A Mild Dyssynchronous Contraction Pattern Detected by SPECT Myocardial Perfusion Imaging Predicts Super-Response to Cardiac Resynchronization Therapy

Background: Using single photon emission computed tomography myocardial perfusion imaging (SPECT MPI) with phase analysis (PA), we aimed to identify the predictive value of a new contraction pattern in cardiac resynchronization therapy (CRT) response. Methods: Left ventricular mechanical dyssynchrony (LVMD) was evaluated using SPECT MPI with PA in non-ischemic dilated cardiomyopathy (DCM) patients with left bundle branch block (LBBB) indicated for CRT. CRT super-response was defined as LV ejection fraction (EF) ≥50% or an absolute increase of LVEF \u3e15%. The LV contraction was categorized as the mild dyssynchronous pattern when the phase standard deviation (PSD) ≤ 40.3° and phase histogram bandwidth (PBW) ≤ 111.9°, otherwise it was defined as severe dyssynchronous pattern which was further characterized as U-shaped, heterogeneous or homogenous pattern. Results: The final cohort comprised 74 patients, including 32 (43.2%) in mild dyssynchronous group, 17 (23%) in U-shaped group, 19 (25.7%) in heterogeneous group, and 6 (8.1%) in homogenous group. The mild dyssynchronous group had lower PSD and PBW than U-shaped, heterogeneous, and homogenous groups ( \u3c 0.0001). Compared to patients with the heterogeneous pattern, the odds ratios (ORs) with 95% confidence intervals (CIs) for CRT super-response were 10.182(2.43-42.663), 12.8(2.545-64.372), and 2.667(0.327-21.773) for patients with mild dyssynchronous, U-shaped, and homogenous pattern, respectively. After multivariable adjustment, mild dyssynchronous group remained associated with increased CRT super-response (adjusted OR 5.709, 95% CI 1.152-28.293). Kaplan-Meier curves showed that mild dyssynchronous group demonstrated a better long-term prognosis. Conclusions: The mild dyssynchronous pattern in patients with DCM is associated with an increased CRT super-response and better long-term prognosis

Design and synthesis of cabotegravir derivatives bearing 1,2,3-triazole and evaluation of anti-liver cancer activity

Based on the structure of the anti-HIV drug cabotegravir, we introduced 1,2,3-triazole groups with different substituents to obtain 19 cabotegravir derivatives and tested their activity against HepG2 cells. The proliferation of HepG2 cells was examined following treatment with derivatives. Most of the compounds demonstrated significant inhibitory effects, particularly compounds KJ-5 and KJ-12 with IC50 values of 4.29 ± 0.10 and 4.07 ± 0.09 μM, respectively. Furthermore, both compounds 5 and 12 significantly caused cell apoptosis, G2/M arrest, and DNA damage, and suppressed invasion and migration in a concentration-dependent manner. In addition, KJ-5 and KJ-12 could trigger apoptosis via the mitochondrial pathway by increasing the ratio of Bax/Bcl-2 and activating cleaved caspase-9, cleaved caspase-3, and cleaved PARP

Machine Learning for Prediction of Sudden Cardiac Death in Heart Failure Patients With Low Left Ventricular Ejection Fraction: Study Protocol for a Retrospective Multicentre Registry in China

Introduction: Left ventricular ejection fraction (LVEF) ≤35%, as current significant implantable cardioverter-defibrillator (ICD) indication for primary prevention of sudden cardiac death (SCD) in heart failure (HF) patients, has been widely recognised to be inefficient. Improvement of patient selection for low LVEF (≤35%) is needed to optimise deployment of ICD. Most of the existing prediction models are not appropriate to identify ICD candidates at high risk of SCD in HF patients with low LVEF. Compared with traditional statistical analysis, machine learning (ML) can employ computer algorithms to identify patterns in large datasets, analyse rules automatically and build both linear and non-linear models in order to make data-driven predictions. This study is aimed to develop and validate new models using ML to improve the prediction of SCD in HF patients with low LVEF. Methods and analysis: We will conduct a retroprospective, multicentre, observational registry of Chinese HF patients with low LVEF. The HF patients with LVEF ≤35% after optimised medication at least 3 months will be enrolled in this study. The primary endpoints are all-cause death and SCD. The secondary endpoints are malignant arrhythmia, sudden cardiac arrest, cardiopulmonary resuscitation and rehospitalisation due to HF. The baseline demographic, clinical, biological, electrophysiological, social and psychological variables will be collected. Both ML and traditional multivariable Cox proportional hazards regression models will be developed and compared in the prediction of SCD. Moreover, the ML model will be validated in a prospective study. Ethics and dissemination: The study protocol has been approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (2017-SR-06). All results of this study will be published in international peer-reviewed journals and presented at relevant conferences

Noninvasive quantification of granzyme B in cardiac allograft rejection using targeted ultrasound imaging

