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Competing Interests: Conflict of interest: None declared.

Background: Hepatocellular carcinoma (HCC) is an aggressive subtype of liver cancer and is one of the most common cancers with high mortality worldwide. Reprogrammed lipid metabolism plays crucial roles in HCC cancer cell survival, growth, and evolution. Emerging evidence suggests the importance of fatty acid binding proteins (FABPs) in contribution to cancer progression and metastasis; however, how these FABPs are dysregulated in cancer cells, especially in HCC, and the roles of FABPs in cancer progression have not been well defined., Aim: To understand the genetic alterations and expression of FABPs and their associated cancer hallmarks and oncogenes in contributing to cancer malignancies., Methods: We used The Cancer Genome Atlas datasets of pan cancer and liver hepatocellular carcinoma (LIHC) as well as patient cohorts with other cancer types in this study. We investigated genetic alterations of FABPs in various cancer types. mRNA expression was used to determine if FABPs are abnormally expressed in tumor tissues compared to non-tumor controls and to investigate whether their expression correlates with patient clinical outcome, enriched cancer hallmarks and oncogenes previously reported for patients with HCC. We determined the protein levels of FABP5 and its correlated genes in two HCC cell lines and assessed the potential of FABP5 inhibition in treating HCC cells., Results: We discovered that a gene cluster including five FABP family members ( FABP4, FABP5, FABP8, FABP9 and FABP12 ) is frequently co-amplified in cancer. Amplification, in fact, is the most common genetic alteration for FABPs, leading to overexpression of FABPs. FABP5 showed the greatest differential mRNA expression comparing tumor with non-tumor tissues. High FABP5 expression correlates well with worse patient outcomes ( P < 0.05). FABP5 expression highly correlates with enrichment of G2M checkpoint ( r = 0.33, P = 1.1e-10), TP53 signaling pathway ( r = 0.22, P = 1.7e-5) and many genes in the gene sets such as CDK1 ( r = 0.56, P = 0), CDK4 ( r = 0.49, P = 0), and TP53 ( r = 0.22, P = 1.6e-5). Furthermore, FABP5 also correlates well with two co-expressed oncogenes PLK1 and BIRC5 in pan cancer especially in LIHC patients ( r = 0.58, P = 0; r = 0.58, P = 0; respectively). FABP5 high Huh7 cells also expressed higher protein levels of p53, BIRC5, CDK1, CDK2, and CDK4 than FABP5 low HepG2 cells. FABP5 inhibition more potently inhibited the tumor cell growth in Huh7 cells than in HepG2 cells., Conclusion: We discovered that FABP5 gene is frequently amplified in cancer, especially in HCC, leading to its significant elevated expression in HCC. Its high expression correlates well with worse patient outcome, enriched cancer hallmarks and oncogenes in HCC. FABP5 inhibition impaired the cell viability of FABP5 high Huh7 cells. All these support that FABP5 is a novel therapeutic target for treating FABP5 high HCC., Competing Interests: Conflict-of-interest statement: All authors have seen and agreed with the contents of the manuscript and there is no conflict of interest to declare., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Decisions regarding the optimal timing of intervention for asymptomatic aortic stenosis (AS) are controversial. The study aims to identify potential risk factors for asymptomatic patients with severe AS that are associated with worse prognosis and to evaluate the benefits of early interventions for asymptomatic patients presenting with one or more additional risk factors., Methods and Analysis: This is a non-interventional, prospective, open-label, multicentre registry study across China. A total of 1000 patients will be enrolled and categorised as symptomatic or asymptomatic. The primary endpoint is the occurrence of all-cause mortality, stroke, acute myocardial infarction and heart failure-related hospitalisation at 1-year follow-up. In asymptomatic severe AS patients presenting with one or more risk factors, the occurrence rate of the primary endpoint between those who undergo transcatheter aortic valve replacement (TAVR) and those who do not will be compared. We will also compare the occurrence rate of the primary endpoint for asymptomatic severe AS patients with additional risk factors who undergo TAVR with those presenting with symptoms. This study is believed to provide additional evidence to help clinicians identify and refer severe AS patients who are asymptomatic but present with additional risk factors for early intervention of TAVR., Ethics and Dissemination: The study protocol has been approved by the local ethics committee of each participating site: West China Hospital, Sichuan University; Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; Second Hospital of Hebei Medical University; Tianjin Chest Hospital; and First Affiliated Hospital of Nanchang University. All participants will provide written informed consent. Study results will be published through academic conferences and peer-reviewed journals., Trial Registration: This study was registered at the Chinese Clinical Trial Registry (https:// www.chictr.org.cn), with the registration number ChiCTR2200064853., Competing Interests: Competing interests: Dr Chen and Feng are consultants and proctors for Venus MedTech, MicroPort and TaurusOne. All other authors have nothing relevant to disclosure., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Data concerning the outcomes of transcatheter aortic valve replacement in type 0 bicuspid aortic stenosis (AS) are scarce. The study aims to compare the outcomes of transcatheter aortic valve replacement for AS in patients with type 0 bicuspid, type 1 bicuspid, and tricuspid aortic valve anatomy., Methods: We enrolled consecutive patients undergoing transcatheter aortic valve replacement for severe AS between 2012 and 2022 in this single-center retrospective cohort study. The primary outcome was mortality, while secondary outcomes included in-hospital complications such as stroke and pacemaker implantation and transcatheter heart valve hemodynamic performance., Results: The number of patients with AS with type 0 bicuspid, type 1 bicuspid, and tricuspid aortic valve anatomy was 328, 302, and 642, respectively. Self-expanding transcatheter heart valves were used in the majority of patients (n=1160; 91.4%). In the matched population, differences in mortality (30 days: 4.2% versus 1.7% versus 1.7%, P overall =0.522; 1 year: 10% versus 2.3% versus 6.2%, P overall =0.099) and all stroke (30 days: 1.0% versus 0.9% versus 0.0%, P overall =0.765; 1 year: 1.4% versus 1.6% versus 1.3%, P overall =NS) were nonsignificant, and the incidence of overall in-hospital complications was comparable among groups. Ascending aortic diameter was the single predictor of 1-year mortality in type 0 bicuspid patients (hazard ratio, 1.59 [95% CI, 1.03-2.44]; P =0.035). The proportion of patients with a mean residual gradient ≥20 mm Hg was the highest in those with type 0 bicuspid anatomy, although the need for permanent pacemaker implantation was the lowest in this group., Conclusions: Major clinical outcomes of transcatheter aortic valve replacement for AS in patients with type 0 bicuspid, type 1 bicuspid, and tricuspid aortic valve anatomy are equivalent at short- and mid-term follow-up. These observations merit further exploration in prospective international registries and randomized controlled trials., Competing Interests: Disclosures M. Chen and Dr Feng are proctors/consultants of Venus MedTech, MicroPort, and Peijia Medical. Dr Mylotte is a proctor and consultant for Medtronic and Microport and a consultant for Boston Scientific. Dr Piazza is a consultant and proctor for Medtronic and Peijia Medical. Dr Prendergast has received institutional educational and research grants from Edwards Lifesciences and speaker/consultancy fees from Abbott, Anteris, Edwards Lifesciences, Medtronic, and Microport. The other authors report no conflicts.

Despite encouraging advances in early diagnosis and treatment, cardiovascular diseases (CVDs) remained a leading cause of morbidity and mortality worldwide. Increasing evidence has shown that the electromagnetic field (EMF) influences many biological processes, which has attracted much attention for its potential therapeutic and diagnostic modalities in multiple diseases, such as musculoskeletal disorders and neurodegenerative diseases. Nonionizing EMF has been studied as a therapeutic or diagnostic tool in CVDs. In this review, we summarize the current literature ranging from in vitro to clinical studies focusing on the therapeutic potential (external EMF) and diagnostic potential (internal EMF generated from the heart) of EMF in CVDs. First, we provided an overview of the therapeutic potential of EMF and associated mechanisms in the context of CVDs, including cardiac arrhythmia, myocardial ischemia, atherosclerosis, and hypertension. Furthermore, we investigated the diagnostic and predictive value of magnetocardiography in CVDs. Finally, we discussed the critical steps necessary to translate this promising approach into clinical practice., (© 2023 Federation of American Societies for Experimental Biology.)

