Thrombocytopenia Following Perceval Sutureless Aortic Valve Replacement in Asian Patients.

BACKGROUND: This study analyzed the safety and performance of the Perceval valve for aortic valve replacement (AVR) in patients at 1 year after undergoing aortic stenosis (AS) treatment, and its effect on significant declines in the platelet count during the immediate postoperative period.Methods and Results: Data were collected retrospectively for the initial 121 patients (median age 77 years; 47.1% females) who underwent Perceval sutureless AVR between May 2019 and July 2022. Implantation was successful in all (100%), with median cross-clamp and CPB times of 59 and 100 min, respectively. Postoperative thrombocytopenia (platelet count <50×103/µL) was noted in 80 (66.1%) patients. Multivariate analysis showed advanced age (>80 years), preoperative low platelet count (<200×103/µL), and a sternotomy approach as significant risk factors for postoperative thrombocytopenia. One (0.8%) patient died within 30 days after the procedure. The 2-year site-reported event rate was 14% (n=17) for all-cause mortality, 0.8% (n=1) for cardiac mortality, 4.1% (n=5) for stroke, and 1.7% (n=2) for endocarditis and valve-related reoperation; there were no instances of paravalvular leakage or structural valve deterioration. CONCLUSIONS: Thrombocytopenia was common after Perceval sutureless AVR, although its impact was not significant. Although Perceval sutureless AVR was found to be a safe and effective option, preoperative assessment of potential bleeding should be performed and the Perceval valve should not be used for patients with a high bleeding risk.

Effect of Narrow Chest on Minimally Invasive Mitral Valve Surgery via Right Minithoracotomy.

BACKGROUND: The effect of a narrow chest on minimally invasive mitral valve surgery (MIMVS) is unclear.Methods and Results: We enrolled 206 MIMVS patients and measured anteroposterior diameter (APD) between the sternum and vertebra, transverse thoracic diameter (TD), right and left APD of the hemithorax (RD and LD, respectively), and the Haller index (HI; TD/APD ratio) on computed tomography. Preoperative characteristics and operative outcomes were compared between patients with a narrow chest (Group N; HI >2.5; n=53) and those with a normal chest (control [C]; HI ≤2.5; n=153), and the correlations of these measurements with operation time were evaluated in 133 patients undergoing an isolated mitral procedure. Groups N and C differed significantly in APD (89.4 vs. 114.3 mm, respectively; P<0.001), TD (251.5 vs. 240.3 mm, respectively; P=0.002), RD (152.5 vs. 172.5 mm, respectively; P<0.001), LD (155.0 vs. 172.4 mm, respectively; P<0.001), and HI (2.84 vs. 2.12, respectively; P<0.001). Procedural characteristics were comparable, except for a longer aortic cross-clamp time (ACCT) in Group N (118.7 vs. 105.8 min; P=0.047). Rates of surgical death, re-exploration, cerebral infarction, and prolonged ventilation were comparable between the 2 groups. TD was significantly correlated with ACCT (R2=0.037, P=0.028) in patients undergoing an isolated mitral procedure. CONCLUSIONS: Early MIMVS outcomes in patients with narrow chests are satisfactory. TD prolongs ACCT during MIMVS.

In vitro screening of chemically synthesized dipeptide-antisense oligonucleotide conjugates to identify ligand molecules enhancing their activity.

Oligonucleotide therapeutics, particularly antisense oligonucleotides (ASOs), have emerged as promising candidates in drug discovery. However, their effective delivery to the target tissues and cells remains a challenge, necessitating the development of suitable drug delivery technologies for ASOs to enable their practical application. In this study, we synthesized a library of chemically modified dipeptide-ASO conjugates using a recent synthetic method based on the Ugi reaction. We then conducted in vitro screening of this library using luciferase-expressing cell lines to identify ligands capable of enhancing ASO activity. Our findings suggest that N-(4-nitrophenoxycarbonyl)glycine may interact with the thiophosphate moiety of the phosphorothioate-modification in ASO. Through our screening efforts, we identified two ligands that modestly reduced luciferase luminescence in a cell type-selective manner. Furthermore, quantification of luciferase mRNA levels revealed that one of these promising dipeptide-ASO conjugates markedly suppressed luciferase RNA levels through its antisense effect in prostate-derived DU-145 cells compared to the ASOs without ligand modification.

Synthesis of multivalent fatty acid-conjugated antisense oligonucleotides: Cell internalization, physical properties, and in vitro and in vivo activities.

