Structural Investigation of Diclofenac Binding to Ovine, Caprine, and Leporine Serum Albumins.

Free drug concentration in the blood sera is crucial for its appropriate activity. Serum albumin, the universal blood carrier protein, is responsible for transporting drugs and releasing them into the bloodstream. Therefore, a drug's binding to SA is especially important for its bioavailability and it is a key problem in the drug design process. In this paper, we present crystal structures of three animal serum albumin complexes: ovine, caprine, and leporine, with diclofenac, a popular non-steroidal anti-inflammatory drug that is used in therapy of chronic and acute pain. Details of diclofenac binding mode by the presented serum albumins are compared with analogous complexes of human and equine serum albumins. The analysis of the occupied binding pockets in crystal structures of the investigated serum albumins from different mammals shows that they have two common and a number of unique diclofenac binding sites. The most intriguing is the fact that the albumins from the described species are able to bind different numbers of molecules of this popular anti-inflammatory drug, but none of the binding sites overlap with ones in the human serum albumin.

Application of Spectroscopic Methods for the Identification of Superoxide Dismutases in Cyanobacteria.

Superoxide dismutases (SODs) belong to the group of metalloenzymes that remove superoxide anion radicals and they have been identified in three domains of life: Bacteria, Archaea and Eucarya. SODs in Synechocystis sp. PCC 6803, Gloeobacter violaceus CCALA 979, and Geitlerinema sp. ZHR1A were investigated. We hypothesized that iron (FeSOD) and/or manganese (MnSOD) dominate as active forms in these cyanobacteria. Activity staining and three different spectroscopic methods of SOD activity bands excised from the gels were used to identify a suitable metal in the separated samples. FeSODs or enzymes belonging to the Fe-MnSOD superfamily were detected. The spectroscopic analyses showed that only Fe is present in the SOD activity bands. We found FeSOD in Synechocystis sp. PCC 6803 while two forms in G. violaceus and Geitlerinema sp. ZHR1A: FeSOD1 and FeSOD2 were present. However, no active Cu/ZnSODs were identified in G. violaceus and Geitlerinema sp. ZHR1A. We have shown that selected spectroscopic techniques can be complementary to the commonly used method of staining for SOD activity in a gel. Furthermore, the occurrence of active SODs in the cyanobacteria studied is also discussed in the context of SOD evolution in oxyphotrophs.

Incidence and Predictors of Clinically Significant Bleedings after Transcatheter Left Atrial Appendage Closure.

BACKGROUND: Transcatheter left atrial appendage closure (LAAC) is performed in patients unsuitable for long-term anticoagulation, predominantly due to prior bleeding events. The study aimed to investigate the incidence and predictors of clinically significant bleeding (CSB) post-LAAC. METHODS: Consecutive patients after LAAC with an Amplatzer or WATCHMAN device were analyzed (05.2014-11.2019). Bleeding was classified as CSB when associated with at least one of the following: death, ≥2 g/dL hemoglobin drop, ≥2 blood units transfusion, critical anatomic site, or hospitalization/invasive procedure. RESULTS: Among 195 patients (age 74 (68-80), 43.1% females, HAS-BLED score 2.0 (2.0-3.0)), during median follow-up of 370 (IQR, 358-392) days, there were 15 nonprocedural CSBs in 14 (7.2%) patients. Of those, 9 (60.0%) occurred during postprocedural dual antiplatelet therapy (DAPT) (median 46 (IQR: 16-60) days post-LAAC) vs. 6 (40%) after DAPT discontinuation (median 124 (81-210) days post-LAAC), translating into annualized CSB rates of 14.0% (per patient-year on DAPT) vs. 4.6% (per patient-year without DAPT). In 92.9% (13/14) of patients, the post-LAAC nonprocedural CSB was a recurrence from the same site as bleeding pre-LAAC. In the multivariable model, admission systolic blood pressure (SBP) > 127 mmHg (HR = 10.73, 1.37-84.26, p = 0.024), epistaxis history (HR = 5.84, 1.32-25.89, p = 0.020), permanent atrial fibrillation (AF) (HR = 4.55, 1.20-17.20, p = 0.025), and prior gastrointestinal bleeding (HR = 3.35, 1.01-11.08, p = 0.048) predicted post-LAAC CSB. CONCLUSIONS: Nonprocedural CSBs after LAAC, with a similar origin as the pre-LAAC bleedings, were observed predominantly during postprocedural DAPT and predicted by elevated admission SBP, prior epistaxis, permanent AF, and gastrointestinal bleeding history. Whether a more reserved post-LAAC antiplatelet regimen and stringent blood pressure control may improve LAAC outcomes remains to be studied.