Background: The correlation between stable geomagnetic fields and unstable geomagnetic activities with mortality, incidence, and prevalence of cardiovascular diseases (CVDs) remains ambiguous., Method: To investigate the correlations between geomagnetic field (GMF) intensity and geomagnetic disturbance (GMD) and CVDs events in global, long-period scale, global and 204 countries and territories were included on the base of 2019 Global Burden of Disease study (GBD 2019). Data of GMF intensity, GMD frequency, CVDs events, weather and health economic indicators from 1996 to 2019 of included locations were collected. Linear regression and panel data modelling were conducted to identify the correlations between GMF intensity and CVDs events, multi-factor panel data analysis was also generated to adjust the effect of confounding factors., Results: For the average data during 1996-2019, linear regression model revealed consistent positive correlations between total GMF (tGMF) intensity and mortality of total CVDs [coef = 0.009, (0.006,0.011 95%CI)], whereas negative correlations were found between horizonal GMF (hGMF) intensity and total CVD mortality [coef = -0.010 (-0.013, -0.007 95%CI)]. When considering the time trend, panel data analysis still demonstrated positive correlation between tGMF and total CVDs mortality [coef = 0.009, (0.008,0.009 95%CI)]. Concurrently, the hGMF negatively correlated with total CVDs mortality [coef = -0.008, (-0.009, -0.007 95%CI)]. When the panel models were adjusted for confounding factors, no reverse of correlation tendency was found between tGMF, hGMF and CVDs events. In high-income territories, positive correlation was found between geomagnetic storm (GMS) frequency and mortality of total CVDs [coef = 14.007,(2.785, 25.229 95%CI)], however, this positive trend faded away gradually with the latitude decreasing from polar to equator., Conclusions: Stable and long-term horizontal component of GMF may be beneficial to cardiac health. Unstable and short-term GMF called GMD could be a hazard to cardiac health. Our results suggest the importance of regular GMF in maintaining cardio-health state and the adverse impacts of GMD on cardiac health., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The snare-assisted technique has been described to facilitate transcatheter aortic valve replacement (TAVR) delivery system advancement in complex aortic anatomies. However, the evidence is limited to case reports. To evaluate the safety profile of the snare-facilitated approach and its impact on self-expanding (SE) TAVR outcomes, we collected consecutive patients who underwent transfemoral SE-TAVR for aortic stenosis, using propensity score matching (PSM) separately in tricuspid and type-0 and type-1 bicuspid aortic valve morphology between the snare and non-snare groups. In 766 patients, despite the snare group having significantly larger annulus angulation and maximal ascending aortic diameter, both groups achieved comparable 30-day device success rates, regardless of first-generation or new-generation valve use. After PSM, the snare group had a significantly lower new permanent pacemaker implantation rate among 193 type-0 patients (3.3% vs. 18.3%, p = 0.01). The ipsilateral group used new-generation valves less frequently (23.0% vs. 75.4%, p < 0.001), but there were no significant inter-group differences in procedure-related events, except for a lower incidence of PVL ≥ mild in the ipsilateral group (14.9% vs. 32.3%, p = 0.01). In conclusion, the snare-assisted technique appears useful in SE-TAVR with angulated aortic root anatomy, and the benefits were comparable between ipsilateral and contralateral snare techniques.

Competing Interests: Conflict of interest: None declared.

Background: It is unknown whether the sex difference whereby female transcatheter aortic valve replacement (TAVR) candidates had a lower risk profile, a higher incidence of in-hospital complications, but more favorable short- and long-term survival observed in tricuspid cohorts undergoing TAVR would persist in patients with bicuspid aortic valves (BAVs)., Objectives: The aim of this study was to reexamine the impact of sex on outcomes following TAVR in patients with BAVs., Methods: In this single-center study, patients with BAVs undergoing TAVR for severe aortic stenosis from 2012 to 2021 were retrospectively included. Baseline characteristics, aortic root anatomy, and in-hospital and 1-year valve hemodynamic status and survival were compared between sexes., Results: A total of 510 patients with BAVs were included. At baseline, women presented with fewer comorbidities. Men had a greater proportion of Sievers type 1 BAV, higher calcium volumes (549.2 ± 408.4 mm 3 vs 920.8 ± 654.3 mm 3 ; P < 0.001), and larger aortic root structures. Women experienced more vascular complications (12.9% vs 4.9%; P = 0.002) and bleeding (11.1% vs 5.3%; P = 0.019) and higher residual gradients (16.9 ± 7.7 mm Hg vs 13.2 ± 6.4 mm Hg; P < 0.001), while men were more likely to undergo second valve implantations during index TAVR (6.3% vs 15.9%; P = 0.001). Death at 1 year was not significantly different between sexes (HR: 1.15; 95% CI: 0.56-2.35; P = 0.70). Bleeding (adjusted HR: 4.62; 95% CI: 1.51-14.12; P = 0.007) was the single independent predictor of 1-year death for women., Conclusions: In patients with BAVs undergoing TAVR, women presented with fewer comorbidities, while men had a greater proportion of type 1 BAV, more calcification, and larger aortic roots. In-hospital outcomes favored men, with fewer complications except for the need for second valve implantation, but 1-year survival was comparable between sexes., Competing Interests: Funding Support and Author Disclosures This work was supported by the National Natural Science Foundation of China (grants 81970325, 82170375, and 82102129); Sichuan Province Department of Science and Technology (grant number 2022YFS0364); West China Hospital “1·3·5” Discipline of Excellence Project “Percutaneous Transcatheter Aortic Valve Implantation” and “Mechanisms of Aortic Stenosis and the Clinical Applications”; and a fellowship of the China Postdoctoral Science Foundation (2020M683327). Drs Mao Chen and Feng are proctors and consultants for Venus MedTech, MicroPort, and Peijia Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Some patients referred for transcatheter aortic valve replacement (TAVR) have excessively large annuli (ELA) without device options according to current sizing charts. This retrospective study aims to summarize the presentation and outcomes of ELA patients receiving first-generation self-expanding valves., Methods: The TAVR database was reviewed in search for cases of self-expanding valves. Patients who had annuli exceeding the perimeter limit on the device sizing chart were referred to as the ELA group. Patients who had annuli within the range covered by the two largest sizes and received the corresponding valve size served as the control group (CG). Baseline, procedures, outcomes, and imaging characteristics on multislice computed tomography (MSCT), such as native anatomy and postimplant stent geometry, were compared., Results: A total of 28 patients were included in the ELA group and 82 in the CG. The patients in the ELA group were younger than those in the CG (72.5 ± 6.2 vs. 75.4 ± 5.8 years, P = 0.03). The median intended perimeter oversizing in relation to the annulus in the ELA group was much smaller than in the CG (-0.4 [-4.6, 4.1] % vs. 16.1 [11.7, 20.8] %, P < 0.01). The calcium burden in the aortic root was around 1.3-fold greater in the ELA group than the CG (756.0 [534.5, 1670.9] vs. 582.1 [310.3, 870.9] mm 3 , P = 0.01). The need for second valve implantation was higher in ELA (21.4% vs. 12.2%, P = 0.23) but no valve embolization was encountered. The 1‑year follow-up was comparable, including >mild paravalvular leak., Conclusion: Under cautious patient selection using MSCT, TAVR with self-expanding valves in patients with ELA appears feasible. Supra-annular structures likely provide the extra anchoring., (© 2020. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Hepatocellular carcinoma (HCC), often diagnosed at advanced stages without curative therapies, is the fifth most common malignant cancer and the second leading cause of cancer-related mortality. Polo-like kinase 1 (PLK1) is activated in the late G2 phase of the cell cycle and is required for entry to mitosis. Interestingly, PLK1 is overexpressed in many HCC patients and is highly associated with poor clinical outcome. Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) is also highly overexpressed in HCC and plays key roles in this malignancy., Aim: To determine the expression patterns of PLK1 and BIRC5, as well as their correlation with p53 mutation status and patient clinical outcome., Methods: The expression patterns of PLK1 and BIRC5, and their correlation with p53 mutation status or patient clinical outcome were analyzed using a TCGA HCC dataset. Cell viability, cell apoptosis, and cell cycle arrest assays were conducted to investigate the efficacy of the PLK1 inhibitors volasertib and GSK461364 and the BIRC5 inhibitor YM155, alone or in combination. The in vivo efficacy of volasertib and YM155, alone or in combination, was assessed in p53-mutated Huh7-derived xenograft models in immune-deficient NSIG mice., Results: Our bioinformatics analysis using a TCGA HCC dataset revealed that PLK1 and BIRC5 were overexpressed in the same patient subset and their expression was highly correlated. The overexpression of both PLK1 and BIRC5 was more frequently detected in HCC with p53 mutations. High PLK1 or BIRC5 expression significantly correlated with poor clinical outcome. PLK1 inhibitors (volasertib and GSK461364) or a BIRC5 inhibitor (YM155) selectively targeted Huh7 cells with mutated p53, but not HepG2 cells with wild-type p53. The combination treatment of volasertib and YM155 synergistically inhibited the viability of Huh7 cells via apoptotic pathway. The efficacy of volasertib and YM155, alone or in combination, was validated in vivo in a Huh7-derived xenograft model., Conclusion: PLK1 and BIRC5 are highly co-expressed in p53-mutated HCC and inhibition of both PLK1 and BIRC5 synergistically compromises the viability of p53-mutated HCC cells in vitro and in vivo ., Competing Interests: Conflict-of-interest statement: All authors have nothing to disclose., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: To explore why bicuspid aortic stenosis has certain clinical differences from the tricuspid morphology, we evaluated the metabolomics profile involved in bicuspid aortic valve (BAV) aortic stenosis prior to and after transcatheter aortic valve replacement (TAVR) in comparison with tricuspid aortic valve (TAV)., Methods: In this TAVR cohort with prospectively collected data, blood samples were obtained before TAVR valve deployment and at the 7th day after TAVR, which were then sent for liquid and gas chromatography-mass spectrometry detection. Besides comparisons between BAV and TAV, BAV patients were also divided in subgroups according to baseline hemodynamics (i.e. maximal transaortic velocity, V max ) and post-procedural reverse left ventricular (LV) remodeling (i.e. the change in LV mass index from baseline, ∆LVMI) for further analysis. Metabolic differences between groups were identified by integrating univariate test, multivariate analysis and weighted correlation network analysis algorithm., Results: A total of 57 patients were enrolled including 33 BAV patients. The BAV group showed lower arginine and proline metabolism both before and post TAVR than TAV represented by decreased expression of L-Glutamine. In BAV subgroup analysis, patients with baseline V max  > 5 m/s (n = 11) or the 4 th quartile of change in ∆LVMI at one-year follow-up (i.e. poorly-recovered LV, n = 8) showed elevated arachidonic acid metabolism compared with V max  < 4.5 m/s (n = 12) or the 1 st quartile of ∆LVMI (i.e. well-recovered LV, n = 8) respectively., Conclusions: Difference in arginine and proline metabolism was identified between BAV and TAV in TAVR recipients. Elevated arachidonic acid metabolism may reflect more severe baseline hemodynamics and worse LV reserve remodeling after TAVR in BAV.

