Efficient production of natural sunscreens shinorine, porphyra-334, and mycosporine-2-glycine in Saccharomyces cerevisiae.

Mycosporine-like amino acids (MAAs) are promising natural sunscreens mainly produced in marine organisms. Until now, metabolic engineering efforts to produce MAAs in heterologous hosts have mainly focused on shinorine production, and the low production levels are still not suitable for industrial applications. In this study, we successfully developed Saccharomyces cerevisiae strains that can efficiently produce various disubstituted MAAs, including shinorine, porphyra-334, and mycosporine-2-glycine (M2G), which are formed by conjugating serine, threonine, and glycine to mycosporine-glycine (MG), respectively. We first generated an MG-producing strain by multiple integration of the biosynthetic genes from cyanobacteria and applying metabolic engineering strategies to increase sedoheptulose-7-phosphate pool, a substrate for MG production. Next, five mysD genes from cyanobacteria, which encode D-Ala-D-Ala ligase homologues that conjugate an amino acid to MG, were introduced into the MG-producing strain to determine the substrate preference of each MysD enzyme. MysDs from Lyngbya sp., Nostoclinckia, and Euhalothece sp. showed high specificity toward serine, threonine, and glycine, resulting in efficient production of shinorine, porphyra-334, and M2G, respectively. This is the first report on the production of porphyra-334 and M2G in S. cerevisiae. Furthermore, we identified that the substrate specificity of MysD was determined by the omega loop region of 43-45 amino acids predicted based on its structural homology to a D-Ala-D-Ala ligase from Thermus thermophilus involved in peptidoglycan biosynthesis. The substrate specificities of two MysD enzymes were interchangeable by swapping the omega loop region. Using the engineered strain expressing mysD from Lyngbya sp. or N. linckia, up to 1.53 g/L shinorine or 1.21 g/L porphyra-334 was produced by fed-batch fermentation in a 5-L bioreactor, the highest titer reported so far. These results suggest that S. cerevisiae is a promising host for industrial production of different types of MAAs, providing a sustainable and eco-friendly alternative for the development of natural sunscreens.

The Dipeptide Gly-Pro (GP), Derived from Hibiscus sabdariffa, Exhibits Potent Antifibrotic Effects by Regulating the TGF-ß1-ATF4-Serine/Glycine Biosynthesis Pathway.

TGF-ß1, a key fibrotic cytokine, enhances both the expression and translocation of the activating transcriptional factor 4 (ATF4) and activates the serine/glycine biosynthesis pathway, which is crucial for augmenting collagen production. Targeting the TGF-ß1-ATF4-serine/glycine biosynthesis pathway might offer a promising therapeutic approach for fibrotic diseases. In this study, we aimed to identify a proline-containing dipeptide in Hibiscus sabdariffa plant cells that modulates collagen synthesis. We induced Hibiscus sabdariffa plant cells and screened for a proline-containing dipeptide that can suppress TGF-ß1-induced collagen synthesis in fibroblasts. Analyses were conducted using LC-MS/MS, RT-qPCR, Western blot analysis, and immunocytochemistry. We identified Gly-Pro (GP) from the extract of Hibiscus sabdariffa plant cells as a dipeptide capable of suppressing TGF-ß1-induced collagen production. GP inhibited the phosphorylation of Smad2/3 and reduced the expression of ATF4, which is upregulated by TGF-ß1. Notably, GP also decreased the expression of enzymes involved in the serine/glycine biosynthesis and glucose metabolism pathways, such as PHGDH, PSAT1, PSPH, SHMT2, and SLC2A1. Our findings indicate that the peptide GP, derived from Hibiscus sabdariffa plant cells, exhibits potent anti-fibrotic effects, potentially through its regulation of the TGF-ß1-ATF4-serine/glycine biosynthesis pathway.

Comparative Analysis of Water Extracts from Roselle (Hibiscus sabdariffa L.) Plants and Callus Cells: Constituents, Effects on Human Skin Cells, and Transcriptome Profiles.

