Comparative Data of Procedural and Midterm Outcomes in Patients Who Underwent Percutaneous Left Atrial Appendage Closure Between the WATCHMAN FLX and WATCHMAN 2.5 Devices　- Insight From the OCEAN-LAAC Registry.

BACKGROUND: Limited data are available regarding clinical outcomes after percutaneous left atrial appendage closure using WATCHMAN FLX (WM-FLX) and WATCHMAN-2.5 (WM2.5) devices in Asian patients.Methods and Results: Data of 1,464 consecutive patients (WM-FLX, n=909; WM2.5, n=555) were extracted from a Japanese multicenter registry, and clinical data were compared between the 2 groups. No in-hospital deaths, periprocedural stroke, or device embolization occurred. Procedural success was significantly higher in the WM-FLX than WM2.5 group (95.8% vs. 91.9%; P=0.002) owing to the lower incidence of periprocedural pericardial effusion (0.55% vs. 1.8%; P=0.021). No significant differences in all-cause death, postprocedural stroke, and device-related thrombus were observed between the 2 groups. However, the cumulative bleeding rate at 1 year was substantially lower in the WM-FLX group (7.8% vs. 16.4%; P<0.001). Landmark analysis of bleeding events highlighted lower bleeding rates in the WM-FLX than WM2.5 group within the first 6 months (6.4% vs. 14.8%; P<0.001), with comparable bleeding rates over the 6- to 12-month period (1.5% vs. 3.2%, respectively; P=0.065). CONCLUSIONS: This study demonstrated higher early safety and lower 1-year bleeding rates in the WM-FLX than WM2.5 group. The lower bleeding events with WM-FLX are likely due to multiple factors other than purely difference in devices, such as postprocedural drug regimen.

Cardiac Damage in Degenerative Mitral Regurgitation Treated With Transcatheter Mitral Edge-to-Edge Repair.

BACKGROUND: The extent of cardiac damage and its association with clinical outcomes in patients undergoing transcatheter edge-to-edge repair (TEER) for degenerative mitral regurgitation remains unclear. This study was aimed to investigate cardiac damage in patients with degenerative mitral regurgitation treated with TEER and its association with outcomes. METHODS: We analyzed patients with degenerative mitral regurgitation treated with TEER in the Optimized Catheter Valvular Intervention-Mitral registry, which is a prospective, multicenter observational data collection in Japan. The study subjects were classified according to the extent of cardiac damage at baseline: no extravalvular cardiac damage (stage 0), mild left ventricular or left atrial damage (stage 1), moderate left ventricular or left atrial damage (stage 2), or right heart damage (stage 3). Two-year mortality after TEER was compared using Kaplan-Meier analysis. RESULTS: Out of 579 study participants, 8 (1.4%) were classified as stage 0, 76 (13.1%) as stage 1, 319 (55.1%) as stage 2, and 176 (30.4%) as stage 3. Two-year survival was 100% in stage 0, 89.5% in stage 1, 78.9% in stage 2, and 75.3% in stage 3 (P=0.013). Compared with stage 0 to 1, stage 2 (hazard ratio, 3.34 [95% CI, 1.03-10.81]; P=0.044) and stage 3 (hazard ratio, 4.51 [95% CI, 1.37-14.85]; P=0.013) were associated with increased risk of 2-year mortality after TEER. Significant reductions in heart failure rehospitalization rate and New York Heart Association functional scale were observed following TEER (both, P<0.001), irrespective of the stage of cardiac damage. CONCLUSIONS: Advanced cardiac damage is associated with an increased risk of mortality in patients undergoing TEER for degenerative mitral regurgitation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: UMIN000023653.

Transcatheter aortic valve replacement in patients with severe aortic stenosis reduced the frequency of intradialytic hypotension.

