Cholesterol 25-hydroxylase prevents type 2 diabetes mellitus induced cardiomyopathy by alleviating cardiac lipotoxicity.

OBJECTIVES: Diabetic cardiomyopathy (DCM) is the leading cause of mortality in type 2 diabetes mellitus (T2DM) patients, with its underlying mechanisms still elusive. This study aims to investigate the role of cholesterol-25-monooxygenase (CH25H) in T2DM induced cardiomyopathy. METHODS: High fat diet combined with streptozotocin (HFD/STZ) were used to establish a T2DM model. CH25H and its product 25-hydroxycholesterol (25HC) were detected in the hearts of T2DM model. Gain- or loss-of-function of CH25H were performed by receiving AAV9-cTNT-CH25H or CH25H knockout (CH25H-/-) mice with HFD/STZ treatment. Cardiac function was evaluated using echocardiography, and cardiac tissues were collected for immunoblot analysis, histological assessment and quantitative polymerase chain reaction (qPCR). Mitochondrial morphology and function were evaluated using transmission electron microscopy (TEM) and Seahorse XF Cell Mito Stress Test Kit. RNA-sequence analysis was performed to determine the molecular changes associated with CH25H deletion. RESULTS: CH25H and 25HC were significantly decreased in the hearts of T2DM mice. CH25H-/- mice treated with HFD/STZ exhibited impaired mitochondrial function and structure, increased lipid accumulation, and aggregated cardiac dysfunction. Conversely, T2DM mice receiving AAV9-CH25H displayed cardioprotective effects. Mechanistically, RNA sequencing and qPCR analysis revealed that CH25H deficiency decreased peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and its target gene expression. Additionally, administration of ZLN005, a potent PGC-1α activator, partially protected against high glucose and palmitic acid induced mitochondria dysfunction and lipid accumulation in vitro. CONCLUSION: Our study provides compelling evidence supporting the protective role of CH25H in T2DM-induced cardiomyopathy. Furthermore, the regulation of PGC-1α may be intricately involved in this cardioprotective process.

Mitophagy: A Potential Target for Pressure Overload-Induced Cardiac Remodelling.

The pathological mechanisms underlying cardiac remodelling and cardiac dysfunction caused by pressure overload are poorly understood. Mitochondrial damage and functional dysfunction, including mitochondrial bioenergetic disorder, oxidative stress, and mtDNA damage, contribute to heart injury caused by pressure overload. Mitophagy, an important regulator of mitochondrial homeostasis and function, is triggered by mitochondrial damage and participates in the pathological process of cardiovascular diseases. Recent studies indicate that mitophagy plays a critical role in the pressure overload model, but evidence on the causal relationship between mitophagy abnormality and pressure overload-induced heart injury is inconclusive. This review summarises the mechanism, role, and regulation of mitophagy in the pressure overload model. It also pays special attention to active compounds that may regulate mitophagy in pressure overload, which provide clues for possible clinical applications.

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.

Deep Learning in Prediction of Late Major Bleeding After Transcatheter Aortic Valve Replacement.

PURPOSE: Late major bleeding is one of the main complications after transcatheter aortic valve replacement (TAVR). We aimed to develop a risk prediction model based on deep learning to predict major or life-threatening bleeding complications (MLBCs) after TAVR. PATIENTS AND METHODS: This was a retrospective study including TAVR patients from West China Hospital of Sichuan University Transcatheter Aortic Valve Replacement Registry (ChiCTR2000033419) between April 17, 2012 and May 27, 2020. A deep learning-based model named BLeNet was developed with 56 features covering baseline, procedural, and post-procedural characteristics. The model was validated with the bootstrap method and evaluated using Harrell's concordance index (c-index), receiver operating characteristics (ROC) curve, calibration curve, and Kaplan-Meier estimate. Captum interpretation library was applied to identify feature importance. The BLeNet model was compared with the traditional Cox proportional hazard (Cox-PH) model and the random survival forest model in the metrics mentioned above. RESULTS: The BLeNet model outperformed the Cox-PH and random survival forest models significantly in discrimination [optimism-corrected c-index of BLeNet vs Cox-PH vs random survival forest: 0.81 (95% CI: 0.79-0.92) vs 0.72 (95% CI: 0.63-0.77) vs 0.70 (95% CI: 0.61-0.74)] and calibration (integrated calibration index of BLeNet vs Cox-PH vs random survival forest: 0.007 vs 0.015 vs 0.019). In Kaplan-Meier analysis, BLeNet model had great performance in stratifying high- and low-bleeding risk patients (p < 0.0001). CONCLUSION: Deep learning is a feasible way to build prediction models concerning TAVR prognosis. A dedicated bleeding risk prediction model was developed for TAVR patients to facilitate well-informed clinical decisions.