Herein, we describe the design and synthesis of multi-conjugatable fatty acid monomer phosphoramidites and their conjugation to antisense oligonucleotides (ASOs). Multivalent long-chain fatty acid conjugation improved the cellular uptake of ASOs but decreased in vitro activity due to alterations in physical properties and cellular localization. In addition, multivalently fatty acid-conjugated ASOs showed different organ specificity compared with that of unconjugated ASO in in vivo experiment. Although optimization of the linker structure between the fatty acid moiety and the ASO may be required, divalent long-chain fatty acid conjugation provides a new approach to increase endocytosis, thereby potentially improving the activity of therapeutic ASOs.

Sutureless Aortic Valve Replacement Through Lateral Mini-Thoracotomy　- Feasibility and Effectiveness.

BACKGROUND: Minimally invasive sutureless aortic valve replacement with the Perceval bioprosthetic heart valve (MISUAVR) is commonly performed through a right anterior thoracotomy (AT). However, a lateral thoracotomy (LT) may be superior as it does not require rib and right internal thoracic artery (RITA) cutting.Methods and Results: In total, 38 MISUAVRs performed from May 2019 to approximately August 2021 were retrospectively reviewed; 21 through LT (Group L), and 17 through AT (Group A). In Group L, the skin incision was made on the right anterior axillary line and third intercostal space, and in group A, on the right anterior chest and second or third intercostal space. All other surgical techniques were the same. Age, body surface area, EuroSCORE II, and ejection fraction were similar between the patients. Cardiopulmonary bypass (L: 82±19 vs. A: 93±28 min, P=0.19) and cross-clamp times (L: 57±13, vs. A: 64±23 min, P=0.19) were similar. Rib and/or RITA cutting were required in 94.6% of patients in group A and in none of group L (P<0.001). Surgical visualization score was better in group L (L: 1.19±0.40 vs. A: 1.94±0.69, P<0.01). Total amount of intraoperative bleeding was lower in group L (L: 623±141 vs. A: 838±316 mL, P<0.01). Duration of hospital stay was similar (P=0.30). CONCLUSIONS: MISUAVR through LT has multiple advantages over AT.

Synthesis and physical and biological properties of 1,3-diaza-2-oxophenoxazine-conjugated oligonucleotides.

The artificial nucleobase 1,3-diaza-2-oxophenoxazine (tCO) and its derivative G-clamp strongly bind to guanine and, when incorporated into double-stranded DNA, significantly increase the stability of the latter. As the phenoxazine skeleton is a constituent of major pharmaceuticals, we hypothesized that oligonucleotides (ONs) containing phenoxazine bases would induce property changes related to intracellular uptake and migration in tissues. In this study, we designed and synthesized a novel G-clamp-linker antisense oligonucleotide (ASO) in which a G-clamp base with a flexible linker was introduced into the 5'-end of an ASO targeting mouse long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (mMALAT1). Compared to unconjugated ASO, the G-clamp-linker ASO induced significantly more effective knockdown of mMALAT1 in mouse skeletal muscle. The ASOs conjugated with 2'-deoxyribonucleotide(s) bearing a tCO nucleobase at the 5'-end exhibited a similar knockdown effect in skeletal muscle. Thus, it may be possible to improve therapeutic effects against skeletal muscle diseases, such as muscular dystrophy, by using ONs with incorporated phenoxazine nucleobases.

An Ambidextrous Polyphenol Glycosyltransferase PaGT2 from Phytolacca americana.

The glycosylation of small hydrophobic compounds is catalyzed by uridine diphosphate glycosyltransferases (UGTs). Because glycosylation is an invaluable tool for improving the stability and water solubility of hydrophobic compounds, UGTs have attracted attention for their application in the food, cosmetics, and pharmaceutical industries. However, the ability of UGTs to accept and glycosylate a wide range of substrates is not clearly understood due to the existence of a large number of UGTs. PaGT2, a UGT from Phytolacca americana, can regioselectively glycosylate piceatannol but has low activity toward other stilbenoids. To elucidate the substrate specificity and catalytic mechanism, we determined the crystal structures of PaGT2 with and without substrates and performed molecular docking studies. The structures have revealed key residues involved in substrate recognition and suggest the presence of a nonconserved catalytic residue (His81) in addition to the highly conserved catalytic histidine in UGTs (His18). The role of the identified residues in substrate recognition and catalysis is elucidated with the mutational assay. Additionally, the structure-guided mutation of Cys142 to other residues, Ala, Phe, and Gln, allows PaGT2 to glycosylate resveratrol with high regioselectivity, which is negligibly glycosylated by the wild-type enzyme. These results provide a basis for tailoring an efficient glycosyltransferase.