Association of left atrial enlargement and increased left ventricular wall thickness with arrhythmia recurrence after cryoballoon ablation for atrial fibrillation.

BACKGROUND: Left atrial enlargement (LAE) predicts atrial fibrillation (AF) recurrence after cryoballoon-based pulmonary vein isolation (CB). Increased left ventricular wall thickness (LVWT) is pathophysiologically associated with LAE and atrial arrhythmias. AIMS: To assess effect of increased LVWT on long-term outcomes of CB depending on coexistence of LAE. METHODS: LAE was defined using either echocardiography ( > 48 cm³/m²) or multislice computer tomography (MSCT, ≥63 cm³/m²). Increased LVWT was echocardiographic septal/posterior wall thickness > 10 mm in males and > 9 mm in females. All patients achieved 2-year follow-up. RESULTS: Of 250 patients (median [interquartile range, IQR] age of 61 [49.0-67.3] years; 30% female) with AF (40% non-paroxysmal), 66.5% had hypertension, and 27.2% underwent redo procedure. MSCT was done in 76%. During follow-up of 24.5 (IQR, 6.0-31.00) months the clinical success rate was 72%, despite 46% of patients having arrhythmia recurrence. Arrhythmia recurrence risk was increased by LAE and increased LVWT (hazard ratio [HR], 1.801; P = 0.002 and HR, 1.495; P = 0.036; respectively). The highest arrhythmia recurrence (61.9% at 2 years) was among patients with LAE and increased LVWT (33.6% of patients); intermediate (41.8%) among patients with isolated LAE; and lowest among patients with isolated increased LVWT or patients without LAE or increased LVWT (36.8% and 35.2% respectively, P = 0.004). After adjustment for body mass index (BMI), paroxysmal AF, CHA2DS2-VASc score, clinically-significant valvular heart disease, and cardiomyopathy, patients with LAE and concomitant increased LVWT diagnosis had a 1.8-times increased risk of arrhythmia recurrence (HR, 1.784; 95% confidence interval [CI], 1.017-3.130; P = 0.043). CONCLUSION: Joint occurrence of LAE and increased LVWT is associated with the highest rate of arrhythmia recurrence after CB for AF.

Residual stroke risk after left atrial appendage closure in patients with prior oral anticoagulation failure.

BACKGROUND: Patients with atrial fibrillation (AF) and oral anticoagulation (OAC) failure may benefit from left atrial appendage closure (LAAC), however, the evidence is scarce. We report outcomes of LAAC in patients with OAC failure compared to those with classic indications of OAC contraindications. METHODS: Prospective registry of LAAC with Amplatzer or WATCHMAN device followed by dual antiplatelet therapy (DAPT) was analyzed (05.2014-11.2019). The study group included patients with OAC failure defined as stroke/TIA/PE/LAA thrombus (n = 39) during OAC, whereas the control group consisted of patients with OAC contraindications (n = 156). Structured follow-up at 3, 6, and 12 months was done. RESULTS: The study group compared to controls was younger [73 (IQR, 62-77) vs 74 (IQR, 68-81) years, P = 0.046], with higher CHA2DS2-VASc [5.0 (IQR, 3.0-6.0) vs 4.0 (IQR, 3.0-5.0), P = 0.001)], lower HAS-BLED [2.0 (IQR, 1.0-3.0) vs 3.0 (IQR, 2.0-3.0), P = 0.006] and similar proportion of WATCHMAN implantations (43.6% vs 44.2%, P = 1.000). The reduction from CHA2DS2-VASc predicted to observed annual stroke/TIA/PE rate was markedly smaller in the study vs control group (14% vs 77%) with 10.3% vs 1.9% stroke/TIA/PE respectively (P = 0.031). The reduction from HAS-BLED predicted to observed annual major nonprocedural bleeding rate was higher (100% vs 7.4%) with 0.0% vs 5.1% major bleedings respectively (P = 0.361). The device-related thrombosis remained similar (13.2% vs 11.3%, P = 0.778). CONCLUSIONS: Patients after LAAC for OAC failure and unremarkable prior bleeding history presented with high residual stroke and low bleeding risks. Therefore concomitant long-term OAC or prolonged DAPT should strongly be considered in this population.

