Identification of a putative α-galactoside ß-(1 → 3)-galactosyltransferase involved in the biosynthesis of galactomannan side chain of glucuronoxylomannogalactan in Cryptococcus neoformans.

The cell surface of Cryptococcus neoformans is covered by a thick capsular polysaccharide. The capsule is the most important virulence factor of C. neoformans; however, the complete mechanism of its biosynthesis is unknown. The capsule is composed of glucuronoxylomannan (GXM) and glucuronoxylomannogalactan (GXMGal). As GXM is the most abundant component of the capsule, many studies have focused on GXM biosynthesis. However, although GXMGal has an important role in virulence, studies on its biosynthesis are scarce. Herein, we have identified a GT31 family ß-(1 → 3)-galactosyltransferase Ggt2, which is involved in the biosynthesis of the galactomannan side chain of GXMGal. Comparative analysis of GXMGal produced by a ggt2 disruption strain revealed that Ggt2 is a glycosyltransferase that catalyzes the initial reaction in the synthesis of the galactomannan side chain of GXMGal. The ggt2 disruption strain showed a temperature-sensitive phenotype at 37°C, indicating that the galactomannan side chain of GXMGal is important for high-temperature stress tolerance in C. neoformans. Our findings provide insights into complex capsule biosynthesis in C. neoformans.

Discovery of α-(1→6)-linked mannan structures resembling yeast N-glycan outer chains in Aspergillus fumigatus mycelium.

The cellular surface of the pathogenic filamentous fungus Aspergillus fumigatus is enveloped in a mannose layer, featuring well-established fungal-type galactomannan and O-mannose-type galactomannan. This study reports the discovery of cell wall component in A. fumigatus mycelium, which resembles N-glycan outer chains found in yeast. The glycosyltransferases involved in its biosynthesis in A. fumigatus were identified, with a focus on two key α-(1→2)-mannosyltransferases, Mnn2 and Mnn5, and two α-(1→6)-mannosyltransferases, Mnn9 and Van1. In vitro examination revealed the roles of recombinant Mnn2 and Mnn5 in transferring α-(1→2)-mannosyl residues. Proton nuclear magnetic resonance (1H-NMR) analysis of cell wall extracts from the ∆mnn2∆mnn5 strain indicated the existence of an α-(1→6)-linked mannan backbone in the A. fumigatus mycelium, with Mnn2 and Mnn5 adding α-(1→2)-mannosyl residues to this backbone. The α-(1→6)-linked mannan backbone was absent in strains where mnn9 or van1 was disrupted in the parental ∆mnn2∆mnn5 strain in A. fumigatus. Mnn9 and Van1 functioned as α-(1→6)-linked mannan polymerases in heterodimers when co-expressed in Escherichia coli, indicating their crucial role in biosynthesizing the α-(1→6)-linked mannan backbone. Disruptions of these mannosyltransferases did not affect fungal-type galactomannan biosynthesis. This study provides insights into the complexity of fungal cell wall architecture and a better understanding of mannan biosynthesis in A. fumigatus. IMPORTANCE: This study unravels the complexities of mannan biosynthesis in A. fumigatus, a key area for antifungal drug discovery. It reveals the presence of α-(1→6)-linked mannan structures resembling yeast N-glycan outer chains in A. fumigatus mycelium, offering fresh insights into the fungal cell wall's design. Key enzymes, Mnn2, Mnn5, Mnn9, and Van1, are instrumental in this process, with Mnn2 and Mnn5 adding specific mannose residues and Mnn9 and Van1 assembling the α-(1→6)-linked mannan structures. Although fungal-type galactomannan's presence in the cell wall is known, the existence of an α-(1→6)-linked mannan adds a new dimension to our understanding. This intricate web of mannan biosynthesis opens avenues for further exploration and enhances our understanding of fungal cell wall dynamics, paving the way for targeted drug development.

