Real-time 3D-3D image fusion of CTA/CBCT roadmap fluoroscopy in the transcatheter mitral intervention.

Absence of periprocedural visualization of three-dimensional (3D) left heart anatomy and its surrounding structures in fluoroscopy may reduce the rate of successful transcatheter mitral valve repair. We proposed a multimodal imaging strategy based on 3D computed tomography (CT) angiography and 3D cone beam CT fusion images, which enabled real-time visual inspection of 3D cardiac structures on fluoroscopy, to optimize transcatheter mitral intervention. This new image fusion technology, together with standard transesophageal echocardiography guidance, improved the efficiency and safety of the procedure, and could be considered as a new workflow for transcatheter mitral valve intervention.

Angioplasty Guidewire-Assisted vs. Conventional Transseptal Puncture for Left Atrial Appendage Occlusion: a multicentre randomized controlled trial.

AIMS: This study was performed to compare the usability, efficiency, and safety of a modified angioplasty guidewire-assisted transseptal puncture (TSP) technique vs. the conventional approach in facilitating access into the left atrium during left atrial appendage occlusion (LAAO) procedures for the treatment of atrial fibrillation. METHODS AND RESULTS: The ADVANCE-LAAO trial (Angioplasty Guidewire-Assisted vs. Conventional Transseptal Puncture for Left Atrial Appendage Occlusion) was an investigator-initiated, prospective, multicentre, randomized controlled trial (NCT05125159). Patients with atrial fibrillation who underwent LAAO were prospectively enrolled from four centres and randomly assigned to an angioplasty guidewire-assisted TSP group (n = 131) or to a conventional Brockenbrough needle TSP group (n = 132). The primary endpoint was the one-time success rate of TSP. We also analysed the TSP procedure time, failure rate of the assigned TSP type, radiation dose, contrast dose, and procedural complications in both groups. All patients in the guidewire-assisted group underwent successful TSP, whereas five in the standard conventional group switched to the guidewire-assisted approach. The guidewire-assisted puncture improved the one-time success rate (92.4 vs. 77.3%, P = 0.001), shortened the TSP procedure time (109.2 ± 48.2 vs. 120.5 ± 57.6 s, P = 0.023), and tended to have a higher rate of good coaxial orientation of the sheath with the left atrial appendage during the LAAO procedure (66.4 vs. 54.5%, P = 0.059). No TSP-related complications occurred in the guidewire-assisted TSP group, whereas two complications occurred in the conventional TSP group. There was no significant difference in the failure rate of the assigned TSP type, the total procedure time, the total radiation dose, the rate of successful LAAO implantation, or the procedural complication rate between the two groups (all P > 0.05). CONCLUSION: This study confirmed that angioplasty guidewire-assisted puncture can effectively improve the success rate of TSP during LAAO procedures. This novel technique has high potential for application in interventional therapies requiring TSP.

Pulmonary vein perforation into the respiratory tract with systemic air embolism: a rare complication of left atrial appendage closure.

BACKGROUND: Pulmonary vein perforation is an uncommon complication during cardiac intervention. We present a rare case of pulmonary vein perforation into the respiratory tract with systemic air embolism during left atrial appendage closure (LAAC). CASE PRESENTATION: A 77-year-old man with persistent nonvalvular atrial fibrillation was referred for percutaneous LAAC under local anaesthesia (CHA2DS2-VASc score of 4, HAS-BLED score of 3, and prior ischaemic stroke). During the procedure, after delivering a super-stiff guidewire into the left superior pulmonary vein (LSPV), the patient suddenly developed a severe cough with haemoptysis upon advancement of a delivery sheath along the guidewire. Fluoroscopy showed signs of blood entering the left main bronchus, and fast transthoracic echocardiography revealed bubbles in the left heart without pericardial effusion. The procedure was terminated because of a major complication indicated by the repeated haemoptysis and headache, and haemostatic drugs were immediately administered. Subsequent chest computed tomography angiography (CTA) revealed a filling defect in the LSPV branches and bubbles in the aorta. The patient was transferred to the critical care unit for haemostasis and antibacterial treatment. Transthoracic echocardiography later that day showed no bubbles in the heart. The headache and haemoptysis significantly abated the following day. The bubbles in the aorta disappeared on chest CTA 7 days later. CONCLUSIONS: Interventional cardiologists should pay attention to anatomical variations of the pulmonary vein, which are associated with a high risk of complications of pulmonary vein perforation during LAAC. Preoperative CTA examination and intraoperative transoesophageal echocardiography might be helpful to avoid this complication.

Prevalence, Predictors and Mechanisms of Steam Pops in Ablation Index-Guided High-Power Pulmonary Vein Isolation.