Intradialytic hypotension (IDH) is a common complication during hemodialysis that increases cardiovascular morbidity and mortality. Aortic stenosis (AS) is a cause of IDH. Transcatheter aortic valve replacement (TAVR) has become an established treatment for patients with severe AS. However, whether TAVR reduce the frequency of IDH has not been investigated. This study aims to verify the efficacy of TAVR for reduction of the frequency of IDH. Consecutive hemodialysis patients who underwent TAVR at Sendai Kosei Hospital from February 2021 to November 2021 with available records 1 month before and 3 months after TAVR were included in the study. IDH was defined as a decrease in systolic blood pressure by 20 mmHg or a decrease in the mean blood pressure by 10 mmHg associated with hypotensive symptoms or requiring intervention. Patients with ≥ 3 episodes of IDH in ten hemodialysis sessions comprised the IDH group. Overall, 18/41 (43.9%) patients were classified into the IDH group. In ten hemodialysis sessions, IDH events were observed 2.1, 4.3, and 0.4 times in the overall cohort, IDH group, and non-IDH group, respectively. After TAVR, the incidence of IDH decreased from 43.2 to 10.3% (p < 0.0001) and IDH improved significantly in 15 patients in the IDH group. The result suggested that severe AS was the major cause of IDH in this cohort, and TAVR may be an effective treatment option for reduction of the frequency of IDH in patients with severe AS.

Predictive Factors of Cardiac Mortality Following TEER in Patients with Secondary Mitral Regurgitation.

Background: Transcatheter edge-to-edge mitral valve repair (TEER) has emerged as a viable approach to addressing substantial secondary mitral regurgitation. In the contemporary landscape where ultimate heart failure-specific therapies, such as cardiac replacement modalities, are available, prognosticating a high-risk cohort susceptible to early cardiac mortality post-TEER is pivotal for formulating an effective therapeutic regimen. Methods: Our study encompassed individuals with secondary mitral regurgitation and chronic heart failure enlisted in the multi-center (Optimized CathEter vAlvular iNtervention (OCEAN)-Mitral registry. We conducted an assessment of baseline variables associated with cardiac death within one year following TEER. Results: Amongst the 1517 patients (median age: 78 years, 899 males), 101 experienced cardiac mortality during the 1-year observation period after undergoing TEER. Notably, a history of heart failure-related admissions within the preceding year, utilization of intravenous inotropes, and elevated plasma B-type natriuretic peptide levels emerged as independent prognosticators for the primary outcome (p < 0.05 for all). Subsequently, we devised a novel risk-scoring system encompassing these variables, which significantly stratified the cumulative incidence of the 1-year primary outcome (16%, 8%, and 4%, p < 0.001). Conclusions: Our study culminated in the development of a new risk-scoring system aimed at predicting 1-year cardiac mortality post-TEER.

Initial results of transcatheter modification of left atrial appendage by obliteration with device in patients with nonvalvular atrial fibrillation: Real-world data from the TERMINATOR registry.

BACKGROUND: Percutaneous left atrial appendage closure (LAAC) has increased for those who need alternative to long-term anticoagulation with non-valvular atrial fibrillation (NVAF). METHODS AND RESULTS: From September 2019, after initiating WATCHMAN (Boston Scientific, Maple Grove, MN, USA) device implantation, we established Transcatheter Modification of Left Atrial Appendage by Obliteration with Device in Patients from the NVAF (TERMINATOR) registry. Utilizing 729 patients' data until January 2022, we analyzed percutaneous LAAC data regarding this real-world multicenter prospective registry. A total of 729 patients were enrolled. Average age was 74.9 years and 28.5 % were female. Paroxysmal AF was 37.9 % with average CHADS2 3.2, CHA2DS2-VASc 4.7, and HAS-BLED score of 3.4. WATCHMAN implantation was successful in 99.0 %. All-cause deaths were 3.2 %, and 1.2 % cardiovascular or unexplained deaths occurred during follow-up [median 222, interquartile range (IQR: 93-464) days]. Stroke occurred in 2.2 %, and the composite endpoint which included cardiovascular or unexplained death, stroke, and systemic embolism were counted as 3.4 % [median 221, (IQR: 93-464) days]. Major bleeding defined as BARC type 3 or 5 was seen in 3.7 %, and there was 8.6 % of all bleeding events in total [median 219, (IQR: 93-464) days]. CONCLUSIONS: These preliminary data demonstrated percutaneous LAAC with WATCHMAN device might have a potential to reduce stroke and bleeding events for patients with NVAF. Further investigation is mandatory to confirm the long-term results of this strategy using this transcatheter local therapy instead of life-long systemic anticoagulation.

