the mechanisms of their penetration into infarcted areas. Additionally, we evaluated the potential of oxygen delivery to ischemic myocardium using ultrasound-targeted bubble destruction. Results: hGVs produced significantly positive contrast enhancement and could last for a longer time in the infarcted area. Immunofluorescence and TEM examination confirmed that hGVs penetrated out the blood vessels into the ischemic myocardium and eGVs primarily retained around endothelial cells, while Sonovue could not pass through the damaged vessels. Mechanistic analysis revealed that inflammatory cytokines results in leaky blood vessels, facilitating the penetration of nanoscale GVs into the infarcted myocardial tissue. Moreover, hGVs exhibited excellent imaging performance across different pathological stages, especially during the inflammatory phase. More importantly, oxygen delivery into the ischemic myocardium through ultrasound-targeted bubble destruction technology greatly promoted the functional recovery of the ischemic myocardium. Conclusions: hGVs demonstrated superior imaging performance and penetration capabilities specifically at the myocardial infarction sites in rats.Their ability to provide positive contrast and deliver oxygen via ultrasound-targeted bubble destruction enables improved diagnosis and treatment of MI.

Patients with advanced cervical cancer have a poor prognosis, and sonodynamic therapy (SDT) is expected to offer a new approach for improving the therapeutic outcome of cervical cancer due to its noninvasiveness and ability to penetrate deeply into tissues. In order to overcome the problems of the rapid elimination and low water solubility of organic acoustic sensitizers in SDT, DSPE-PEG2000-coated tetragonal-phase barium titanate nanoparticles (BTO@PEG) were employed in this study to replace the conventional nanoacoustic sensitizers. It was found that BTO@PEG could continuously generate ROS through SDT and the piezoelectric effect under ultrasound (US) stimulation, which subsequently promoted the apoptosis of cervical cancer cells and inhibited the growth of subcutaneously transplanted HeLa-derived cervical cancer tumors in nude mice. BTO@PEG showed good biocompatibility, as confirmed by cytology and animal experiments.

Background:The arterial stiffening is attributed to the intrinsic structural stiffening and/or load-dependent stiffening by increased blood pressure (BP). The respective lifetime alterations and major determinants of the two components with normal aging are not clear. Methods:A total of 3053 healthy adults (1922 women) aged 18-79 years were enrolled. The carotid intima-media thickness, diameter, and local BPs were automatically determined by the radio frequency ultrasound system. The Peterson and Young elastic moduli were then calculated to represent total arterial stiffness. Structural stiffness was recalculated at a reference BP of 120/80 mmHg with established models. Load-dependent stiffness was the difference between total and structural stiffness. Results:Both structural and load-dependent stiffness increased with aging, with much larger changes in the structural components. The age-related increasing rates were higher in women for the structural stiffness than men (P < 0.05), but similar for the load-dependent stiffness. The clinical characteristics and arterial stiffness were widely correlated, but most correlations were quite weak (r < 0.3) other than BPs. Multiple regression analyses adjusted for sex, age and other clinical correlates showed that structural stiffness increased with pulse pressure (PP) and load-dependent stiffness increased with mean arterial pressure (MAP), respectively. Conclusion:The age-related arterial stiffening is mainly caused by the intrinsic structural stiffening, which demonstrated significant age-sex interaction. BPs were the major clinical determinants of arterial stiffness, with PP and MAP associated with different arterial stiffness components. The differentiation of the structural and load-dependent arterial stiffness should be highlighted for the optimal vascular health management.

AIM:To assess the utility of three-dimensional speckle-tracking echocardiography (3D-STE) in detecting coronary artery microcirculation dysfunction (CMCD) with non-obstructive coronary artery (INOCA) disease. MATERIALS AND METHODS:Twenty-one patients diagnosed with INOCA were enrolled and underwent echocardiography and [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) myocardial metabolic imaging, which is used as the gold standard for diagnosing CMCD. Further, a total of 357 myocardial segments across these 21 participants were categorized into the control group and the CMCD group according to the results of [18F]FDG PET/CT. Subsequently, 2D regional systolic peak longitudinal strain (2D-RLS), 2D regional systolic peak circumferential strain (2D-RCS), regional systolic peak 3D main strain (R3D strain), longitudinal strain (3D-RLS), circumferential strain (3D-RCS), and radial strain (3D-RRS) of the left ventricle were assessed. At last, the receiver operating characteristic (ROC) curves of 3D-STE parameters were calculated to evaluate the diagnostic value of 3D-STE for CMCD. RESULTS:The absolute value of total R3D strain is decreased in the CMCD group (p < 0.05). In addition, R3D and 3D-RLS in the CMCD group exhibited a significant reduction in the basal, middle, and apical segments compared to the control group (p < 0.05). No difference was observed in 2D strain parameters between the CMCD group and the control group. Among all strain parameters, the R3D strain in the apical segments had the highest diagnostic efficacy, with an optimal cutoff of -41.5 (sensitivity, 88.4%; specificity, 80.5%). CONCLUSION:Our findings indicate that the 3D-STE could serve as an advantageous diagnostic instrument for discriminating individuals with CMCD.