Roselle (Hibiscus sabdariffa L.) is a plant that has traditionally been used in various food and beverage products. Here, we investigated the potential of water extracts derived from Roselle leaves and callus cells for cosmetic and pharmaceutical purposes. We generated calluses from Roselle leaves and produced two different water extracts through heat extraction, which we named Hibiscus sabdariffa plant extract (HSPE) and Hibiscus sabdariffa callus extract (HSCE). HPLC analysis showed that the two extracts have different components, with nucleic acids and metabolites such as phenylalanine and tryptophan being the most common components in both extracts. In vitro assays demonstrated that HSCE has strong anti-melanogenic effects and functions for skin barrier and antioxidant activity. Transcriptome profiling of human skin cells treated with HSPE and HSCE showed significant differences, with HSPE having more effects on human skin cells. Up-regulated genes by HSPE function in angiogenesis, the oxidation-reduction process, and glycolysis, while up-regulated genes by HSCE encode ribosome proteins and IFI6, functioning in the healing of radiation-injured skin cells. Therefore, we suggest that the two extracts from Roselle should be applied differently for cosmetics and pharmaceutical purposes. Our findings demonstrate the potential of Roselle extracts as a natural source for skincare products.

Effect of Perioperative Intravenous Iron Supplementation for Complex Cardiac Surgery on Transfusion Requirements: A Randomized, Double-blinded Placebo-controlled Trial.

OBJECTIVES: We investigated whether routine perioperative intravenous iron replenishment reduces the requirement for packed erythrocytes (pRBC) transfusion. SUMMARY OF BACKGROUND DATA: Patients undergoing complex cardiac surgery are at high risk of developing postoperative iron deficiency anemia, thus requiring transfusion, which is associated with adverse outcomes. METHODS: Patients were randomized to receive either ferric derisomaltose 20 mg/kg (n = 103) or placebo (n = 101) twice during the perioperative period: 3 days before and after the surgery. The primary endpoint was the proportion of patients who received pRBC transfusion until postoperative day (POD) 10. Hemoglobin, reticulocyte count, serum iron profile, hepcidin, and erythropoietin were serially measured. RESULTS: pRBC was transfused in 60.4% and 57.2% of patients in the control and iron group, respectively (P = 0.651). Hemoglobin concentration at 3 weeks postoperatively was higher in the iron group than in the control group (11.6 ± 1.5 g/dL vs 10.9 ± 1.4 g/dL, P < 0.001). The iron group showed higher reticulocyte count [205 (150-267)×103/µL vs 164 (122-207)×103/µL, P = 0.003] at POD 10. Transferrin saturation and serum ferritin were significantly increased in the iron group than in the control group (P < 0.001). Serum hepcidin was higher in the iron group than in the control group at POD 3 [106.3 (42.9-115.9) ng/mL vs 39.3 (33.3-43.6) ng/mL, P < 0.001]. Erythropoietin concentration increased postoperatively in both groups (P = 0.003), with no between-group difference. CONCLUSIONS: Intravenous iron supplementation during index hospitalization for complex cardiac surgery did not minimize pRBC transfusion despite replenished iron store and augmented erythropoiesis, which may be attributed to enhanced hepcidin expression.

Feasibility of Aortic Annular Measurements Using Noncontrast-Enhanced Cardiac Computed Tomography in Preprocedural Evaluation of Transcatheter Aortic Valve Replacement: A Comparison With Contrast-Enhanced Computed Tomography.