Background: The 3rd generations of transcatheter heart valve system, including Edwards SAPIEN S3 (ES3) and Medtronic's Evolut R, has been developed to specifically improve the safety of transcatheter aortic valve implantation (TAVI). The aim of this work was to provide a summary effect estimate of the peri-procedural characteristics and clinical outcome of patients treated with ES3 versus the Evolut R., Methods: We conducted a literature search of PubMed, Ovid and EMBASE (2002 to 2018). Two authors extracted the data independently. The safety and feasibility of Sapien 3 and Evolut R were compared by odds ratios (ORs) with 95% confidence intervals (CIs) in inverse variance method., Results: After a multi-step assessment, a total 6 studies were finally included, yielding 1,664 patients, of which, 768 (46%) used ES3 and 896 (54%) used Evolut R. There was no statistical difference with device success rate (OR 1.15, 95% CI: 0.70-1.91, I2 =0%), 30-day mortality [OR: 0.72 (0.33-1.57), I2 =0%], pre-dilation rate, 30-day stroke, bleeding complication (BC) (major and life-threating), major vascular complication (VC), and paravalvular leakage between the two groups. However, the ES3 group was associated with a higher risk of acute kidney injury (AKI), higher mean aortic valve gradient and better mean left ventricular ejection fraction (LVEF) after TAVR procedure. Moreover, the Evolut R group had a higher rate of post-dilation and new permanent pacemaker implantation (PPMI)., Conclusions: Both devices had demonstrated excellent procedural success rate and short-term safety. At 30-day follow-up, both devices shared similar rates of mortality, BC, VC, stroke, and paravalvular leakage (PVL). However, the rate of AKI was higher in the ES3 group, and the rate of PPM was higher in the Evolut R group.

Objectives: We evaluated the safety and usefulness of preparatory anatomical reshaping with a geometric hourglass-shaped balloon to optimize transcatheter aortic valve replacement (TAVR) outcomes in bicuspid aortic valve (BAV) stenosis., Background: TAVR has been increasingly performed for BAV stenosis; however, technical challenges remain. Procedural results are suboptimal given unfavorable valvular anatomies., Methods: Eligible patients with BAV stenosis were enrolled to undergo aortic valve predilatation with the hourglass-shaped TAV8 balloon before TAVR using the self-expandable Venus A-Valve. Procedural details and outcomes were compared to a sequential group of patients with BAV who underwent TAVR with the same device following preparatory dilatation using a cylindrical balloon., Results: A total of 22 patients were enrolled in the TAV8 group and 53 were included in the control group. Valve downsizing was less common in the TAV8 group (36.4 vs. 67.9%; p = .012). Stable valve release and optimal implant depth were consistently achieved in the TAV8 group with no requirement for a second valve (0 vs. 17.0%; p = .039) and with higher device success rates (100.0 vs 77.4%; p = .014). Residual aortic regurgitation graded as ≥mild was less common in the TAV8 group (13.6 vs 45.3%; p = .009). Mortality was similar (0 vs. 3.8%; p = 1); no major/disabling stroke or conversion to open-heart surgery was seen in either group within 30 days., Conclusions: Compared with standard cylindrical balloon valvuloplasty, preparatory reshaping with the hourglass-shaped balloon before self-expandable TAVR in BAV was associated with significantly better procedural results and may encourage more promising outcomes., (© 2020 Wiley Periodicals, Inc.)

Purpose: Studies on genetic alterations of the heterogenous small cell lung cancer (SCLC) are rare. We carried out the present study to clarify the genomic alterations and TMB levels of Chinese SCLC patients by whole-exome sequencing., Materials and Methods: Whole-exome sequencing by next-generation sequencing technique was implemented on twenty SCLC samples. Significant somatic mutations and copy number variations were screened, followed by comparison with the data extracted from COSMIC. Besides, altered signaling pathways were examined in order to figure out actionable targets., Results: A total of 8,062 nonsynonymous mutations were defined. The number of mutations for each case ranged from 98 to 864. As for base substitutions, a total of 15,817 substitutions were detected with C > A conversion which was correlated to smoking occupying 25.57%. The TMB values ranged from 2.51/Mb to 22.1/Mb with a median value of 9.95/Mb. RB1 was the most frequently mutated gene altered in 18 (90%) cases, followed by TP53 altered in 17 (85%) cases. Other commonly changed genes were PTEN , and RBL1 , with frequencies of 55% and 50%, respectively. SOX2 significantly amplified in 6 (30%) cases and MYCN amplified in 1 (5%) patient. Notch signaling pathway and PI3K/AKT/mTOR signaling pathway were universally and significantly changed. Major genomic alterations were in consistency with data from COSMIC, but frequencies of less common mutations were different., Conclusion: TP53 and RB1 inactivations were universally detected in SCLC. The Notch and PI3K/AKT/mTOR signaling pathways were both significantly altered, implying potential actionable targets., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Shan Su et al.)

