Edoxaban versus Vitamin K Antagonist for Atrial Fibrillation after TAVR.

BACKGROUND: The role of direct oral anticoagulants as compared with vitamin K antagonists for atrial fibrillation after successful transcatheter aortic-valve replacement (TAVR) has not been well studied. METHODS: We conducted a multicenter, prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban with vitamin K antagonists in patients with prevalent or incident atrial fibrillation as the indication for oral anticoagulation after successful TAVR. The primary efficacy outcome was a composite of adverse events consisting of death from any cause, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding. The primary safety outcome was major bleeding. On the basis of a hierarchical testing plan, the primary efficacy and safety outcomes were tested sequentially for noninferiority, with noninferiority of edoxaban established if the upper boundary of the 95% confidence interval for the hazard ratio did not exceed 1.38. Superiority testing of edoxaban for efficacy would follow if noninferiority and superiority were established for major bleeding. RESULTS: A total of 1426 patients were enrolled (713 in each group). The mean age of the patients was 82.1 years, and 47.5% of the patients were women. Almost all the patients had atrial fibrillation before TAVR. The rate of the composite primary efficacy outcome was 17.3 per 100 person-years in the edoxaban group and 16.5 per 100 person-years in the vitamin K antagonist group (hazard ratio, 1.05; 95% confidence interval [CI], 0.85 to 1.31; P = 0.01 for noninferiority). Rates of major bleeding were 9.7 per 100 person-years and 7.0 per 100 person-years, respectively (hazard ratio, 1.40; 95% CI, 1.03 to 1.91; P = 0.93 for noninferiority); the difference between groups was mainly due to more gastrointestinal bleeding with edoxaban. Rates of death from any cause or stroke were 10.0 per 100 person-years in the edoxaban group and 11.7 per 100 person-years in the vitamin K antagonist group (hazard ratio, 0.85; 95% CI, 0.66 to 1.11). CONCLUSIONS: In patients with mainly prevalent atrial fibrillation who underwent successful TAVR, edoxaban was noninferior to vitamin K antagonists as determined by a hazard ratio margin of 38% for a composite primary outcome of adverse clinical events. The incidence of major bleeding was higher with edoxaban than with vitamin K antagonists. (Funded by Daiichi Sankyo; ENVISAGE-TAVI AF ClinicalTrials.gov number, NCT02943785.).

Intramolecular [π4s + π4s] photocycloaddition of carbon- and nitrogen-bridged [32](1,4)naphthalenophanes.

[32](1,4)Naphthalenophanes, bearing carbon-bridge chains (syn- and anti-NPs) and nitrogen-bridge chains (syn- and anti-ANPs), were synthesized, and their X-ray structures and photoreactions were investigated. The intramolecular separation distance between the naphthalene cores for ANPs was shorter than that for NPs, suggesting that intramolecular interactions between the naphthalene rings  were more efficient for ANPs compared to NPs. Upon photoirradiation at 300 nm, anti-NP, syn-ANP and anti-ANP produced the corresponding intramolecular [π4s + π4s] cycloadducts, whereas syn-NP gave an unidentified complex product mixture. Quantum yields for the photo-consumption (ΦPC) of NPs and ANPs were evaluated to quantitatively compare their photoreactivity. The ΦPC values of ANPs were approximately two-fold higher than those of ANPs.Noteworthily, the ΦPC value of syn-ANP was estimated to be unity. Based on these results we discuss the effects of the alignments of the naphthalene cores (anti vs. syn) and the bridging elements (C-bridge vs. N-bridge) on the photoreaction efficiencies of [32](1,4)naphthalenophanes.

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.

Clinical efficacy of tolvaptan in acute decompensated heart failure patients with severe aortic stenosis and atrial fibrillation: a sub-analysis from the LOHAS registry.