OBJECTIVE: Noncontrast-enhanced (NCE) cross-sectional images other than contrast-enhanced (CE)-computed tomography (CT) may be necessary for annular sizing before transcatheter aortic valve replacement (TAVR), because of the risk of contrast-induced nephropathy. We aimed to investigate the feasibility of aortic annular measurements using NCE-CT in TAVR candidates by comparing them with CE-CT measurements. METHODS: We retrospectively enrolled 46 patients who underwent CT for the purpose of pre-TAVR evaluation (17 men; mean age, 82.3 ± 5.0 years). On CE and NCE examination, measurements of the average diameter and perimeter of aortic annulus were performed by 2 observers, and coronary ostial heights were measured. Differences in annular parameters and coronary ostial heights between NCE and CE examinations were assessed using Bland-Altman analysis and intraclass correlation coefficients (ICCs). RESULTS: Aortic annulus measurement values were significantly larger in the NCE examinations compared with those in the CE examinations according to both readers (mean differences of 0.8 mm for the average diameter and 2.1 mm for the perimeter according to observer 1, and 1.1 mm for the average diameter and 3.4 mm for the perimeter according to observer 2; ICC, 0.771-0.923). The mean difference between coronary ostial height measurement on NCE and CE examination was 0.6 mm for left coronary ostium (ICC, 0.795) and 0.7 mm for right coronary ostium (ICC, 0.802). No case showed disagreement between NCE and CE examinations for hypothetical valve sizing. CONCLUSIONS: Noncontrast-enhanced cardiac CT examination may be feasible for aortic annular measurements before TAVR and provides comparable measurement values to CE examination.

Aortic valve replacement in patients aged 50 to 69 years: Analysis using Korean National Big Data.

BACKGROUND: The aim of this study was to compare the clinical outcomes and long-term survival in patients who underwent isolated aortic valve replacement (AVR) with mechanical versus bioprosthetic valves. METHODS: Patients aged 50-69 years who had undergone AVR from 2002 to 2018 were identified and their characteristics were collected from Korean National Health Information Database formed by the National Health Insurance Service, Republic of Korea. Of the 5792 patients, 1060 patients were excluded due to missing values on characteristics. Of the 4732 study patients, 1945 patients (41.1%) had received bioprosthetic valves (Group B) and 2787 patients (58.9%) had received mechanical valves (Group M). A propensity score-matched analysis was performed to match 1429 patients in each group. Data on mortality, cardiac mortality, reoperations, cerebrovascular accidents, and bleeding complications were obtained. RESULTS: The overall survival rates at 5 and 10 years postoperatively were 87.8% and 75.2% in the matched Group B and 91.2% and 76.7% in the matched Group M, respectively (p = .140). Freedom from cardiac death rates at postoperative 5 and 10 years were 95.6% and 92.4% in the matched Group B and 96.0% and 92.1% in the matched Group M, respectively (p = .540). The cumulative incidence of reoperation was higher in the matched Group B than in the matched Group M (p = .007), and the cumulative incidence of major bleeding was higher in the matched Group M than in the matched Group B (p = .039). CONCLUSION: In patients aged 50-69 years who underwent isolated AVR, the patients who received bioprosthetic valves showed similar cardiac mortality-free survival and long-term survival rates to the patients who received mechanical valves.

Differentiation of left atrial appendage thrombus from circulatory stasis using cardiac CT radiomics in patients with valvular heart disease.

OBJECTIVES: To determine whether quantitative radiomic features from cardiac CT could differentiate the left atrial appendage (LAA) thrombus from circulatory stasis in patients with valvular heart disease. METHODS: Ninety-five consecutive patients with valvular heart disease and filling defects in LAA on two-phase cardiac CT from March 2016 to August 2018 were retrospectively enrolled and classified as having thrombus or stasis by transesophageal echocardiography or cardiac surgery. The ratio of Hounsfield units in the filling defects to those in the ascending aorta (AA) was calculated on early- and late-phase CT (LAA/AAE and LAA/AAL, respectively). Radiomic features were extracted from semi-automated three-dimensional segmentation of the filling defect on early-phase CT. The diagnostic ability of radiomic features for differentiating thrombus from stasis was assessed and compared to LAA/AAE and LAA/AAL by comparing the AUC of ROC curves. Diagnostic performances of CT attenuation ratios and radiomic features were validated with an independent validation set. RESULTS: Thrombus was diagnosed in 25 cases and stasis in 70. Sixty-eight radiomic features were extracted. Values of 8 wavelet-transformed features were lower in thrombus than in stasis (p < 0.001). The AUC value of a radiomic feature, wavelet_LHL, for diagnosing thrombus was 0.78, which was higher than that of LAA/AAE (AUC = 0.54, p = 0.025) and similar to that of LAA/AAL (AUC = 0.76, p = 0.773). In the validation set, the AUC of wavelet_LHL was 0.71, which was higher than that of LAA/AAE (AUC = 0.57, p = 0.391) and similar to that of LAA/AAL (AUC = 0.75, p = 0.707). CONCLUSIONS: Quantitative radiomic features from the early phase of cardiac CT may help diagnose LAA thrombus in patients with valvular heart disease. KEY POINTS: • Wavelet-transformed grey-level non-uniformity values from radiomic analysis are significantly lower for LAA thrombus than for circulatory stasis. • Radiomic features may have an additional value for differentiating LAA thrombus from circulatory stasis when interpreting single-phase cardiac CT. • Radiomic features extracted from single-phase images may show similar diagnostic ability as conventional quantitative analysis from two-phase images.