Comparative proteomic analysis provides new insights into regulation of microspore embryogenesis induction in winter triticale (× Triticosecale Wittm.) after 5-azacytidine treatment.

Effective microspore embryogenesis (ME) requires substantial modifications in gene expression pattern, followed by changes in the cell proteome and its metabolism. Recent studies have awakened also interest in the role of epigenetic factors in microspore de-differentiation and reprogramming. Therefore, demethylating agent (2.5-10 µM 5-azacytidine, AC) together with low temperature (3 weeks at 4 °C) were used as ME-inducing tiller treatment in two doubled haploid (DH) lines of triticale and its effect was analyzed in respect of anther protein profiles, expression of selected genes (TAPETUM DETERMINANT1 (TaTPD1-like), SOMATIC EMBRYOGENESIS RECEPTOR KINASE 2 (SERK2) and GLUTATHIONE S-TRANSFERASE (GSTF2)) and ME efficiency. Tiller treatment with 5.0 µM AC was the most effective in ME induction; it was associated with (1) suppression of intensive anabolic processes-mainly photosynthesis and light-dependent reactions, (2) transition to effective catabolism and mobilization of carbohydrate reserve to meet the high energy demand of cells during microspore reprograming and (3) effective defense against stress-inducing treatment, i.e. protection of proper folding during protein biosynthesis and effective degradation of dysfunctional or damaged proteins. Additionally, 5.0 µM AC enhanced the expression of all genes previously identified as being associated with embryogenic potential of microspores (TaTPD1-like, SERK and GSTF2).

Serial Baseline, 12-, 24-, and 60-Month Optical Coherence Tomography Evaluation of ST Segment Elevation Myocardial Infarction Patients Treated with Absorb Bioresorbable Vascular Scaffold.

Data on long-term neointimal healing and neoatherosclerosis progression after primary percutaneous coronary intervention (PCI) with implantation of everolimus-eluting bioresorbable vascular scaffold (BVS) (ABSORB BVS 1.0, Abbott Vascular) are limited. The mechanisms underlying very late scaffold failure remain to be further elucidated. This study sought to assess healing pattern and presence of neoatherosclerosis. This was a single-center, prospective, longitudinal study with serial optical coherence tomography (OCT) assessment at baseline, 12, 24 and 60 months after PCI performed in 12 patients presenting with ST-segment elevation myocardial infarction (STEMI). The median follow-up was 59 months. The diameter stenosis increased from 7.11 ± 4.99% at 1-year to 21.00 ± 11.31% at 5 years, (p = 0.03), whereas minimum lumen diameter remained stable throughout the follow-up period, as assessed by angiography. Minimum and mean lumen area declined over the 5-year follow-up by 1.00 ± 1.57 mm2 and 1.75 ± 0.87 mm2, respectively; a significant decrease in minimum and mean lumen area in the first two years, was followed by stable luminal dimensions between 2 and 5 years of follow-up. The lumen eccentricity (0.85 ± 0.03) and asymmetry (0.43 ± 0.10) indexes showed no change over 60-month follow-up. The incidence of atherosclerosis was high both in the in-scaffold (IS) and out-scaffold (OS) regions consisting of calcifications (IS = 100%, OS = 92%, p = 0.99), macrophages (IS = 92% and OS = 67%, p = 0.31), neovascularization (IS = 75%, OS = 50%, p = 0.40). In conclusion, serial OCT imaging up to 5 years after implantation of BVS in STEMI indicated complete scaffold resorption, stable lumen area following period of neointima growth in the first two years after PCI and high incidence of neoatherosclerosis.