BACKGROUND: Severe aortic valve stenosis (AS) and atrial fibrillation (AF) are risk factors of hemodynamic instability in heart failure (HF) management due to low cardiac output, respectively. Therefore, the treatment of HF due to severe AS complicated with AF is anticipated to be difficult. Tolvaptan, a vasopressin V2 receptor inhibitor, is effective in controlling acute decompensated heart failure (ADHF) with hemodynamic stability. However, its clinical efficacy against ADHF caused by AS with AF remains to be determined. METHODS: Clinical information (from September 2014 to December 2017) of 59 patients diagnosed with ADHF due to severe AS (20 patients with AF; 39 patients with sinus rhythm [SR]) was obtained from the LOHAS registry. The registry collected data from seven hospitals and assessed the short-term effects of tolvaptan in patients hospitalized for ADHF with severe AS. We attempted to identify clinical differences from baseline up to 4 days, comparing patients with AF (AF group) versus those with SR (SR group). RESULTS: There were no significant differences between the groups in age (83.7 ± 4.5 vs. 85.8 ± 6.9 years, respectively; p = 0.11) and aortic valve area (0.60 [0.46-0.73] vs. 0.56 [0.37-0.70] cm2, respectively; p = 0.50). However, left atrial volume was larger (104 [85-126] vs. 87 [64-103] mL, respectively; p < 0.01), whereas stroke volume was lower (51.6 ± 14.8 vs. 59.0 ± 18.7 mL, respectively; p = 0.08) in the AF group versus the SR group. Body weight decreased daily from baseline up to day 4 in both groups (from 55.4 to 53.2 kg [p < 0.01] and from 53.5 to 51.0 kg [p < 0.01], respectively) without change in heart rate. Notably, the systolic blood pressure decreased slightly in the AF group after 2 days of treatment with tolvaptan. CONCLUSIONS: Short-term treatment with tolvaptan improved HF in patients hospitalized for severe AS, regardless of the presence of AF or SR. After achieving sufficient diuresis, a slight decrease in blood pressure was observed in the AF group, suggesting an appropriate timeframe for safe and effective use of tolvaptan.

Solid-State Schikorr Reaction from Ferrous Chloride to Magnetite with Hydrogen Evolution as the Kinetic Bottleneck.

The selective formation of meta-stable Fe3O4 from ferrous sources by suppressing its oxidative conversion to the most stable hematite (α-Fe2O3) is challenging under oxidative conditions for solid-state synthesis. In this work, we investigated the conversion of iron(II) chloride (FeCl2) to magnetite (Fe3O4) under inert atmosphere in the presence of steam, and the obtained oxides were analyzed by atomic-resolution TEM, 57Fe Mössbauer spectroscopy, and the Verwey transition temperature (Tv). The reaction proceeded in two steps, with H2O as the oxide source in the initial step and as an oxidant in the second step. The initial hydrolysis occurred at temperatures higher than 120 °C to release gaseous HCl, via substituting lattice chloride Cl- with oxide O2-, to give iron oxide intermediates. In the first step, the construction of the intermediate oxides was not topotactic. The second step as a kinetic bottleneck occurred at temperatures higher than 350 °C to generate gaseous H2 through the oxidation of FeII by H+. A substantially large kinetic isotope effect (KIE) was observed for the second step at 500 °C, and this indicates the rate-determining step is the hydrogen evolution. Quantitative analysis of evolved H2 revealed that full conversion of ferrous chloride to magnetite at 500 °C was followed by additional oxidation of the outer sphere of magnetite to give a Fe2O3 phase, as supported by X-ray photoelectron spectroscopy (XPS), and the outer phase confined the conductive magnetite phase within the insulating layers, enabling kinetic control of magnetite synthesis. As such, the reaction stopped at meta-stable magnetite with an excellent saturation magnetization (σs) of 86 emu g-1 and Tv > 120 K without affording the thermodynamically stable α-Fe2O3 as the major final product. The study also discusses the influence of parameters such as reaction temperature, initial grain size of FeCl2, the extent of hydration, and partial pressure of H2O.

Surface defect healing in annealing from nanoporous carbons to nanoporous graphenes.