Sodium-Glucose Cotransporter-2 Inhibitors Stabilize Coronary Plaques in Acute Coronary Syndrome With Diabetes Mellitus.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are widely used in cardiology and are effective in treating acute coronary syndrome (ACS). Their effects on unstable plaque in patients with ACS remains unclear. This study aimed to examine the effectiveness of SGLT2is in coronary plaque based on optical coherence tomography (OCT) images and the prognosis of ACS with type 2 diabetes mellitus. This retrospective study included 109 patients in the total cohort and 29 patients in the OCT cohort. Based on SGLT2i administration after ACS, the total cohort was categorized into non-SGLT2i (n = 69) and SGLT2i (n = 40) groups. The OCT cohort had 15 and 14 patients in the non-SGLT2i and SGLT2i groups, respectively. The OCT images of unstable plaque were analyzed in nonstented lesions during ACS catheterization and at the 6-month follow-up. The total cohort was assessed after 1 year for major adverse cardiovascular events, including all-cause mortality, revascularization, cerebrovascular disease, and heart failure hospitalization. SGLT2is improved unstable lesions with a significantly thicker fibrous cap (48 ± 15 µm vs 26 ± 24 µm, p = 0.005), reduced lipid arc (-29 ± 12° vs -18 ± 14°, p = 0.028), higher % decrease in total lipid arc (-35 ± 13% vs -19 ± 18%, p = 0.01), and lower major adverse cardiovascular event incidence (log-rank p = 0.023, hazard ratio 4.72 [1.08 to 20.63]) and revascularization rate (adjusted hazard ratio 6.77 [1.08 to 42.52]) than the non-SGLT2i group. In conclusion, SGLT2is can improve the markers of plaque stability and may improve the prognosis in patients with type 2 diabetes mellitus.

One-carbon metabolizing enzyme ALDH1L1 influences mitochondrial metabolism through 5-aminoimidazole-4-carboxamide ribonucleotide accumulation and serine depletion, contributing to tumor suppression.

Tumor cells generally require large amounts of nucleotides, and thus activate de novo purine synthesis (dnPS). In the dnPS reactions, 10-formyltetrahydorofolate (10-fTHF) supplied by one-carbon metabolism is utilized as a formyl group donor. We focused on aldehyde dehydrogenase 1 family member L1 (ALDH1L1), which metabolizes 10-fTHF to tetrahydrofolate and whose expression is often attenuated in hepatocellular carcinoma (HCC). We generated ALDH1L1-expressing HuH-7 cells to perform metabolome analysis and found that intracellular levels of serine were reduced and glycine was increased. In addition, 5-aminoimidazole-4-carboxamide ribonucleotide (ZMP), a dnPS intermediate, accumulated due to the consumption of 10-fTHF by ALDH1L1, which inhibited ZMP formylation. Importantly, ALDH1L1-expressing cells showed reduced ZMP sensitivity and higher mitochondrial activity. The suppression of mitochondrial serine catabolism by ALDH1L1 expression was speculated to be closely related to this phenotype. Gene set enrichment analysis utilizing The Cancer Genome Atlas data revealed that genes related to oxidative phosphorylation were enriched in HCC patients with high ALDH1L1 expression. Moreover, drug sensitivity data analysis demonstrated that HCC cell lines with low expression of ALDH1L1 were sensitive to ZMP and cordycepin, a structural analog of ZMP and AMP. Our study revealed that ZMP and AMP analogs might be effective in the pharmacotherapy of HCC patients with low expression of ALDH1L1.

Impact of High Implantation of Transcatheter Aortic Valve on Subsequent Conduction Disturbances and Coronary Access.

BACKGROUND: Data regarding the impact of high transcatheter heart valve (THV) implantation on coronary access after transcatheter aortic valve replacement (TAVR) as assessed by postimplantation computed tomography (CT) are scarce. OBJECTIVES: The authors sought to assess the impact of high THV implantation on coronary access after TAVR. METHODS: We included 160 and 258 patients treated with Evolut R/PRO/PRO+ and SAPIEN 3 THVs, respectively. In the Evolut R/PRO/PRO+ group, the target implantation depth was 1 to 3 mm using the cusp overlap view with commissural alignment technique for the high implantation technique (HIT), whereas it was 3 to 5 mm using 3-cusp coplanar view for the conventional implantation technique (CIT). In the SAPIEN 3 group, the HIT employed the radiolucent line-guided implantation, whereas the central balloon marker-guided implantation was used for the CIT. Post-TAVR CT was performed to analyze coronary accessibility. RESULTS: HIT reduced the incidence of new conduction disturbances after TAVR for both THVs. In the Evolut R/PRO/PRO+ group, post-TAVR CT showed that the HIT group had a higher incidence of the interference of THV skirt (22.0% vs 9.1%; P = 0.03) and a lower incidence of the interference of THV commissural posts (26.0% vs 42.7%; P = 0.04) with access to 1 or both coronary ostia compared with the CIT group. These incidences were similar between the HIT and CIT groups in the SAPIEN 3 group (THV skirt: 0.9% vs 0.7%; P = 1.00; THV commissural tabs: 15.7% vs 15.3%; P = 0.93). In both THVs, CT-identified risk of sinus sequestration in TAVR-in-TAVR was significantly higher in the HIT group compared with the CIT group (Evolut R/PRO/PRO+ group: 64.0% vs 41.8%; P = 0.009; SAPIEN 3 group: 17.6% vs 5.3%; P = 0.002). CONCLUSIONS: High THV implantation substantially reduced conduction disturbances after TAVR. However, post-TAVR CT revealed that there is a risk for unfavorable future coronary access after TAVR and sinus sequestration in TAVR-in-TAVR. (Impact of High Implantation of Transcatheter Heart Valve during Transcatheter Aortic Valve Replacement on Future Coronary Access; UMIN000048336).