One-Year Outcomes and Their Relationship to Residual Mitral Regurgitation After Transcatheter Edge-to-Edge Repair With MitraClip Device: Insights From the OCEAN-Mitral Registry.

Background Limited data are available about clinical outcomes and residual mitral regurgitation (MR) after transcatheter edge-to-edge repair in the large Asian-Pacific cohort. Methods and Results From the Optimized Catheter Valvular Intervention (OCEAN-Mitral) registry, a total of 2150 patients (primary cause of 34.6%) undergoing transcatheter edge-to-edge repair were analyzed and classified into 3 groups according to the residual MR severity at discharge: MR 0+/1+, 2+, and 3+/4+. The mortality and heart failure hospitalization rates at 1 year were 12.3% and 15.0%, respectively. Both MR and symptomatic improvement were sustained at 1 year with MR ≤2+ in 94.1% of patients and New York Heart Association functional class I/II in 95.0% of patients. Compared with residual MR 0+/1+ (20.4%) at discharge, both residual MR 2+ (30.2%; P < 0.001) and 3+/4+ (32.4%; P = 0.007) were associated with the higher incidence of death or heart failure hospitalization (adjusted hazard ratio [HR], 1.59; P < 0.001, and adjusted HR, 1.73; P = 0.008). New York Heart Association class III/IV at 1 year was more common in the MR 3+/4+ group (20.0%) than in the MR 0+/1+ (4.6%; P < 0.001) and MR 2+ (6.4%; P < 0.001) groups, and the proportion of New York Heart Association class I is significantly higher in the MR 1+ group (57.8%) than in the MR 2+ group (48.3%; P = 0.02). Conclusions The OCEAN-Mitral registry demonstrated favorable clinical outcomes and sustained MR reduction at 1 year in patients undergoing transcatheter edge-to-edge repair. Both residual MR 2+ and 3+/4+ after transcatheter edge-to-edge repair at discharge were associated with worse clinical outcomes compared with residual MR 0+/1+. Registration Information https://upload.umin.ac.jp. Identifier: UMIN000023653.

Initial Japanese Multicenter Experience and Age-Related Outcomes Following Left Atrial Appendage Closure: The OCEAN-LAAC Registry.

Background: Limited data are available describing left atrial appendage closure (LAAC) and age-related outcomes in Asians. Objectives: This study summarizes the initial experience with LAAC in Japan and determines age-related clinical outcomes in patients with nonvalvular atrial fibrillation undergoing percutaneous LAAC. Methods: In an ongoing, prospective, investigator-initiated, multicenter, observational registry of patients undergoing LAAC in Japan, we analyzed short-term clinical outcomes in patients with nonvalvular atrial fibrillation who underwent LAAC. Patients were classified into younger, middle-aged, and elderly groups (≤70, 70 to 80, and >80 years of age, respectively) to determine age-related outcomes. Results: Patients (n = 548; mean age, 76.4 ± 8.1 years; male, 70.3%) who underwent LAAC at 19 Japanese centers between September 2019 and June 2021 were enrolled in the study, including 104, 271, and 173 patients in the younger, middle-aged, and elderly groups, respectively. Participants had a high-risk of bleeding and thromboembolism with a mean CHADS2 score of 3.1 ± 1.3, a mean CHA2DS2-VASc score of 4.7 ± 1.5, and a mean HAS-BLED score of 3.2 ± 1.0. Device success rates were 96.5% and anticoagulants discontinuation at the 45-day follow-up was achieved in 89.9%. In-hospital outcomes were not significantly different, but major bleeding events during the 45-day follow-up were significantly higher in the elderly group compared to the other groups (younger vs middle-aged vs elderly, 1.0% vs 3.7% vs 6.9%, respectively; P = 0.047) despite the same postoperative drug regimens. Conclusions: The initial Japanese experience with LAAC demonstrated safety and efficacy; however, perioperative bleeding events were more common in the elderly and postoperative drug regimens must be tailored (OCEAN-LAAC [Optimized Catheter Valvular Intervention-Left Atrial Appendage Closure] registry; UMIN000038498).