Nanoporous graphene (NPG) materials have the pronounced electrochemical stability of the seamless graphene structures developed over the 3D space. We revisited the Raman spectra of nanoporous carbons (NPCs) synthesized using θ-/γ-Al2O3 templates and NPGs converted from NPCs by annealing at 1800 °C to identify the type and density of defects. We found that both the NPCs and NPGs mostly consist of single-layered graphene with a few single vacancies and Stone-Wales defects. The density of vacancy defect per hexagon in the graphene sheet is estimated to be 10-2 for NPCs, while the annealing reduced the value to 10-3-10-4 for NPGs. This supports the outstanding chemical and electrochemical stability of the novel porous carbon materials.

Validation of reliability and predictivity of membrane septum length measurements for pacemaker need after transcatheter aortic valve replacement.

OBJECTIVES: To assess the inter methodological agreement of membrane septum (MS) length measurement and additive value for risk stratification of new pacemaker implantation (PMI) over the established predictors after transcatheter aortic valve replacement (TAVR). BACKGROUND: Recent studies have suggested MS length and implantation depth (ID) as predictors for PMI after TAVR. However, the measurement of MS length is neither uniform nor validated in different cohort. METHODS: We retrospectively analyzed patients who underwent TAVR at five centers. The MS length was measured by two previously proposed methods (coronal and annular view method). Predictive ability of risk factors, including MS length and ID, for new PMI within 30 days after TAVR were evaluated. RESULTS: Among 754 patients of study population, 31 patients (4.1%) required new PMI within 30 days of TAVR. There was a weak correlation (ρ = 0.47) and a poor agreement between the two methods. The ID and the difference between MS length and ID (ΔMSID), were independent predictors for new PMI, whereas MS length alone was not. Further, for predicting new PMI after TAVR, discrimination performance was not significantly improved when MS length was added to the model with ID alone (integrated discrimination improvement = 0, p= 0.99; continuous net-reclassification improvement = 0.10, p= 0.62). CONCLUSIONS: External validity and predictive accuracy of MS length for PMI after TAVR were not sufficient to provide better risk stratification over the established predictors in our cohort. Moreover, the ID and ΔMSID, but not MS length alone, are predictive of future PMI after TAVR.

Fascia Iliaca Block Reduces Remifentanil Requirement in Conscious Sedation for Transcatheter Aortic Valve Implantation　- A Randomized Clinical Trial.

BACKGROUND: Whether nerve block improves the quality of conscious sedation (CS) in patients undergoing transcatheter aortic valve implantation (TAVI) is unclear. This study investigated whether fascia iliaca block (FIB) reduced the remifentanil requirement and relieved pain in CS for TAVI.Methods and Results: This prospective study randomized 72 patients scheduled for elective TAVI under CS into 2 groups, with (FIB) and without (control) FIB (n=36 in each group). The sedation targeted a Bispectral Index <90 with a Richmond Agitation-Sedation Scale of -2 to -1. Dexmedetomidine (0.7 µg/kg, i.v.) combined with remifentanil (0.03 µg/kg/min, i.v.) and propofol (0.3 mg/kg/h, i.v.) was used to commence sedation. FIB using 30 mL of 0.185% ropivacaine was implemented 2 min before TAVI. Patient sedation was maintained with dexmedetomidine (0.4 µg/kg/h, i.v.) supplemented with remifentanil (0-0.02 µg/kg/min, i.v.). Remifentanil (20 µg, i.v.) was used as a rescue dose for intraprocedural pain. Compared with the control group, FIB reduced the both the total (median [interquartile range] 83.0 [65.0-98.0] vs. 34.5 [26.0/45.8)] µg; P<0.001) and continuous (25.3 [20.9/31.5] vs. 9.5 [6.8/12.5] ng/kg/min; P<0.001) doses of remifentanil administered. CONCLUSIONS: FIB reduced the remifentanil requirement and relieved pain in patients undergoing TAVI with CS. Therefore, FIB improved the quality of CS in TAVI.

Iatrogenic Atrial Septal Defect Requiring Transcatheter Closure Following Transcatheter Mitral Valve Repair.

