Transthoracic echocardiographic Doppler metrics in evaluating bioprosthetic tricuspid valve dysfunction.

PURPOSE: There is currently limited information on the utility of transthoracic echocardiography (TTE)-derived Doppler parameters for assessing bioprosthetic tricuspid valve (BTV) dysfunction. Our study aimed to establish the precision and appropriate reference ranges for routinely collected transthoracic Doppler parameters in the assessment of BTV dysfunction. METHODS: We retrospectively evaluated 100 BTV patients who underwent TTE. Based on redo surgical confirmation or more than 2 repeat TTE or transesophageal echocardiography (TEE) examinations, patients were allocated to normal (n = 61), regurgitant (n = 24), or stenotic (n = 15) BTV group. Univariate and multivariate binary logistic regression were performed to identify TTE Doppler parameters that detected BTV dysfunction. RESULTS: The VTI ratio (VTITV/VTILVOT) was the most accurate Doppler parameter for detecting BTV dysfunction, with a ratio of >2.8 showing 84.6% sensitivity and 90.2% specificity. VTI ratio > 3.2, mean gradient (MGTV) > 6.2 mmHg and pressure half-time > 218 ms detected significant BTV stenosis, with sensitivities of 100%, 93.3% and 93.3% and specificities of 82.4%, 75.3% and 87.1%, respectively. After multivariate analysis, the VTI ratio > 2.8 (OR = 9.00, 95% CI = 2.13-41.61, p = .003) and MGTV > 5.1 mmHg (OR = 6.50, 95% CI = 1.69-27.78, p = .008) were the independent associations of BTV dysfunction. With these cutoff values, 75.0%-92.2% of normal and 62.5%-96.0% of dysfunctional BTV were identified. CONCLUSIONS: Doppler parameters from TTE can accurately identify BTV dysfunction, particularly with VTI ratio > 2.8 and MGTV > 5.1 mmHg, to assess the need for additional testing with TEE.

A Membrane-Targeting Aggregation-Induced Emission Probe for Monitoring Lipid Droplet Dynamics in Ischemia/Reperfusion-Induced Cardiomyocyte Ferroptosis.

Myocardial ischemia/reperfusion injury (MIRI) is the leading cause of irreversible myocardial damage. A pivotal pathogenic factor is ischemia/reperfusion (I/R)-induced cardiomyocyte ferroptosis, marked by iron overload and lipid peroxidation. However, the impact of lipid droplet (LD) changes on I/R-induced cardiomyocyte ferroptosis is unclear. In this study, an aggregation-induced emission probe, TPABTBP is developed that is used for imaging dynamic changes in LD during myocardial I/R-induced ferroptosis. TPABTBP exhibits excellent LD-specificity, superior capability for monitoring lipophagy, and remarkable photostability. Molecular dynamics (MD) simulation and super-resolution fluorescence imaging demonstrate that the TPABTBP is specifically localized to the phospholipid monolayer membrane of LDs. Imaging LDs in cardiomyocytes and myocardial tissue in model mice with MIRI reveals that the LD accumulation level increase in the early reperfusion stage (0-9 h) but decrease in the late reperfusion stage (>24 h) via lipophagy. The inhibition of LD breakdown significantly reduces the lipid peroxidation level in cardiomyocytes. Furthermore, it is demonstrated that chloroquine (CQ), an FDA-approved autophagy modulator, can inhibit ferroptosis, thereby attenuating MIRI in mice. This study describes the dynamic changes in LD during myocardial ischemia injury and suggests a potential therapeutic target for early MIRI intervention.

Progress in extracellular vesicle homeostasis as it relates to cardiovascular diseases.