OBJECTIVE:By evaluating the myocardial mechanics and microcirculation perfusion in different pathological phases of acute myocardial infarction (AMI) using speckle tracking imaging (STI) and myocardial contrast echocardiography (MCE). we aim to provide a non-invasive ultrasound diagnosis strategy to distinguish different pathological phases of AMI. METHODS:The C57/BL6 mouse model of acute myocardial infarction (AMI) was created by ligating the left anterior descending coronary artery. Microvessel density (MVD) and pathological changes in the infarct area were analyzed quantitatively and qualitatively using TTC, HE, Masson staining, immunohistochemistry, and immunofluorescence during the inflammatory, proliferative, and mature phases. Global longitudinal strain (GLS), circumferential strain (GCS), and radial strain (GRS) were measured by STI, while myocardial perfusion peak enhancement (PE) and Wish-in-rate (WIR) were measured by MCE. RESULTS:For the inflammatory phase, MVD was 52.8/0.1mm², and inflammatory factors IL-6, IL-1β, and TNFα were up-regulated. WIR showed the best accuracy at this phase, with a value of 12.29 ± 2.24 dB, AUC of 0.93, sensitivity of 1.00, specificity of 0.83, and cut-off of 9.24. For the proliferative phase, MVD dropped to 21.6/0.1mm²; GLS and WIR had high diagnostic performance, with AUCs of 0.89 and 0.97, sensitivities of 0.75 and 1.00, and specificities of 1.00 and 0.91, respectively. In the mature phase, the infarct area became fibrotic, inflammatory factors disappeared, and MVD decreased to 8.6/0.1mm². GRS analysis has diagnostic value, with an AUC of 0.77, sensitivity of 0.91, specificity of 0.66, and a cut-off of 14.36. PE maintained high diagnostic accuracy, with an AUC of 0.93, sensitivity of 1.00, specificity of 0.75, and a cut-off of 5.47. CONCLUSION:The combination of MCE and STI can act as a reliable non-invasive ultrasound diagnosis to distinguish different pathological phases of AMI.

This study quantitatively analyzed myocardial microcirculation perfusion in nonobstructive hypertrophic cardiomyopathy (HCM) patients and evaluated their mechanical properties. A total of 56 individuals were involved, consisting of 28 nonobstructive HCM patients and an equal number of healthy volunteers. Each participant underwent comprehensive diagnostic procedures, including two-dimensional echocardiography, contrast-enhanced myocardial ultrasound (MCE), and two-dimensional speckle tracking imaging. Nonobstructive HCM patients were further classified into two groups based on the extent of myocardial hypertrophy: hypertrophic segmental (HS) myocardium and non-hypertrophic segmental myocardium. The study's findings indicated no significant differences in essential demographic factors such as age, height, and weight between the nonobstructive HCM and control groups. However, significant disparities were observed in myocardial perfusion and mechanical properties between these groups, particularly in aspects such as myocardial thickness, tricuspid regurgitation, and left atrial volume. Notably, the myocardial global longitudinal strain (GLS) is significantly decreased in patients with nonobstructive HCM, whereas the global circumferential strain changes are not easily discernible. A notable positive correlation existed within the HS between myocardial perfusion parameters and mechanical properties. The study concluded that myocardial microcirculation perfusion and GLS are impaired in nonobstructive HCM patients, with more pronounced damage in HS, closely associated with alterations in myocardial mechanical characteristics.