The Role of Selected Wavelengths of Light in the Activity of Photosystem II in Gloeobacter violaceus.

Gloeobacter violaceus is a cyanobacteria species with a lack of thylakoids, while photosynthetic antennas, i.e., phycobilisomes (PBSs), photosystem II (PSII), and I (PSI), are located in the cytoplasmic membrane. We verified the hypothesis that blue-red (BR) light supplemented with a far-red (FR), ultraviolet A (UVA), and green (G) light can affect the photosynthetic electron transport chain in PSII and explain the differences in the growth of the G. violaceus culture. The cyanobacteria were cultured under different light conditions. The largest increase in G. violaceus biomass was observed only under BR + FR and BR + G light. Moreover, the shape of the G. violaceus cells was modified by the spectrum with the addition of G light. Furthermore, it was found that both the spectral composition of light and age of the cyanobacterial culture affect the different content of phycobiliproteins in the photosynthetic antennas (PBS). Most likely, in cells grown under light conditions with the addition of FR and G light, the average antenna size increased due to the inactivation of some reaction centers in PSII. Moreover, the role of PSI and gloeorhodopsin as supplementary sources of metabolic energy in the G. violaceus growth is discussed.

Venoarterial Extracorporeal Membrane Oxygenation for Postcardiotomy Shock-Analysis of the Extracorporeal Life Support Organization Registry.

OBJECTIVES: Refractory postcardiotomy cardiogenic shock complicating cardiac surgery yields nearly 100% mortality when untreated. Use of venoarterial extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock has increased worldwide recently. The aim of the current analysis was to outline the trends in use, changing patient profiles, and in-hospital outcomes including complications in patients undergoing venoarterial extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock. DESIGN: Analysis of extracorporeal life support organization registry from January 2010 to December 2018. SETTING: Multicenter worldwide registry. PATIENTS: Seven-thousand one-hundred eighty-five patients supported with venoarterial extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock. INTERVENTIONS: Venoarterial extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Hospital death, weaning from extracorporeal membrane oxygenation, hospital complications. Mortality predictors were assessed by multivariable logistic regression. Propensity score matching was performed for comparison of peripheral and central cannulation for extracorporeal membrane oxygenation. A significant trend toward more extracorporeal membrane oxygenation use in recent years (coefficient, 0.009; p < 0.001) was found. Mean age was 56.3 ± 14.9 years and significantly increased over time (coefficient, 0.513; p < 0.001). Most commonly, venoarterial extracorporeal membrane oxygenation was instituted after coronary artery bypass surgery (26.8%) and valvular surgery (25.6%), followed by heart transplantation (20.7%). Overall, successful extracorporeal membrane oxygenation weaning was possible in 4,520 cases (56.4%), and survival to hospital discharge was achieved in 41.7% of cases. In-hospital mortality rates remained constant over time (coefficient, -8.775; p = 0.682), whereas complication rates were significantly reduced (coefficient, -0.009; p = 0.003). Higher mortality was observed after coronary artery bypass surgery (65.4%), combined coronary artery bypass surgery with valve (68.4%), and aortic (69.6%) procedures than other indications. Lower mortality rates were observed in heart transplantation recipients (46.0%). Age (p < 0.001), central cannulation (p < 0.001), and occurrence of complications while on extracorporeal membrane oxygenation were independently associated with poorer prognosis. CONCLUSIONS: The analysis confirmed increased use of venoarterial extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock. Mortality rates remained relatively constant over time despite a decrease in complications, in the setting of supporting older patients.