BACKGROUND: Transcatheter mitral valve repair with the MitraClip system has been established in selected high-risk patients. The MitraClip procedure results in a relatively large iatrogenic atrial septal defect (iASD). This study aimed to investigate the prevalence and clinical course of iASD requiring transcatheter closure following the MitraClip procedure.Methods and Results: This study was conducted at all 59 institutions that perform transcatheter mitral valve repair with the MitraClip system in Japan. The data of patients on whom transcatheter iASD closure was performed were collected. Of the 2,722 patients who underwent the MitraClip procedure, 30 (1%) required transcatheter iASD closure. The maximum iASD size was 9±4 mm (range, 3-18 mm). The common clinical course of transcatheter iASD closure was hypoxemia with right-to-left shunt or right-sided heart failure with left-to-right shunt. Of the 30 patients, 22 (73%) required transcatheter closure within 24 h following the MitraClip procedure, including 12 with hypoxemia and 5 with right-sided heart failure complicated with cardiogenic shock. Of the 5 patients, 2 required mechanical circulatory support devices. Twenty-one patients immediately underwent transcatheter iASD closure, and hemodynamic deteriorations were resolved; however, 1 patient died without having undergone transcatheter closure. CONCLUSIONS: Transcatheter iASD closure was required in 1% of patients who underwent the MitraClip procedure. Many of these patients immediately underwent transcatheter iASD closure because of hypoxemia with right-to-left shunt or right-sided heart failure with left-to-right shunt.

Edoxaban vs. Vitamin K Antagonist for Atrial Fibrillation After Transcatheter Aortic Valve Replacement in Japanese Patients　- A Subanalysis of the ENVISAGE-TAVI AF Trial.

BACKGROUND: Japanese patients undergoing transcatheter aortic valve replacement (TAVR) are often female and have a small body size, potentially impacting bleeding risk with antithrombotic therapy. Outcomes of direct oral anticoagulant use in these patients with atrial fibrillation (AF) need to be clarified.Methods and Results: This prespecified analysis included Japanese patients from ENVISAGE-TAVI AF, a prospective, randomized, open-label, adjudicator-masked trial that compared treatment with edoxaban and vitamin K antagonists (VKAs) in patients with AF after TAVR. The primary efficacy and safety outcomes were net adverse clinical events (NACE; composite of all-cause death, myocardial infarction, ischemic stroke, systemic embolic event, valve thrombosis, and International Society on Thrombosis and Haemostasis [ISTH]-defined major bleeding) and ISTH-defined major bleeding, respectively. Intention-to-treat (ITT) and on-treatment analyses were performed. Overall, 159 Japanese patients were enrolled (edoxaban group: 82, VKA group: 77) and followed for on average 483 days. Mean patient age was 83.8 years; 52.2% were female. In the ITT analysis, NACE rates were 10.9%/year with edoxaban and 12.5%/year with VKA (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.38-1.90); major bleeding occurred in 8.9%/year and 7.3%/year, respectively (HR, 1.17; 95% CI, 0.45-3.05). In edoxaban- and VKA-treated patients, rates of ischemic stroke were 1.8%/year and 1.0%/year, respectively; fatal bleeding rates were 0.9%/year and 2.0 %/year. On-treatment results were similar to ITT. CONCLUSIONS: In Japanese patients with AF after successful TAVR, edoxaban and VKA treatment have similar safety and efficacy profiles.

The carbon chain growth during the onset of CVD graphene formation on γ-Al2O3 is promoted by unsaturated CH2 ends.