Objectives: We aimed to assess the procedural and clinical results of transcatheter aortic valve replacement (TAVR) for nonraphe bicuspid aortic stenosis (AS) with coronary vs mixed cusp fusion., Background: It remains unclear whether cusp fusion morphology affects TAVR outcomes in patients with nonraphe bicuspid AS., Methods: This retrospective study enrolled consecutive patients with severe symptomatic AS and type-0 bicuspid aortic valve, who underwent TAVR at our institution between 2012 and 2017. TAVR outcomes were defined based on the Valve Academic Research Consortium-2 recommendations., Results: Compared to patients with mixed cusp fusion (44/71), those with coronary cusp fusion (27/71) had a larger ellipticity index for the aortic annulus (21.9% ± 9.0% vs 15.6% ± 9.3%, p =0.007) and increased left ventricular outflow tract obstruction (31.1% ± 9.4% vs 26.9% ± 7.5%, p =0.04) but comparable rates of second valve implantation (15.9% vs 14.8%), mild paravalvular leakage (PVL, 38.5% vs 30.2%), permanent pacemaker implantation (PPM, 25.9% vs 15.9%), and 30-day mortality (7.4% vs 6.8%). Use of a first-generation transcatheter heart valve was associated with higher risk for mild PVL (odds ratio (OR) = 4.37; 95% confidence interval (95% CI) = 1.14-16.75; p =0.03) but not PPM (OR = 0.77; 95% CI = 0.22-2.62; p =0.67), whereas a larger oversizing ratio tended to be associated with a higher PPM rate (OR = 1.49; 95% CI = 0.46-4.86; p =0.51) but lower incidence of mild PVL (OR = 0.51; 95% CI = 0.19-1.35; p =0.17)., Conclusions: In AS patients with type-0 bicuspid valves, cusp fusion morphology does not affect the procedural or clinical results of TAVR. Use of second-generation transcatheter heart valves may provide more favorable results in such patients. This trial is registered with NCT01683474., Competing Interests: Yuan Feng and Mao Chen are consultants/proctors of Venus MedTech. Other authors declared no conflicts of interest., (Copyright © 2019 Wen-hua Lei et al.)

The present study was designed to analyze and compare phytochemical activities of four different cultivars of kiwifruit. Among all investigated varieties, Hua You (HY) and Cui Xiang (CUX) displayed the maximum concentration of phytochemical content, and the highest total phenolic results were observed in HY and CUX cultivars with 220.20 ± 1.12 mg GAE/100 g and 218.04 ± 1.11 mg GAE/100 g FW, respectively. Likewise, the richest total flavonoids results were estimated in red kiwifruit (RKF) and CUX varieties with 49.082 ± 0.14 mg CE/100 g FW and 48.327 ± 0.14 mg CE/100 g FW, respectively. Moreover, tests for oxygen radical scavenging capacity (ORAC) and peroxyl radical scavenging capacity (PSC) were observed maximum in RKF cultivar showing 131.229 ± 5.91 μM Trolox equivalent/g FW and 85.957 ± 11.75 μM vitamin C equivalent/g FW, respectively. Furthermore, the highest cellular antioxidant activity (CAA) with No PBS wash protocol was depicted in RKF 237.544 ± 4.12 μM QE equivalent/g FW with the lowest EC 50 0.0128 mg/ml. In addition, high-performance liquid chromatography (HPLC) analysis confirmed the presence of ferulic acid, naringin, gallic acid, syringic acid, caffeic acid, rutin, protocatechuic acid, salicylic acid, and catechin in kiwifruit. Catechin as one main content in our study is consistent with the recent reports. The result suggested that the phytochemical profile and bioactivities were significantly affected by the type of cultivars. PRACTICAL APPLICATIONS: Kiwifruit is widely consumed over the world for its rich nutritious and medicinal values. Currently, phytochemicals are considered as one of the main bioactive components of kiwifruits, which are responsible for lots of bioactivities, such as antitumor, anti-inflammatory, antioxidant, hypoglycemic, and hypolipidemic activities. There are varieties of kiwifruits, and the bioactive components and bioactivities are greatly affected by the cultivars. But there have been no comparative studies on the phytochemicals from different varieties. This study aimed to make a comprehensive assessments of the free, bound, and total phenolics and flavonoids, as well as the chemical-based and cell-based antioxidant activities of four different subspecies of kiwifruit. This work would be beneficial to elucidate the function differences of different kiwifruit phytochemicals, promote its further research, as well as provide a basis for selecting cultivars., (© 2019 Wiley Periodicals, Inc.)

Stromal cell-derived factor-1 (SDF-1) is a well-characterized cytokine that protects heart from ischaemic injury. However, the beneficial effects of native SDF-1, in terms of promoting myocardial repair, are limited by its low concentration in the ischaemic myocardium. Annexin V (AnxA5) can precisely detect dead cells in vivo. As massive cardiomyocytes die after MI, we hypothesize that AnxA5 can be used as an anchor to carry SDF-1 to the ischaemic myocardium. In this study, we constructed a fusion protein consisting of SDF-1 and AnxA5 domains. The receptor competition assay revealed that SDF-1-AnxA5 had high binding affinity to SDF-1 receptor CXCR4. The treatment of SDF-1-AnxA5 could significantly promote phosphorylation of AKT and ERK and induce chemotactic response, angiogenesis and cell survival in vitro. The binding membrane assay and immunofluorescence revealed that AnxA5 domain had the ability to specifically recognize and bind to cells injured by hypoxia. Furthermore, SDF-1-AnxA5 administered via peripheral vein could accumulate at the infarcted myocardium in vivo. The treatment with SDF-1-AnxA5 attenuated cell apoptosis, enhanced angiogenesis, reduced infarcted size and improved cardiac function after mouse myocardial infarction. Our results suggest that the bifunctional SDF-1-AnxA5 can specifically bind to dead cells. The systemic administration of bifunctional SDF-1-AnxA5 effectively provides cardioprotection after myocardial infarction., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Objectives: The natural history of ascending aortic diameter after transcatheter aortic valve implantation (TAVI) has not been investigated. Our aim was to determine the progression of ascending aortic diameter in patients undergoing TAVI., Methods: We retrospectively included 134 patients undergoing TAVI for aortic stenosis at our institution from June 2012 to November 2016, including 79 patients with bicuspid aortic valve (BAV) and 55 patients with tricuspid aortic valve (TAV). Preoperative measurements of the ascending aorta were compared with aortic measurements at 1-year follow-up based on computed tomography images., Results: A very slight decrease in median aortic diameter was identified in overall patients: 4.07 cm (interquartile range [IQR], 3.76-4.54 cm) vs 4.06 cm (IQR, 3.74-4.51 cm); P=.04. Further subgroup analysis found that the decrease remained statistically significant in the subgroup of TAV and mild aortic dilation. In addition, no aortic events occurred during long-term follow-up (median, 27 months; IQR, 20-42 months)., Conclusions: TAVI could prevent a further progression of aortic diameter for both BAV or TAV patients by correcting hemodynamic derangements, especially for patients with TAV, mild aortic dilation, and small annulus angles. Aortic events appeared rarely during long-term follow-up after TAVI. However, our results need further confirmation with future investigations in a larger population with longer-term follow-up.