Objective This study aimed to investigate the correlation between left ventricular (LV) mechanical and electrical dyssynchrony in patients with chronic heart failure (CHF). Methods A total of 412 patients with CHF were prospectively enrolled and stratified into a left ventricular synchrony group (LVs, n = 239) and a left ventricular dyssynchrony group (LVas, n = 173), based on the standard deviation of time to peak systolic velocity across 18 LV segments (SD18STE > 33 ms). Lasso regression was applied for variable selection, followed by multivariate logistic regression to identify independent factors influencing LV synchrony. Statistical methods were employed to evaluate the contribution of the 18 LV segments to heart failure pathology. Results Patients with CHF exhibited ventricular remodeling characterized by cardiac enlargement, reduced LV ejection fraction (LVEF), and impaired ventricular electrical conduction, as evidenced by prolonged QRS duration (≥ 120 ms). Compared with the LVs group, the LVas group showed significantly higher QRS duration (132.30 vs. 116.00 ms), NT-proBNP levels (2520 vs. 1820 ng/ml), LV end-diastolic volume (EDV: 211.05 vs. 142.00 ml), LV end-systolic volume (ESV: 170.70 vs. 96.50 ml), and prevalence of left bundle branch block (LBBB: 26.1% vs. 3.35%), along with significantly lower LVEF (20.70% vs. 34.20%) (all P < 0.05). Multivariate analysis identified QRS duration ≥ 120 ms (odds ratio [OR] = 1.65), ESV ≥ 155.36 ml (OR = 3.79), and LVEF < 35% (OR = 2.39) as independent predictors of LV dyssynchrony. Lasso regression identified eight key variables—including QRS duration, LBBB, ESV, LVEF, and SD values of time-to-peak systolic velocity in the anterior septal apex, posterior wall apex, posterior wall base, and inferior wall mid-segment—which were all significantly correlated with LV dyssynchrony (P < 0.05). Conclusion QRS duration ≥ 120 ms, ESV ≥ 155.36 ml, and LVEF < 35% are independent risk factors for LV dyssynchrony. Furthermore, QRS duration, LBBB, ESV, LVEF, and segmental time-to-peak systolic velocity variability demonstrate significant associations with mechanical dyssynchrony (P < 0.05).

Background:Ultrasound can be used to quantitatively assess cardiac mechanical dyssynchrony. The differences between and prognoses of chronic heart failure (CHF) patients with left heart dysfunction and remodeling for different combinations of intra-left ventricular (intra-LV) and interventricular (inter-V) mechanical dyssynchrony or synchrony remain unclear. This study sought to assess the relationships among intra-LV dyssynchrony, inter-V dyssynchrony, and left heart function and remodeling in CHF patients. Methods:CHF patients with a left ventricular (LV) ejection fraction <50% and control subjects presenting with no abnormalities in their medical history or on physical examination, electrocardiography, or echocardiography during the concurrent physical assessment were retrospectively included in the study. The patients were divided into four groups based on the standard deviation of the time to peak longitudinal strain in 12 LV segments according to speckle-tracking echocardiography (SD12STE) and the interventricular mechanical delay (IVMD). All the patients underwent speckle-tracking echocardiography (STE) to assess LV and left atrial (LA) function, and the QRS width and echocardiographic findings were recorded. All patients were followed up for any cardiac events from the date of enrollment. A multivariable analysis was performed, and the Kaplan-Meier method was used to assess cardiac events. Results:In total, 52 control subjects (60.79±13.3 years, 32 males) and 208 patients (59.9±12.6 years, 160 males) were included in the study. Of the subjects, 58 had intra-LV and interventricular synchrony (IntrasInters), 40 had intra-LV synchrony and interventricular dyssynchrony (IntrasInterds), 51 had intra-LV dyssynchrony and interventricular synchrony (IntradsInters), and 59 had intra-LV and interventricular dyssynchrony (IntradsInterds). There was no significant difference in the LV and LA function between the IntradsInter and IntradsInterds groups (P>0.05), or between the IntrasInters and IntrasInterds groups (P>0.05). The IntradsInters and IntradsInterds groups had lower LV and LA function than the IntrasInters and IntrasInterds groups (P<0.05). The SD12STE was more strongly associated with LV functional deterioration and LV remodeling than IVMD (P<0.05). The multivariable linear regression analysis indicated that SD12STE independently predicted global longitudinal strain (GLS) (R2=0.834, P<0.001). LA functional deterioration was closely related to LV functional impairment. Compared with the other CHF groups, the IntradsInterds group had a wider QRS complex, a greater LV end-diastolic volume index, and a greater incidence of cardiac events, and a greater proportion of patients in the IntradsInterds group received cardiac resynchronization therapy (CRT) (P<0.05). Conclusions:Compared with IVMD, intra-LV dyssynchrony is more strongly associated with LV dysfunction and remodeling in CHF patients, and LA dysfunction is predominantly contingent upon/is largely dependent on LV dysfunction. When both intra-LV and inter-V dyssynchrony are present, the extent of the LV volumetric increase and electrical remodeling is the most pronounced. This patient group had a higher incidence of cardiac events during follow up and a greater likelihood of receiving CRT.