Identification of galactofuranose antigens such as galactomannoproteins and fungal-type galactomannan from the yellow koji fungus (Aspergillus oryzae).

Filamentous fungi belonging to the genus Aspergillus are known to possess galactomannan in their cell walls. Galactomannan is highly antigenic to humans and has been reported to be involved in the pathogenicity of pathogenic filamentous fungi, such as A. fumigatus, and in immune responses. In this study, we aimed to confirm the presence of D-galactofuranose-containing glycans and to clarify the biosynthesis of D-galactofuranose-containing glycans in Aspergillus oryzae, a yellow koji fungus. We found that the galactofuranose antigen is also present in A. oryzae. Deletion of ugmA, which encodes UDP-galactopyranose mutase in A. oryzae, suppressed mycelial elongation, suggesting that D-galactofuranose-containing glycans play an important role in cell wall integrity in A. oryzae. Proton nuclear magnetic resonance spectrometry revealed that the galactofuranose-containing sugar chain was deficient and that core mannan backbone structures were present in ΔugmA A. oryzae, indicating the presence of fungal-type galactomannan in the cell wall fraction of A. oryzae. The findings of this study provide new insights into the cell wall structure of A. oryzae, which is essential for the production of fermented foods in Japan.

Device indication for calcified coronary lesions based on coronary imaging findings.

Performing percutaneous coronary intervention (PCI) for calcified lesions is still a major challenge. Calcified lesions are a cause of inadequate dilatation, leading to poor short- and long-term PCI outcomes. It has been suggested that modification for calcification before stent implantation might improve outcomes by providing adequate dilation. Intravascular lithotripsy (IVL) is available under insurance reimbursement in December 2022 in Japan. IVL is one candidate for a treatment device to modify calcified lesions in addition to atherectomy, such as rotational and orbital atherectomy, and special balloons, such as scoring and cutting balloons. Although the evidence for the indications, of these devices is insufficient, they must be used appropriately in clinical practice. In this report, we propose a method for determining an indication of these devices solely as per the coronary imaging findings with intravascular ultrasound or optical coherent tomography. This consensus document represents the collective opinion of experts on the best current indications and should be changed based on future evidence. However, we believe that it represents the optimal criteria for selecting treatment options in the current situation.

Discordance between fractional flow reserve and instantaneous wave-free ratio in patients with severe aortic stenosis: A retrospective cohort study.