Objectives: The authors sought to better understand the stent geometry of the Lotus valve after transcatheter aortic valve replacement (TAVR) and its potential implications for valve size selection., Background: The authors hypothesized that the greatest interference between the frame and aortic valvar complex occurs across the aortic valve leaflets., Methods: The authors retrospectively analyzed the multidetector computed tomography (MDCT) scans of 32 consecutive patients undergoing Lotus valve (Boston Scientific, Natick, Massachusetts) implantation. The prosthesis cross section was analyzed at 3-mm increments along its length. The plane where the frame had the smallest area was defined as the waist. The corresponding plane of the waist on pre-procedural MDCT was identified by surrounding structures such as calcium deposits, commissural fusion, and commissural gaps, and was referred to as the supra-annulus. The spline of the supra-annulus was circumscribed with reference to the post-implant stent geometry at the waist., Results: The waist was 5.8 ± 1.7 mm higher than the native annulus on post-procedural MDCT. The waist had a nearly 2-fold larger compression rate than the stent at the native annulus level (36.3 ± 10.4% vs. 18.9 ± 9.6%; p < 0.01), irrespective of valve morphologies. The supra-annulus was 5.9 ± 1.6 mm higher than the annulus on pre-procedural MDCT. Patients had an approximately 17% decrease in area from the annulus to the supra-annulus (18.3 ± 4.4% for bicuspid morphology and 16.0 ± 3.5% for tricuspid morphology)., Conclusions: Major interference between the implanted prosthesis and anatomy occurred at a level above the annulus. The decrease in area from the annulus to supra-annulus may explain the feasibility of implanting a smaller valve than that suggested by traditional annular measurements., (Copyright © 2019. Published by Elsevier Inc.)

Background: The role of triglyceride (TG) in secondary prevention of patients with coronary artery disease (CAD) was debated. In the present study, we assessed the association between admission TG levels and long-term mortality risk in CAD patients., Methods: A retrospective analysis was conducted from a single registered database. 3061 consecutive patients with CAD confirmed by coronary angiography were enrolled and were grouped into 3 categories by the tertiles of admission serum TG levels. The primary end point in this study was all-cause mortality and the secondary end point was cardiovascular mortality., Results: The mean follow-up time was 26.9 ± 13.6 months and death events occurred in 258 cases and cardiovascular death events occurred in 146 cases. Cumulative survival curves indicated that the risk of all-cause death decreased with increasing TG level (Tertile 1 vs. Tertile 2 vs. Tertile 3 = 10.3% vs. 8.6% vs. 6.3%, log rank test for overall p = 0.001). Cox regression analysis showed an independent correlation between TG level and risk of all-cause mortality [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58-0.86] and cardiovascular mortality (HR 0.67, 95% CI 0.51-0.89) in total patients with CAD. Subgroup analysis found the similar results in patients with acute coronary syndrome and acute myocardial infarction., Conclusions: This study found an inverse association between TG levels and mortality risk in CAD patients, which suggests that the "TG paradox" may exist in CAD patients., Trial Registration: ChiCTR, ChiCTR-OOC-17010433 . Registered 17 February 2017 - Retrospectively registered.

Background: Studies of permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR) specifically for bicuspid aortic valve (BAV) patients are lacking. We aim to delineate possible aspects that might affect the incidence of PPI in a retrospective cohort of BAV patients treated with early-generation self-expanding devices., Methods: A total of 80 patients with bicuspid morphology who successfully underwent TAVR by self-expanding devices without prior PPI were included. Baseline clinical, echocardiographic, and angiographic characteristics, procedural and post-procedural details were collected., Results: The incidence of PPI after early-generation self-expanding valves in this BAV cohort was 26.3%. Baseline characteristics were comparable between patients requiring PPI post-TAVR or not. Perimeter oversizing greater than 20% significantly increased the risk of PPI compared with an oversizing of 10-20% (OR 5.08 [1.22, 21.07], P = 0.03). The proportion of patients with a depth of implantation greater than 6 mm was significantly higher in those who required PPI (82.4% vs 54.3%, P = 0.04). When testing the impact of depth of implantation >6 mm and oversizing in different morphologies, only in type 1 bicuspid patients and by oversizing>20% increased the risk of PPI (OR 12.00 [1.25, 115.36], P = 0.03) compared with an oversizing of 10-20%., Conclusions: Excessive perimeter oversizing in relation to aortic annulus and depth of implantation greater than 6 mm should be avoided to improve PPI post-TAVR for BAV patients receiving self-expanding devices, especially for type 1 BAV., (© 2018 Wiley Periodicals, Inc.)

To compare reverse left ventricular (LV) remodeling after transcatheter aortic valve replacement (TAVR) between patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). We retrospectively reviewed data of patients with at least two serial echocardiographic follow-ups (1, 3, 6 months and 1 year) post-TAVR. A total of 116 patients were identified. BAV morphology was documented in 67 patients. LV mass index (LVMi) at baseline was not significantly different between the TAV and BAV group (178.0 ± 6.9 vs. 166.3 ± 6.4 g/m 2 , P = 0.14). Reverse LV remodeling was observed in both BAV and TAV patients, but the reduction of LVMi from baseline was significantly more pronounced in TAV patients compared with BAV patients from 6 months post-TAVR (- 56.3 ± 8.1 vs. - 30.0 ± 4.7 g/m 2 , P < 0.01 at 6-month follow-up; - 60.6 ± 7.6 vs. - 37.9 ± 6.2 g/m 2 , P = 0.02 at 1-year follow-up). EDV value changes during follow-up were similar between patient with TAV and BAV. There were no significant differences in the proportions of patients with more than mild PVL or new permanent pacemaker between TAV and BAV morphology throughout the follow-up. Patients with bicuspid morphology might experience less pronounced reverse LV remodeling post-TAVR than patients with tricuspid morphology.

Subclinical leaflet thrombosis has been increasingly recognized as a common imaging finding after surgical or transcatheter aortic valve replacement (TAVR) in recent studies. This finding has raised concerns over TAVR valve durability and debates on optimal postprocedural antithrombotic regime. Hypoattenuated leaflet thickening (HALT) and the associated reduced leaflet motion (RELM) were noted as computed tomography hallmarks of the phenomenon. The coexistence of HALT and significant RELM has been suggested as a threshold for reporting of subclinical leaflet thrombosis. This methodology may contribute to the standardization of reporting for research collaboration, hence the better understanding and management of this common yet largely unknown phenomenon., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The imaging finding of hypo-attenuated leaflet thickening (HALT) on bioprosthesis after transcatheter aortic valve replacement (TAVR) has been reported. The underlying mechanism is not clear, but leaflet thrombosis is speculated to be the cause. Heterogeneous antiplatelet responses may play a role in the process. This is a prospective, single-center pilot study in patients who received successful TAVR from June 2012 to November 2016. HALT on post-procedural multi-detector computed tomography. We thoroughly genotyped 34 SNPs and 8 SNPs that have been reported for clopidogrel and aspirin resistance. A total of 148 patients were enrolled. There were 15 patients demonstrating signs of HALT. Patients with HALT had a higher rate of atrial fibrillation (AF) pre-TAVR (33.3 vs. 7.5%, P = 0.01). We found that rs4244285 G>A polymorphism of the CYP2C19 gene was associated with the risk of HALT in the overdominant model (OR 4.00 [1.15-13.97], P = 0.02 for GA vs. GG+AA) adjusted by sex and the presence of pre-TAVR AF. Antiplatelet drug resistance is a reasonable possibility involved in HALT. Potential directions were suggested in polymorphisms of the CYP2C19 gene.