Clinical and Hemodynamic Outcomes in 121 Patients Who Underwent Perceval Sutureless Aortic Valve Implantation　- Early Results From a Single Korean Institution.

BACKGROUND: This study aimed to evaluate the early outcomes of Perceval sutureless valves in the Korean population and to introduce a modified technique of guiding suture placement during valve deployment.Methods and Results:From December 2014 to April 2019, 121 patients (mean age: 74.7±6.2 years; 53.7% female) received a Perceval sutureless aortic valve replacement. To prevent conduction system injury, the depth of guiding suture placement (1 mm below the nadir of the annulus) was modified. All patients underwent echocardiographic evaluation at discharge and 6-12 months postoperatively, with a mean follow up of 13.7±11.2 months. Concomitant surgeries, such as coronary artery bypass grafting, and other valvular surgeries, were performed in 45.5% of cases. The mean aortic cross-clamp times for isolated and minimal procedures were 32.8±7.9, and 41.2±8.0 min, respectively. The overall transvalvular mean gradients were 13.1±3.8 mmHg at discharge and 11.5±4.7 mmHg at the last follow up. After modifying the guiding suture placement, permanent pacemaker implantation risk decreased from 9.9% to 2.5%. Cardiac-related mortality was 0.8%, with no patient developing valvular or paravalvular aortic regurgitation, valve thrombosis, or endocarditis. CONCLUSIONS: Perceval valve implantation provided a significant cardiac-related survival benefit with excellent early hemodynamic and clinical outcomes. Further research is needed to determine whether adjusting the implantation depth, such as modification of the guiding suture technique, can reduce the risk of permanent pacemaker implantation.

Early and Two-year Outcomes after Sutureless and Conventional Aortic Valve Replacement: a Nationwide Population-based Study.

BACKGROUND: We compared early and 2-year clinical outcomes of sutureless aortic valve replacement (SAVR) with conventional aortic valve replacement (CAVR) in a nationwide study based on claims data. METHODS: From December 2016 to November 2018, 3,173 patients underwent bioprosthetic aortic valve replacements. SAVR and CAVR were performed in 641 and 2,532 patients, respectively. Propensity score-matched analysis was performed in 640 patient pairs. RESULTS: Operative mortality rate was 2.8% without significant differences between the SAVR (3.4%) and CAVR (2.3%) groups (P = 0.324). There were no significant differences in postoperative morbidities between the groups except for permanent pacemaker (PPM) implantation. PPM implantation rate was significantly higher in the SAVR (3.8%) than in the CAVR group (0.9%) (P < 0.001). One- and two-year overall survival was 89.1% and 87.5%, respectively, without significant differences between the groups (SAVR group vs. CAVR grouP = 89.9% and 90.5% vs. 87.2% and 88.7%, respectively; P = 0.475). There were no significant differences in the cumulative incidence of cardiac death, stroke, aortic valve reoperation and infective endocarditis between the groups. Cumulative PPM implantation incidence at 6 months in the CAVR was 1.1%, and no patient required PPM implantation after 6 months. In the SAVR, the cumulative PPM implantation incidence at 0.5, one, and two years was 3.9%, 5.0% and 5.6%, respectively. The cumulative PPM implantation rate was higher in the SAVR group than in the CAVR group (P < 0.001). CONCLUSION: Early and 2-year clinical outcomes between SAVR and CAVR were not different except for a high rate of permanent pacemaker implantation in the SAVR group.

