Anesthetic Management of Thoracoscopic Pulmonary Cystectomy in a Patient With Fontan Circulation and Disturbed Lung Inflation During Leakage Testing: A Case Report.

Congenital heart disease may require multiple cardiac surgeries during childhood. Subsequent non-cardiac surgeries increase the perioperative bleeding and hypoxia because of changes in circulation. An 18-year-old male patient with a history of multiple cardiac interventions, including Fontan surgery, underwent a thoracoscopic right lung suture and coverage for recurrent right spontaneous pneumothorax under general anesthesia with one lung ventilation (OLV). The superior dorsal and inferior lobes, which were inflatable before surgery, failed to expand during leakage testing. The trachea's condition was examined using a flexible bronchoscope, and no obstructions were found. A thoracic drainage catheter was inserted, and the lower lobe was dilated from outside the body using negative pressure control in a sealed environment. In the patient with previously treated Fontan circulation, both lungs were expanded by inserting a thoracic catheter during thoracoscopic right lung suture and maintaining negative external pressure.

Initial Results of Intra-Annular Self-Expandable Valves: Insights From the OCEAN-TAVI Registry.

Background: Navitor, an intra-annular self-expanding heart valve (IA-SEV), is the third transcatheter heart valve introduced in Japan (in April 2022) as the next generation of the Portico valve ahead of other Asian countries. Objectives: The purpose of this study was to assess the patient-prosthesis mismatch (PPM) after IA-SEV implantation in Asian patients. Methods: All clinical data were collected from the database of an ongoing prospective Japanese multicenter registry (OCEAN-TAVI [Optimised Catheter Valvular Intervention transcatheter aortic valve implantation]). The primary endpoint was the rate of no PPM; the secondary endpoint included the rate of in-hospital mortality and hemodynamics after IA-SEV implantation. Results: A total of 463 patients (median age 86; 69.7% female) were enrolled in the registry. The percentages of implanted valves sized 23 mm, 25 mm, 27 mm, and 29 mm were 26.1% (n = 121), 41.7% (n = 193), 22.9% (n = 106), and 9.3% (n = 43), respectively. The primary endpoint of no PPM was achieved in 91.7% of the entire cohort and in 87.3%, 94.2%, 91.4%, and 93.0% of each valve size. The rate of in-hospital mortality was 1.9%. Postprocedural mean pressure gradient was 8.3 ± 4.3 mm Hg. The overall rate of pacemaker implantation was 9.7%; the incidence of pacemaker rate tended to be reduced when dividing the first and second half of operator experiences (13.0% vs. 8.0%; P = 0.08). Conclusions: The initial results for the IA-SEV were excellent regarding hemodynamics and reduction of paravalvular leakage regardless of valve size. The IA-SEV is a useful transcatheter heart valve, especially for Asian patients with a high prevalence of small annulus.

Impaired Gastrointestinal Motility and Worsening Heart Failure in Patients Receiving Trans-Catheter Aortic Valve Replacement.

Background: Impaired gastric motility in the form of constipation may often occur in elderly patients with chronic heart failure. Candidates for trans-catheter aortic replacement (TAVR) are of old age and have multiple comorbidities, probably including constipation. However, the clinical implication of a history of constipation in patients receiving TAVR remains unknown. Methods: Patients who underwent TAVR at our large academic center between 2015 and 2022 were eligible. The prognostic impact of the prescribed laxative type and number, which was assumed as the severity of constipation, on the incidence of death or heart failure readmission two years after index discharge was investigated. Results: A total of 344 patients were included. Median age was 85 years, and 99 patients were men. Patients with any laxatives (N = 166) had higher systolic blood pressure, higher plasma B-type natriuretic peptide levels, and a lower prescription rate of renin-angiotensin system inhibitors at the time of index discharge after TAVR (p < 0.05 for all). The number of laxative types was independently associated with the composite primary outcome with an adjusted hazard ratio of 1.83 (95% confidence interval 1.27-2.63, p = 0.001) with a cutoff of one type of laxative used, which significantly stratified the 2-year cumulative incidence of the primary outcome (18% versus 7%, p = 0.001). Conclusions: The presence of constipation was associated with worse clinical outcomes following TAVR. The prognostic impact of an aggressive intervention for constipation remains a future concern in this cohort.