Extracellular vesicles (EVs) are involved in both physiological and pathological processes in many organ systems and are essential in mediating intercellular communication and maintaining organismal homeostasis. It is helpful to propose new strategies for disease treatment by elucidating the mechanisms of EV release and sorting. An increasing number of studies have shown that there is specific homeostasis in EVs, which is helpful for the human body to carry out physiological activities. In contrast, an EV homeostasis im-balance promotes or accelerates disease onset and development. Alternatively, regulating the quality of EVs can maintain homeostasis and even achieve the purpose of treating conditions. An analysis of the role of EV homeostasis in the onset and development of cardiovascular disease is presented in this review. This article also summarizes the methods that regulate EV homeostasis and their application in cardiovascular diseases. In particular, this study focuses on the connection between EV steady states and the cardiovascular system and the potential value of EVs in treating cardiovascular diseases.

Platelet membrane-derived biomimetic microbubbles with enhanced targeting ability for the early detection of myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion injury (MIRI) is a widely recognized cardiovascular disease that significantly impacts the prognosis of patients undergoing myocardial infarction recanalization. This condition can be fatal and involves complex pathophysiological mechanisms. Early diagnosis of MIRI is crucial to minimize myocardial damage and reducing mortality. Based on the inherent relationship between platelets and MIRI, we developed biomimetic microbubbles coated with platelet membrane (MB-pla) for early identification of MIRI. The MB-pla were prepared through a recombination process involving platelet membrane obtained from rat whole blood and phospholipids, blended in appropriate proportions. By coating the microbubbles with platelet membrane, MB-pla acquired various adhesion molecules, thereby gaining the capability to selectively adhere to damaged endothelial cells in the context of MIRI. In vitro experiments demonstrated that MB-pla exhibited remarkable targeting characteristics, particularly toward type IV collagen and human umbilical vein endothelial cells that had been injured through hypoxia/reoxygenation procedures. In a rat model of MIRI, the signal intensity produced by MB-pla was notably higher than that of control microbubbles. These findings were consistent with results obtained from fluorescence imaging of isolated hearts and immunofluorescence staining of tissue sections. In conclusion, MB-pla has great potential as a non-invasive early detection method for MIRI. Furthermore, this approach can potentially find application in other conditions involving endothelial injury in the future.

Echocardiographic diagnosis of rupture of mitral valve papillary muscle.

OBJECTIVE: To explore the value of echocardiography in diagnosing papillary muscle rupture (PMR) of the mitral valve, and summarize the characteristic echocardiographic features of different types. METHODS: Echocardiograms of 13 PMR patients confirmed by surgery in Wuhan Union Hospital between January 2009 and December 2022 were retrospectively analyzed and their preoperative transthoracic echocardiography (TTE) was compared with surgical findings. RESULTS: A total of 9020 patients underwent mitral valve repair or replacement surgery during the study period including 13 (0.14%) for PMR. Of the 13 PMRs, 8 cases were partial PMR(P-PMR), 5 cases were complete PMR(C-PMR); 3 cases were anterolateral PMR, and 10 were posteromedial PMR. The diagnostic accuracy, sensitivity, and specificity of the preoperative TTE were 99.9%, 53.8% and 99.9% respectively. Echocardiographic features of 10 patients (5-C-PMR and 5 P-PMR) with detailed TTE and intraoperative transesophageal echocardiography (TEE) data included: both anterior and posterior leaflets prolapse (C-PMR 60% vs P-PMR 60%); flail leaflet (C-PMR100% vs P-PMR 40%); All C-PMRs and P-PMRs have severe, eccentric and lateral regurgitation; flail attachment (chordae tendinae and ruptured PM) at the tip of prolapsed leaflet (C-PMR100% vs P-PMR 60%); high-echo masses resembled "champagne glasses" in 100% of the C-PMR; high-echo masses resembled "lotus-seedpod" in 60% and "dumbbell-shaped" torn PM in remaining 40% of the P-PMR. CONCLUSIONS: Different PMR subtypes have different echocardiographic characteristics. Combining TTE and TEE can accurately identify the typical features of PMR such as ipsilateral hemipetal leaflet prolapse, high-echoic mass at the tip of the leaflet, massive eccentricity and lateral regurgitation.