Detection of left coronary ostial obstruction during transcatheter aortic valve replacement by coronary flow velocity measurement in the left main trunk by intraoperative transesophageal echocardiography.

BACKGROUND: Coronary obstruction is a rare but catastrophic complication of transcatheter aortic valve replacement (TAVR) and occurs mostly at the left coronary artery (LCA) ostium. However, some patients do not show any clinical findings, and thus, its detection is sometimes difficult. The peak diastolic flow velocity in left main coronary artery (LM) was reportedly increased in significant stenosis lesions. We evaluated the effectiveness of measuring blood flow velocities in LM by transesophageal echocardiography (TEE) for the detection of LCA ostial obstruction during a TAVR procedure. METHODS: A total of 1105 consecutive patients who underwent TAVR in Sendai Kousei Hospital between September 2014 and December 2020 were enrolled. The LM blood flow velocity was measured at pre- and post-valve implantation. RESULTS: Among the 1105 patients, 9 had LCA ostial obstruction. The peak LM blood flow velocity at post-TAVR [0.90 (0.39-1.15) vs. 0.37 (0.28-0.50) m/s; p = 0.0046) was significantly higher in 9 patients who had LCA ostial obstruction, compared with the remaining 1096 patients who had not (controls), although no significant difference was observed before the TAVR procedures between the two groups. The post- to pre-TAVR LM flow velocity ratio [2.26 (1.31-3.42) vs. 1.06 (0.82-1.36); p = 0.0030] was also significantly higher in patients with LCA obstruction, compared to the controls. Furthermore, the post- to pre-TAVR LM blood flow velocity ratio was >2.0 in all six hemodynamically stable patients with LCA obstruction, whereas <2.0 in all three patients with LCA obstruction who showed hemodynamic collapse at post-TAVR procedure. CONCLUSION: Coronary blood flow velocity in LM significantly increased in hemodynamically stable LCA obstruction patients. The intraprocedural TEE measurement of the LM flow velocities would be potentially useful to detect asymptomatic and hemodynamically stable LCA ostial obstruction.

Usefulness of 3-Dimensional Reconstruction Images of Coronary Computed Tomography Angiogram in Percutaneous Coronary Intervention After Bentall Operation.

Anastomotic complications of the coronary arteries were observed in approximately 5% of patients undergoing Bentall-type surgery. Given the high surgical risk of reoperation, percutaneous coronary intervention could be a treatment for anastomotic complications but is challenging because of the complicated anatomy after Bentall-type surgery. Here, a 70-year-old man underwent a Bentall operation during which the left main coronary artery was accidentally injured. Therefore, coronary artery bypass using a saphenous vein graft was performed. The saphenous vein graft was anastomosed from the right side of the aortic graft to the left main coronary artery. Three years later, the patient presented with an anterior non-ST-segment elevation myocardial infarction. Because his unusual anatomy, the saphenous vein graft could not be cannulated with diagnostic catheters, even after perusing the surgical record of the Bentall surgery. Subsequently, coronary computed tomography angiography was performed. Three-dimensional reconstructed images visualized the positional relationship between the saphenous vein graft and anatomical landmarks, such as the implanted surgical valve prosthesis. The angiogram angle was adjusted using these landmarks and projection angles estimated by the images. Then, the ASAHI Hyperion Judkins right 4 catheter could be easily inserted, and percutaneous coronary intervention was successfully performed. Three-dimensional reconstruction images were useful for performing percutaneous coronary intervention by aiding in the identification of the anatomic location of the saphenous vein graft and the positional relationship between the saphenous vein graft and anatomic landmarks. In patients with unusual anatomy, as in this case, coronary computed tomography angiography should be strongly considered.

Fine-tuned cholesterol solubilizer, mono-6-O-α-D-maltosyl-γ-cyclodextrin, ameliorates experimental Niemann-Pick disease type C without hearing loss.