Introduction of novel intravascular ultrasound preceding with angled guiding catheter (I-PAD) technique to treat chronic total occlusions in peripheral artery disease.

BACKGROUND: The optimal endovascular treatment (EVT) for chronic total occlusion (CTO) lesions in patients with peripheral artery disease (PAD) has remained unestablished. We encountered a patient with PAD in whom CTO was successfully treated using a novel technique that involved intravascular ultrasound (IVUS) and angled guiding catheter: IVUS Preceding with Angled guiDing catheter (I-PAD) technique. CASE PRESENTATION: A 74-year-old male presented with intermittent claudication attributed to CTO of the right external iliac artery. EVT was performed via the right common femoral artery. We retrogradely advanced the I-PAD system (i.e. partially extending the IVUS transducer portion from the tip of the angled guiding catheter) in the CTO lesion under the real-time guidance of IVUS imaging. We successfully traversed the CTO lesion without the use of a guidewire in approximately three minutes. The procedure concluded successfully without any procedure-related complications, following optimal stenting. CONCLUSIONS: The I-PAD might be an effective technique to accurately, quickly, and safely pass through CTO lesions.

Robustanic acid as a glutaminase and Na+, K+-ATPase inhibitor from leaves of Eucalyptus globulus.

This study was to compare glutaminase and Na+, K+-ATPase inhibitory activities of 20 herbal extracts and investigate the isolation, structural elucidation and those inhibitory activities of three triterpenes from the selected extract of Eucalyptus globulus Labill. Three triterpenes, ursolic acid (1), robustanic acid (2) and ursolic acid lactone (3), were identified by analyzing their NMR and MS spectral data and comparison of these with reported data. The IC50 values of 1-3 and the control compound against glutaminase, 6-diazo-5-oxo-l-norleucine (DON), were 443 µM, 334 µM, 963 µM and 134 µM, respectively. The IC50 values of 1, 2 and the control compound against Na+, K+-ATPase and ouabain, were 180 µM, 56 µM and 0.5 µM, respectively. Compounds 1 and 2 may serve as potential lead compounds for the prevention and treatment of neurodegenerative and lifestyle-related diseases by targeting glutaminase and Na+, K+-ATPase. This is the first report on glutaminase and Na+, K+-ATPase inhibitory activities of 2.

Prognostic impact of increase in left atrial volume following left atrial appendage closure: Insights from the OCEAN-LAAC registry.

Background: Percutaneous left atrial appendage closure (LAAC) is an effective therapy to prevent thromboembolic events among patients with atrial fibrillation (AF). However, since the left atrial appendage (LAA) contributes to left atrial volume and serves as a buffer for increasing left atrial pressure, this procedure may impair left atrium (LA) compliance, enlarge LA, and deteriorate diastolic function. In this study, we sought to investigate the change in left atrial volume index (LAVI) following LAAC and its effect on prognosis. Methods and Results: We analyzed 225 patients from the OCEAN-LAAC registry, an ongoing, multicenter Japanese study. Comparing LAVI measurements at baseline and 6 months after LAAC, no significant increase was observed (55.0 [44.0, 70.0] ml/m2 vs. 55.0 [42.0, 75.6] ml/m2; P = 0.31). However, some patients underwent LAVI increase. Particularly, a smaller LAVI (odds ratio [OR]: 0.98 [95 % confidence interval (CI): 0.97-0.996]) and elevated tricuspid regurgitation pressure (TRPG) at baseline (OR: 1.04 [95 % CI: 1.00 - 1.08]) were significantly related to the increase in LAVI at 6-month follow-up. In addition, a 5 ml/m2 increase in LAVI was significantly associated with subsequent heart failure hospitalization (HFH) (hazard ratio: 3.37 [95 % CI: 1.18-9.65]). This association, however, was not observed in patients with lower baseline LAVI (≤55 ml/m2) but was only seen in those with a baseline LAVI over 55 ml/m2. Conclusion: Our study demonstrated an increase in LAVI after LAAC was related to smaller LAVI or elevated TRPG at baseline. The LAVI increase was significantly associated with subsequent HFH.