Background: Limited date describing the procedural, clinical and valve performance results of transcatheter aortic valve replacement (TAVR) in patients with bicuspid versus tricuspid aortic stenosis (TAV)., Methods: Procedural and clinical results were defined and reported according to VARC-2 criteria., Results: Consecutive 87 patients with BAV and 70 patients with TAV were included. Compared to patients with TAV, patients with BAV had similar incidence of second valve implantation (14.9% vs 12.9%, p=0.708), more than mild paravalvular leakage (PVL, 40.2% vs 31.9%, p=0.288), permanent pacemaker implantation (PPM, 24.1% vs 28.6%, p=0.53). Furthermore, the procedural and clinical results of TAVR also did not differ between patients with type 0 and type 1 (second valve implantation: 18.4% vs 11.8%, p=0.71, PVL: 38.8% vs 41.2%, p=0.83, PPM: 18.4% vs 31.6%, p=0.16). The hemodynamic outcomes were similar in patients with BAV and TAV at 1-year (maximum velocity, 2.3 vs 2.2m/s, p=0.307) and 2-year (2.3 vs 2.1m/s, p=0.184) follow-up respectively. Adjusted binary logistic regression analysis found oversizing ratio at 14.45-20.57% is at lower risk for more than mild PVL (OR, 0.069, 95% CI, 0.011-0.428, p=0.004). Moreover, the Kaplan-Meier survival analysis revealed that TAVR in type 0 BAV, type 1 BAV and TAV have comparable risk for midterm mortality (Log rank, p=0.772)., Conclusion: TAVR in whatever type of BAV appeared to be safe and efficacy, and TAVR in BAV was associated with comparable bioprosthetic function during follow up compared to patients with TAV., (Copyright © 2017. Published by Elsevier B.V.)

Aims: Limited information exists describing the results of transcatheter aortic valve replacement (TAVR) in patients with symptomatic severe non-calcific aortic stenosis (AS). We aimed to compare procedural, echocardiographic, and clinical outcomes among patients with non-calcific AS with those of senile calcific AS undergoing TAVR., Methods and Results: We retrospectively identified patients with non-calcific AS who received TAVR with self-expanding transcatheter heart valves in our centre. Clinical and echocardiographic outcomes, and post-procedural multi-detector computed tomography (MDCT) measures were compared to those in patients undergoing TAVR for calcific AS. Among 136 patients, 21 patients (15.4%) with native leaflet thickening and minimal calcification were identified (non-calcific group). The patients were significantly younger in the non-calcific group (70.0 [64.0-75.5] vs. 75.0 [69.0-78.0] years) with comparable STS-PROM scores (6.7 [4.8-8.9] vs. 8.2 [4.8-10.9] %). Predilation was performed less frequently (42.9% vs. 93.9%) and post-dilation more often (71.4% vs. 42.6%) in the non-calcific group. Both 30-day and one-year mortality were similar between groups (0% vs. 7.8% and 0% vs. 17.6%). Rates of post-implantation paravalvular leak ≥mild at six months (17.6% vs. 25.7%) were comparable despite lower implantation depth among non-calcific AS patients (10.9±5.7 vs. 7.2±4.3 mm) on post-implantation MDCT., Conclusions: TAVR with self-expanding transcatheter heart valves appears to be safe and effective in patients with non-calcific AS.

The aim of this study was to investigate the incidence, predictors and outcome of prosthesis-patient mismatch (PPM) following transcatheter aortic valve replacement (TAVR). A total of 30 articles incorporating 4,691 patients were identified. The pooled incidences of overall, moderate and severe PPM following TAVR were 33.0%, 25.0% and 11.0% respectively. Medtronic CoreValve (MCV) had lower incidence of overall (32% vs: 40%, P < 0.0001) and moderate (23% vs 32%, P < 0.0001) than Edwards Sapien (ESV). PPM was associated with a younger age, smaller annulus diameter and lower left ventricular ejection fraction in comparison with those patients without PPM. Post-dilation (OR, 0.51, 95% CI, 0.38 to 0.68, p < 0.001) during TAVR would decrease the incidence of PPM. Although PPM was common after TAVR, no significant differences were observed both in short- and mid-term all-cause mortality (30 day: OR: 1.1, 95% CI, 0.70 to 1.73 and 2 year: OR: 1.01, 95% CI, 0.74 to 1.38) between patients with PPM and those without PPM. In conclusion, despite being common after TAVR, the incidence of PPM was lower than that of surgical aortic valve replacement (SAVR) and decreased with the experience accumulating, and PPM was not seen to impact on short- and mid-term survival, regardless of its magnitude.

Aims: The aim of this systematic review and meta-analysis was to investigate the predictors and outcome of acute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI)., Methods and Results: There were 35 articles recruiting 13,256 patients included in our study. Hypertension (odds ratio [OR] 1.92, 95% CI: 1.44 to 2.56), diabetes mellitus (OR 1.33, 95% CI: 1.20 to 1.47), peripheral artery disease (OR 1.28, 95% CI: 1.14 to 1.45) and a left ventricular ejection fraction <40% (OR 1.50, 95% CI: 1.19 to 1.88) were identified as significant independent predictors of AKI. In addition to the aforementioned comorbidities, procedure-related/post-TAVI factors such as transapical access (OR 1.68, 95% CI: 1.44 to 1.97), major bleeding (OR 1.82, 95% CI: 1.37 to 2.40) and transfusion (OR 1.30, 95% CI: 1.12 to 1.51) were also associated with a higher risk of AKI. Importantly, the risk of short-term all-cause death increased progressively with the aggravating severity of AKI (OR, 30 days: stage 1: 3.41; stage 2: 4.0; stage 3: 11.02; one year: stage 1: 1.95; stage 2: 2.82; stage 3: 7.34), as determined by a univariate analysis. After eliminating confounders, AKI remained linked to a higher risk for both short-term (30 days: HR 2.12, 95% CI: 1.59 to 2.83) and long-term (≥3 years: HR 1.37, 95% CI: 1.27 to 1.48) all-cause mortality., Conclusions: The reason for the occurrence of AKI was multifactorial, including baseline characteristics, procedure-related and post-TAVI factors. It appeared that even stage 1 AKI exerted detrimental effects on survival within one year, and AKI was also independently linked to mortality beyond three years.

Background: Transcatheter aortic valve implantation (TAVI) has been demonstrated to be an effective alternative to surgical aortic valve replacement (SAVR) in patients with aortic stenosis who are deemed high risk or inoperable. Currently, TAVI procedures in China mostly make use of the domestic Venus A-Valve and the CoreValve; however, there is no data on their comparative performance., Methods: Consecutive patients undergoing TAVI with the aforementioned devices were included. The outcomes were reported according to the Valve Academic Research Consortium-2 (VARC) definitions., Results: A total of 54 TAVI procedures were performed, 27 with the CoreValve and the other 27 with the Venus A-Valve. An additional valve was required in 4 (14.8%) and 3 (11.1%) patients, and the VARC-2 device success rates were 81.5 and 85.2%, respectively. The incidences of common complications were similar, except for the significantly less frequent pacemaker insertion in the Venus A-Valve group (7.4 vs. 37.0%, P = 0.03). Within 30 days, 2 (3.7%) patients died, 1 in each group, and both had a bicuspid aortic valve (BAV). No other serious complications, such as annular rupture, coronary obstruction and aortic dissection, occurred in the 32 BAV patients treated with the Venus A-Valve (14) or the CoreValve (18). After 2-years of follow-up, there was no significant difference between CoreValve group and Venus-A group (11.1 vs. 7.4%, P = 0.64)., Conclusion: TAVI with the domestic Venus A-Valve is feasible, safe, and can produce favorable short-term outcomes comparable to those with the CoreValve in inoperable or high-risk patients with tricuspid and bicuspid aortic valve stenosis. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background: To investigate the individual sequential hemodynamic changes after transcatheter aortic valve implantation (TAVI), especially for patients with bicuspid aortic valve (BAV), in comparison with tricuspid aortic valve (TAV)., Methods: The study population comprised 85 patients with severe aortic stenosis who underwent TAVI for BAV (n = 49) or TAV (n = 36) with at least two serial echocardiographic follow-ups. Doppler echocardiography was scheduled to be performed at discharge and 1, 3, 6 months and 1 year after the procedure. D peak transvalvular velocities and D mean transvalvular gradients were calculated as the difference at follow-up time points and discharge. Paravalvular leak (PVL) was assessed as another indicator for prosthesis performance., Results: Comparisons between patients with BAV and TAV revealed similar gradient performances (1.00 [-2.00, 2.00] vs. 1.00 [-0.25, 5.00] mm Hg, p = 0.57 at 1 month; -0.71 ± 7.52 vs. 1.55 ± 3.97 mm Hg, p = 0.21 at 3 months; 0.96 ± 7.81 vs. 1.53 ± 5.85 mm Hg, p = 0.79 at 6 months; 1.00 [-0.50, 2.25] vs. 3.00 [-0.50, 7.50] mm Hg, p = 0.07 at 1 year). Moreover, the incidence of ≥ mild PVL was not significantly different in patients with BAV and TAV during follow-up (34.88% vs. 19.35%, p = 0.14 at 1 month; 45.83% vs. 27.27%, p = 0.19 at 3 months; 30.00% vs. 23.53%, p = 0.89 at 6 months; 30.00% vs. 17.65%, p = 0.56 at 1 year)., Conclusions: TAVI is effective and applicable in BAV anatomy with sustained and acceptable mid- -term prosthesis hemodynamic performance. (Cardiol J 2017; 24, 4: 350-357).