BACKGROUND: Discordance between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) occurs in approximately 20 % of cases. However, no studies have reported the discordance in patients with severe aortic stenosis (AS). We aimed to evaluate the diagnostic discordance between FFR and iFR in patients with severe AS. METHODS: We examined 140 consecutive patients with severe AS (164 intermediate coronary artery stenosis vessels). FFR and iFR were calculated in four quadrants based on threshold FFR and iFR values of ≤0.8 and ≤0.89, respectively (Group 1: iFR >0.89, FFR >0.80; Group 2: iFR ≤0.89, FFR >0.80; Group 3: iFR >0.89, FFR ≤0.80; and Group 4: iFR ≤0.89, FFR ≤0.80). Concordant groups were Groups 1 and 4, and discordant groups were Groups 2 and 3. Positive and negative discordant groups were Groups 3 and 2, respectively. RESULTS: The median (Q1, Q3) FFR and iFR were 0.84 (0.76, 0.88) and 0.85 (0.76, 0.91), respectively. Discordance was observed in 48 vessels (29.3 %). In the discordant group, negative discordance (Group 2: iFR ≤0.89 and FFR >0.80) was predominant (45 cases, 93.6 %). Multivariate analysis showed that the left anterior descending artery [odds ratio (OR), 3.88; 95 % confidence interval (CI): 1.54-9.79, p = 0.004] and peak velocity ≥5.0 m/s (OR, 3.21; 95%CI: 1.36-7.57, p = 0.008) were independently associated with negative discordance (FFR >0.8 and iFR ≤0.89). CONCLUSIONS: In patients with severe AS, discordance between FFR and iFR was predominantly negative and observed in 29.3 % of vessels. The left anterior descending artery and peak velocity ≥5.0 m/s were independently associated with negative discordance.

Conventional and Kampo Medicine Treatment for Mild-to-moderate COVID-19: A Multicenter, Retrospective, Observational Study by the Integrative Management in Japan for Epidemic Disease (IMJEDI Study-observation).

Objective Patients in whom coronavirus disease 2019 (COVID-19) was suspected or confirmed between January 1, 2020, and October 31, 2021, were enrolled from Japanese hospitals in this multicenter, retrospective, observational study. Methods Data on the treatment administered (including conventional and Kampo medicine) and changes in common cold-like symptoms (such as fever, cough, sputum, dyspnea, fatigue, and diarrhea) were collected from their medical records. The primary outcome was the number of days without a fever (with a body temperature <37°C). The secondary outcomes were symptomatic relief and the worsening of illness, defined as the presence of a condition requiring oxygen inhalation. The outcomes of patients treated with and without Kampo medicine were compared. Patients We enrolled 962 patients, among whom 528 received conventional and Kampo treatment (Kampo group) and 434 received conventional treatment (non-Kampo group). Results Overall, after adjusting for the staging of COVID-19 and risk factors, there were no significant between-group differences in the symptoms or number of days being afebrile. After performing propensity score matching and restricting the included cases to those with confirmed COVID-19 who did not receive steroid administration and initiated treatment within 4 days from the onset, the risk of illness worsening was significantly lower in the Kampo group than in the non-Kampo group (odds ratio=0.113, 95% confidence interval: 0.014-0.928, p=0.0424). Conclusion Early Kampo treatment may suppress illness worsening risk in COVID-19 cases without steroid use. Further randomized controlled studies are needed to confirm the clinical benefit of Kampo medicine for COVID-19.

Identification of an α-(1→6)-Mannosyltransferase Contributing To Biosynthesis of the Fungal-Type Galactomannan α-Core-Mannan Structure in Aspergillus fumigatus.

Fungal-type galactomannan, a cell wall component of Aspergillus fumigatus, is composed of α-(1→2)-/α-(1→6)-linked mannan and ß-(1→5)-/ß-(1→6)-linked galactofuran side chains. Recently, CmsA and CmsB were identified as the α-(1→2)-mannosyltransferases involved in the biosynthesis of the α-core-mannan. However, the α-(1→6)-mannosyltransferase involved in the biosynthesis of the α-core-mannan has not been identified yet. In this study, we analyzed 9 putative α-(1→6)-mannosyltransferase gene disruption strains of A. fumigatus. The ΔanpA strain resulted in decreased mycelial elongation and reduced conidia formation. Proton nuclear magnetic resonance analysis revealed that the ΔanpA strain failed to produce the α-core-mannan of fungal-type galactomannan. We also found that recombinant AnpA exhibited much stronger α-(1→6)-mannosyltransferase activity toward α-(1→2)-mannobiose than α-(1→6)-mannobiose in vitro. Molecular simulations corroborated the fact that AnpA has a structure that can recognize the donor and acceptor substrates suitable for α-(1→6)-mannoside bond formation and that its catalytic activity would be specific for the elongation of the α-core-mannan structure in vivo. The identified AnpA is similar to Anp1p, which is involved in the elongation of the N-glycan outer chain in budding yeast, but the building sugar chain structure is different. The difference was attributed to the difference in substrate recognition of AnpA, which was clarified by simulations based on protein conformation. Thus, even proteins that seem to be functionally identical due to amino acid sequence similarity may be glycosyltransferase enzymes that make different glycans upon detailed analysis. This study describes an example of such a case. IMPORTANCE Fungal-type galactomannan is a polysaccharide incorporated into the cell wall of filamentous fungi belonging to the subphylum Pezizomycotina. Biosynthetic enzymes of fungal-type galactomannan are potential targets for antifungal drugs and agrochemicals. In this study, we identified an α-(1→6)-mannosyltransferase responsible for the biosynthesis of the α-core-mannan of fungal-type galactomannan, which has not been known for a long time. The findings of this study shed light on processes that shape this cellular structure while identifying a key enzyme essential for the biosynthesis of fungal-type galactomannan.