Contribution of Gamma-Aminobutyric Amino Acid and Free Amino Acids to Low-Salt Whole-Wheat Bread through the Addition of Spice Extracts-An Approach Based on Taste Quality.

Given the link between excessive salt consumption and hypertension, reducing salt levels in bread, an important staple food in Japan, is essential. γ-Aminobutyric acid (GABA) has a salty taste-enhancing effect in vivo, and its production is influenced by the type of spice extract in vitro. However, the effects of spices on GABA levels, total free amino acid composition, and taste quality in whole-wheat bread remain unclear. Therefore, this study aimed to investigate whether the addition of spice extracts, which do not affect bread flavor and taste, can increase the GABA level in low-salt whole-wheat bread and whether free amino acid content affects the taste quality of bread using an automatic home bread maker. Through free amino acid composition analysis and sensory testing, we evaluated the influence of six spice extracts on the composition of free amino acids, including GABA, in whole-wheat bread. We found that cumin and anise extracts were effective in increasing the GABA level to approximately twice that in whole-wheat bread. Moreover, both the preference and saltiness of the bread were favorable, indicating that these extracts are useful for reducing the salt content of whole-wheat bread. This study provides a theoretical basis for guiding industrial production.

Size of Self-Expandable Transcatheter Heart Valve and Mid-Term Adverse Events After Transcatheter Aortic Valve Replacement.

The hemodynamic performance of self-expandable valves (SEVs) is a preferable choice for small aortic annuli in transcatheter aortic valve replacement (TAVR). However, no data are, so far, available regarding the relation between the size of SEVs and clinical outcomes. This study aimed to evaluate the impact of prosthesis size on adverse events after TAVR using SEVs. We retrospectively analyzed 1,400 patients (23-mm SEV: 13.6%) who underwent TAVR using SEVs at 12 centers. The impact of SEV size on all-cause death and heart failure (HF) after TAVR was evaluated by multivariate Cox regression and propensity score (PS) matching analysis. During the follow-up period (median 511 days), 201 all-cause deaths and 87 HF rehospitalizations were observed. The incidence of all-cause death was comparable between small- (23-mm SEV) and larger-sized (26- or 29-mm SEV) (16.8% vs 13.9%, log-rank p = 0.29). The size of SEV was not associated with a higher incidence of all-cause death (hazard ratio [HR] 1.21, 95% confidence interval [CI] 0.79 to 1.86 in Cox regression; HR 1.31, 95% CI 0.77 to 2.23 in PS matching) and HF after TAVR (subdistribution HR 0.79, 95% CI 0.37 to 1.72 in Cox regression; subdistribution HR 1.00, 95% CI 0.44 to 2.30 in PS matching). The multivariate model including postprocedural prosthesis-patient mismatch showed consistent results. In conclusion, small SEVs had comparable midterm clinical outcomes to larger-sized SEVs, even if the prosthesis-patient mismatch was observed after TAVR.

Dairy consumption, bone turnover biomarkers, and osteo sono assessment index in Japanese adults: A cross-sectional analysis of data from the Iwaki Health Promotion Project.