The incidence and predictors of high-degree atrioventricular block in patients with bicuspid aortic valve receiving self-expandable transcatheter aortic valve implantation.

BACKGROUND: The high-degree atrioventricular block (HAVB) in patients with bicuspid aortic valve (BAV) treated with transcatheter aortic valve implantation (TAVI) remains high. The study aims to explore this poorly understood subject of mechanisms and predictors for HAVB in BAV self-expandable TAVI patients. METHODS: We retrospectively included 181 BAV patients for analysis. Using computed tomography data, the curvature of ascending aorta (AAo) was quantified by the angle (AAo angle) between annulus and the cross-section at 35 mm above annulus (where the stent interacts with AAo the most). The valvular anatomy and leaflet calcification were also characterized. RESULTS: The 30-day HAVB rate was 16.0% (median time to HAVB was three days). Type-1 morphology was found in 79 patients (43.6%) (left- and right-coronary cusps fusion comprised 79.7%). Besides implantation below membrane septum, large AAo angle [odds ratio (OR) = 1.08, P = 0.016] and type-1 morphology (OR = 4.97, P = 0.001) were found as the independent predictors for HAVB. Together with baseline right bundle branch block, these predictors showed strong predictability for HAVB with area under the cure of 0.84 (sensitivity = 62.1%, specificity = 92.8%). Bent AAo and calcified raphe had a synergistic effect in facilitating high implantation, though the former is associated with at-risk deployment (device implanted above annulus + prothesis pop-out, versus straight AAo: 9.9% vs. 2.2%, P = 0.031). CONCLUSIONS: AAo curvature and type-1 morphology are novel predictors for HAVB in BAV patients following self-expandable TAVI. For patients with bent AAo or calcified raphe, a progressive approach to implant the device above the lower edge of membrane septum is favored, though should be done cautiously to avoid pop-out.

Force distribution within the frame of self-expanding transcatheter aortic valve: Insights from in-vivo finite element analysis.

We sought to assess the amount and distribution of force on the valve frame after transcatheter aortic valve replacement (TAVR) via patient-specific computer simulation. Patients successfully treated with the self-expanding Venus A-Valve and multislice computed tomography (MSCT) pre- and post-TAVR were retrospectively included. Patient-specific finite element models of the aortic root and prosthesis were constructed. The force (in Newton) on the valve frame was derived at every 3 mm from the inflow and at every 22.5° on each level. Twenty patients of whom 10 had bicuspid aortic valve (BAV) were analyzed. The total force on the frame was 74.9 N in median (interquartile range 24.0). The maximal force was observed at level 5 that corresponds with the nadir of the bioprosthetic leaflets and was 9.9 (7.1) N in all patients, 10.3 (6.6) N in BAV and 9.7 (9.2) N for patients with tricuspid aortic valve (TAV). The level of maximal force located higher from the native annulus in BAV and TAV patients (8.8 [4.8] vs. 1.8 [7.4] mm). The area of the valve frame at the level of maximal force decreased from 437.4 (239.7) mm2 at the annulus to 377.6 (114.3) mm2 in BAV, but increased from 397.5 (114.3) mm2 at the annulus to 406.7 (108.9) mm2 in TAV. The maximum force on the bioprosthetic valve frame is located at the plane of the nadir of the bioprosthetic leaflets. It remains to be elucidated whether this may be associated with bioprosthetic frame and leaflet integrity and/or function.