Risk Factors for Closure Failure following Percutaneous Transfemoral Transcatheter Aortic Valve Implantation.

BACKGROUND: The percutaneous access site of transfemoral transcatheter aortic valve implantation (TAVI) procedures is commonly closed using a preclosure technique with suture-type closure devices. We sought to evaluate the predictors and outcomes of percutaneous closure device (PCD) failure during transfemoral TAVI. METHODS AND RESULTS: This single-center retrospective analysis included 184 patients who underwent transfemoral TAVI using 2 ProGlide sutures for severe aortic stenosis between July 2011 and September 2018. PCD failure was observed in 11.4%. The causes of PCD failure included 5 cases of insufficient hemostasis, 13 cases of arterial stenosis or occlusion, and 3 cases of dissection. Closure failures were managed by surgical repair in 10 patients and endovascular treatment in 11 patients. In a multivariate binary logistic model, a minimum lumen diameter of the common femoral artery (CFA) (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.15-0.83, P = 0.017) and left femoral access (OR 2.89, 95% CI 1.01-8.30, P = 0.048) was identified as a predictor of PCD failure. PCD failure was not associated with increased mortality (0% vs. 2.5%, P = 1.000) or a major adverse cardiovascular event (MACE; 4.8% vs. 4.3%, P = 1.000) at 30 days. CONCLUSIONS: PCD failures were not uncommon in patients undergoing percutaneous transfemoral TAVI. Small CFA diameter and left femoral access are predictors of PCD failure. However, PCD failures were not associated with increased mortality or MACE.

Late open conversion after thoracic endovascular aortic repair.

OBJECTIVE: With the increasing use of endovascular aortic repair, open repair after aortic stent grafting is of increasing interest. We retrospectively reviewed cases of late open conversion for complications after thoracic endovascular aortic repair (TEVAR). METHODS: TEVAR due to aortic aneurysm and dissection was performed in 538 patients between 1994 and 2017. A total of 33 patients, including 4 patients referred from other centers, required late conversion to open repair; 14 (42.4%) patients required circulatory arrest for aortic arch involvement. The mean interval to open conversion after TEVAR was 33.9 months (range, 1-123 months). Demographics of the patients, reason for conversion, surgical techniques, surgical outcomes, and survival were reviewed. RESULTS: Indications for late open conversion included type I endoleak (14), stent graft-induced new entry intimal tear (6), retrograde type A dissection (4), stent migration and fracture (3), stent graft infection (3), sac enlargement without endoleak (1), aortopulmonary fistula (1), and stent implantation failure (1). Hospital mortality was 9.1% (3/33). All occurred in the patients with arch involvement. The patients had several major morbidities; six patients (18.1%) had pulmonary complications, two (6.1%) suffered a stroke, one (3.0%) experienced paraplegia, and one (3.0%) had renal failure. Overall survival rates at 1 year, 5 years, and 10 years were 84.5% ± 6.4%, 74.5% ± 8.7%, and 67.1% ± 10.1%, respectively. The arch involvement group (48.1% ± 15.7%) had significantly worse 10-year survival than the no arch involvement group (86.1% ± 9.4%; P = .048). CONCLUSIONS: Despite the complexity of TEVAR, open conversion due to late complications can be performed successfully with acceptable results. However, cases involving the aortic arch have relatively worse outcomes. Lifelong surveillance is mandatory, and early decision-making about open conversion before the development of a complicated aortic arch lesion is suggested to achieve better outcomes.

Differences in Flow-Gradient Patterns Between Severe Bicuspid Aortic Stenosis and Severe Tricuspid Aortic Stenosis　- Mechanistic Insight From Multimodal Imaging.