Niemann-Pick disease type C (NPC) is a fatal disorder with abnormal intracellular cholesterol trafficking resulting in neurodegeneration and hepatosplenomegaly. A cyclic heptasaccharide with different degrees of substitution of 2-hydroxypropyl groups, 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD), acts as a strong cholesterol solubilizer and is under investigation for treating this disease in clinical trials, but its physicochemical properties and ototoxicity remain a concern. Here, we evaluated the potential of mono-6-O-α-maltosyl-γ-CD (G2-γ-CD), a single-maltose-branched cyclic octasaccharide with a larger cavity than HP-ß-CD, for treating NPC. We identified that G2-γ-CD ameliorated NPC manifestations in model mice and showed lower ototoxicity in mice than HP-ß-CD. To investigate the molecular mechanisms of action behind the differential ototoxicity of these CDs, we performed cholesterol solubility analysis, proton nuclear magnetic resonance spectroscopy, and molecular modeling, and estimated that the cholesterol inclusion mode of G2-γ-CD maintained solely the 1:1 inclusion complex, whereas that of HP-ß-CD shifted to the highly-soluble 2:1 complex at higher concentrations. We predicted the associations of these differential complexations of CDs with cholesterol with the profile of disease attenuation and of the auditory cell toxicity using specific cell models. We proposed that G2-γ-CD can serve as a fine-tuned cholesterol solubilizer for treating NPC, being highly biocompatible and physicochemically suitable for clinical application.

Delivery balloon volume positively correlates with the diameter and effective orifice area of implanted SAPIEN 3.

BACKGROUND: In transcatheter aortic valve replacement (TAVR) using SAPIEN 3 (S3) (Edwards Lifesciences, Irvine, CA, USA), some clinicians decrease or increase the delivery balloon volume (VOL) when deploying S3 or conducting post-dilatation. However, the effects of controlling VOL on transcatheter heart valve diameter (THVD) and valve function remain unclear. We assessed associations among VOL, THVD, and effective orifice area (EOA) of S3. METHODS: We enrolled patients undergoing TAVR using 23- and 26-mm S3 in Sendai Kousei Hospital between 2017 and 2019. VOL was controlled based on preprocedural computed tomography and intraprocedural transesophageal echocardiography (TEE). THVD were defined as the diameters of transcatheter heart valve at mid-level measured by TEE. RESULTS: In enrolled 332 patients (23-mm, n = 188; 26-mm, n = 144), one (0.3%) and two (0.6%) developed annulus rupture and moderate/severe paravalvular leak, respectively. VOL at deployment was positively correlated with THVD on deployment (23-mm, r = 0.44, p < 0.001; 26-mm, r = 0.57, p < 0.001) and EOA (23-mm, r = 0.23, p = 0.0019; 26-mm, r = 0.22, p = 0.0094). In multiple regression analyses, VOL and post-dilatation were significant determinants of THVD, although aortic annulus area, calcium volume, and pre-dilatation were not. The areas under the receiver operating characteristic curve that were used to evaluate the accuracy of the index obtained by dividing THVD by body surface area (indexed THVD) to predict patient-prosthesis mismatch (PPM) were 0.744 and 0.811 in the 23- and 26-mm cohorts, respectively. A cut-off indexed THVD of ≤11.5 and 12.1 mm/m2 well predicted PPM (23-mm, odds ratio, 5.20; 95% confidence interval, 1.33-20.3; 26-mm, odds ratio 14.1, 95% confidence interval 2.40-81.0). CONCLUSION: VOL was positively correlated with THVD and EOA. Smaller indexed THVD was associated with a higher incidence of PPM. Controlling VOL under on-site THVD evaluation may be useful in reducing the PPM incidence.

En face view of the transcatheter heart valve from deep right-anterior-oblique cranial position for coronary access after transcatheter aortic valve implantation: a case series.

BACKGROUND: Coronary access after transcatheter aortic valve implantation (TAVI) is challenging due to the changes in aortic geometry. The perpendicular (long-axis) view of the transcatheter heart valve (THV) is usually used as the primary fluoroscopic angle. However, it does not always provide sufficient information on the rotational axis needed for selective coronary ostia engagement. The en face (short-axis) view from the deep right-anterior-oblique cranial position gives us additional information about three-dimensional spatial relationship of the THV and coronary ostia. CASE SUMMARY: We present three cases of coronary access after TAVI. We were successful in the use of the 'en face' view along with the perpendicular view in these cases. DISCUSSION: The use of the en face view complements that of the perpendicular long-axis view since it allows the understanding of the three-dimensional spatial relationship of the THV and the coronary ostia during fluoroscopy and control of catheter manipulation in two directions (up/down for perpendicular and clockwise/counterclockwise for en face view). We believe that the en face view helps improve the technical success of coronary access after TAVI.