Sodium Lactate Accelerates M2 Macrophage Polarization and Improves Cardiac Function after Myocardial Infarction in Mice.

BACKGROUND: After myocardial infarction, anti-inflammatory macrophages perform key homeostatic functions that facilitate cardiac recovery and remodeling. Several studies have shown that lactate may serve as a modifier that influences phenotype of macrophage. However, the therapeutic role of sodium lactate in myocardial infarction (MI) is unclear. METHODS: MI was established by permanent ligation of the left anterior descending coronary artery followed by injection of saline or sodium lactate. Cardiac function was assessed by echocardiography. The cardiac fibrosis area was assessed by Masson trichrome staining. Macrophage phenotype was detected via qPCR, flow cytometry, and immunofluorescence. Signaling proteins were measured by Western blotting. RESULTS: Sodium lactate treatment following MI improved cardiac performance, enhanced anti-inflammatory macrophage proportion, reduced cardiac myocytes apoptosis, and increased neovascularization. Flow-cytometric analysis results reported that sodium lactate repressed the number of the IL-6+, IL-12+, and TNF-α+ macrophages among LPS-stimulated bone marrow-derived macrophages (BMDMs) and increased the mRNA levels of Arg-1, YM1, TGF-ß, and IL-10. Mechanistic studies revealed that sodium lactate enhanced the expression of P-STAT3. Furthermore, a STAT3 inhibitor eliminated sodium lactate-mediated promotion macrophage polarization. CONCLUSION: Sodium lactate facilitates anti-inflammatory M2 macrophage polarization and protects against MI by regulating P-STAT3.

Turn-on fluorescent probe for lipid droplet specific imaging of fatty liver and atherosclerosis.

Fluorescence imaging plays an important role in researching the biological function of lipid droplets (LDs). However, the short-wave emission, tedious synthesis process and insufficient specificity have significantly limited the applications of commercially available probes. Herein, we have prepared a novel one-step synthesized near-infrared (NIR) fluorescent probe, TNBD, with a very low emission in aqueous solution and the solid state, but a significantly enhanced fluorescence emission is exhibited in oleic acid. Moreover, TNBD exhibited an impressive lipid droplet (LD) specific fluorescence turn-on ability in cells, fatty liver and atherosclerosis (AS) samples with a good biocompatibility and high signal-to-noise ratio. Our study not only establishes a novel LD turn-on fluorescence probe, but also provides a novel way to prepare a NIR LD targeted fluorescence probe.

MARCH5 restores endothelial cell function against ischaemic/hypoxia injury via Akt/eNOS pathway.

MARCH5 is a critical regulator of mitochondrial dynamics, apoptosis and mitophagy. However, its role in cardiovascular system remains poorly understood. This study aimed to investigate the role of MARCH5 in endothelial cell (ECs) injury and the involvement of the Akt/eNOS signalling pathway in this process. Rat models of myocardial infarction (MI) and human cardiac microvascular endothelial cells (HCMECs) exposed to hypoxia (1% O2 ) were used in this study. MARCH5 expression was significantly reduced in ECs of MI hearts and ECs exposed to hypoxia. Hypoxia inhibited the proliferation, migration and tube formation of ECs, and these effects were aggravated by knockdown of MARCH5 but antagonized by overexpressed MARCH5. Overexpression of MARCH5 increased nitric oxide (NO) content, p-eNOS and p-Akt, while MARCH5 knockdown exerted the opposite effects. The protective effects mediated by MARCH5 overexpression on ECs could be inhibited by eNOS inhibitor L-NAME and Akt inhibitor LY294002. In conclusion, these results indicated that MARCH5 acts as a protective factor in ischaemia/hypoxia-induced ECs injury partially through Akt/eNOS pathway.

Correction: A lipid droplet targeted fluorescent probe for high-efficiency image-guided photodynamic therapy of renal cell carcinoma.