BACKGROUND: We investigated the flow-gradient pattern characteristics and associated factors in severe bicuspid aortic stenosis (AS) compared with severe tricuspid AS.Methods and Results:A total of 252 patients with severe AS (115 bicuspid vs. 137 tricuspid) who underwent aortic valve (AV) replacement were retrospectively analyzed. Patients were classified into 4 groups according to stroke volume index and mean pressure gradient across the AV [normal-flow-high-gradient (NF-HG), low-flow-high-gradient, normal-flow-low-gradient, low-flow-low-gradient (LF-LG)]. In 89 patients who underwent cardiac computed tomography (CT), influential structural parameters of the left ventricular outflow tract (LVOT), AV and ascending aorta were assessed. Bicuspid AS was more likely to present a NF-HG pattern (83.5% vs. 64.2%, P<0.001), and significantly fewer presented a LF-LG pattern compared with tricuspid AS. In bicuspid AS, there was a significant mismatch between geometric orifice area (GOA) on CT planimetry and effective orifice area (EOA) calculated using the echocardiographic continuity equation. Bicuspid AS presented with a larger angle between the LVOT-AV and aorta. Multivariate analysis of bicuspid AS revealed that systemic arterial compliance (ß=-0.350, P=0.031) and the LVOT-AV-aorta angle (ß=-0.538, P=0.001), and stroke volume index (ß=0.409, P=0.008) were associated with a discrepancy between GOA and EOA. CONCLUSIONS: Flow-gradient patterns in bicuspid AS differ from those of tricuspid AS and are associated with the structural and functional characteristics of the aorta.

Hybrid Treatment: Expanding the Armamentarium for Infected Infrarenal Abdominal Aortic and Iliac Aneurysms.

PURPOSE: To investigate safety and efficacy of hybrid treatment for infected aortic and iliac aneurysms. MATERIALS AND METHODS: Between July 2007 and May 2011, hybrid treatment was performed in 6 male patients (mean age, 67.7 y; range, 57-76 y). Hybrid treatment consisted of extraanatomic bypass (EAB) and isolation of infected aneurysm with vascular plugs. Aneurysms were divided into primary and secondary infected aneurysms. Primary infected aneurysm refers to an aneurysm arising from bacterial infection of the native arterial wall; secondary infected aneurysm refers to infection involving an aneurysm that was previously treated with graft placement. RESULTS: The infected aneurysm involved the infrarenal abdominal aorta in 4 patients and common iliac artery in 2 patients. Hybrid treatment was successful in all 6 patients. The 3 patients with primary infected aneurysms required only hybrid treatment, whereas infected graft excision and new graft interposition was performed in 2 of the 3 patients with secondary infected aneurysms. No 30-day mortality or complications were reported. During mean follow-up of 58.6 months (range, 32.6-75.8 months), 1 patient (17%) with a secondary infected aneurysm who did not undergo additional surgery died 32.6 months after hybrid treatment from hypovolemic shock secondary to recurrent aortoenteric fistula. Cumulative survival was 100%, 100%, 83%, and 83% at 3 months, 1 year, 3 years, and 5 years. CONCLUSIONS: Hybrid treatment appears to be a stand-alone, curative treatment for primary infected aneurysms and serves as bridge therapy to subsequent surgery for secondary infected aneurysms.

Effect of Recurrent Mitral Regurgitation After Mitral Valve Repair in Patients With Degenerative Mitral Regurgitation.

BACKGROUND: This study investigated the consequences of recurrent mitral regurgitation (MR) after mitral valve (MV) repair in patients with degenerative MR and risk factors for recurrence.Methods and Results:From January 1990 to December 2015, 792 patients underwent MV repair due to degenerative MR. Recurrent MR was defined as moderate-to-severe MR on follow-up echocardiography. Mean follow-up duration was 8.71±5.58 years. During the follow-up period, MR recurred in 133 (16.8%) patients, and the MR recurrence-free rate at 20 years was 77.5±2.0%. In the recurrence group, the degree of MR decreased in 8 (6.0%) patients and was aggravated in 46 (34.6%) patients. Recurrent MR was associated with increased mortality and adverse left ventricular (LV) remodeling. Independent risk factors for MR recurrence were MV repair performed before 2000, preoperative atrial fibrillation, high LV end-diastolic dimension (LVEDD), prolapse of the isolated anterior leaflet or multiple segments, and absence of ring annuloplasty. Predictors of MR progression were high LVEDD and repair without artificial chordae implantation. CONCLUSIONS: Recurrent MR after MV repair in patients with degenerative MR showed a tendency to progress and was associated with increased mortality and adverse LV remodeling. Early referral for MV repair before development of atrial fibrillation and LV enlargement may reduce the risk of MR recurrence. Moreover, artificial chordae implantation and ring annuloplasty may assure the long-term durability of MV repair.