Purpose: Dairy foods are nutritional sources of calcium, phosphorus, protein, and other nutrients that improve bone health. However, the effects of dairy consumption on bone biomarkers in the Japanese population remain unclear. This study explored the association between dairy consumption and bone biomarkers in Japanese adults. Methods: This cross-sectional study was conducted as part of the Iwaki Health Promotion Project in Aomori, Japan. In total, 1063 adults were included in the analysis. Bone turnover marker levels were measured in local citizens during their annual medical checkups. The calcaneus osteo sono assessment index (OSI) was calculated using a quantitative ultrasound technique. The dietary intake of foods and nutrients was estimated using a food frequency questionnaire. Linear regression models were established using dairy consumption and bone biomarkers with adjustments. Statistic significance was considered by P < 0.05. Results: In multivariate models, the tartrate-resistant acid phosphatase 5b and parathyroid hormone concentrations were inversely associated with dietary dairy consumption after adjusting for age and sex. The undercarboxylated osteocalcin, a procollagen type I N-terminal peptide to bone alkaline phosphatase ratio, and OSI were the directly associated with dairy consumption in multivariate models with adjustment. Conclusions: Dairy consumption is partially associated with bone turnover biomarkers and OSI in adult Japanese participants. Habitual consumption of dairy foods may contribute to the nutritional supplementation for maintaining bone health, including turnover and structure. Clinical trial registry number and website where it was obtained: The Japanese Clinical Trials Registry (UMIN000040459), https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000046175.

Impella support for refractory cardiogenic shock accompanied by diabetic ketoacidosis: a case report.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are strongly recommended in patients with heart failure, regardless of the presence of diabetes mellitus. A 74 year-old woman with a reduced left ventricular ejection fraction and diabetes mellitus (the types were unknown), receiving insulin and SGLT2 inhibitor, was hospitalized for altered consciousness with systemic hypotension. Upon admission, she was diagnosed with cardiogenic shock due to diabetic ketoacidosis. Intensive fluid resuscitation under Impella CP support successively improved her metabolic acidosis, preventing worsening pulmonary congestion by mechanically unloading the heart. After hemodynamic stabilization, she was diagnosed with type 1 diabetes mellitus for the first time. She was discharged on day 54 and was followed for 6 months without any recurrences. We must remain vigilant regarding the risk of diabetic ketoacidosis in patients using SGLT2 inhibitors, particularly those on insulin therapy or with diabetes mellitus of unknown types. Impella device shows promise as a circulatory support system in alleviating the left ventricle's workload and averting exacerbated pulmonary congestion, especially in cases where patients necessitate aggressive fluid replacement therapy, such as in the treatment of diabetic ketoacidosis concurrent with compromised cardiac function.

Performance and outcomes of the SAPIEN 3 Ultra RESILIA transcatheter heart valve in the OCEAN-TAVI registry.

BACKGROUND: Data on the performance of the latest-generation SAPIEN 3 Ultra RESILIA (S3UR) valve in patients who undergo transcatheter aortic valve replacement (TAVR) are scarce. AIMS: We aimed to assess the clinical outcomes, including valve performance, of the S3UR. METHODS: Registry data of 618 consecutive patients with S3UR and of a historical pooled cohort of 8,750 patients who had a SAPIEN 3 (S3) valve and underwent TAVR were collected. The clinical outcomes and haemodynamics, including patient-prosthesis mismatch (PPM), were compared between the 2 groups and in a propensity-matched cohort. RESULTS: The incidence of in-hospital death, vascular complications, and new pacemaker implantation was similar between the S3UR and the S3 groups (allp>0.05). However, both groups showed significant differences in the degrees of paravalvular leakage (PVL) (none-trivial: 87.0% vs 78.5%, mild: 12.5% vs 20.5%, ≥moderate: 0.5% vs 1.1%; p<0.001) and the incidence of PPM (none: 94.3% vs 85.1%, moderate: 5.2% vs 12.8%, severe: 0.5% vs 2.0%; p<0.001). The prevalence of a mean pressure gradient ≥20 mmHg was significantly lower in the S3UR group (1.6% vs 6.2%; p<0.001). Better haemodynamics were observed with the smaller 20 mm and 23 mm S3UR valves. The results were consistent in a matched cohort of patients with S3UR and with S3 (n=618 patients/group). CONCLUSIONS: The S3UR has equivalent procedural complications to the S3 but with lower rates of PVL and significantly better valve performance. The better valve performance of the S3UR, particularly in smaller valve sizes, overcomes the remaining issue of balloon-expandable valves after TAVR.