Patient-specific computational fluid dynamics for hypertrophic obstructive cardiomyopathy.

BACKGROUND: The heterogeneous morphologic and functional expression of hypertrophic obstructive cardiomyopathy (HOCM) is evidenced by established imaging, multimodality imaging is essential for a comprehensive assessment but may remain uncertain. This study aimed to develop a patient-specific hemodynamics assessment with cardiac computed tomography angiography (CCTA) based computational fluid dynamics (CFD) and prove its usability in cohorts of HOCM patients. METHODS: A retrospective study was performed on eight HOCM patients with septal myectomy who had both preoperative and postoperative CCTA as well as transthoracic echocardiography (TTE). The three-dimensional models were reconstructed from CCTA data, following which patient-specific CFD simulations were performed to estimate the blood velocity, pressure gradient, and wall shear stress. The simulation output was compared with TTE. Based on CFD simulations, retrospective and blinded virtual myectomy was also performed, to predict the minimum resected volume for improving obstruction in patients. RESULT: The complex HOCM anatomy was successfully reconstructed for all 8 patients. The CFD simulation accurately assessed the pressure gradient, flow velocity. There was a good correlation between the peak pressure gradient measured by CFD and TTE in the pre- and post-operative assessments (r = 0.87 and 0.84, respectively), and the flow velocity (r = 0.87 and 0.90, respectively). The volumes of minimal resection myocardium predicted by CFD and virtual myectomy were consistent with the actual resection volumes. CONCLUSION: CCTA-based CFD for HOCM patients may play a unique role in the assessment of patient-specific morphology and hemodynamics. Combination with virtual myectomy might allow for optimizing therapy planning in septal myectomy. CLINICAL PERSPECTIVE: CFD based CCTA may emerge as a complement to established imaging strategies, with accurate three-dimensional reconstruction and hemodynamic simulation of the left ventricle in this retrospective study. Combined with virtual myectomy, CFD simulation might allow for predicting the volume of resected myocardium for septal myectomy. Moving forward, this technology may be used by clinicians to better assess the conditions of HOCM patients, and guide the extent and depth of resection during septal myectomy. Therefore, further prospective clinical evaluation is clearly warranted.

Research on the Relationship between Exosome Production and Atherosclerosis.

Atherosclerosis (AS) is the leading cause of cardiovascular disease, causing a major burden on patients as well as families and society. Exosomes generally refer to various lipid bilayer microvesicles originating from different cells that deliver various bioactive molecules to the recipient cells, exerting biological effects in cellular communication and thereby changing the internal environment of the body. The mechanisms of correlation between exosomes and the disease process of atherosclerosis have been recently clarified. Exosomes are rich in nucleic acid molecules and proteins. For example, the exosome miRNAs reportedly play important roles in the progression of atherosclerotic diseases. In this review, we focus on the composition of exosomes, the mechanism of their biogenesis and release, and the commonly used methods for exosome extraction. By summarizing the latest research progress on exosomes and atherosclerosis, we can explore the advances in the roles of exosomes in atherosclerosis to provide new ideas and targets for atherosclerosis prevention, diagnosis, and treatment.

Biventricular longitudinal strain as a predictor of functional improvement after D-shant device implantation in patients with heart failure.