Chemical vapor deposition of methane onto a template of alumina (Al2O3) nanoparticles is a prominent synthetic strategy of graphene meso-sponge, a new class of nano porous carbon materials consisting of single-layer graphene walls. However, the elementary steps controlling the early stages of graphene growth on Al2O3 surfaces are still not well understood. In this study, density functional theory calculations provide insights into the initial stages of graphene growth. We have modelled the mechanism of CH4 dissociation on the (111), (110), (100), and (001) γ-Al2O3 surfaces. Subsequently, we have considered the reaction pathway leading to the formation of a C6 ring. The γ-Al2O3(110) and γ-Al2O3(100) are both active for CH4 dissociation, but the (100) surface has higher catalytic activity towards the carbon growth reaction. The overall mechanism involves the formation of the reactive intermediate CH2* that then can couple to form CnH2n* (n = 2-6) intermediates with unsaturated CH2 ends. The formation of these species, which are not bound to the surface-active sites, promotes the sustained carbon growth in a nearly barrierless process. Also, the short distance between terminal carbon atoms leads to strong interactions, which might lead to the high activity between unsaturated CH2* of the hydrocarbon chain. Analysis of the electron localization and geometries of the carbon chains reveals the formation of C-Al-σ bonds with the chain growing towards the vacuum rather than C-Al-π bonds covering the γ-Al2O3(100) surface. This growth behaviour prevents catalyst poisoning during the initial stage of graphene nucleation.

Late kidney injury after transcatheter aortic valve replacement.

BACKGROUND: Information on early to late-phase kidney damage in patients who underwent transcatheter aortic valve replacement (TAVR) is scarce. We aimed to identify the predictive factors for late kidney injury (LKI) at 1-year and patient prognosis beyond 1-year after TAVR. METHODS: We retrospectively reviewed 1,705 patients' data from the Japanese TAVR multicenter registry. Acute kidney injury (AKI) and LKI, defined as an increase of at least 0.3 mg/dL in creatinine level, a relative 50% decrease in kidney function from baseline to 48 hours and 1-year, were evaluated. The patients were categorized into the 4 groups as AKI-/LKI- (n = 1.362), AKI+/LKI- (n = 95), AKI-/LKI+ (n = 199), and AKI+/LKI+ (n = 46). RESULTS: The cumulative 3-year mortality rates were significantly increased across the four groups (12.5%, 15.8%, 24.6%, 25.8%, P < .001). Multivariate analysis revealed that chronic kidney disease, coronary artery disease, periprocedural AKI, and heart failure-related re-admission within 1-year were significantly associated with LKI. The Cox regression analysis revealed that AKI-/LKI+ and AKI+/LKI+ were independent predictors of increased late mortality beyond 1-year after TAVR (P = .001 and P = .01). CONCLUSIONS: LKI was influenced by adverse cardio-renal events and was associated with increased risks of late mortality beyond 1-year after TAVR.

Predictors of prolonged guidewire manipulation time for native coronary chronic total occlusion percutaneous coronary intervention via primary antegrade approach.

OBJECTIVES: This study aimed to identify the predictive factors for the guidewire manipulation time (GWMT) of ≥20 and 30 min for chronic total occlusion-percutaneous coronary intervention (CTO-PCI) via the primary antegrade approach (PAA). BACKGROUND: Selection of primary retrograde approach (PRA) and the optimal timing to switch from antegrade to retrograde approach for coronary CTO-PCI is still debatable. METHODS: Using the Japanese CTO-PCI expert registry data, we selected and analyzed 4461 patients who underwent CTO-PCI via PAA alone. The considerable lesion/anatomical factors for GWMT ≥20 and 30 min were analyzed. The risks of prolonged GWMT ≥20 and 30 min were stratified as easy, intermediate, difficult, and very difficult according to the multivariate analysis. RESULTS: Nine lesion/anatomical characteristics (blunt stump, side branch at proximal cap, bifurcation at the exit point, calcification, tortuosity, occlusion length ≥ 20 mm, reattempt, nonleft anterior descending artery (nonleft anterior descending artery [LAD]), and tandem CTO) were independent predictors of GWMT ≥20 min (all p < 0.05). Excluding the nonLAD and tandem CTO, the same factors of GWMT ≥20 min correlated with GWMT ≥30 min (all p < 0.05). The distributions were increased in easy, intermediate, difficult, and very difficult subsets of GWMT ≥20 min (58.3%, 77.2%, 89.1%, and 100%) and GWMT ≥30 min (47.5%, 69.2%, 83.9%, and 100%). CONCLUSIONS: These predictive factors of prolonged GWMT should be assessed before CTO-PCI via PAA and when considering an adequate timing to switch the retrograde or PRA if clinically available.