Surgical Strategy and Clinical Outcome in Patients with Bronchial Carcinoids.

Carcinoids are malignant neuroendocrine neoplasms showing good long-term survival after oncologic therapy. The study evaluated the influence of operative strategies and individual decision-making on the outcome and long-term survival in 222 patients with bronchial carcinoids. The patients underwent preoperative pulmonary function tests and bronchoscopy to facilitate surgical decision-making. A hundred and twelve tumors were detected endoscopically, including 32 in the main and lobar bronchi. We performed 5 isolated bronchus resections, 4 segmentectomies, 15 wedge resections, 10 pneumonectomies, 19 sleeve resections, 26 bilobectomies, 138 lobectomies, and 2 chest wall resections. Three patients were technically inoperable. Systematic mediastinal lymphadenectomy was routinely performed although most patients' computer tomography scans showed N0. A hundred and sixty-two patients had typical (155 N0, 7 N+) and 60 patients had atypical carcinoids (39 N0, 21 N+). There was no intraoperative mortality. The hospital mortality was below 2%. Overall, 1-, 5-, and 10-year survival rates were 99%, 94%, and 89%, respectively, in typical carcinoids. Atypical carcinoids show similar 1- and 5-year survival rates, but the 10-year survival rate was below 70%, decreasing in higher N-stages. The N-stage was the most important survival factor. In conclusion, bronchial carcinoids should be surgically treated the way lung cancer is. Anatomic resection and systematic lymphadenectomy are the treatments of choice. The availability of bronchoplastic techniques and preoperative assessment is essential for individual decision-making, focusing predominantly on postoperative quality of life.

Focal Intimal Disruption Size at Multidetector CT and Disease Progression in Type B Aortic Intramural Hematoma.

Background Recent imaging techniques show that patients with aortic intramural hematoma (IMH) have various sizes of focal intimal disruptions (FIDs) that may affect clinical outcomes. Purpose To evaluate the relationship between size of FIDs detected at multidetector CT and disease progression in patients with type B IMH. Materials and Methods This retrospective study analyzed consecutive patients with type B IMH who underwent multidetector CT at admission within 24 hours after symptom onset from January 2011 to March 2017. FID was defined as a focal contrast material-filled pouch projecting outside of the aorta lumen with a communicating orifice greater than 3 mm. Large FID was defined as an FID of at least 10 mm in length and width and at least 5 mm in depth. Aorta-related events were defined as a composite of aortic rupture, surgical or endovascular aortic repair, progressive aortic enlargement, and development of aortic dissection. Results Seventy-six patients (mean age, 72 years ± 11 [standard deviation]; 54 men) were evaluated. Fifty patients (66%; 50 of 76) had 91 FIDs. Twenty-eight patients had large FIDs and 22 patients had small FIDs. Aorta-related events occurred in 15 of 28 patients with large FIDs, two of 22 patients with small FIDs, and four of 26 patients with no FID. Patients with large FIDs showed lower aorta-related event-free survival rates than did patients with small FIDs or no FID (small FIDS, 63% ± 10 vs 90% ± 7 at 3 years, respectively [P = .001]; and no FIDS, 63% ± 10 vs 84% ± 7 at 3 years, respectively [P = .005]). Multivariable analysis showed that a maximum aortic diameter of at least 40 mm (hazard ratio, 4.8; 95% CI: 1.8, 12.6; P = .001) and large FID (hazard ratio, 3.2; 95% CI: 1.1, 8.9; P = .03) were the independent predictors of aorta-related events. Conclusion A large portion of patients with B-intramural hematoma (IMH) had focal intimal disruption (FID) detected at CT at admission. Large FIDs were associated with disease progression of IMH. © RSNA, 2021 See also the editorial by Raptis and Braverman in this issue. Online supplemental material is available for this article.