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.

Long-term prognostic value of the H2FPEF score in patients undergoing transcatheter aortic valve implantation.

AIMS: A considerable proportion of candidates for transcatheter aortic valve implantation (TAVI) have underlying heart failure (HF) with preserved ejection fraction (HFpEF), which can be challenging for diagnosis because significant valvular heart disease should be excluded before diagnosing HFpEF. This study investigated the long-term prognostic value of the pre-procedural H2FPEF score in patients with preserved ejection fraction (EF) undergoing TAVI. METHODS AND RESULTS: Patients who underwent TAVI between October 2013 and May 2017 were enrolled from the Optimized CathEter vAlvular iNtervention-Transcatheter Aortic Valve Implantation Japanese multicentre registry. After excluding 914 patients, 1674 patients with preserved EF ≥ 50% (median age: 85 years, 72% female) were selected for calculation of the H2FPEF score and were dichotomized into two groups: the low H2FPEF score [0-5 points; n = 1399 (83.6%)] group and the high H2FPEF score [6-9 points; n = 275 (16.4%)] group. Patients with high H2FPEF scores were associated with a higher prevalence of New York Heart Association Functional Class III/IV (59.3% vs. 43.7%, P < 0.001), diabetes (24.4% vs. 18.5%, P = 0.03), and paradoxical low-flow, low-gradient aortic stenosis (15.9% vs. 6.2%, P < 0.001). These patients showed worse prognoses than those with low H2FPEF scores regarding the cumulative 2 year all-cause mortality (26.3% vs. 15.5%, log-rank P < 0.001), cardiovascular mortality (10.5% vs. 5.4%, log-rank P < 0.001), HF hospitalization (16.2% vs. 6.7%, log-rank P < 0.001), and the composite endpoint of cardiovascular mortality and HF hospitalization (23.8% vs. 10.8%, log-rank P < 0.001). After adjustment for several confounders, the high H2FPEF scores were independently associated with increased risk for all-cause mortality [adjusted hazard ratio (HR), 1.48; 95% confidence interval (CI), 1.09-2.00; P = 0.011] and for the composite endpoint of cardiovascular mortality and HF hospitalization (adjusted HR, 1.95; 95% CI, 1.38-2.74; P < 0.001). Subgroup analysis confirmed the excess risk of high H2FPEF scores relative to low H2FPEF scores for the composite endpoint of cardiovascular mortality and HF hospitalization increased with a lower Society of Thoracic Surgeons (STS) score (STS score <8%: adjusted HR, 2.40; 95% CI, 1.50-3.85; P < 0.001; STS score ≥8%: adjusted HR, 1.34; 95% CI, 0.79-2.28; P = 0.28; Pinteraction = 0.030). CONCLUSIONS: The H2FPEF score is useful for predicting long-term adverse outcomes after TAVI, including all-cause mortality, cardiovascular mortality, and HF hospitalization for patients with preserved EF. More aggressive interventions targeting HFpEF in addition to the TAVI procedure might be relevant in patients with high H2FPEF scores, particularly in those with a lower surgical risk.

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.

Enhanced reactivity of Li+@C60 toward thermal [2 + 2] cycloaddition by encapsulated Li+ Lewis acid.