Objectives: This study sought to evaluate transcatheter aortic valve replacement (TAVR) in bicuspid aortic valve (BAV) aortic stenosis (AS), with a particular emphasis on TAVR-directed bicuspid aortic valve imaging (BAVi) of morphological classification., Background: TAVR has been used to treat BAV-AS but with heterogeneous outcomes and uncertainty regarding the relevance of morphology., Methods: In 14 centers in the United States, Canada, Europe, and Asia, 130 BAV-AS patients underwent TAVR. Baseline cardiac computed tomography (CT) was analyzed by a dedicated Corelab. Outcomes were assessed in line with Valve Academic Research Consortium criteria., Results: Bicommissural BAV (vs. tricommissural) accounted for 68.9% of those treated in North America, 88.9% in Europe, and 95.5% in Asia (p = 0.003). For bicommissural bicuspids, non-raphe type (vs. raphe type) BAV accounted for 11.9% of those treated in North America, 9.4% in Europe, and 61.9% in Asia (p < 0.001). Overall rates of 30-day mortality (3.8%) and cerebrovascular events (3.2%) were favorable and similar among anatomical subsets. The rate of new permanent pacemaker insertion was high (26.2%) and similar between balloon-expandable (BE) and self-expanding (SE) designs (BE: 25.5% vs. SE: 26.9%; p = 0.83); there was a trend to greater permanent pacemaker insertion in BE TAVR in the presence of coronary cusp fusion BAV morphology. Paravalvular aortic regurgitation (PAR) ≥ moderate was 18.1% overall but lower at 11.5% in those with pre-procedural CT. In the absence of pre-procedural CT, there was an excess of PAR in BE TAVR that was not the case in those with a pre-procedural CT; SE TAVR required more post-dilation. Predictors of PAR included intercommissural distance for bicommissural bicuspids (odd ratio [OR]: 1.37; 95% confidence interval [CI]: 1.02 to 1.84; p = 0.036) and lack of a baseline CT for annular measurement (OR: 3.03; 95% CI: 1.20 to 7.69; p = 0.018)., Conclusions: In this multicenter study, TAVR achieved favorable outcomes in patients with pre-procedural CT, with the exception of high permanent pacemaker rates for all devices and shapes., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Evidence regarding the safety and feasibility of transcatheter aortic valve implantation without balloon predilation (BP) is scarce. A literature search of PubMed, EMBASE, CENTRAL, and major conference proceedings was performed from January 2002 to July 2015. There were 18 studies incorporating 2,443 patients included in the present study. No differences were observed in the baseline characteristics between patients without BP (no-BP) and with BP. Compared with BP, no-BP had a shorter procedure time (no-BP vs BP, 124.2 vs 138.8 minutes, p = 0.008), used less-contrast medium (no-BP vs BP, 126.3 vs 156.3 ml, p = 0.0005) and had a higher success rate (odds ratio [OR] 2.24, 95% CI 1.40 to -3.58). In addition, no-BP was associated with lower incidences of permanent pacemaker implantation (OR 0.45, 95% CI 0.3 to 0.67), grade 2 or greater paravalvular leakage (OR 0.55, 95% CI 0.37 to 0.83), and stroke (OR 0.57, 95% CI 0.32 to 1.0). Furthermore, no-BP was associated with a 0.6-fold decreased risk for 30-day all-cause mortality (OR 0.60, 95% CI 0.39 to 0.92). However, the difference in the risk for permanent pacemaker implantation, grade 2, or higher aortic regurgitation, stroke was noted to be significant only in the subgroup of the CoreValve-dominating studies. In conclusion, no-BP before transcatheter aortic valve implantation was not only safe and feasible but was also associated with fewer complications and short-term mortality in selected patients especially using self-expandable valve., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Despite strong evidence linking decreased estimated glomerular filtration rate (eGFR) to worse cardiovascular outcome, the impact of eGFR on mortality in coronary artery disease (CAD) patients with different left ventricular ejection fraction (EF) is not well defined., Methods: A retrospective cohort study. From Jul. 2008 to Jan. 2012, consecutive patients with CAD of West China Hospital were enrolled and were grouped into 3 eGFR categories: ≥90, 60-90, and <60mL/min/1.73m(2). Patients with EF≥50% or <50% were defined as preserved EF or reduced EF, respectively. The endpoints were all-cause mortality and cardiac mortality., Results: There are 2161 patients according to the inclusion criteria and follow-up requirement. The mean follow-up time was 30.97±11.70months. Cumulative survival curves showed that in patients with reduced EF, renal insufficiency significantly increases all-cause mortality and cardiovascular mortality in a graded fashion (mortality rate, moderate or severe vs. normal: 29.3% vs. 5.4%, p<0.001; cardiac mortality rate, moderate or severe vs. normal: 18.2% vs. 4.5%, p=0.001, respectively). Cox regression analysis showed that in CAD patients with reduced EF, moderate to severe renal insufficiency increased all-cause mortality by 6.10-fold (HR 6.10, 95% CI 2.50 to 14.87) and cardiac mortality by 4.10-fold (HR 4.10, 95% CI 1.51 to 11.13). Use of beta-blockers, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), and statins was associated with decreased risk of mortality, but the use was lower in renal insufficiency patients, especially in combination of reduced EF., Conclusion: This study has found that the effect of renal function on prognosis in patients with CAD is closely related to cardiac function. In patients with reduced EF, renal insufficiency accompanies the higher risks of all-cause mortality and cardiovascular mortality. A higher number of treatments from beta-blocker, ACEIs or ARBs, and statin therapy were associated with decreased risk of mortality, even in the combination of renal insufficiency or declining cardiac function., (Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objective: The present study was performed to investigate the relationship between chronic obstructive pulmonary disease (COPD) and transcatheter aortic valve implantation (TAVI)., Background: Controversies regarding the relationship between COPD and TAVI have intensified., Methods: A literature review of the PubMed online database was performed, and articles published between January 1, 2002 and March 20, 2015 were analyzed. Random-effect and fixed-effect models were used, depending on the between-study heterogeneity., Results: A total of 28 studies, involving 51,530 patients, were identified in our review. The burden of COPD ranged from 12.5% to 43.4%, and COPD negatively impacted both short-term and long-term all-cause survival (30 days: odds ratio [OR], 1.43, 95% CI, 1.14-1.79; >2 years: hazard ratio [HR], 1.34, 95% CI, 1.12-1.61). COPD was also associated with increased short-term and mid-term cardiac-cause mortality (30 days: OR, 1.29, 95% CI, 1.02-1.64; 1 year: HR: 1.09, 1.02-1.17). Moreover, COPD (OR, 1.97, 95% CI, 1.29-3.0) predicted post-TAVI acute kidney disease. Importantly, chronic kidney disease (CKD) (HR, 1.2, 95% CI, 1.1-1.32) and the distance of the 6 minute walk test (6MWT) (HR, 1.16, 1.06-1.27) predicted TAVI futility in patients with COPD., Conclusion: COPD is common among patients undergoing TAVI, and COPD impacts both short- and long-term survival. COPD patients, who had a lower BMI, shorter distance of 6MWT and CKD, were at higher risk for TAVI futility., (© 2016 Wiley Periodicals, Inc.)