Impact of diabetes mellitus on outcome after transcatheter aortic valve replacement: Identifying high-risk diabetic population from the OCEAN-TAVI registry.

OBJECTIVES: To identify the vulnerable diabetic cohort in patients undergoing transcatheter aortic valve replacement (TAVR). BACKGROUNDS: Considerable controversy remains about whether specific cohort exists in which presence of diabetes mellitus (DM) carries adverse risk of mortality after TAVR. METHODS: Of the 2588 patients who were enrolled in the OCEAN-TAVI registry, 2526 patients with glycohemoglobin data were analyzed. The individuals were divided into DM and non-DM groups according to previous medical history of DM or using diabetic medicine, and increased HbA1c values (≥6.5%) at baseline. The primary endpoint of this study was 2-year all-cause mortality after TAVR. RESULTS: The follow up rate of clinical outcome at 1-year was 2514/2526 (99.5%) and median follow-up period was 22.5 months. DM group had 699 (27.7%) patients, in which 153 (21.9%) was diagnosed by increased HbA1c levels without previous medical history of DM. Kaplan-Meier curve of 2-year all-cause mortality presented significant difference between patients with and without DM (p = 0.029). In addition, patients with low-density lipoprotein cholesterol (LDL-C) levels > 100 mg/dl and left ventricular ejection fraction (LVEF) < 40% had great risk of mortality after TAVR (LDL-C: hazard ratio [HR] 1.82, p < 0.001; LVEF: HR 2.61, p = 0.002, respectively). CONCLUSIONS: Presence of DM was significantly associated with poor outcome after TAVR and adverse effect of DM was remarkable in patients with relatively higher LDL-C levels and reduced LVEF under 40%. These subtypes may need intensive control of cardiovascular risk factors, including DM, before and after TAVR.

Transcatheter aortic valve replacement with Evolut R versus Sapien 3 in Japanese patients with a small aortic annulus: The OCEAN-TAVI registry.

OBJECTIVES: To compare safety, efficacy, and hemodynamics of transfemoral transcatheter aortic valve replacement (TAVR) using self-expanding and balloon-expandable transcatheter heart valves (THVs) in patients with a small aortic annulus. BACKGROUND: Few studies have directly compared TAVR outcomes using third-generation THVs, focusing on patients with small aortic annuli. METHODS: In a multicenter TAVR registry, we analyzed data from 576 patients with a small annulus and who underwent transfemoral TAVR using third-generation THVs. Propensity score matching was used to adjust baseline clinical characteristics. RESULTS: The device success rate in the overall cohort was 92.0% (Evolut R: 92.1% vs. Sapien 3:92.0%, p = 0.96). One year after TAVR, patients treated with Evolut R maintained a lower mean pressure gradient (mPG) and a higher indexed effective orifice area (iEOA) in the matched cohort {mPG: 9.0 [interquartile range (IQR): 6.0-11.9] vs. 12.0 [IQR: 9.9-16.3] mmHg, p < .001; iEOA: 1.20 [IQR: 1.01-1.46] vs. 1.08 [IQR: 0.90-1.28] cm2 /m2 , p < .001}. However, no significant differences were reported in the incidence of severe prosthesis-patient mismatch and aortic regurgitation at 1 year. Furthermore, both groups showed comparable outcomes with no differences in terms of all-cause mortality (log-lank test, p = .81). CONCLUSIONS: TAVR for patients with a small annulus using third-generation THVs was associated with high device success. Evolut R seems to be superior to Sapien 3 in hemodynamic performance for patients with a small annulus and body surface area up to 1 year after TAVR. Nevertheless, all-cause mortality at 1 year was similar between both groups.

Clinical outcomes of transcatheter aortic valve implantation (TAVI) in nonagenarians from the optimized catheter valvular intervention-TAVI registry.