Galactosylation of cell-surface glycoprotein required for hyphal growth and cell wall integrity in Schizosaccharomyces japonicus.

Schizosaccharomyces japonicus is a dimorphic yeast, transiting between unicellular and hyphal growth. The glycoproteins of fission yeast contain, in addition to mannose (Man), a large number of galactose (Gal) residues. Previously, we reported that the cell-surface O-glycans of S. japonicus comprise mainly tri-saccharides (Gal-Man-Man) as a main component, in contrast to the tetra-saccharides observed in other Schizosaccharomyces species. Here we have investigated the function of cell-surface Gal residues in S. japonicus. Because disruption of gms1+, encoding the UDP-Gal transporter required for galactomannan synthesis, abolishes cell-surface galactosylation in Schizosaccharomyces pombe, we constructed a deletion mutant of the homologous gene in S. japonicus gms1Δ [gms1 (S.j)] and determined the N- and O-linked oligosaccharide structures present on the cell surface. Disruption of gms1 (S.j) resulted in a complete lack of Gal on the cell surface, indicating that Gms1 plays an essential role in supplying UDP-Gal from the cytoplasm to the Golgi lumen. Analytical microscopy of gms1Δ demonstrated that the lack of cell-surface Gal did not affect cell growth or morphology during vegetative growth. However, hyphal development was blocked in gms1Δ, even in the presence of the topoisomerase I inhibitor camptothecin, which is known to induce hyphal differentiation in wild-type S. japonicus. Collectively, these findings show that Gal-containing oligosaccharides are required for cell wall integrity during filamentous growth in S. japonicus.

Distal Transradial Access For Cardiac Catheterization in Patients Undergoing Hemodialysis.

OBJECTIVES: Although a distal radial artery (DRA) approach has recently been used in patients undergoing cardiac catheterization, no studies have so far investigated the safety and feasibility of DRA in patients undergoing hemodialysis (HD). We aimed to investigate the incidence of conventional radial artery (CRA) occlusion and puncture site complications after DRA puncture in patients undergoing HD. METHODS: We retrospectively analyzed the data of 117 consecutive patients with HD who underwent coronary angiography or percutaneous coronary intervention via a DRA approach at our institution from September 2017 to December 2019. The primary endpoint was the incidence of CRA occlusion after DRA puncture, as assessed via vascular ultrasonography. Secondary endpoints included difficulty achieving hemostasis, DRA occlusion, aneurysm, arteriovenous shunt, and acute ischemia. RESULTS: The DRA puncture was successful in 106 patients (success rate: 90.5%). Because 21 patients lacked postprocedural vascular ultrasonography data, the primary endpoint was evaluated in 85 patients. CRA occlusion occurred in three patients (3.5%) following DRA puncture. DRA occlusion and aneurysm occurred in five patients (5.9%) and one patient (1.2%), respectively. CONCLUSIONS: Catheterization through DRA is feasible in patients undergoing HD, with a clinically acceptable incidence of CRA and complications.

Mnt1, an α-(1 → 2)-mannosyltransferase responsible for the elongation of N-glycans and O-glycans in Aspergillus fumigatus.