Early and midterm results of minimally invasive aortic and mitral valve surgery via right mini-thoracotomy.

OBJECTIVES: There are few reports regarding minimally invasive aortic valve replacement concomitant with mitral valve surgery (MIAMVS). The aim of this study was to evaluate early and midterm MIAMVS results. METHODS: We reviewed the medical records of 21 consecutive patients (nine females, 43%) who underwent MIAMVS through a right mini-thoracotomy from December 2014 to April 2017. Mean patient age was 73 ± 7.4 years and four (19%) were New York Heart Association Class III or IV. Aortic stenosis and mitral valve insufficiency were the most common pathologies. All patients were followed for a mean period of 30 ± 8.5 months. RESULTS: The types of surgery consisted of aortic valve replacement with mitral valve repair in 11 (52%) patients, and replacement of both aortic and mitral valves in 10 (48%), while a tricuspid valve repair, was performed in four. No conversion to a full sternotomy was necessary in any of the cases. Postoperatively, the median intensive care unit and hospital stays were 4.7 and 11.8 days, respectively, with no in-hospital mortality. Following the initial treatment, all 21 patients were followed for a mean period of 30 ± 8.5 months (14-45 months). All patients returned to NYHA Class I or II following the procedure. During the follow-up period, there was no need for a heart valve reoperation for any of the patients and none showed recurrent mitral regurgitation (>mild), though one died from respiratory failure caused by pneumonia. CONCLUSIONS: MIAMVS can be performed via a right mini-thoracotomy, with acceptable early and midterm results expected. This may be a feasible alternative to the standard median sternotomy approach.

Silent brain infarction after minimally invasive cardiac surgery with retrograde perfusion.

BACKGROUND AND AIM: There is no report on silent brain infarction (SBI) after minimally invasive cardiac surgery (MICS) with retrograde perfusion. Thus, the current study aimed to investigate the incidence of SBI after MICS using magnetic resonance imaging (MRI). METHODS: This study included 174 patients who underwent MICS with retrograde perfusion between July 2014 and July 2018. Preoperative computed tomography (CT) angiography was routinely performed and vascular pathology was evaluated for patient selection. Postoperative MRI was performed to investigate the occurrence of SBI. RESULTS: Out of the total 174 patients, 26 (14.9%) presented with SBI. A total of 61 SBI lesions were found in the 26 patients; of these, 34 (56%) SBI lesions were in the right hemisphere and 27 (44%) in the left hemisphere. SBIs were primarily observed in the posterior cerebral artery territory. Multivariate analysis revealed aortic stenosis to be the only risk factor of SBI. CONCLUSIONS: Retrograde perfusion via femoral cannulation may not increase the incidence of SBI in selected MICS patients based on preoperative CT findings.

Inhibition of Atherosclerotic Plaque Development by Oral Administration of α-Glucosyl Hesperidin and Water-Dispersible Hesperetin in Apolipoprotein E Knockout Mice.

OBJECTIVE: Hesperidin, an abundant flavonoid in citrus fruit, and its aglycone, hesperetin, have been reported to possess various physiological activities, including antioxidant, anti-inflammatory, hypolipidemic, and antihypertensive activities. In this study, we investigated whether α-glucosyl hesperidin and water-dispersible hesperetin have protective effects on atherosclerotic progression in apolipoprotein E knockout (Apo-E KO) mice. METHODS: Ten-week-old male Apo-E KO mice were randomly assigned a regular high-fat diet, a high-fat diet with 0.5% α-glucosyl hesperidin, or a high-fat diet with 0.1% water-dispersible hesperetin for 12 weeks. Measurement of plasma total cholesterol levels, histological staining of aortic root, and immunohistochemistry for macrophages were performed to evaluate atherosclerotic plaque formation. Vascular reactivity of mouse aortic rings was also measured. RESULTS: Both α-glucosyl hesperidin and water-dispersible hesperetin reduced plasma total cholesterol level. They also reduced plaque formation area, adipose deposition, and macrophage infiltration into atherosclerotic lesion. Vascular-endothelium-dependent relaxation in response to acetylcholine was improved in both experimental diet groups compared to the high-fat diet group. CONCLUSIONS: Our study suggests that both α-glucosyl hesperidin and water-dispersible hesperetin exert protective effects on atherosclerotic progression in Apo-E KO mice because they exhibit hypolipidemic activity, reduce inflammation through macrophages, and prevent endothelial dysfunction.