OBJECTIVES: The purpose of this study was to investigate 30-day and 2-year clinical outcomes, and predictors of 2-year mortality in nonagenarians undergoing transcatheter aortic valve implantation (TAVI). BACKGROUND: TAVI has been applied to nonagenarians. However, sufficient clinical data in nonagenarians who could benefit from TAVI are limited. METHODS: We evaluated the data from the optimized catheter valvular intervention-TAVI registry. Clinical outcomes were compared between patients' age ≥90 years and age <90 years. Predictive factors of 2-year mortality were assessed by multivariable Cox regression analyses. RESULTS: From October 2013 to May 2017, a total of 375 nonagenarians (age ≥90 years) and 2,213 younger patients (age <90 years) were included. Although nonagenarians had a higher surgical risk score, 30-day clinical outcomes were similar between two groups. There were no significant differences in 2-year mortality (22.0% vs. 17.3%; p = .11) and stroke (5.5% vs. 3.9%; p = .31); however, 2-year heart failure readmission was higher in nonagenarians (13.3% vs. 9.0%; p = .03). After adjusting covariates, age ≥90 years was not independent predictor for 2-year outcomes. In nonagenarians, female sex (hazard ratio [HR] = 0.43; 95% confidence interval [CI] = 0.26-0.74; p = .002), chronic kidney disease grade ≥4 (HR = 2.14; 95% CI = 1.21-3.64; p = .01), and Clinical Frailty Scale ≥4 (HR = 1.82; 95% CI = 1.02-3.42; p = .04) were independently associated with 2-year mortality. CONCLUSIONS: Clinical outcomes of TAVI in selected nonagenarians were favorable. Severe renal dysfunction and frailty may be important factors to predict mid-term mortality after TAVI in nonagenarians.

Midterm outcomes after the rescue THV-in-THV procedure: Insights from the multicenter prospective OCEAN-TAVI registry.

OBJECTIVES: To confirm whether the rescue transcatheter heart valve in the transcatheter heart valve (THV-in-THV) procedure is effective and feasible, we aimed to assess the midterm outcomes following rescue THV-in-THV procedures. The trends in the usage of the rescue THV-in-THV procedure at the time of transcatheter aortic valve implantation (TAVI) have also been explored. BACKGROUND: Midterm outcomes of the rescue THV-in-THV procedure have been poorly defined, though it is popular as an effective method to bail-out some complications in TAVI. METHODS: We reviewed data from the Optimized transCathEter vAlvular iNtervention-Transcatheter Aortic Valve Implantation (OCEAN-TAVI) registry and compared the outcomes of TAVI with rescue THV-in-THV and TAVI without rescue THV-in-THV. We also examined the annual rates of rescue THV-in-THV procedures in all the TAVI procedures between 2013 and 2017. RESULTS: Among 2,588 patients who underwent TAVI, 26 patients have required rescue THV-in-THV for valve malposition (n = 23) or severe transvalvular regurgitation because of stuck THV leaflets (n = 3). Three cases needed an open conversion, and two died in the hospital. The rates of new permanent pacemaker implantation, acute kidney injury, and stroke were higher in the THV-in-THV group. A two-year cumulative survival and echocardiographic outcomes succeeding rescue THV-in-THV procedure were comparable to non-THV-in-THV cases. The rate of rescue THV-in-THV procedure lessened from 2.6% in 2013 to 0.6% in 2017. CONCLUSIONS: The rescue THV-in-THV procedure is an effective and feasible option for THV malpositioning and stuck valve. It has given a comparable survival and a stable valve function over midterm observation periods.

Clinical risk model for predicting 1-year mortality after transcatheter aortic valve replacement.