Correction for 'A lipid droplet targeted fluorescent probe for high-efficiency image-guided photodynamic therapy of renal cell carcinoma' by Ping Tan et al., Chem. Commun., 2021, DOI: 10.1039/d0cc07336a.

A lipid droplet targeted fluorescent probe for high-efficiency image-guided photodynamic therapy of renal cell carcinoma.

A one-step synthesized LD specific fluorescent probe TTIE with high specificity, good photostability and great capacity in generating cytotoxic reactive oxygen species (ROS) under low powered white light irradiation is designed and synthesized for LD specific image-guided photodynamic therapy (PDT) in human clear cell renal cell carcinoma (ccRCC) primary cells and tissues.

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.

Efficacy and Safety of Emergent Transcatheter Aortic Valve Implantation in Patients with Acute Decompensated Aortic Stenosis: Systematic Review and Meta-Analysis.

INTRODUCTION: The aim of this systematic review and meta-analysis was to investigate the efficacy and safety of emergent transcatheter aortic valve implantation (TAVI) in patients with decompensated aortic stenosis (AS) by comparing the clinical outcomes with the patients who had received the elective TAVI. METHODS: By searching PubMed, EMBASE, and Cochrane databases, we obtained the studies comparing the clinical outcomes of emergent TAVI and elective TAVI. Finally, 14 studies were included. RESULTS: A total of 14 eligible articles with 73,484 patients were included in this meta-analysis. Emergent TAVI was associated with a higher mortality during hospitalization (HR 2.09, 95% CI [1.39 to 3.14]), 30 days (HR 2.29, 95% CI [1.69 to 3.10]), and 1 year (HR 1.96, 95% CI [1.55 to 2.49]). Consistently, the incidence of acute kidney injury (AKI) (RR 2.48, 95% CI [1.85 to 3.32]), dialysis (RR 2.37, 95% CI [1.95 to 2.88]), bleeding (RR 1.62, 95% CI [1.27 to 2.08]), major bleeding (RR 1.05, 95% CI [1.00 to 1.10]), and 30-day rehospitalization (RR 1.30, 95% CI [1.07, 1.58]) were more common in patients receiving emergent TAVI. No statistical differences were found in the occurrence rate of vascular complications (RR 1.11, 95% CI [0.90, 1.36]), major vascular complications (RR 1.14, 95% CI [0.52, 2.52]), permanent pacemaker (PPM) placement (RR 1.05, 95% CI [0.99, 1.11]), cerebrovascular events (RR 1.11, 95% CI [0.98, 1.25]), moderate to severe paravalvular leakage (PVL) (RR 1.23, 95% [CI 0.94 to 1.61]), and device success (RR 0.99, 95% CI [0.97, 1.01]). CONCLUSION: Emergent TAVI is associated with some postoperative complications and increased mortality compared with elective TAVI. Emergent TAVI should be implemented cautiously and individually.

Impact of renin-angiotensin system blocker after aortic valve replacement-a systematic review and meta-analysis.

BACKGROUND: Data reporting the impact of renin-angiotensin system inhibitor (RASi) after aortic valve replacement (AVR) is controversy. METHODS: The PubMed database was systematically searched for studies reporting the mortality and hazard ratios (HRs) of RASi following surgical and transcatheter AVR (SAVR, TAVR). Random-effects model was used when the I2 statistic was more than 50% and its P value was less than 0.05, otherwise, the fixed-effects model was conducted. RESULTS: Nine articles incorporating 33,063 patients were eligible. Patients having the description of RASi were associated with lower all-cause mortality at 30 days (OR, 0.80, 95% CI, 0.69 to 0.94), 1 year (OR, 0.75, 95% CI, 0.69 to 0.81) and beyond 1 year (OR, 0.52, 95% CI, 0.38 to 0.73) after AVR. Consistently, patients with RASi had lower risk for all-cause mortality (HR, 0.87, 95% CI, 0.84 to 0.91) beyond 1 year following AVR albeit adjusting confounders. Interestingly, beneficial effect of RASi was still observed in patients with preserved ejection fraction following TAVR (HR, 0.90, 95% CI, 0.87 to 0.94). In addition, patients taking RASi had lower cardiovascular mortality than those patients without RASi after TAVR (30 days, OR, 0.63, 95% CI, 0.44 to 0.90; 1 year, OR, 0.60, 95% CI, 0.50 to 0.73; beyond 1 year, OR, 0.63, 95% CI, 0.54 to 0.74). CONCLUSIONS: Patients with RASi exhibited better short- and long-term survival following AVR compared to those patients without RASi, which warranted further studies to support such findings.