Background: The creation of an atrial shunt is a novel approach for the management of heart failure (HF), and there is a need for advanced methods for detection of cardiac function response to an interatrial shunt device. Ventricular longitudinal strain is a more sensitive marker of cardiac function than conventional echocardiographic parameters, but data on the value of longitudinal strain as a predictor of improvement in cardiac function after implantation of an interatrial shunt device are scarce. We aimed to investigate the exploratory efficacy of the D-Shant device for interatrial shunting in treating heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), and to explore the predictive value of biventricular longitudinal strain for functional improvement in such patients. Methods: A total of 34 patients were enrolled (25 with HFrEF and 9 with HFpEF). All patients underwent conventional echocardiography and two-dimensional speckle tracking echocardiogram (2D-STE) at baseline and 6 months after implantation of a D-Shant device (WeiKe Medical Inc., WuHan, CN). Left ventricular global longitudinal strain (LVGLS) and right ventricular free wall longitudinal strain (RVFWLS) were evaluated by 2D-STE. Results: The D-Shant device was successfully implanted in all cases without periprocedural mortality. At 6-month follow-up, an improvement in New York Heart Association (NYHA) functional class was observed in 20 of 28 patients with HF. Compared with baseline, patients with HFrEF showed significant reduced left atrial volume index (LAVI) and increased right atrial (RA) dimensions, as well as improved LVGLS and RVFWLS, at 6-month follow-up. Despite reduction in LAVI and increase in RA dimensions, improvements in biventricular longitudinal strain did not occur in HFpEF patients. Multivariate logistic regression demonstrated that LVGLS [odds ratio (OR): 5.930; 95% CI: 1.463-24.038; P = 0.013] and RVFWLS (OR: 4.852; 95% CI: 1.372-17.159; P = 0.014) were predictive of improvement in NYHA functional class after D-Shant device implantation. Conclusion: Improvements in clinical and functional status are observed in patients with HF 6 months after implantation of a D-Shant device. Preoperative biventricular longitudinal strain is predictive of improvement in NYHA functional class and may be helpful to identify patients who will experience better outcomes following implantation of an interatrial shunt device.

Robot-Assisted Percutaneous Balloon Compression in Elderly Patients with Trigeminal Neuralgia.

Objective: To investigate the clinical effects of percutaneous balloon compression (PBC) for trigeminal neuralgia in elderly patients with the assistance of a neurosurgical navigation and positioning planning system (referred to hereafter as the robot). Methods: We performed a retrospective analysis of 11 patients with trigeminal neuralgia. Preoperative TOF MRA, T2WI-SPACE, and thin-slice CT scans were performed, and the volume of Meckel's Cave was calculated by multi-modal image fusion on a workstation. Surgical planning involved two paths. Path A was the actual puncture path, the target point was the anterior inner quadrant of the inner opening of the foramen ovale; Path B represented a virtual path for measurement, and was used to plan the depth of balloon placement. The foramen ovale puncture for path A was completed under the guidance of a robotic arm adapter, while path B was completed under lateral X-ray fluoroscopy with a DSA machine. The balloon was placed at a predetermined depth, and filled to a "pear" shape to complete the operation. Preliminary follow-up results were obtained by considering VAS score and BNI classification. Results: The foramen ovale was successfully punctured in all 11 patients and entered Meckel's Cave, the balloon was then filled to create a "pear shape". Immediate complete healing was achieved in 10 patients and delayed healing was achieved in one patient by the 5th postoperative day. No serious complications were identified that were related to surgery, and over a follow-up time of 1-12 months, there was no recurrence of pain, and a BNI numbness grade of 2-3 points. The appropriate ratio of the balloon inflated volume to the preoperative Meckel's Cave volume was approximately 1.7. Conclusion: Preliminary clinical application and short-term follow-up showed that robot-assisted PBC surgery is a safe and effective surgical method for elderly patients with trigeminal neuralgia.

Granzyme B-responsive fluorescent probe for non-invasive early diagnosis of transplant rejection.

Allograft rejection has always been a major obstacle in organ transplantation. The current clinical diagnostic gold standard for allograft rejection is an invasive biopsy. However, biopsy has some limitations, such as sampling errors, risk of serious complications, and high cost. In this study, we have rationally developed an activatable fluorescent probe CYGB for imaging of granzyme B, which is a biomarker released by CD8+T cells attacking the graft. Moreover, the ability of CYGB to detect rejection early in mouse heart and skin transplantation models was evaluated. The probe CYGB consists of a caged hemicyanine-based fluorophore and a GzmB-specifically cleaved peptide substrate linked via a self-immolating spacer, p-aminobenzyl alcohol. Endogenous GzmB in CD8+ T cells specifically activated the near-infrared fluorescence (NIRF) signal of CYGB. In vivo imaging in mice skin and heart graft models, showed that CYGB preferentially accumulates in grafts, enabling early diagnosis of rejection. Moreover, CYGB enables non-invasive assessment of the level of immunosuppression in allogeneic mice treated with FK506. This study provides an alternative method for monitoring the status of allografts without biopsy.