A trimeric structural fusion of an antagonistic tumor necrosis factor-α mutant enhances molecular stability and enables facile modification.

Tumor necrosis factor-α (TNF) exerts its biological effect through two types of receptors, p55 TNF receptor (TNFR1) and p75 TNF receptor (TNFR2). An inflammatory response is known to be induced mainly by TNFR1, whereas an anti-inflammatory reaction is thought to be mediated by TNFR2 in some autoimmune diseases. We have been investigating the use of an antagonistic TNF mutant (TNFR1-selective antagonistic TNF mutant (R1antTNF)) to reveal the pharmacological effect of TNFR1-selective inhibition as a new therapeutic modality. Here, we aimed to further improve and optimize the activity and behavior of this mutant protein both in vitro and in vivo Specifically, we examined a trimeric structural fusion of R1antTNF, formed via the introduction of short peptide linkers, as a strategy to enhance bioactivity and molecular stability. By comparative analysis with R1antTNF, the trimeric fusion, referred to as single-chain R1antTNF (scR1antTNF), was found to retain in vitro molecular properties of receptor selectivity and antagonistic activity but displayed a marked increase in thermal stability. The residence time of scR1antTNF in vivo was also significantly prolonged. Furthermore, molecular modification using polyethylene glycol (PEG) was easily controlled by limiting the number of reactive sites. Taken together, our findings show that scR1antTNF displays enhanced molecular stability while maintaining biological activity compared with R1antTNF.

[Simultaneous Transapical Transcatheter Aortic Valve Implantation and Coronary Artery Bypass Grafting;Report of a Case].

Coronary artery disease(CAD) is often found concurrently in patients presenting with severe aortic stenosis(AS). Surgical aortic valve replacement(SAVR) and coronary artery bypass grafting(CABG) were usually selected with such patients. Recently, transcatheter aortic valve implantation (TAVI) is considered as a less invasive and more feasible treatment option in high-risk AS patients. A 74-year-old woman admitted due to acute myocardial infarction and treated with percutaneous coronary intervention revealed severe AS. Because of her comorbidities, concomitant transapical TAVI and CABG were performed with an excellent clinical course.

Epiregulin Recognition Mechanisms by Anti-epiregulin Antibody 9E5: STRUCTURAL, FUNCTIONAL, AND MOLECULAR DYNAMICS SIMULATION ANALYSES.

Epiregulin (EPR) is a ligand of the epidermal growth factor (EGF) family that upon binding to its epidermal growth factor receptor (EGFR) stimulates proliferative signaling, especially in colon cancer cells. Here, we describe the three-dimensional structure of the EPR antibody (the 9E5(Fab) fragment) in the presence and absence of EPR. Among the six complementarity-determining regions (CDRs), CDR1-3 in the light chain and CDR2 in the heavy chain predominantly recognize EPR. In particular, CDR3 in the heavy chain dramatically moves with cis-trans isomerization of Pro(103). A molecular dynamics simulation and mutational analyses revealed that Arg(40) in EPR is a key residue for the specific binding of 9E5 IgG. From isothermal titration calorimetry analysis, the dissociation constant was determined to be 6.5 nm. Surface plasmon resonance analysis revealed that the dissociation rate of 9E5 IgG is extremely slow. The superimposed structure of 9E5(Fab)·EPR on the known complex structure of EGF·EGFR showed that the 9E5(Fab) paratope overlaps with Domains I and III on the EGFR, which reveals that the 9E5(Fab)·EPR complex could not bind to the EGFR. The 9E5 antibody will also be useful in medicine as a neutralizing antibody specific for colon cancer.

[Redo Coronary Artery Bypass Grafting Through Left Thoracotomy in Patient with Patent Left Internal Thoracic Artery Graft;Report of a Case].

A 61-year-old man was admitted because of unstable angina. The patient had a history of CABG [LITA-left anterior descending artery(LAD), aorta-saphenous vein graft(SVG)-posterolateral branch (PL)-diagonal branch (D1)]4 years ago. Coronary angiography revealed an occlusion of old SVG at proximal anastomosis site and a stenosis of native high lateral artery (HL). To reduce the risk of cardiac injury and damage to the patent grafts due at sternal reentry, we performed redo CABG through left thoracotomy. The proximal site of SVG was anastomosed to descending aorta using automated proximal anastomosis system. The SVG was anastomosed to the HL and old SVG in a sequential mode. Postoperative course was uneventful and the patient was discharged on postoperative day 14. Redo CABG through left thoracotomy provides safe and effective surgical approach in patient who requires revascularization of left circumflex territory.

