Indications and outcomes of the MitraClip G4 device with controlled gripper actuation system.

The MitraClip G4 device has controlled gripper actuation (CGA) system, which allows the anterior and posterior grippers operate separately in transcatheter edge-to-edge repair (TEER). We investigated the indications and outcomes of the use of CGA system during TEER for significant mitral regurgitation (MR). We reviewed 158 patients undergoing TEER with MitraClip G4 from September 2020 to July 2023. The CGA indications were: (1) for grasping and (2) for leaflet insertion confirmation. Leaflet grasping was completed with CGA in 18 patients (11 and 7 patients for grasping and leaflet insertion confirmation, respectively). Patients with flail leaflets or coaptation gap more frequently required CGA, indicating more complex mitral valve anatomy. The procedural success and adverse event rates (death, leaflet tear and single leaflet device attachment) were not different between the CGA and non-CGA groups. In patients requiring CGA, single leaflet device attachment was observed in 1 patient and leaflet tear in 1 patient during follow-up. In these two cases, CGA was required for grasping, and the clip was moved over a large distance (6.5 and 12.4 mm, respectively). In patients who had undergone CGA for confirmation, no device-related adverse event or MR recurrence was noted. In patients with complex mitral valve anatomy, CGA may be a safe and effective method for confirming leaflet insertion. It should be noted that when using CGA for leaflet grasping, especially when the clip is moved significantly, attention should be paid to leaflet adverse events.

Association between preprocedural thromboembolic and bleeding events under oral anticoagulation therapy and mid-term outcomes after percutaneous left atrial appendage closure.

Currently, no consensus has been established on the most effective antithrombotic therapy to prevent thromboembolic and bleeding events in patients undergoing percutaneous left atrial appendage closure (LAAC) with preprocedural thromboembolic or bleeding events under oral anticoagulation (OAC) therapy. We retrospectively investigated the incidence of device-related thrombosis (DRT), thromboembolic events, and bleeding events in patients who underwent LAAC from September 2019 to October 2022. After categorizing patients into three groups based on preprocedural thromboembolic or bleeding events under OAC therapy, we compared the incidence of DRT and prognosis according to the postprocedural antithrombotic therapy. In patients who received the conventional antithrombotic therapy (OAC with and without single antiplatelet therapy for 45 days after LAAC and dual-antiplatelet therapy from 45 days to 6 months followed by single antiplatelet therapy), preprocedural thromboembolic events despite OAC were independently associated with DRT or postprocedural thromboembolic events at the 3 year follow-up (hazard ratio [HR] 4.55; 95% confidence interval [CI] 1.32-15.6; P = 0.016), whereas preprocedural bleeding events were independently associated with postprocedural bleeding events (HR 8.01, 95% CI 1.45-58.3; P = 0.036). Continuation of OAC for 12 months among patients who developed preprocedural thromboembolic events during OAC significantly decreased the incidence of DRT or postoperative thromboembolic events (P = 0.002) with no increase in the bleeding events (P = 0.522). Preprocedural thromboembolic and bleeding events can predict adverse events after LAAC with the conventional antiplatelet-based antithrombotic therapy. Patients who develop thromboembolic events under continuous OAC may benefit from continuous OAC for 1 year after LAAC.

Transition from WATCHMAN generation-2.5 device to WATCHMAN FLX device for percutaneous left atrial appendage closure: Incidence and predictors of device-related thrombosis and short- to mid-term outcomes.

BACKGROUND: Patients with nonvalvular atrial fibrillation (AF) not suitable for long-term anticoagulant therapy undergo percutaneous left atrial appendage closure (LAAC) using the WATCHMAN device. The safety and efficacy of WATCHMAN-FLX (WM-FLX) compared with WATCHMAN-2.5 (WM-2.5), particularly in Asian populations, is unknown. METHODS: We evaluated the background, procedure, and clinical outcomes of 199 patients who underwent LAAC between September 2019 and December 2022 and compared WM-2.5 (72 patients) with WM-FLX (127 patients). RESULTS: The mean age was 76 years, with 128 men, and 100 had nonparoxysmal AF (non-PAF). The mean CHA2DS2-VASc, and HAS-BLED were 5.1, and 3.2 points, respectively. WM-FLX group demonstrated a shorter procedure time than WM-2.5 group (50 vs. 42 min, p = 0.001). The WM-FLX group demonstrated no procedural-related acute cardiac tamponade, which was significantly low (5.6% vs. 0%, p = 0.02), and a significantly higher rate of complete seal at 45-day (63% vs. 80%, p = 0.04). WM-FLX group had a significantly higher cumulative 1-year incidence of device-related thrombosis (DRT) than WM-2.5 group (3.4% vs. 7.0%, Log-rank p = 0.01). Univariate analysis identified two DRT risk factors in the WM-FLX group: non-PAF (odds ratio [OR] 7.72; 95% confidence interval [CI] 1.20-48.7; p = 0.04), and 35-mm device (OR 5.13; 95% CI 1.31-19.8; p = 0.02). CONCLUSIONS: WM-FLX significantly improved the procedural quality and safety of LAAC. However, DRT remains an important issue even in the novel LAAC device, being a hazard for patients with high DRT risk, such as having non-PAF and using 35-mm devices.