Synthesis of Pyrazolo[1,5-a]pyridinyl, Pyrazolo[1,5-a]quinolinyl, and Pyrazolo[5,1-a]isoquinolinyl Sulfonyl Fluorides via a [3 + 2] Annulation.

A [3 + 2] cycloaddition reaction of N-aminopyridines, N-aminoquinolines, and N-aminoisoquinolines with 1-bromoethene-1-sulfonyl fluoride (BESF) was performed to obtain optimum yields of various useful pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]quinolinyl, and pyrazolo[5,1-a]isoquinolinyl sulfonyl fluorides (43-90% yield). The transformation process showed broad substrate specificity, mild reaction conditions, and operational simplicity. Therefore, the reaction has great applicable value in the field of medicinal chemistry and other disciplines.

In-Situ TEM Investigation of Helium Implantation in Ni-SiOC Nanocomposites.

Ni-SiOC nanocomposites maintain crystal-amorphous dual-phase nanostructures after high-temperature annealing at different temperatures (600 °C, 800 °C and 1000 °C), while the feature sizes of crystal Ni and amorphous SiOC increase with the annealing temperature. Corresponding to the dual-phase nanostructures, Ni-SiOC nanocomposites exhibit a high strength and good plastic flow stability. In this study, we conducted a He implantation in Ni-SiOC nanocomposites at 300 °C by in-situ transmission electron microscope (TEM) irradiation test. In-situ TEM irradiation revealed that both crystal Ni and amorphous SiOC maintain stability under He irradiation. The 600 °C annealed sample presents a better He irradiation resistance, as manifested by a smaller He-bubble size and lower density. Both the grain boundary and crystal-amorphous phase boundary act as a sink to absorb He and irradiation-induced defects in the Ni matrix. More importantly, amorphous SiOC ceramic is immune to He irradiation damage, contributing to the He irradiation resistance of Ni alloy.

miR-590-3p protects against ischaemia/reperfusion injury in an oxygen-glucose deprivation and reoxygenation cellular model by regulating HMGB1/TLR4/MyD88/NF-κB signalling.

miR-590-3p has been reported to be reduced in myocardial ischaemia-reperfusion (I/R) injury, but its specific role in cerebral I/R injury is still uncertain. Thus, we explored the function and mechanism of miR-590-3p in cerebral I/R injury using a cellular model. miR-590-3p, high mobility group Box 1 (HMGB1), and signalling-related factor levels were assessed using qPCR or a western blot analysis. Cell apoptosis was measured by flow cytometry. Inflammatory factors were detected by ELISA. The target of miR-590-3p was confirmed by dual-luciferase reporter assay and western blot analysis. We found that miR-590-3p was decreased and HMGB1 was increased in the OGD/R model. Upregulation of miR-590-3p reduced cell apoptosis and inflammation in the OGD/R model, and the TLR4/MyD88/NF-κB signalling pathway was suppressed. However, inhibition of miR-590-3p showed the opposite effects. Moreover, HMGB1 was verified as a target gene of miR-590-3p. HMGB1 reversed the decrease in apoptosis and inflammation caused by overexpression of miR590-3p, and the TLR4/MyD88/NF-κB signalling pathway was activated. Our results suggest that miR-590-3p regulates the TLR4/MyD88/NF-κB pathway by interacting with HMGB1 to protect against OGD/R-induced I/R injury. Thus, miR-590-3p may serve as a potential therapeutic target in cerebral I/R repair.