The purpose of this study was to discuss the present situation of discharge medications in coronary artery disease (CAD) patients with different levels of renal function and assess the potential impact of these medications on the prognosis of this patient population.A retrospective cohort study was conducted. From July 2008 to Jan 2012, consecutive patients with CAD confirmed by coronary angiography of West China Hospital were enrolled and were grouped into 3 estimated glomerular filtration rate (eGFR) categories: ≥60, 30 to 60, and <30 mL/min/1.73 m. The endpoints were all-cause mortality and cardiac mortality.There are 3002 patients according to the inclusion criteria and follow-up requirement. The mean follow-up time was 29.1 ± 12.5 months. CAD patients with worse renal function included more cardiovascular risk factors (advanced age, history of hypertension or diabetes, and diagnosis of acute myocardial infarction). The cumulative survival curves of the patients according to renal function showed that the eGFR <30 mL/min and 30 mL/min ≤ eGFR <60 mL/min groups had a significantly higher risk of all-cause death and cardiovascular death than the group with an eGFR ≥60 mL/min. The prescription of evidence-based medicines (EBMs) at discharge (antiplatelet agents, beta-blockers, statins, and angiotensin-converting enzyme inhibitors [ACEIs] or angiotensin-receptor blockers [ARBs]) was a factor in reducing the risk of all-cause death and cardiovascular death. However, EBMs prescribed at discharge revealed an obvious underuse in renal insufficiency (RI) patients. The results of Cox regression showed that irrespective of the eGFR level, greater use of EBMs resulted in a greater reduction in the risk of all-cause death and cardiovascular death.A higher percentage of patients with CAD and concomitant RI suffered from cardiovascular disease (CVD) risk factors, whereas a lower percentage of these patients used EBMs to prevent CVD events. Strict use of EBMs, including beta-blockers, statins, and ACEIs or ARBs, can lead to more clinical benefits, even for patients with CAD and concomitant RI. Thus, treatment of this patient population with EBMs should be stressed.

Serum potassium homeostasis play an important role in myocardial function, but the impact of serum potassium levels on long-term mortality has not been well evaluated. In the current study, we investigated patients with acute coronary syndrome (ACS) and analyzed the relationship between admission serum potassium levels and long-term mortality. Between July 2008 and September 2012, 2369 patients with ACS that was confirmed by coronary angiography were enrolled in this study and completed the follow-up. The serum potassium level was evaluated within first 24 h after admission. The primary outcome in this study was all-cause mortality. Patients were categorized into five groups to determine the relation between admission serum potassium levels and long-term mortality: < 3.5, 3.5 to < 4.0, 4.0 to < 4.5, 4.5 to < 5.0, and > 5 mEq/L. There was a U-shaped relationship between admission serum potassium levels and long-term mortality that persisted after multivariable adjustment. The mortality risk was lowest in the group of patients with potassium levels of 3.5 to < 4.0 mEq/L, whereas mortality was higher in patients with potassium levels > 4.5 [hazard ratio (HR) 1.62, 95 % confidence interval (CI) 0.90 to 2.93 and HR 1.55, 95 % CI 0.54 to 4.49, for patients with potassium levels of 4.5 to < 5.0 mEq/L and ≥ 5.0 mEq/L, respectively] or < 3.5 mEq/L (HR 2.14, 95 % CI 1.28 to 3.59). There was a U-shaped relationship between admission serum potassium levels and long-term mortality for ACS patients; in particular, among the examined patients, the lowest mortality was observed in those with admission serum potassium levels of between 3.5 and < 4.5 mEq/L compared with those who had higher or lower potassium levels.

Background: Studies focusing on the relationship between calcified lesions and adverse outcomes in the drug-eluting stent (DES) era have presented inconsistent conclusions. The aim of this study was to assess the association between target lesion calcification and adverse outcomes in patients undergoing DES implantation., Methods: A systematic search was conducted on Medline (Ovid SP, 1946 to 28 February 2014), Embase (Ovid SP, 1974 to 28 February 2014), and the Chinese Biomedical Literature Database (CBM, 1978 to 28 February 2014). Abstracts from the 2012 and 2013 scientific meetings of the American College of Cardiology and American Heart Association were manually searched. Hazard ratios (HRs) were pooled using a fixed or random effects model in the context of heterogeneity., Results: A total of 13 studies comprising 66,361 patients were included. Target lesion calcification was associated with an increased risk of all-cause mortality (HR = 1.41; 95 % CI = 1.27-1.56), cardiac death (HR = 1.97; 95 % CI = 1.68-2.31), myocardial infarction (HR = 1.33; 95 % CI = 1.13-1.57), target lesion revascularization (TLR; HR 1.47, 95 % CI 1.18-1.83), stent thrombosis (HR 1.63, 95 % CI 1.36-1.96), and major cardiovascular events (HR 1.37, 95 % CI 1.19-1.58). The results proved robust in subgroup analyses for TLR and stent thrombosis., Conclusion: Calcified target lesions are risk factors for adverse outcomes in the DES era. Further studies focusing on comprehensive therapy in patients with coronary calcification are urgently needed.

Our aim was to compare the efficacy and safety of bivalirudin (Biv) versus heparin (Hep) with or without similar usage rate of glycoprotein IIb/IIIa inhibitors (GPIs) during percutaneous coronary intervention (PCI). The PubMed and EMbase were searched. Randomized trials comparing Biv versus Hep were eligible for inclusion. With imbalanced GPI use, Biv had significantly lower major bleeding (pooled risk ratio [RR], 0.67; 95% confidence interval [CI], 0.54-0.83) without difference in mortality (pooled RR, 0.95; 95% CI, 0.80-1.14). With comparable GPI use, no significant difference was observed in major bleeding (pooled RR, 0.95; 95% CI, 0.82-1.10) and mortality (pooled RR, 1.13; 95% CI, 0.85-1.50). With no GPI use, Biv was associated with numerically higher mortality (pooled RR, 1.17; 95% CI, 0.83-1.65) without significant difference in major bleeding (pooled RR, 0.81; 95% CI, 0.64-1.02). In conclusion, when comparing different anticoagulants during PCI, the effect of GPIs should not be underestimated. Heparin as such was found noninferior to Biv., (© The Author(s) 2015.)

Background: Transcatheter aortic valve replacement (TAVR) is an effective alternative to surgical aortic valve replacement in patients at high surgical risk. However, there is little published literature on the exact causes of death., Methods and Results: The PubMed database was systematically searched for studies reporting causes of death within and after 30 days following TAVR. Twenty-eight studies out of 3934 results retrieved were identified. In the overall analysis, 46.4% and 51.6% of deaths were related to noncardiovascular causes within and after the first 30 days, respectively. Within 30 days of TAVR, infection/sepsis (18.5%), heart failure (14.7%), and multiorgan failure (13.2%) were the top 3 causes of death. Beyond 30 days, infection/sepsis (14.3%), heart failure (14.1%), and sudden death (10.8%) were the most common causes. All possible subgroup analyses were made. No significant differences were seen for proportions of cardiovascular deaths except the comparison between moderate (mean STS score 4 to 8) and high (mean STS score >8) -risk patients after 30 days post-TAVR (56.0% versus 33.5%, P=0.005)., Conclusions: Cardiovascular and noncardiovascular causes of death are evenly balanced both in the perioperative period and at long-term follow-up after TAVR. Infection/sepsis and heart failure were the most frequent noncardiovascular and cardiovascular causes of death. This study highlights important areas of clinical focus that could further improve outcomes after TAVR., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)