Degenerative Calcification of Pericardial Bioprostheses: Comparison of Five Implantation Methods in a Rabbit Model.

BACKGROUND AND AIM OF THE STUDY: The degenerative calcification of bioprosthetic heart valves remains a clinical challenge, especially among young adults and children. Animal models that are based on subcutaneous and intramuscular implantation and are typically used to assess interventions to prevent bioprosthetic heart valve calcification do not reflect actual hemodynamic stress and lack direct blood contact. Thus, the study aim was to investigate bioprosthesis calcification at different implantation sites. METHODS: The calcification degrees of five valve implantation methods, namely subcutaneous, intramuscular and intravenous implantation, and arterial and venous patch angioplasty, were simultaneously investigated in 10 New Zealand White rabbits. RESULTS: Ultrasonography and computed tomography images showed vascular patency to be well maintained in all implanted vessels. Histologically, cellular infiltrates around the implant and within the collagen fibers were only found in the intravenous implantation group, which also had the highest calcium level among the methods. CONCLUSION: The present study was the first to compare the degree of calcification after applying five implantation methods simultaneously in one animal species. The rabbit intravenous implantation model, which involved direct contact with blood factors, is expected to serve as a useful animal model for research into the prevention of bioprosthetic heart valve degeneration.

Preoperative coronary angiography within one day of valve surgery is not associated with postoperative acute kidney injury in patients with preserved renal function.

BACKGROUND: Acute kidney injury (AKI) is a common complication after cardiac surgery. Associations between the time interval (TI) from preoperative coronary angiography (CAG) to cardiac surgery have been investigated, although with conflicting results. METHODS: We evaluated data collected from a retrospective review of consecutive patients who underwent preoperative CAG and heart valve surgery at our institution between September 2008 and February 2013. A total of 426 patients met the study criteria. Patients were divided into two groups according to the length of time between preoperative CAG and valve surgery: within one day (group A) or longer than one day (group B). Logistic regression was applied to analyze the relationships between TI and postoperative AKI. RESULTS: Of 426 patients, 140 (33%) underwent CAG on preoperative day 1, while 286 (67%) underwent CAG on preoperative day 2 or sooner. AKI occurred in 19 (13.6%) patients in group A and in 35 (12.2%) patients in group B (p = 0.70). CAG on preoperative day 1 was not associated an increased risk of AKI relative to CAG on preoperative day 2 or sooner (p = 0.49; odds ratio, 1.26; 95% CI, 0.66 to 2.41). CONCLUSIONS: Preoperative CAG within one day of elective heart valve surgery is not associated with an increase in postoperative AKI in patients with normal renal function.

Posttreatment platelet reactivity on clopidogrel is associated with the risk of adverse events after off-pump coronary artery bypass.

BACKGROUND: Dual antiplatelet therapy with aspirin and clopidogrel is currently recommended in off-pump coronary artery bypass (OPCAB). However, no data exist concerning platelet reactivity on clopidogrel after OPCAB. The aim of this study was to assess the relationship between platelet reactivity and late major adverse cardiovascular events (MACEs) after OPCAB. METHODS: In this prospective, single-center, observational study, on-clopidogrel platelet reactivity was measured using a point-of-care assay (VerifyNow system; Accumetrics Inc, San Diego, CA) in 859 patients who underwent OPCAB with 1 or more vein grafts. The primary end point was late MACEs (30 days-1 year) including cardiac death, nonfatal myocardial infarction, and target vessel revascularization. Receiver operating characteristic curve analysis was used to estimate the cutoff value of P2Y12 reaction units (PRUs) for MACEs. RESULTS: The optimal cutoff value for posttreatment reactivity for the incidence of late MACEs was ≥188 PRU (area under the curve 0.72, 95% CI 0.68-0.75, P = .002). The incidence of late MACEs was significantly higher in the high platelet reactivity (HPR; ≥188 PRU) group than in the low platelet reactivity (<188 PRU) group (3.6% vs. 1.4%, P = .040). Kaplan-Meier analysis revealed 1-year MACE-free survival rates of 98.4% ± 0.5% and 95.9% ± 1.3% in the low platelet reactivity and HPR groups, respectively (P = .034). According to a Cox regression hazard model, HPR was an independent risk factor for late MACE-free survival (hazard ratio 3.51, 95% CI 1.27-9.69, P = .015). CONCLUSION: High residual platelet reactivity after clopidogrel administration is strongly associated with 1-year MACE-free survival. Routine measurement of platelet reactivity and thorough monitoring of patients with HPR after OPCAB are warranted.