Objective To investigate the diagnostic value and correlation strength of echocardiographic parameters in evaluating and predicting fetal coarctation of the aorta (CoA). Methods PubMed, Web of Science, GeenMedical, The Cochrane Library, CMB, CNKI, Wanfang, and VIP were searched to obtain all data on the echocardiographic diagnosis of aortic coarctation collected from the database to December 1, 2023. Related literature. The quality of the included literature was evaluated using the QUADAS-2 risk assessment standard provided by Revman 5.3 statistical software. The majority of the parameters were analyzed by the Z-score and the corresponding ratio. The results were analyzed using Stata15.1 software, which combined sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) for the data that were pooled. The diagnostic odds ratio (DOR) and publication bias analysis were performed for all included studies. Results A total of 17 studies were included containing a total of 1,373 patients. The mean mitral valve diameter Z score, ascending aorta Z score, ascending aorta diameter, aortic isthmus mean diameter Z score ( Three-vessel tracheal section), and ductus arteriosus/aortic isthmus diameter (P < 0.05) of the fetuses with aortic coarctation were lower compared with those of the normal fetuses (P = 0.007, P = 0.032, P = 0.006, P = 0.011, P = 0.019, respectively). The aortic isthmus/ductus arteriosus (diameter, mm), mean pulmonary valve diameter Z score, right ventricle/left ventricle (diameter), and right ventricle/left ventricle (area) were higher than those noted in normal fetuses (P = 0.455, P = 0.557, P = 0.408, P = 0.522, respectively). The echocardiographic parameter of neonates and infants was the carotid-subclavian artery index. Following combination of the data, the following results were obtained: Sensitivity: 0.90 (95% CI: 0.72–0.97), specificity: 0.97 (95% CI: 0.92–0.99), positive likelihood ratio: 26.7 (95% CI: 10.7–66.5), negative likelihood ratio: 0.10 (95%CI: 0.03–0.32), diagnostic odds ratio: 262 (95% CI: 37-1875), subject area under the operating characteristic curve (AUC): 0.98. Conclusion For fetuses at risk, the cardiac parameters of the aforementioned ultrasound signs can be more accurately evaluated and can predict the occurrence of CoA before and after birth.

To compare the merits and drawbacks of three approaches for establishing a rabbit model of nonobstructive coronary microcirculatory disease, namely, open thoracic subtotal ligation of coronary arteries, ultrasoundguided cardiac microsphere injection, and sodium laurate injection. New Zealand rabbits were allocated to four groups: a normal group (Blank group), an Open-chest group (Open-chest), a microsphere group (Echo-M), and a sodium laurate group (Echo-SL), each comprising 10 rabbits. The rabbits were sacrificed 24 h after the procedures, and their echocardiography, stress myocardial contrast echocardiography, pathology, and surgical times were compared. The results demonstrated varying degrees of reduced cardiac function in all three experimental groups, the Open-chest group exhibiting the most significant decline. The myocardial filling in the affected areas was visually analyzed by myocardial contrast echocardiography, revealing sparse filling at rest but more after stress. Quantitative analysis of perfusion parameters (beta, A, MBF) in the affected myocardium showed reduced values, the Open-chest group having the most severe reductions. No differences were observed in stress myocardial acoustic imaging parameters between the Echo-M and Echo-SL groups. Among the pathological presentations, the Open-chest model predominantly exhibited localized ischemia, while the Echo-M model was characterized by mechanical physical embolism, and the Echo-SL model displayed in situ thrombosis as the primary pathological feature. Inflammatory responses and collagen deposition were observed in all groups, with the severity ranking of Open-chest > Echo-SL > Echo-M. The ultrasound-guided intracardiac injection method used in this experiment outperformed open-chest surgery in terms of procedural efficiency, invasiveness, and maneuverability. This study not only optimizes established cardiac injection techniques but also offers valuable evidence to support clinical investigations through a comparison of various modeling methods.