OBJECTIVES: Estimating 1-year life expectancy is an essential factor when evaluating appropriate indicators for transcatheter aortic valve replacement (TAVR). BACKGROUND: It is clinically useful in developing a reliable risk model for predicting 1-year mortality after TAVR. METHODS: We evaluated 2,588 patients who underwent TAVR using data from the Optimized CathEter vAlvular iNtervention (OCEAN) Japanese multicenter registry from October 2013 to May 2017. The 1-year clinical follow-up was achieved by 99.5% of the entire population (n = 2,575). Patients were randomly divided into two cohorts: the derivation cohort (n = 1,931, 75% of the study population) and the validation cohort (n = 644). Considerable clinical variables including individual patient's comorbidities and frailty markers were used for predicting 1-year mortality following TAVR. RESULTS: In the derivation cohort, a multivariate logistic regression analysis demonstrated that sex, body mass index, Clinical Frailty Scale, atrial fibrillation, peripheral artery disease, prior cardiac surgery, serum albumin, renal function as estimated glomerular filtration rate, and presence of pulmonary disease were independent predictors of 1-year mortality after TAVR. Using these variables, a risk prediction model was constructed to estimate the 1-year risk of mortality after TAVR. In the validation cohort, the risk prediction model revealed high discrimination ability and acceptable calibration with area under the curve of 0.763 (95% confidence interval, 0.728-0.795, p < .001) in the receiver operating characteristics curve analysis and a Hosmer-Lemeshow χ2 statistic of 5.96 (p = .65). CONCLUSIONS: This risk prediction model for 1-year mortality may be a reliable tool for risk stratification and identification of adequate candidates in patients undergoing TAVR.

Effect of Sex on Mortality and Left Ventricular Remodeling After Transcatheter Aortic Valve Implantation.

BACKGROUND: The effect of sex on mortality is controversial; furthermore, sex differences in left ventricular (LV) remodeling after transcatheter aortic valve implantation (TAVI) remain unknown.Methods and Results:This study included 2,588 patients (1,793 [69.3%] female) enrolled in the Optimized CathEter vAlvular iNtervention (OCEAN)-TAVI Japanese multicenter registry between October 2013 and May 2017. We retrospectively analyzed the effect of sex on mortality, and evaluated changes in the LV mass index (LVMI) after TAVI. Female sex was significantly associated with lower all-cause and cardiovascular mortality (log-rank P<0.001 for both). Multivariate analysis showed that female sex was independently associated with lower cumulative long-term mortality (hazard ratio 0.615; 95% confidence interval 0.512-0.738; P<0.001). Regression in the LVMI was observed in both sexes, and there was no significant difference in the percentage LVMI regression from baseline to 1 year after TAVI between women and men. Women had a survival advantage compared with men among patients with LVMI regression at 1 year, but not among patients with no LVMI regression. CONCLUSIONS: We found that female sex is associated with better survival outcomes after TAVI in a large Japanese registry. Although LVMI regression was observed in women and men after TAVI, post-procedural LV mass regression may be related to the sex differences in mortality.

Short-term dual anti-platelet therapy decreases long-term cardiovascular mortality after transcatheter aortic valve replacement.

No data are available on extended dual anti-platelet therapy (DAPT) duration which may influence long-term prognosis (later than 1 year) after transcatheter aortic valve replacement (TAVR). Therefore, this study is aimed to evaluate whether discontinuing DAPT within 1 year had an impact on adverse events after TAVR. Using data from the OCEAN-TAVI registry, we assessed 1008 patients who survived the first year after TAVR with DAPT since discharge. Patients were divided into 'DAPT group' (n = 462), comprising patients who took DAPT at both discharge and 1 year, and 'stop-DAPT group' (n = 546), comprising patients who took DAPT at discharge and single anti-platelet therapy (SAPT) at 1 year. We compared the incidence of cardiovascular (CV) death, major and minor bleeding, and ischemic stroke later than 1 year after TAVR between the two groups. A total of 28 CV deaths were observed later than 1 year after TAVR. The stop-DAPT group had a significantly lower incidence of CV death than the DAPT group (1.8% vs. 4.9%, log-rank P = 0.029). Stop DAPT was associated with lower CV death later than 1 year of TAVR in Cox regression analysis (adjusted hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.20-0.99), and in analysis with inverse probability of treatment weighting method using propensity score (adjusted HR, 0.45; 95% CI, 0.20-0.98). Our study demonstrated that switching from DAPT to SAPT within 1 year of TAVR was significantly associated with a lower CV death later than 1 year after TAVR.