Predictors of prognosis in patients with mild to moderate paravalvular leakage after mitral valve replacement.

BACKGROUND: The aim of this study was to evaluate predictors of clinical events in patients with mild to moderate paravalvular leakage (PVL) after mitral valve replacement (MVR). METHODS AND RESULTS: We retrospectively reviewed all the medical records and echocardiography of 60 patients with PVL after MVR. After excluding 18 patients who required immediate surgical repair for severe symptoms or regurgitation and four patients with severe anemia who required transfusion, two patients with concomitant infective endocarditis, two patients with severe stenosis or regurgitation of other valves, and one patient with severe left ventricular systolic dysfunction, the remaining 33 patients who were not indicated for reoperation or immediate blood transfusion comprised the study population. During a median follow-up period of 19 months, there were 18 events, including two cardiac deaths, one noncardiac death, 13 repeat surgeries, and two admissions for heart failure. Cox regression analysis revealed that the presence of hemolytic anemia at the diagnosis of PVL was the only independent predictor of event-free survival (p=0.035). The estimated three-year event-free survival rates were 78 ± 12% in patients without hemolytic anemia and 16 ± 10% in those with hemolytic anemia (p=0.004). CONCLUSION: Presence of hemolytic anemia was associated with poor short-term clinical outcome in mild to moderate PVL after MVR, even in the cases when the degree of anemia was not severe at the time of diagnosis. Therefore, in PVL patients after MVR with hemolytic anemia, more early aggressive therapeutic approaches should be considered, regardless of the severity of anemia.

Effects of dexmedetomidine on renal function after cardiac surgery for infective endocarditis: An interim analysis of a randomized controlled trial.

BACKGROUND: Patients undergoing cardiac surgery for infective endocarditis (IE) are at a high risk of postoperative acute kidney injury (AKI) owing to heightened systemic inflammation. Therefore, we aimed to investigate the effect of dexmedetomidine on postoperative AKI in patients who underwent cardiac surgery for IE. METHODS: A total of 63 patients who underwent cardiac surgery for IE were randomly assigned to receive either intravenous dexmedetomidine infusion of 0.4 µg kg-1 h-1 (DEX group) or normal saline infusion (control group) for 24 h after induction of anesthesia. The occurrence of AKI within seven days postoperation, epinephrine, norepinephrine, and interleukin-6 levels, as well as postoperative morbidities, were assessed. An intertrim analysis was conducted using Pocock's alpha spending function at α = 0.05 and ß = 0.2. RESULTS: This trial was early terminated according to the results of interim analysis performed when 60 % of the pre-set number of patients have been collected. The incidence of AKI was significantly lower in the DEX group than in the control group (32.3 % vs. 9.4 %, p = 0.025). Patients in the DEX group had significantly lower epinephrine levels than those in the control group, whereas norepinephrine and interleukin-6 levels were similar. Perioperative mean arterial pressure or heart rate did not differ between the groups. CONCLUSIONS: Dexmedetomidine administration for 24 h starting from induction of anesthesia significantly reduced the incidence of postoperative AKI after cardiac surgery for IE (by 29 % vs. control) without hemodynamic side effects. This was accompanied by a significant attenuation of postoperative increase in serum epinephrine levels.