[Patch plasty of intraoperative acute aortic dissection in a patient with severe aortic valve stenosis;report of a case].

Intraoperative aortic dissection is a rare complication, but is associated with a high mortality. We report a case of 79-year-old woman with severe aortic valve stenosis who underwent aortic valve replacement(AVR). After cardiopulmonary bypass(CPB) was established, aortic dissection started at the inflow cannulation site. Because hemodynamics were stable, we performed AVR as scheduled. After declamping, excessive bleeding from the arterial cannulation site continued. CPB was reestablished by placing the arterial cannula in the left femoral artery. The ascending aorta was opened at the site of cannulation under deep hypothermic circulatory arrest. The entry tear was successfully repaired by entry resection and Hemashield patch plasty. The postoperative course was uneventful, and the patient was discharged on the 22nd postoperative day. Patch plasty may be useful for the management of intraoperative aortic dissection.

[Reconstruction of pulmonary blood flow in the Norwood procedure; Blalock-Taussig shunt; from bench to surgery].

Although the right-ventricle to pulmonary artery( RV-PA) shunt as a source of pulmonary blood supply of Norwood procedure has improved early outcomes, disadvantages including right ventricular dysfunction or arrhythmias have been reported. So it has been still remained controversial whether BT shunt or RV-PA conduit should be selected. We examined the influence of Blalock-Taussig( BT) shunt size on regulation of the pulmonary blood flow in experimental model of a univentricular heart to determine the specific guidelines regarding suitable shunt size in the Norwood procedure. The canine univentricular heart model with the ratio of shunt size to body weight (SS/BW) of 0.8 to 1.1 showed significant negative correlation between the pulmonary/systemic blood flow ratio( Qp/Qs)and arterial PCo2, but those with SS/BW of 1.1 to 1.4 did not. Similar phenomena were shown with the grouped data on relationship between the Qp/Qs and inspired oxygen fraction. These findings imply that when SS/BW is 0.8 to 1.1, the Qp/Qs is controllable by physiologic respiratory manipulations. In the context of our clinical experiences, SS/BW of 0.9 to 1.0 is considered a useful index for suitable BT shunt in the Norwood procedure.

Totally thoracoscopic atrial fibrillation surgery following massive small bowel resection due to superior mesenteric artery embolization: report of two cases.

BACKGROUND: Thromboembolic occlusion of the superior mesenteric artery (SMA) is a grave complication in individuals diagnosed with atrial fibrillation (AF). This condition often necessitates extensive bowel resection, culminating in short bowel syndrome, which presents challenges for anticoagulant administration and/or antiarrhythmic therapy. CASE PRESENTATION: Presented here are findings of two patients, aged 78 and 72 years, respectively, who underwent comprehensive thoracoscopic AF surgery subsequent to extensive small bowel resection following SMA embolization. In each, onset of AF precipitated an embolic event, while the concurrent presence of short bowel syndrome complicated anticoagulation management. Total thoracoscopic AF surgery, comprised stapler-closure of the left atrial appendage (LAA) and bilateral epicardial clamp-isolation of the pulmonary veins, an operative modality aimed at addressing AF rhythm control and mitigating embolic events such as cerebral infarction, led to favorable outcomes in both cases. Additionally, computed tomography (CT) conducted one month post-surgery revealed the absence of residual tissue in the LAA, with the left atrium demonstrating a well-rounded, spherical shape. At the time of writing, the patients have remained asymptomatic following surgery regarding thromboembolic and arrhythmic manifestations for 29 and 10 months, respectively, notwithstanding the absence of anticoagulant or antiarrhythmic pharmacotherapy. Additionally, electrocardiographic surveillance has revealed persistent sinus rhythm. CONCLUSIONS: The present findings underscore the feasibility and efficacy of a total thoracoscopic AF surgery procedure for patients presented with short bowel syndrome complicating SMA embolization, thus warranting consideration for its broader clinical application.

Protective effects of selective mineralocorticoid receptor antagonist against aortic aneurysm progression in a novel murine model.