Lithium ion-endohedral fullerene (Li+@C60), a member of the burgeoning family of ion-endohedral fullerenes, holds substantial promise for diverse applications owing to its distinctive ionic properties. Despite the high demand for precise property tuning through chemical modification, there have been only a few reports detailing synthetic protocols for the derivatization of this novel material. In this study, we report the synthesis of Li+@C60 derivatives via the thermal [2 + 2] cycloaddition reaction of styrene derivatives, achieving significantly higher yields of monofunctionalized Li+@C60 compared to previously reported reactions. Furthermore, by combining experimental and theoretical approaches, we clarified the range of applicable substrates for the thermal [2 + 2] cycloaddition of Li+@C60, highlighting the expanded scope of this straightforward and selective functionalization method.

Prognostic impact of insomnia in patients receiving trans-catheter aortic valve replacement.

BACKGROUND: The presence of insomnia exhibits a profound association with diverse cardiovascular pathologies. However, its prognostic implications in patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis remain ambiguous. METHODS: This retrospective study enrolled patients who underwent TAVR for severe aortic stenosis at a prominent academic center from 2015 to 2022. The impact of insomnia, operationally defined as the prescription of soporific agents, on the two-year composite primary outcome comprising all-cause mortality and hospital readmissions was scrutinized. RESULTS: A cohort of 345 patients (median age 85 years, 99 males) was encompassed in the analysis. All subjects underwent successful TAVR and subsequent discharge. The presence of insomnia (N = 91) emerged as an independent predictor of the two-year composite endpoint, with an adjusted hazard ratio of 1.66 (95 % confidence interval 1.08-2.57, p = 0.022), significantly delineating the two-year cumulative incidence of the primary endpoint (40 % versus 30 %, p = 0.035). CONCLUSION: Approximately one-fourth of TAVR candidates manifested symptoms of insomnia, a condition autonomously correlated with heightened mortality and morbidity following the TAVR procedure. The optimal strategy for addressing insomnia in TAVR candidates constitutes a paramount consideration for future interventions.

Paradoxical prognostic impact of severe aortic stenosis following trans-catheter aortic valve implantation.

BACKGROUND: Aortic valve replacement is recommended for patients with "very severe" aortic stenosis (AS), irrespective of symptomatic manifestation. Nonetheless, the prognostic ramifications of "very severe" AS, as opposed to "severe" AS, subsequent to trans-catheter aortic valve implantation (TAVI) remain enigmatic. METHODS: We enrolled consecutive patients who received TAVI at our institute between May 2015 and April 2021. We scrutinized the impact of baseline "very severe" AS upon 3-year all-cause death or heart failure hospitalization following TAVI, in comparison to "severe" AS. RESULTS: A total of 239 patients (84.8 ±â€¯5.4 years old, 58 men) were included. Baseline "very severe" AS was observed in 65 (27 %) patients, who exhibited more advanced hypertrophy and higher B-type natriuretic peptide levels compared to those with "severe" AS (p < 0.05 for both). Baseline "very severe" AS was paradoxically associated with higher freedom from the primary endpoint following TAVI compared to those with "severe" AS (p = 0.01). CONCLUSIONS: The presence of baseline "very severe" AS was paradoxically associated with improved clinical outcomes subsequent to TAVI, in contrast to the cases of "severe" AS.

Pre-Existing Left Bundle Branch Block and Clinical Outcomes After Transcatheter Aortic Valve Replacement.