ObjectiveEndomyocardial biopsy is the gold standard method for the diagnosis of cardiac allograft rejection. However, it causes damage to the heart. In this study, we developed a noninvasive method for quantification of granzyme B (GzB) in vivo by targeted ultrasound imaging, which detects and provides quantitative information for specific molecules, for acute rejection assessment in a murine cardiac transplantation model.MethodsMicrobubbles bearing anti-GzB antibodies (MBGzb) or isotype antibodies (MBcon) were prepared. Hearts were transplanted from C57BL/6J (allogeneic) or C3H (syngeneic) donors to C3H recipients. Target ultrasound imaging was performed on Days 2 and 5 post-transplantations. A pathologic assessment was performed. The expression of granzyme B and IL-6 in the heart was detected by Western blotting.ResultsAfter MB injection, we observed and collected data at 3 and 6 min before and after the flash pulse. Quantitative analysis revealed that the reduction in peak intensity was significantly higher in the allogeneic MBGzb group than in the allogeneic MBcon group and the isogeneic MBcon group at PODs 2 and 5. In the allogeneic groups, granzyme B and IL-6 expression levels were higher than those in the isogeneic group. In addition, more CD8 T cells and neutrophils were observed in the allogeneic groups.ConclusionUltrasound molecular imaging of granzyme B can be used as a noninvasive method for acute rejection detection after cardiac transplantation

Characterisation of tissue microstructure on excised dog livers using the structure factor model

International audienceQuantitative ultrasound (QUS) techniques utilize the amplitude and frequency dependence of the backscatter coefficient (BSC) to determine the physical properties of the average tissue microstructure. QUS techniques typically rely on theoretical scattering models to fit the BSC from biological tissues to an estimated BSC using an appropriate theoretical model. The Structure Factor Model (SFM) was recently shown to better explain the BSCs from tissue-mimicking biophantoms (Franceschini et al JASA 2014). The aim of this study is to use the SFM to estimate the tissue microstructure in excised canine livers.Ultrasonic backscatter measurements were performed in excised canine livers at frequencies ranging from 12 MHz to 38 MHz using an ultrasound scanner (Vevo 770, Visualsonics, Toronto, Canada) equipped with the RMV 707 probe. The mean scatterer radius r*, scatterer concentration ϕ* and impedance contrast Gz* were estimated using the SFM. The estimated parameters were classified according to the concentration estimates as a diluted medium (ϕ*<0.08) or a concentrated medium (ϕ*≥0.08).The structural parameters classified as diluted medium (ϕ*<0.08) were equal to r*=5.43±0.95 µm, ϕ*=0.022±0.013 and Gz*=0.12±0.04 for most estimates (77%). The estimated scatterer radius closely corresponded to the actual radius of the hepatocyte nuclei. By assuming that the hepatocyte cells occupy a volume fraction around 0.74 and that 15% of the cells are bi-nucleated, the nuclear volume fraction is expected to equal approximately 0.039. A good match was thus obtained between the estimated and expected nuclear volume fractions using the SFM

Target Characteristics and Voltage Mapping of the Matrix in Idiopathic Premature Ventricular Contractions Originating from the Right Ventricular Outflow Tract

Background. The study was aimed at exploring the electrophysiological characteristics (EPS) of the optimal ablation site and its relationship with electroanatomic voltage mapping (EVM) in idiopathic premature ventricular contractions (PVCs) originating from the right ventricular outflow tract (RVOT). Methods. A total of 28 patients with idiopathic RVOT PVCs underwent successful ablation and EVM using a 3D electroanatomical mapping (CARTO) system. Results. Both bipolar and unipolar EVM showed a similar band-like lower-voltage area (LVA) under the pulmonary valve in all the patients; 21.4% of the targets were located in the band-like LVA. 42.9% of the targets were at the border of the band-like LVA on the bipolar voltage map, but unipolar mapping showed that 53.6% of the targets were located in the band-like LVA, and 35.7% of the targets at the border of the band-like LVA. A significant difference was found in both unipolar and bipolar voltage values between the regions within 0-5 mm above the optimal ablation site and the other regions. A similar difference was observed only in unipolar voltage values below the optimal ablation site. At the ablation site, there were frequent occurrences of a fragmented wave and voltage reversion in the bipolar electrograms, frustrated falling limbs, W bottom, and a QS configuration width>150 ms in the unipolar electrograms. Conclusions. EVM showed that the band-like LVA was an interesting area for the search of the optimal ablation sites of idiopathic RVOT-PVCs, especially the border area. There was focal microscarring around the ablation targets; some characteristics of EPS proved significant for successful ablation

A meta-analysis of risk factors for cage migration after lumbar fusion surgery

Objective: Cage migration is a rare complication after lumbar fusion surgery, and it is also the cause of lumbar revision surgery. Previous studies have reported that many influencing factors can increase the incidence of cage migration. However, there still remains controversial. The current study was conducted to investigate the risk factors influencing incidence of cage migration. Methods: A systematic database search of PubMed, Embase, Web of Science, Cochrane Library and Clinical Trials was performed for relevant articles published until July 2022. According to the inclusion and exclusion criteria, two evaluators independently conducted literature screening, data extraction and quality evaluation of the obtained literature. The Newcastle–Ottawa Scale (NOS) score was used for quality evaluation, and meta-analysis was performed by STATA 16.0 software. Results: A total of 2126 relevant articles were initially identified, and 7 articles were finally included in this study for data extraction and meta-analysis. The results of meta-analysis showed that the bony endplate injury, pear-shaped disc, and screw loosening are significantly correlated with cage migration. The OR values (95%CI) of the three factors were 7.170 (3.015, 17.051), 8.056 (4.050, 16.023), and 12.840 (3.570, 46.177) respectively. Conclusion: Bony endplate injury, pear-shaped disc, and screw loosening are the current risk factors for cage migration postoperatively