Feasibility of contrast-free left atrial appendage closure with WATCHMAN FLX device for patients with chronic kidney disease.

Contrast media are generally necessary for transcatheter left atrial appendage closure (LAAC), however, it should be avoided in patients with chronic kidney disease (CKD). The objective of this study was to evaluate the safety and feasibility of contrast-free LAAC with WATCHMAN FLX device for patients with CKD. Among 141 patients undergoing LAAC using the WATCHMAN FLX between May 2021 and March 2023, we performed LAAC without contrast media in 10 patients. Procedural and follow-up results were evaluated. The device size was selected based on the transesophageal echocardiographic (TEE) measurements. The device shape was assessed by fluoroscopy, and the device position was adjusted by TEE images. The mean age was 78 ± 4.9 years, CHADS2 score was 3.2 ± 1.1, and the estimated glomerular filtration rate (eGFR) was 28 ± 12 mL/min/1.73m2. The procedure was completed without contrast media in ten patients. Partial recapture of the device was required in four patients, but the initially selected device was finally implanted in all patients. Mean procedure time was significantly shorter in the contrast-free LAAC than in the contrast-use LAAC (41.6 ± 14.1 min vs 30.3 ± 7.6 min, p = 0.01). Postprocedural eGFR did not change from baseline, and there were no adverse events during the hospital stay. Follow-up TEE or cardiac computed tomography performed within 3 months after the procedure revealed no device-related thrombus or peri-device leak > 3 mm, and oral antithrombotic therapy was discontinued in all patients. Our experience shows that contrast-free LAAC using the WATCHMAN FLX device was safe and feasible. Non-contrast LAAC is one of the therapeutic options for patients with severe CKD.

Validation study of new left atrial appendage closure device measurement by two-dimensional and three-dimensional transesophageal echocardiography.

BACKGROUND: In left atrial appendage closure using WATCHMAN FLX, accurate device measurement by transesophageal echocardiography (TEE) is important. We aimed to experimentally validate appropriate methods of device measurement with two-dimensional (2D) and three-dimensional (3D) TEE compared with actual size. METHODS: We prepared a full range of device sizes (20, 24, 27, 31, 35 mm), each with five different compression rates. Each device was measured by 2D and 3D TEE at depths of 2, 4, and 6 cm in vitro using inner, outer, and middle line methods. We compared the difference between the actual size by caliper and measurements at each compression rate and depth by the three methods in 2D and 3D TEE. RESULTS: A total of 450 patterns of measurements were analyzed. The differences using the middle line method were much less than those using the inner and outer line methods in 2D and 3D TEE (2D TEE: 0.45 ± 0.36 vs. 2.55 ± 0.99 vs. 2.59 ± 0.72 mm, p < 0.01; 3D TEE: 0.34 ± 0.27 vs. 2.38 ± 0.69 vs. 1.86 ± 0.77 mm, p < 0.01). Moreover, the differences in measurements by 3D TEE were more accurate than those of 2D TEE in the inner (2.47 ± 1.86 vs. 1.86 ± 0.77 mm, p < 0.01) and middle (0.58 ± 0.37 vs. 0.34 ± 0.27 mm, p < 0.01) line methods. CONCLUSIONS: Middle line method by 3D TEE is the most reliable approach for device measurement at left atrial appendage closure using WATCHMAN FLX device.

Simultaneous procedure transcatheter mitral valve repair and leadless pacemaker implantation under transesophageal echocardiography.