Background: Few reports on pre-existing left bundle branch block (LBBB) in patients undergoing transcatheter aortic valve replacement (TAVR) are currently available. Further, no present studies compare patients with new onset LBBB with those with pre-existing LBBB. Objectives: This study aimed to investigate the association between pre-existing or new onset LBBB and clinical outcomes after TAVR. Methods: Using data from the Japanese multicenter registry, 5,996 patients who underwent TAVR between October 2013 and December 2019 were included. Patients were classified into 3 groups: no LBBB, pre-existing LBBB, and new onset LBBB. The 2-year clinical outcomes were compared between 3 groups using Cox proportional hazards models and propensity score analysis to adjust the differences in baseline characteristics. Results: Of 5,996 patients who underwent TAVR, 280 (4.6%) had pre-existing LBBB, while 1,658 (27.6%) experienced new onset LBBB. Compared with the no LBBB group, multivariable Cox regression analysis showed that pre-existing LBBB was associated not only with a higher 2-year all-cause (adjusted HR: 1.39; 95% CI: 1.06-1.82; P = 0.015) and cardiovascular (adjusted HR: 1.60; 95% CI: 1.04-2.48; P = 0.031) mortality, but also with higher all-cause (adjusted HR: 1.43, 95% CI: 1.07-1.91; P = 0.016) and cardiovascular (adjusted HR: 1.81, 95% CI:1.12-2.93; P = 0.014) mortality than the new onset LBBB group. Heart failure was the most common cause of cardiovascular death, with more heart failure deaths in the pre-existing LBBB group. Conclusions: Pre-existing LBBB was independently associated with poor clinical outcomes, reflecting an increased risk of cardiovascular mortality after TAVR. Patients with pre-existing LBBB should be carefully monitored.

Engineering of IF1 -susceptive bacterial F1 -ATPase.

IF1 , an inhibitor protein of mitochondrial ATP synthase, suppresses ATP hydrolytic activity of F1 . One of the unique features of IF1 is the selective inhibition in mitochondrial F1 (MF1 ); it inhibits catalysis of MF1 but does not affect F1 with bacterial origin despite high sequence homology between MF1 and bacterial F1 . Here, we aimed to engineer thermophilic Bacillus F1 (TF1 ) to confer the susceptibility to IF1 for elucidating the molecular mechanism of selective inhibition of IF1 . We first examined the IF1 -susceptibility of hybrid F1 s, composed of each subunit originating from bovine MF1 (bMF1 ) or TF1 . It was clearly shown that only the hybrid with the ß subunit of mitochondrial origin has the IF1 -susceptibility. Based on structural analysis and sequence alignment of bMF1 and TF1 , the five non-conserved residues on the C-terminus of the ß subunit were identified as the candidate responsible for the IF1 -susceptibility. These residues in TF1 were substituted with the bMF1 residues. The resultant mutant TF1 showed evident IF1 -susceptibility. Reversely, we examined the bMF1 mutant with TF1 residues at the corresponding sites, which showed significant suppression of IF1 -susceptibility, confirming the critical role of these residues. We also tested additional three substitutions with bMF1 residues in α and γ subunits that further enhanced the IF1 -susceptibility, suggesting the additive role of these residues. We discuss the molecular mechanism by which IF1 specifically recognizes F1 with mitochondrial origin, based on the present result and the structure of F1 -IF1 complex. These findings would help the development of the inhibitors targeting bacterial F1 .

Label-Free Liquid Chromatography-Mass Spectrometry Quantitation of Relative N- and O-Glycan Concentrations in Human Milk in Japan.

Human milk is abundant in carbohydrates and includes human milk oligosaccharides (HMOs) and N/O-glycans conjugated to proteins. HMO compositions and concentrations vary in individuals according to the maternal secretor status based on the fucosyltransferase 2 genotype; however, the profile of N/O-glycans remains uninvestigated because of the analytical complexity. Herein, we applied a label-free chromatography-mass spectrometry (LC-MS) technique to elucidate the variation in the composition and concentration of N/O-glycans in human milk. We used label-free LC-MS to relatively quantify 16 N-glycans and 12 O-glycans in 200 samples of Japanese human milk (1-2 months postpartum) and applied high performance anion exchange chromatography with pulsed amperometric detection to absolutely quantify the concentrations of 11 representative HMOs. Cluster analysis of the quantitative data revealed that O-glycans and several HMOs were classified according to the presence or absence of fucose linked to galactose while N-glycans were classified into a different group from O-glycans and HMOs. O-glycans and HMOs with fucose linked to galactose were more abundant in human milk from secretor mothers than from nonsecretor mothers. Thus, secretor status influenced the composition and concentration of HMOs and O-glycans but not those of N-glycans in human milk.