Fatty acid binding protein 5 is a novel therapeutic target for hepatocellular carcinoma.

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). FABP5high Huh7 cells also expressed higher protein levels of p53, BIRC5, CDK1, CDK2, and CDK4 than FABP5low 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 FABP5high Huh7 cells. All these support that FABP5 is a novel therapeutic target for treating FABP5high HCC.

Optimal treatment of asymptomatic patients with severe aortic stenosis: protocol of a prospective, multicentre, registry study.

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.

Outcomes Following Transcatheter Aortic Valve Replacement for Aortic Stenosis in Patients With Type 0 Bicuspid, Type 1 Bicuspid, and Tricuspid Aortic Valves.

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%, Poverall=0.522; 1 year: 10% versus 2.3% versus 6.2%, Poverall=0.099) and all stroke (30 days: 1.0% versus 0.9% versus 0.0%, Poverall=0.765; 1 year: 1.4% versus 1.6% versus 1.3%, Poverall=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.

Correlations between geomagnetic field and global occurrence of cardiovascular diseases: evidence from 204 territories in different latitude.

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.

Electromagnetic field and cardiovascular diseases: A state-of-the-art review of diagnostic, therapeutic, and predictive values.

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.

Snaring Self-Expanding Devices to Facilitate Transcatheter Aortic Valve Replacement in Patients with Complex Aortic Anatomies.

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.

Sex Difference in Outcomes Following Transcatheter Aortic Valve Replacement in Bicuspid Aortic Stenosis.

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 mm3 vs 920.8 ± 654.3 mm3; 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.

Patients With Bicuspid Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis.

Objective: We sought to conduct a systematic review and meta-analysis of clinical adverse events in patients undergoing transcatheter aortic valve replacement (TAVR) with bicuspid aortic valve (BAV) vs. tricuspid aortic valve (TAV) anatomy and the efficacy of balloon-expandable (BE) vs. self-expanding (SE) valves in the BAV population. Comparisons aforementioned will be made stratified into early- and new-generation devices. Differences of prosthetic geometry on CT between patients with BAV and TAV were presented. In addition, BAV morphological presentations in included studies were summarized. Method: Observational studies and a randomized controlled trial of patients with BAV undergoing TAVR were included according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Results: A total of 43 studies were included in the final analysis. In patients undergoing TAVR, type 1 BAV was the most common phenotype and type 2 BAV accounted for the least. Significant higher risks of conversion to surgical aortic valve replacement (SAVR), the need of a second valve, a moderate or severe paravalvular leakage (PVL), device failure, acute kidney injury (AKI), and stroke were observed in patients with BAV than in patients with TAV during hospitalization. BAV had a higher risk of new permanent pacemaker implantation (PPI) both at hospitalization and a 30-day follow-up. Risk of 1-year mortality was significantly lower in patients with BAV than that with TAV [odds ratio (OR) = 0.85, 95% CI 0.75-0.97, p = 0.01]. BE transcatheter heart valves (THVs) had higher risks of annular rupture but a lower risk of the need of a second valve and a new PPI than SE THVs. Moreover, BE THV was less expanded and more elliptical in BAV than in TAV. In general, the rates of clinical adverse events were lower in new-generation THVs than in early-generation THVs in both BAV and TAV. Conclusions: Despite higher risks of conversion to SAVR, the need of a second valve, moderate or severe PVL, device failure, AKI, stroke, and new PPI, TAVR seems to be a viable option for selected patients with severe bicuspid aortic stenosis (AS), which demonstrated a potential benefit of 1-year survival, especially among lower surgical risk population using new-generation devices. Larger randomized studies are needed to guide patient selection and verified the durable performance of THVs in the BAV population.

Treating patients with excessively large annuli with self-expanding transcatheter aortic valves: insights into supra-annular structures that anchor the prosthesis.

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] mm3, 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 1­year 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.

Dual targeting of Polo-like kinase 1 and baculoviral inhibitor of apoptosis repeat-containing 5 in TP53-mutated hepatocellular carcinoma.

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.

Differences in metabolic profiles between bicuspid and tricuspid aortic stenosis in the setting of transcatheter aortic valve replacement.

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, Vmax) 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 Vmax > 5 m/s (n = 11) or the 4th quartile of change in ∆LVMI at one-year follow-up (i.e. poorly-recovered LV, n = 8) showed elevated arachidonic acid metabolism compared with Vmax < 4.5 m/s (n = 12) or the 1st 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.

Comparison of third generation balloon-expandable Edwards Sapien 3 versus self-expandable Evolut R in transcatheter aortic valve implantation: a meta-analysis.

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.

Reshaping bicuspid aortic valve stenosis with an hourglass-shaped balloon for transcatheter aortic valve replacement: A pilot study.

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.

Transcatheter Aortic Valve Replacement in Patients with Aortic Stenosis Having Coronary Cusp Fusion versus Mixed Cusp Fusion Nonraphe Bicuspid Aortic Valve.

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.