Mortality Predictors in Elderly Patients With Cardiogenic Shock on Venoarterial Extracorporeal Life Support. Analysis From the Extracorporeal Life Support Organization Registry.

OBJECTIVES: Because significantly higher mortality is observed in elderly patients undergoing venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock, decision-making in this setting is challenging. We aimed to elucidate predictors of unfavorable outcomes in these elderly (≥ 70 yr) patients. DESIGN: Analysis of international worldwide extracorporeal life support organization registry. SETTING: Refractory cardiogenic shock due to various etiologies (cardiac arrest excluded). PATIENTS: Elderly patients (≥ 70 yr). INTERVENTIONS: Venoarterial extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Three age groups (70-74, 75-79, ≥80 yr) were in-depth analyzed. Uni- and multivariable analysis were performed. From January 1997 to December 2018, 2,644 patients greater than or equal to 70 years (1,395 [52.8%] 70-74 yr old, 858 [32.5%] 75-79 yr, and 391 [14.8%] ≥ 80 yr old) were submitted to venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock with marked increase in the most recent years. Peripheral access was applied in majority of patients. Median extracorporeal membrane oxygenation support duration was 3.5 days (interquartile range: 1.6-6.1 d), (3.9 d [3.7-4.6 d] in patients ≥ 80 yr) (p < 0.001). Weaning from extracorporeal membrane oxygenation was possible in 1,236 patients (46.7%). Overall in-hospital mortality was estimated at 68.3% with highest crude mortality rates observed in 75-79 years old subgroup (70.1%). Complications were mostly cardiovascular and bleeding, without apparent differences between subgroups. Airway pressures, 24-hour pH after extracorporeal membrane oxygenation start, extracorporeal membrane oxygenation duration, and renal replacement therapy were predictive of higher mortality. In-hospital mortality was lower in heart transplantation recipients, posttranscatheter aortic valve replacement, and pulmonary embolism; conversely, higher mortality followed extracorporeal membrane oxygenation institution after coronary artery bypass + valve and in decompensated chronic heart failure, and nearly 100% mortality followed in extracorporeal membrane oxygenation for sepsis. CONCLUSIONS: This study confirmed the remarkable increase of venoarterial extracorporeal membrane oxygenation use in elderly affected by refractory cardiogenic shock. Despite in-hospital mortality remains high, venoarterial extracorporeal membrane oxygenation should still be considered in such setting even in elderly patients, since increasing age itself was not linked to increased mortality, whereas several predictors may guide indication and management.

Comparison of myocardial tissue reperfusion of inferior wall and a right ventricle among patients after primary angioplasty for an inferior myocardial infarction with right ventricular infarction.

BACKGROUND: Impaired myocardial tissue reperfusion affects prognosis of patients with ST-segment elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI) and can be identified by ST-segment analysis. To date, evaluation of the myocardial tissue reperfusion of the right ventricle (RV) among the patients treated with PCI for inferior STEMI with right ventricular infarction (RVI) has not been made yet. METHODS: Patients with inferior STEMI were screened for RVI. Tissue reperfusion was evaluated by maximal residual ST-segment deviation post PCI, independently for the RV and for inferior wall. Myocardial injury was assessed by the peak creatine kinase-mb (CK-MB) value. RESULTS: Among 456 patients with inferior STEMI, concomitant RVI occurred in 153 (33.5%) subjects (59.86±10.35 years old, 71.9% females). Tissue reperfusion of LV was present in 75 (49%), whereas 55 (35.9%) had both successful LV and RV reperfusion. Among 97 (63.4%) with successful tissue reperfusion of RV, 55 (56.7%) had associated successful tissue reperfusion of inferior wall. Adequate LV reperfusion was accompanied by RV in over 73.3% of patients (P=0.006). Mean peak CK-MB was lower in the group with adequate versus impaired RV tissue-perfusion (197±143 vs. 305±199 U/L, P=0.021 respectively). CONCLUSIONS: Impaired reperfusion of RV is observed in more than one third of inferior STEMIs with RVI and is not strictly associated with impaired reperfusion of inferior wall and clinical or angiographic variables, therefore ST-segment analysis for RV is mandatory.