Metabolic Modulation and Potential Biomarkers of the Prognosis Identification for Severe Aortic Stenosis after TAVR by a Metabolomics Study.

OBJECTIVES: To investigate the metabolic profile in patients with aortic stenosis (AS) after transcatheter aortic valve replacement (TAVR) and explore the potential biomarkers to predict prognosis after TAVR based on metabolomics. METHODS AND RESULTS: Fifty-nine consecutive AS patients were prospectively recruited. Blood samples from the ascending aorta, coronary sinus, and peripheral vein at before and after TAVR were collected, respectively. Liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry were performed to analyze the metabolic profile before and after TAVR. Influential metabolites were identified by integrating the univariate test, multivariate analysis, and weighted gene coexpression network analysis (WGCNA) algorithm. PLS-DA analysis revealed a significant extremely early (within 30 minutes after TAVR) alterations of metabolites in the ascending aorta, coronary sinus, and peripheral vein. The early (within 7 days after TAVR) changed metabolites in the peripheral vein were involved in purine metabolism, primary bile acid biosynthesis, glycerolipid metabolism, amino sugar and nucleotide sugar metabolism, one carbon pool by folate and alanine, and the aspartate and glutamate metabolism pathway. We used volcano plots to find that the cardiac-specific changed metabolites were enriched to the sphingolipid metabolism pathway after TAVR. Besides, WGCNA algorithm was performed to reveal that arginine and proline metabolites could reflect left ventricle regression to some extent. CONCLUSION: This is the first study to reveal systemic and cardiac metabolites changed significantly in patients with AS after TAVR. Some altered metabolites involved in the arginine and proline metabolism pathway in the peripheral vein could predict left ventricle regression, which merited further study.

Effect of concomitant aortic regurgitation on early hypo-attenuated leaflet thickening after transcatheter aortic valve replacement in patients with symptomatic severe aortic stenosis.

OBJECTIVE: We hypothesize that different degree of pre-existing aortic regurgitation (AR) may affect the presence of hypo-attenuated leaflet thickening (HALT) after transcatheter aortic valve replacement (TAVR). BACKGROUND: The mechanism of the presence of HALT post-TAVR is not fully understood. METHODS: We retrospectively evaluated the post-procedural multi-slice computed tomography (MSCT) before discharge for evidence of HALT. Patients were grouped according to the degree of pre-existing AR. Baseline, native anatomy and procedure details were compared, then multivariate regression was performed. RESULTS: MSCT analyzed was performed at a median of 6 days post-TAVR in 179 patients. HALT was detected in 10.6% of patients. After adjusting for variables that were significantly different between groups, pre-existing ≥ moderate AR was protective to the risk of HALT (OR 0.15, 95% CI 0.03-0.84, p = .03). Stratifying for factors that might explain the impact of pre-existing AR on HALT, patients with a small Sinus of Valsalva, non-eccentric remodeling and receiving a large bioprosthesis experienced a sevenfold higher risk for HALT (OR 7.16, 95% CI 2.05-25.08, p = .002). CONCLUSIONS: Patients underwent TAVR with pre-existing ≥ moderate AR appeared to experience a lower incidence of early HALT compared to those patients with less than moderate AR, which may be explained by a larger Sinus of Valsalva and a higher proportion of LV eccentric remodeling.

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.