The fungal cell wall is necessary for survival as it serves a barrier for physical protection. Therefore, glycosyltransferases responsible for the synthesis of cell wall polysaccharides may be suitable targets for drug development. Mannose is a monosaccharide that is commonly found in sugar chains in the walls of fungi. Mannose residues are present in fungal-type galactomannan, O-glycans, N-glycans, glycosylphosphatidylinositol anchors, and glycosyl inositol phosphorylceramides in Aspergillus fumigatus. Three genes that are homologous to α-(1 â†’ 2)-mannosyltransferase genes and belong to the glycosyltransferase family 15 were found in the A. fumigatus strain, Af293/A1163, genome: cmsA/ktr4, cmsB/ktr7, and mnt1. It is reported that the mutant ∆mnt1 strain exhibited a wide range of properties that included high temperature and drug sensitivity, reduced conidia formation, leakage at the hyphal tips, and attenuation of virulence. However, it is unclear whether Mnt1 is a bona fide α-(1 â†’ 2)-mannosyltransferase and which mannose residues are synthesized by Mnt1 in vivo. In this study, we elucidated the structure of the Mnt1 reaction product, the structure of O-glycan in the Δmnt1 strain. In addition, the length of N-glycans attached to invertase was evaluated in the Δmnt1 strain. The results indicated that Mnt1 functioned as an α-(1 â†’ 2)-mannosyltransferase involved in the elongation of N-glycans and synthesis of the second mannose residue of O-glycans. The widespread abnormal phenotype caused by the disruption of the mnt1 gene is the combined result of the loss of mannose residues from O-glycans and N-glycans. We also clarified the enzymatic properties and substrate specificity of Mnt1 based on its predicted protein structure.

Generalized allergic reaction in response to exercise due to strawberry gibberellin-regulated protein: a case report.

BACKGROUND: The Rosaceae family includes fruits, such as peach, apple, Japanese apricot, cherry (Prunoideae subfamily), and strawberry (Rosoideae subfamily). The allergens responsible for Rosaceae fruit allergies have been reported to include Bet v 1 and profilin, which mainly cause oral symptoms, and lipid transfer protein (LTP). Recently, gibberellin-regulated protein (GRP) has been identified as an allergen that induces generalized symptoms in peach-, orange-, and plum-related allergies. Most patients with food allergies induced by GRP show allergic symptoms accompanied by cofactors, such as exercise or drugs. To date, there are very few reports of generalized symptoms induced by strawberry. CASE PRESENTATION: We evaluated the reactivity of strawberry GRP in a 15-year-old boy who was confirmed to have generalized symptoms induced by strawberry with exercise using an oral food challenge test (OFCT). The patient's serum exhibited a strong positive reaction to strawberry GRP but not to peach GRP or peach LTP. The patient's basophils reacted to strawberry and peach GRP but not to peach LTP. CONCLUSIONS: Strawberry GRP may be a causative component for strawberry with exercise-induced generalized symptoms in this patient. This is the first study to investigate the role of GRP in strawberry with cofactor-induced allergic symptoms. Further epidemiological and clinical researches are necessary to improve diagnostic and therapeutic approaches for patients with strawberry allergy.

Coronary Access After TAVR With a Cylindrical-Shaped Valve: Learning From LOTUS.

BACKGROUND/PURPOSE: Data on the feasibility of coronary access (CA) through above or outside of the cylindrical shaped-transcatheter heart valve (THV) are very limited. The aims of the present study were to assess the feasibility of CA after transcatheter aortic valve replacement (TAVR) with the LOTUS using multi detector computed tomography (MDCT) and the reliability of algorithm detecting unfavorable CA. METHODS/MATERIALS: Post-TAVR MDCT of 41 patients with 82 coronary arteries were evaluated. The relationship and distance between the THV flame and sinotubular junction (STJ) and coronary ostia were assessed. Unfavorable CA was defined as the valve-to-STJ distance < 2-mm or the valve-to-coronary ostia distance < 2-mm if the THV flame was above STJ or coronary ostia. RESULTS: MDCT-identified unfavorable CA was observed in 29.3% for the left coronary artery and 41.5% for the right coronary artery. In total, 53.7% of patients had at least one unfavorable CA and 14.6% of those had unfavorable CA for both left and right coronary artery. While patients underwent coronary angiography after TAVR, the success rates of selective coronary cannulation were significantly lower in patients with MDCT-identified unfavorable CA in comparison to those with favorable CA for left (20.0% vs. 100%, P = 0.002) and right coronary artery (0% vs. 100%, P < 0.001). CONCLUSIONS: Future CA through above or outside of a cylindrical shaped THV may be challenging with a significant probability. Our algorithm identifying unfavorable CA using post-MDCT seems to be useful for estimating the risk of unsuccessful selective cannulation.