ß-1,3-Glucanases and chitinases participate in the stress-related defence mechanisms that are possibly connected with modulation of arabinogalactan proteins (AGP) required for the androgenesis initiation in rye (Secale cereale L.).

This work presents the biochemical, cytochemical and molecular studies on two groups of PR proteins, ß-1,3-glucanases and chitinases, and the arabinogalactan proteins (AGP) during the early stages of androgenesis induction in two breeding lines of rye (Secale cereale L.) with different androgenic potential. The process of androgenesis was initiated by tillers pre-treatments with low temperature, mannitol and/or reduced glutathione and resulted in microspores reprogramming and formation of androgenic structures what was associated with high activity of ß-1,3-glucanases and chitinases. Some isoforms of ß-1,3-glucanases, namely several acidic isoforms of about 26 kDa; appeared to be anther specific. Chitinases were well represented but were less variable. RT-qPCR revealed that the cold-responsive chitinase genes Chit1 and Chit2 were expressed at a lower level in the microspores and whole anthers while the cold-responsive Glu2 and Glu3 were not active. The stress pre-treatments modifications promoted the AGP accumulation. An apparent dominance of some AGP epitopes (LM2, JIM4 and JIM14) was detected in the androgenesis-responsive rye line. An abundant JIM13 epitopes in the vesicles and inner cell walls of the microspores and in the cell walls of the anther cell layers appeared to be the most specific for embryogenesis.

Veno-Arterial Extracorporeal Life Support in Heart Transplant and Ventricle Assist Device Centres. Meta-analysis.

AIMS: Because reported mortality on veno-arterial (V-A) extracorporeal life support (ECLS) substantially varies between centres, the aim of the current analysis was to assess the outcomes between units performing heart transplantation and/or implanting ventricular assist device (HTx/VAD) vs. non-HTx/VAD units in patients undergoing V-A ECLS for cardiogenic shock. METHODS AND RESULTS: Systematic search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was performed using PubMed/MEDLINE databases until 30 November 2019. Articles reporting in-hospital/30-day mortality and centre's HTx/VAD status were included. In-hospital outcomes and long-term survival were analysed in subgroup meta-analysis. A total of 174 studies enrolling n = 13 308 patients were included with 20 series performed in non-HTx/VAD centres (1016 patients, 7.8%). Majority of patients underwent V-A ECLS for post-cardiotomy shock (44.2%) and acute myocardial infarction (20.7%). Estimated overall in-hospital mortality was 57.2% (54.9-59.4%). Mortality rates were higher in non-HTx/VAD [65.5% (59.8-70.8%)] as compared with HTx/VAD centres [55.8% (53.3-58.2%)], P < 0.001. Estimated late survival was 61.8% (55.7-67.9%) without differences between non-HTx/VAD and HTx/VAD centres: 66.5% (30.3-1.02%) vs. 61.7% (55.5-67.8%), respectively (P = 0.797). No differences were seen with respect to ECLS duration, limb complications, and reoperations for bleeding, kidney injury, and sepsis. Yet, weaning rates were higher in HTx/VAD vs. non-HTx/VAD centres: 58.7% (56.2-61.1%) vs. 48.9% (42.0-55.9%), P = 0.010. Estimated rate of bridge to heart transplant was 6.6% (5.2-8.3%) with numerical, yet not statistically significant, difference between non-HTx/VAD [2.7% (0.8-8.3%)] as compared with HTx/VAD [6.7% (5.3-8.6%)] (P = 0.131). CONCLUSIONS: Survival after V-A ECLS differed according to centre's HTx/VAD status. Potentially different risk profiles of patients must be taken account for before definite conclusions are drawn.

Improvement in long-term survival with acute kidney recovery after a successful transcatheter aortic valve replacement.