When we implant leadless pacemaker in patients with contrast agent allergy or poor renal function, the use of sufficient contrast agent is hesitant. Aided by imaging assessment (e.g., intracardiac echocardiography), the procedure may be feasible with a small amount of contrast medium or no contrast medium. In this case, leadless pacemaker implantation was performed at the same time as the transcatheter mitral valve repair, and leadless pacemaker implantation was successful with the use of a very small amount of contrast medium under transesophageal echocardiography guidance.

Long-Term Clinical Outcome After Alcohol Septal Ablation and Its Periprocedural Predictive Factors in Japan　- A Retrospective Observational Study.

BACKGROUND: Evidence is limited regarding long-term clinical outcomes after alcohol septal ablation (ASA) for patients with hypertrophic obstructive cardiomyopathy and its periprocedural predictive factors in Japan.Methods and Results: This retrospective observational study included 44 patients who underwent ASA between 1998 and 2022 in a single center. We evaluated the periprocedural change in variables and long-term clinical outcomes after the procedure. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure. The secondary outcome was all-cause death. Using multivariable Poisson regression with robust error variance, we predicted underlying periprocedural factors related to primary outcome development. ASA decreased the median pressure gradient at the left ventricular outflow tract from 88 to 33 mmHg and reduced moderate or severe mitral regurgitation (MR), present in 53% of patients before ASA, to 16%. Over a median 6-year follow-up, the cumulative incidence of the primary outcome at 5 and 10 years was 16.5% and 25.6%, respectively. After multivariable analysis, moderate or severe MR after ASA was significantly associated with the primary outcome (relative risk 8.78; 95% confidence interval 1.34-57.3; P=0.024). All-cause mortality after ASA was 15.1% and 28.9% at 5 and 10 years, respectively. CONCLUSIONS: This study presents long-term clinical outcomes after ASA in Japan. Moderate or severe MR after ASA was significantly associated with the composite of cardiovascular death or hospitalization for heart failure.

Efficacy of endoscopic samplings during initial biliary drainage for cases of pancreatic head cancer: United diagnostic yields of multiple pathological samplings.

BACKGROUND/OBJECTIVES: The diagnostic ability of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has been fully studied; however, the efficacy of other endoscopic samplings (OESs) is less clear. The aim of this study was to examine the diagnostic efficacies of OESs for pancreatic head cancer (PHC). METHODS: The diagnostic efficacies of endoscopic samplings were retrospectively analyzed in 448 PHC cases and 63 cases of mass-forming pancreatitis (MFP) during initial transpapillary biliary drainage. The OESs included duodenal biopsy (118 PHCs and 50 MFPs), biliary biopsy (218 and 51) with cytology (368 and 53), and pancreatic duct biopsy (23 and 13) with cytology (56 and 43). EUS-FNA was conducted in a different session (149 and 62). Factors associated with OES sensitivity were analyzed. The sensitivity of biliary biopsy was compared between 1.95 mm and 1.8 mm forceps. RESULTS: Cancer cells were confirmed in 87.9% of the EUS-FNA samplings and in 64.1% (268/418) obtained by combined OESs (average 1.7 OES types per case): 68.6% by duodenal biopsy, 59.6% by biliary biopsy, 32.6% by biliary cytology, 73.9% by pancreatic duct biopsy, and 33.9% by pancreatic duct cytology. No MFP cases revealed cancer by any sampling. OESs did not increase adverse events. Duodenal stenosis, serum bilirubin, tumor size, and pancreatic juice amounts were associated with OES sensitivity. Biliary biopsy had the same sensitivity with different forceps. CONCLUSION: EUS-FNA was the most diagnostic protocol; however, OESs can be safely applied during the initial biliary drainage to reduce the demand for EUS-FNA while providing good diagnostic yields.

Left atrial appendage size in patients with atrial fibrillation in Japan and the United States.

Left atrial appendage (LAA) evaluation is important to select the optimal LAA closure device for patients with atrial fibrillation (AF). The LAA characteristics of Japanese patients remain uninvestigated. We compared the LAA size and morphology between 212 Japanese AF patients before catheter ablation and 119 AF patients undergoing LAA closure in the United States (US). We measured the LAA ostial dimension and depth by transesophageal echocardiography in all patients and determined the LAA morphology types of Japanese patients by multidetector cardiac computed tomography and those of US patients by LAA angiography. The maximum LAA ostial dimension was significantly larger in Japanese patients than in US patients (22.6 ± 4.1 mm vs. 21.5 ± 3.5 mm, P = 0.02). Also, Japanese patients had larger maximum dimension and depth corrected by body surface area than US patients in both paroxysmal and nonparoxysmal AF groups. The angle showing the maximum dimension was 0° or 135° in approximately 75% of patients in both groups. The common LAA morphology types were "cauliflower" and "chicken wing" in Japanese patients and "cactus" and "windsock" in US patients. In this study, Japanese patients had a larger LAA size than US patients. Because the maximum LAA dimension was obtained at the same angles, the LAA measurement method for US patients can be applicable to Japanese patients.