Hypertrophic cardiomyopathy (HCM) is an archetypical single-gene disorder with an autosomal dominant pattern of inheritance. Up to date, more than 1400 polytropic sites have been identified in at least 11 genes.1 Due to the high heterogeneity of HCM, it is generally believed that different mutations lead to different phenotypes, and even the same genotype may have different phenotypes in different families or individuals.2 In this report, we discussed two sisters with HCM that show differences in genetic mutation and clinical phenotype. We present the case of two siblings who share a biological relationship as sisters. The 31-year-old elder sister (defined as II-1) was diagnosed with HCM 10 years ago. The diagnosis was prompted by episodes of dizziness, palpitations and post-exercise chest tightness. The 22-year-old younger sister (defined as II-2) was diagnosed with HCM 3 years ago due to atypical chest pain. They both denied any prior history of hypertension, past medical ailments or surgical procedures. It is noteworthy that during the follow-up, II-1 experienced a cerebral infarction, while II-2 remained free from any complications. Of note, II-2 received a septal myectomy 4 months ago because of left ventricular outflow tract (LVOT) obstruction. Their mother (defined as I-1) died of heart disease (details unknown), and their father (defined as I-1) did not show any symptoms related to HCM or any other cardiovascular diseases. A family map was presented in Figure 1. Significant elevations in B-type natriuretic peptide (BNP) (elder: 865 ng/L, younger: 1081 ng/L) were identified by laboratory tests. The electrocardiogram (ECG) showed sinus rhythm in both patients. In detail, II-1 shows ST segment depression in I, II, aVL and V4–V6 leads, and T wave inversion in I, III, aVF, aVL, V1 and V4–V6 leads (Figure 2). For II-2, the ST segment is depressed in II, III, aVR, aVF and V4–V6 leads, and T wave inversion was found in II, III, aVR, aVF and V3–V6 leads (Figure 2). Two-dimensional transthoracic echocardiography (2D-TTE) revealed an asymmetrical left ventricular (LV) myocardial hypertrophy (Maron III) in both patients. In particular, the extent of hypertrophy is more serious in II-2, and the distribution of hypertrophic myocardium is different between II-1 and II-2. For II-1, the maximal wall thickness is 18 mm at the basal level of the LV inferior wall (Figure 3A, yellow star), and the left ventricular mass index (LVMI) is 73.7 g/m2. For II-2, the maximal wall thickness is 32 mm at the anterior interventricular septum (Figure 3B, yellow star), with an LVMI of 340.5 g/m2. The left atrium was enlarged in both patients (elder sister: 43 mm, younger sister: 43 mm). In addition, the right atrial (47 mm) of II-1 was enlarged, and the pulmonary artery was found to be widened (39 mm). Furthermore, the distribution of hypertrophic myocardium in two sisters was confirmed by myocardial contrast echocardiography (MCE) (Figure 3C,D). Moreover, the typical 'SAM' sign can be seen only in the younger sister (Figure 3E,F). Moreover, LVOT obstruction with a pressure gradient of 50 mmHg was detected in the II-2 by Doppler echocardiography, while the II-1 shows no LVOT obstruction (pressure gradient = 16 mmHg). Subsequently, LV systolic and diastolic function were evaluated, and both of them present normal left ventricular ejection fraction (LVEF) (elder sister: 59%; younger sister: 69%). However, the diastolic function of the sisters is significantly compromised according to the E/A, E/e′ and left atrial volume index (LAVI) values (Table 1). Two-dimensional strain revealed a reduced overall myocardial strain (global longitudinal strain [GLS]: elder: 8.7%, younger: 14.2%) in both subjects, especially in the hypertrophic myocardium (Figure 4). Detailed information was displayed in Table 1. The cardiovascular magnetic resonance (CMR) examination shows the same pattern as 2D-TTE (Figure 5). Nevertheless, II-2 received a septal myectomy 4 months ago because of LVOT obstruction and failed to undergo a CMR examination. At last, peripheral venous blood was collected from the sisters and their father, and then full exome sequencing and Sanger sequencing were performed. As shown in Figure 6, the results showed that their father's genetic analysis was normal. Mutations in MYH7 (c.2302, p.G768R, G > A at the 2302 site of exon 21) and RYR2-L4078I (c.12232, p.L4078I, C > A at the 2232 site of exon 90) were detected in both subjects (Figure 5). Strikingly, only the younger sister carried the mutation in the AKAP9 heterozygous missense gene (c.5581, p.I1861V, A > G at the 5581 site of exon 22), which led to the substitution of isoleucine at the 1861st amino acid by valine. In our case, the two sisters both present obvious myocardial hypertrophy, compromised LV diastolic function and reduced longitudinal strain, especially in the hypertrophic myocardium. However, there are differences between the sisters. The II-1 pattern of LV hypertrophy predominantly involves the basal level of the LV inferior wall, while the II-2 pattern involves mainly the inferior ventricular septum and