INTRODUCTION: Chronic kidney disease (CKD) is frequent in patients treated with transcatheter aortic valve replacement. Yet, the procedure can improve kidney function, that is, it can lead to acute kidney recovery (AKR). OBJECTIVES: The aim of the study was to assess kidney function changes after transcatheter aortic valve replacement and their impact on long­term outcomes. PATIENT AND METHODS: In 432 patients (median age, 83 years; female sex, 63.4% ), estimated glomerular filtration rate (eGFR) was measured before and after the procedure. Chronic kidney disease was defined as a prior diagnosis or baseline eGFR of less than 60 ml/min/1.73 m2. Median (interquartile range [IQR]) follow­up was 44.7 (31.2-48) months. RESULTS: Overall, 66.7% of patients had CKD. An increase in eGFR of 10% or greater at 48 hours (median [IQR], 39.8% [26.2%-51.8%]) was observed in 55.2% of patients with CKD and lasted until discharge (31.8% [17.8%-49%]) in 35.8% (the AKR group). In 17.4% of patients (64.3% with CKD), there was a drop in eGFR of 10% or greater at 48 hours, which remained at discharge in 6.5% of patients (the AKI group; median [IQR] eGFR drop, -22.8% [-40.6% to -14.9%] and -22.8% [-37.5% to -16.2%], respectively). There was a stepwise increase in AKR prevalence from CKD stage 1 and 2 (11.5%) to 4 (52%) (P = 0.03). In­hospital mortality (P = 0.01) was highest with AKI (10.7%); intermediate with CKD but no AKR (6.6%); and lowest with neither CKD nor AKI (1.5%) or with AKR (1%). Estimated 4­year mortality was correspondingly different (46.9%, 47.2%, 25.5%, 35.4%, respectively; P <0.001). The nonperipheral access was associated with more AKI and less AKR. Acute kidney recovery was more frequent with a history of stroke or transient ischemic attack or a newer generation self-expanding valves. CONCLUSIONS: Transcatheter aortic valve replacement led to acute kidney recovery in a substantial number of patients with CKD and an improved 4­year survival.

Additive Value of High-Density Lipoprotein Cholesterol and C-Reactive Protein Level Assessment for Prediction of 2-year Mortality After Transcatheter Aortic Valve Implantation.

Available prediction models are inaccurate in elderly who underwent transcatheter aortic valve implantation (TAVI). The aim of present study was to analyze the separate and combined prognostic values of baseline HDL-C and C-reactive protein (CRP) levels in patients treated successfully with TAVI who had complete 2-year follow-up. We analyzed 334 patients treated with TAVI from 01/2010 to 07/2017 who had measurements of HDL-C and CRP on admission or during qualification for the procedure. Baseline HDL-C ≤46 mg/dl (areas under the curve [AUC] = 0.657) and CRP ≥0.20 mg/dl (AUC = 0.634) were predictive of 2-year mortality. After stratification with both cutoffs, patients with low HDL-C and concomitant high CRP most often had LVEF ≤50% and were high risk as per EuroSCORE II. Those with isolated CRP elevation had the lowest frequency of LVEF ≤50%, but more sarcopenia (based on psoas muscle area). After adjustment in the multivariate analysis for other identified predictors including EuroSCORE II and statin therapy, isolated HDL-C ≤46 mg/dl (identified in 40 patients) and isolated CRP ≥0.20 mg/dl (n = 109) were both independent predictors of 2-year mortality (hazard ratio [HR] = 2.92 and HR = 2.42, respectively) compared with patients with both markers within established cutoffs (n = 105) who had the lowest 2-year mortality (9.5%). Patients with both markers exceeding cutoffs (n = 80) had the highest risk (HR = 4.53) with 2-year mortality of 42.5%. High CRP was associated with increased mortality within the first year of follow-up, whereas low HDL-C increased mortality in the second year. The combination of both markers with EuroSCORE II enhanced mortality prediction (AUC = 0.697). In conclusion, low baseline HDL-C and high CRP jointly contribute to the prediction of increased all-cause mortality after TAVI.