Pathological and Molecular Aspects to Improve Endoscopic Ultrasonography-Guided Fine-Needle Aspiration From Solid Pancreatic Lesions.

Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has been applied to pancreatic lesions since the 1990s, and its use is now widespread. Improvements in endoscopic devices and sampling techniques have resulted in excellent diagnostic ability for solid pancreatic lesions. However, clinical improvements alone are not responsible for it; pathological aspects have also played important roles. Rapid on-site evaluation minimizes endoscopic procedures, although its value at improving the diagnostic ratio is still debated. Diagnostic efficacy differs by sample preparations (direct smear, cytospin, liquid-based cytology, cell block, and biopsy) and by staining methods (Papanicoloau, Diff-Quik, hematoxylin-eosin, and Giemsa). Several immunocytochemistry protocols aid in diagnosing epithelial components with cytological atypia and in differentiating various tumor types. One cytopathology diagnostic system is telecytology, which uses transmitted digital images and enables real-time diagnosis of EUS-FNA samples by expert cytologists at remote locations. However, EUS-FNA samples are useful for more than just diagnoses, as molecular analysis of these samples allows the identification of prognostic markers, such as genetic alterations in K-ras and EGFR. Expression of drug-metabolizing enzymes, human equilibrative nucleoside transporter 1, correlates with the response to gemcitabine-based chemotherapy. These pathology efforts have enhanced the diagnostic efficacy of EUS-FNA, thereby leading to better outcomes for patients with pancreatic diseases.

[Cotton-Dam Wash Cytology:A Technique for Diagnosis and Prevention of Dissemination during Resection of Metastatic Brain Tumors].

The management of brain metastases has been important in neurosurgical oncology. Resection of a brain metastasis carries an increased risk of leptomeningeal dissemination than other treatment modalities such as irradiation or pharmacotherapy. We have utilized intraoperative wash cytology of cotton patties covering the brain surface. The cytology information contributes to making a decision of postoperative whole brain radiation. We named the method as "cotton dam", that serves as a check and catch of neoplastic cells on the brain surface during resection surgery.

Size-based isolation of circulating tumor cells in lung cancer patients using a microcavity array system.

BACKGROUND: Epithelial cell adhesion molecule (EpCAM)-based enumeration of circulating tumor cells (CTC) has prognostic value in patients with solid tumors, such as advanced breast, colon, and prostate cancer. However, poor sensitivity has been reported for non-small cell lung cancer (NSCLC). To address this problem, we developed a microcavity array (MCA) system integrated with a miniaturized device for CTC isolation without relying on EpCAM expression. Here, we report the results of a clinical study on CTCs of advanced lung cancer patients in which we compared the MCA system with the CellSearch system, which employs the conventional EpCAM-based method. METHODS: Paired peripheral blood samples were collected from 43 metastatic lung cancer patients to enumerate CTCs using the CellSearch system according to the manufacturer's protocol and the MCA system by immunolabeling and cytomorphological analysis. The presence of CTCs was assessed blindly and independently by both systems. RESULTS: CTCs were detected in 17 of 22 NSCLC patients using the MCA system versus 7 of 22 patients using the CellSearch system. On the other hand, CTCs were detected in 20 of 21 small cell lung cancer (SCLC) patients using the MCA system versus 12 of 21 patients using the CellSearch system. Significantly more CTCs in NSCLC patients were detected by the MCA system (median 13, range 0-291 cells/7.5 mL) than by the CellSearch system (median 0, range 0-37 cells/7.5 ml) demonstrating statistical superiority (p = 0.0015). Statistical significance was not reached in SCLC though the trend favoring the MCA system over the CellSearch system was observed (p = 0.2888). The MCA system also isolated CTC clusters from patients who had been identified as CTC negative using the CellSearch system. CONCLUSIONS: The MCA system has a potential to isolate significantly more CTCs and CTC clusters in advanced lung cancer patients compared to the CellSearch system.