causes LVOT obstruction, which is associated with more severe heart failure.3-5 Moreover, the magnitude of LV hypertrophy as well as LVMI is greater in the II-2. In addition, the BNP level, which is positively correlated with the severity of heart failure, is higher in the II-2. Based on the above information, one might assume that the II-2 must present more obvious and severe clinical manifestations. Nevertheless, the facts are totally on the contrary and push us forward to further investigate their causal genes. After thorough examination, mutations in MYH7 and RYR2 were identified in both subjects. It has been well elucidated that MYH7 is the most common (15%–25%) causal gene of familial HCM,6, 7 and we consider that mutations in MYH7 are the leading cause in these two patients. Mutations in RYR2 were also proven to be closely related to HCM and lead to lethal arrhythmia by causing aberrant Ca2+ release.8, 9 However, no sign of arrhythmia was discovered in these two patients. Notably, a missense variant of the AKAP9 gene was discovered only in the younger sister. AKAP9, known as a genetic modifier of congenital long QT syndrome, was proved associated with HCM for the first time and may act as a disease severity modifier.10 However, the ECG of the younger sister showed a QT interval of 440 ms, which did not conform to the performance of long QT syndrome. Several studies on genotype–phenotype correlation have revealed that different mutations are the reason why HCM patients manifest different severity and prognosis.11 Although the morphological, histological and clinical phenotypes of HCM are the consequence of complex interactions among a large number of determinants, ranging from the causal genetic mutation to environmental factors, the causal mutation is still considered the prerequisite and a major determinant of the phenotype.2 In the present case, the two sisters grew up in the same environment, so the environmental factors could be ignored, leaving us with the only explanation that mutation in AKAP9 is the causal factor behind the difference in phenotype. Previous studies have reported two typical cases: Maron et al.12 described a middle-aged male identical twin with HCM, and both of them carry a missense variant of the CRYAB gene. The concordance of phenotype and clinical course between the two patients is remarkable, including the timing of the onset and progression of heart failure due to LVOT obstruction. Conversely, Wang et al.13 reported a pair of monozygotic twins with HCM carrying the same pathogenic mutation of MYH7 (p.G768R; c.2302G > A), which, like our case, showed different clinical presentation and tissue characteristics. Nevertheless, Wang et al. did not test for other gene mutations like we did, which suggests the likely impact of epigenetics and environmental factors on the HCM phenotype. Several studies suggest that the presence of multiple mutations is associated with more severe hypertrophy in HCM,14 and this view of point explicates why the magnitude of LV hypertrophy as well as LVMI is greater in the younger sister, indicating that AKAP9 solidly acts as a disease severity modifier in this case, yet clinical manifestation of the sisters is confusing and lacks reasonable explanation because of the limited knowledge about the AKAP9 mutation itself. Long-term follow-up is required to observe the disease progression of the two sisters, and its effects should be analysed in functional studies and/or segregation in families. Another thing we notice through the 2 month follow-up is that despite the risk factor for arrhythmia they carry, two patients did not show any signs of atrial fibrillation, ventricular tachycardia or any malignant arrhythmia. However, mutations in RYR2 and AKAP9 might herald a poor prognosis, and we will continue our follow-up for the two sisters. In conclusion, the present case report highlights the fact that sisters sharing the same genetic backgrounds and environmental factors might carry different gene mutations, and clinicians should be aware that a subset of patients with HCM carries ≥2 mutations, especially when family members possess different HCM phenotypes. Multiple genes should be examined instead of one. Additionally, we deduce that AKAP9 is potentially relevant to the pathogenesis of HCM. More efforts are needed in order to understand the associated risk profile between AKAP9 and HCM. Moreover, our case report assumed that echocardiography may enhance the precision and efficiency of genetic counselling and testing in HCM. The authors declare no conflict of interest. Data are available on request due to privacy or ethical restrictions.

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.

Abstract. Background:. Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants. Methods:. A total of 3053 healthy Han Chinese adults (1922 women) aged 18–79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere–Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance. Results:. All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions:. The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.