BACKGROUND: The optimal medical management to delay the progression of aortic aneurysms has not been fully clarified, and the only standard treatment at present is antihypertensive therapy. Previous studies have shown beneficial effects of selective mineralocorticoid receptor (MR) antagonists on cardiovascular remodeling. The aim of the present study was to investigate the effect of a selective MR antagonist on aortic aneurysm progression. METHODS: Seven-week-old C57BL/6J male mice were administered with angiotensin II and ß-aminopropionitrile for 4 weeks. The mice received either vehicle or eplerenone, a selective MR antagonist (100 mg/kg daily) every day by gavage, starting at 7 weeks of age. The production of inflammatory cytokines in cultures of high mobility group box-1-stimulated macrophages with or without a MR antagonist was also analyzed using an enzyme-linked immunosorbent assay. RESULTS: Although no differences were found in the peak systolic blood pressure between the experimental groups, the mice in the eplerenone group showed a significant reduction in aneurysm development. On histologic analysis, coarse and stretched elastic fibers were markedly improved in the aortic wall in the eplerenone group. Real-time polymerase chain reaction of both aortic wall and perivascular adipose tissue demonstrated the expression of tumor necrosis factor-α, interleukin-6, and matrix metalloproteinase-2 was significantly decreased in eplerenone group, and that of monocyte chemoattractant protein-1 in the aortic wall was also significantly decreased. Macrophage infiltration in the aortic wall and perivascular adipose tissue in the eplerenone group was also significantly decreased. The production of tumor necrosis factor-α and interleukin-6 in macrophage culture, which was stimulated by high mobility group box-1 and CpG oligodeoxynucleotides, was also significantly decreased in the eplerenone group. CONCLUSIONS: Eprelenone suppressed aortic aneurysm progression through an anti-inflammatory effect. Thus, selective MR antagonists might be effective in preventing the progression of aortic aneurysms.

Crystallization and preliminary X-ray crystallographic analysis of UDP-glucuronic acid:flavonol-3-O-glucuronosyltransferase (VvGT5) from the grapevine Vitis vinifera.

Grapevine (Vitis vinifera) glycosyltransferase 5 (VvGT5) is a UDP-glucuronic acid:flavonol-3-O-glucuronosyltransferase that catalyses the 3-O-specific glucuronosylation of flavonols using UDP-glucuronic acid as a sugar donor to produce flavonol 3-O-glucosides, which are important bioactive phytochemicals. Recombinant VvGT5 expressed in Escherichia coli cells was purified and crystallized by the sitting-drop vapour-diffusion method. A full set of X-ray diffraction data was collected to 2.2 ŠBragg spacing from a single crystal using a synchrotron-radiation source. The crystal was hexagonal, belonging to space group P6(1)22, with unit-cell parameters a = b = 102.70, c = 535.92 Å. The initial phases were determined by the molecular-replacement method.

Minimally Invasive Surgical Versus Transcatheter Aortic Valve Replacement: A Retrospective Observational Single-Center Study in Japan.

OBJECTIVE: This study aimed to compare the outcomes of minimally invasive aortic valve replacement (MICS-AVR) versus transfemoral transcatheter aortic valve replacement (TF-TAVR) in Asian patients. METHODS: We conducted a retrospective, observational, single-center study in Japan, including cases of MICS-AVR (n = 202) and TF-TAVR (n = 248) between 2014 and 2021. In a total of 450 cases, propensity score matching was performed at a ratio of 1:1, resulting in 96 pairs. Furthermore, we performed competing-risk regression and mediation analyses to determine the treatment effect on outcomes of interests, considering death as a competing risk, and to evaluate the mediation effect of paravalvular leak (PVL) severity. RESULTS: There were similar incidences of all-cause death, cardiac death, stroke and cerebral hemorrhage, and aortic valve reintervention between the 2 groups. However, the TF-TAVR cohort had a longer hospital length of stay and higher rates of significant PVL compared with the MICS-AVR cohort. Multivariable-adjusted Cox regression analyses revealed that heart failure hospitalization (hazard ratio [HR] = 0.129, 95% confidence interval [CI]: 0.038 to 0.445, p = 0.001) and permanent pacemaker implantation (HR = 0.050, 95% CI: 0.006 to 0.409, p = 0.005) favored MICS-AVR. Competing-risk regression analyses confirmed similar findings. All outcomes were unrelated to PVL severity. CONCLUSIONS: To our knowledge, this is the first comparative study of clinical outcomes in Asian patients undergoing MICS-AVR versus TF-TAVR, revealing that MICS-AVR could be a feasible and efficient alternative to TF-TAVR. Future larger-scale randomized controlled trials are needed to validate the present results.