Despite the good cooling effect of the contact-force porous catheter, the risk of steam pops (SP) remains one of the major concerns in high-power circumferential pulmonary vein isolation (CPVI). This study aimed to investigate the prevalence, predictors and possible mechanisms of SPs in CPVI. Patients experiencing SPs in de novo high-power CPVI were 1:3 matched by non-SP patients with gender, age (±5 years) and left atrial diameter (LAD) (±5 mm) to compare the ablation parameters of SP and non-SP lesions. Catheter tip displacement (Tipdisp) was compared between "edge-of-ridge" and "PV-side-of-ridge" placement at anterior and roof segments of the left pulmonary vein (PV). SPs occurred in 11 (1.57%) of 701 patients, including 6 at the antero-superior left PV, 2 at the roof, 1 at the postero-superior left PV, 1 at the bottom left PV and 1 at the antero-superior aspect of the right PV. There was significantly shorter RF delivery duration (13.9 ± 6.3 vs. 23.3 ± 6.0 s), greater Δimpedance (17.6 ± 6.7 vs. 6.7 ± 4.1 Ω) and lower ablation index (357.7 ± 68.8 vs. 430.2 ± 30.7) in SP patients than those in non-SP patients. Δimpedance >12 Ω during ablation could predict SP occurrence. Tipdisp was greater in "PV-side-of-ridge" than that in "edge-of -ridge" placement (3.2 ± 1.6 mm vs. 2.0 ± 0.8 mm) at antero-superior and roof segments of the left PV. The prevalence of SP was 1.57% in high-power CPVI procedures, with the most common site at the antero-superior segment of the left PV. Δimpedance was a significant predictor of SP occurrence. "PV-side-of-ridge" ablation at antero-superior and roof segments of left PV might predispose to SP occurrence due to excessive tissue coverage.

Ultrarare Loss-of-Function Mutations in the Genes Encoding the Ionotropic Glutamate Receptors of Kainate Subtypes Associated with Schizophrenia Disrupt the Interaction with PSD95.

Schizophrenia is a complex mental disorder with a genetic component. The GRIK gene family encodes ionotropic glutamate receptors of the kainate subtype, which are considered candidate genes for schizophrenia. We screened for rare and pathogenic mutations in the protein-coding sequences of the GRIK gene family in 516 unrelated patients with schizophrenia using the ion semiconductor sequencing method. We identified 44 protein-altered variants, and in silico analysis indicated that 36 of these mutations were rare and damaging or pathological based on putative protein function. Notably, we identified four truncating mutations, including two frameshift deletion mutations (GRIK1p.Phe24fs and GRIK1p.Thr882fs) and two nonsense mutations (GRIK2p.Arg300Ter and GRIK4p.Gln342Ter) in four unrelated patients with schizophrenia. They exhibited minor allele frequencies of less than 0.01% and were absent in 1517 healthy controls from Taiwan Biobank. Functional analysis identified these four truncating mutants as loss-of-function (LoF) mutants in HEK-293 cells. We also showed that three mutations (GRIK1p.Phe24fs, GRIK1p.Thr882fs, and GRIK2p.Arg300Ter) weakened the interaction with the PSD95 protein. The results suggest that the GRIK gene family harbors ultrarare LoF mutations in some patients with schizophrenia. The identification of proteins that interact with the kainate receptors will be essential to determine kainate receptor-mediated signaling in the brain.

Transcriptomic and Proteomic Analysis of CRISPR/Cas9-Mediated ARC-Knockout HEK293 Cells.

Arc/Arg3.1 (activity-regulated cytoskeletal-associated protein (ARC)) is a critical regulator of long-term synaptic plasticity and is involved in the pathophysiology of schizophrenia. The functions and mechanisms of human ARC action are poorly understood and worthy of further investigation. To investigate the function of the ARC gene in vitro, we generated an ARC-knockout (KO) HEK293 cell line via CRISPR/Cas9-mediated gene editing and conducted RNA sequencing and label-free LC-MS/MS analysis to identify the differentially expressed genes and proteins in isogenic ARC-KO HEK293 cells. Furthermore, we used bioluminescence resonance energy transfer (BRET) assays to detect interactions between the ARC protein and differentially expressed proteins. Genetic deletion of ARC disturbed multiple genes involved in the extracellular matrix and synaptic membrane. Seven proteins (HSPA1A, ENO1, VCP, HMGCS1, ALDH1B1, FSCN1, and HINT2) were found to be differentially expressed between ARC-KO cells and ARC wild-type cells. BRET assay results showed that ARC interacted with PSD95 and HSPA1A. Overall, we found that ARC regulates the differential expression of genes involved in the extracellular matrix, synaptic membrane, and heat shock protein family. The transcriptomic and proteomic profiles of ARC-KO HEK293 cells presented here provide new evidence for the mechanisms underlying the effects of ARC and molecular pathways involved in schizophrenia pathophysiology.

Cyclophilin A Protects Cardiomyocytes against Hypoxia/Reoxygenation-Induced Apoptosis via the AKT/Nox2 Pathway.

Hypoxia/reoxygenation (H/R) accelerates the process of cardiomyocyte apoptosis during ischemia-reperfusion. Excessive reactive oxygen species (ROS) are a critical driver of oxidative stress injury. Cyclophilin A (CyPA) is a major ROS-induced factor in atherosclerosis. There is a positive feedback mechanism between CyPA and ROS, which enables the oxidative stress response to continue and expand. However, it is unclear whether this positive feedback mechanism exists in cardiomyocytes. Through western blotting and flow cytometric assays and TUNEL assay, we found that CyPA inhibited the apoptosis of H9c2 cardiomyocytes under H/R conditions. By dihydroethidium (DHE) staining and electron spin resonance (ESR) assays, we demonstrated that CyPA reduced ROS production and suppressed O2 - production dependent on reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. By western blotting, we showed that CyPA inhibited the expression of NADPH oxidase 2 (Nox2) protein by the AKT pathway. Through confocal microscopy assay, we found that CyPA reduced the expression of Nox2 membrane-bound subunits. The current study shows that a positive feedback mechanism does not exist in H9c2 cardiomyoblasts. CyPA protects H9c2 cardiomyoblasts against H/R-induced apoptosis via the AKT/Nox2 pathway. This could be a potential target for ischemia-reperfusion injury therapy.