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New cardiovascular biomarkers in patients with advanced cancer-A prospective study comparing MR-proADM, MR-proANP, copeptin, high-sensitivity troponin T and NT-proBNP.

Traditional cardiovascular (CV) biomarkers (high-sensitivity troponinT [hsTnT] and N-terminal pro-B-type natriuretic peptide [NT-proBNP]) are important to monitor cancer patients' cardiac function and to assess prognosis. Newer CV biomarkers (mid-regional pro-adrenomedullin [MR-proADM], C-terminal pro-arginine vasopressin [copeptin], and mid-regional pro-atrial natriuretic peptide [MR-proANP]) might outperform traditional biomarkers. Overall, 442 hospitalized cancer patients without significant CV disease or current infection were enrolled (61 ± 15 years, 52% male, advanced cancer stage: 85%) and concentrations of CV biomarkers were analysed. Differences in echocardiographic, clinical, laboratory parameters were assessed. Patients were followed for up to 69 months for all-cause mortality. In univariable analyses, MR-proADM, hsTnT, copeptin, MR-proANP, and NT-proBNP predicted all-cause mortality. In multivariable analyses (adjusted for sex, age, Eastern Cooperative Oncology Group performance status, estimated glomerular filtration rate [eGFR], C-reactive protein, anti-cancer therapy, reason for hospitalization, cancer stage and type), only MR-proADM remained an independent predictor of mortality (MR-proADM per 1 ln: hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.47-3.50], p < 0.001). MR-proADM had the highest area under the curve (AUC) using receiver operating characteristic analysis (AUC [95% CI] 0.74 [0.69-0.79]; hsTnT: AUC 0.69; copeptin: AUC 0.66; MR-proANP: AUC 0.63; NT-proBNP: AUC 0.62). Optimal cut-point for mortality prediction with MR-proADM was 0.94 nmol/L (HR 2.43 [95% CI 1.92-3.06], p < 0.001). Patients with MR-proADM >0.94 nmol/L were older, more often had cancer stage IV, showed reduced performance status, eGFR, haemoglobin, diastolic left ventricular function, and elevated systolic pulmonary artery pressure. MR-proADM is an independent predictor of mortality in advanced stage, hospitalized cancer patients without significant CV disease or current infection. The optimal MR-proADM cut-point for mortality prediction was 0.94 nmol/L with hazards for mortality being approximately 2.5 times higher. There was a continuous increase in mortality risk with stepwise increase of MR-proADM concentrations. Elevated concentrations of MR-proADM were also associated with reduced performance status and mildly reduced left ventricular diastolic function as well as higher age and more often cancer stage IV.

Gas Adsorption in Flexible COF-506 and COF-506-Cu.

Flexible covalent-organic frameworks (COFs) display a variety of guest-dependent dynamic behaviors, but because these are an emerging class of materials, very little experimental adsorption data exists. This work examines the adsorption properties of COF-506 and COF-506-Cu utilizing various adsorbates as probe molecules. These materials have small surface areas (<100 m2/g) but still have significant capacity for methanol and isopropanol compared to activated carbon, even though the COF contains approximately 1/10th the surface area of many activated carbons. Isotherms for ethane/ethylene collected up to 1 bar show moderate selectivity for ethylene, but interestingly, this selectivity is reversed when the isotherms are measured up to 5 bar. The change in selectivity occurs because the ethane isotherm has a distinct stepwise increase in capacity near 4 bar. The adsorption data indicate broad generalizations and analogies of COFs to activated carbon should be avoided; that the adsorption capacity COFs may not correlate to surface area; and that high-pressure adsorption isotherms may have steps in the adsorption isotherm where capacity increases significantly.

Kinetic Control over Social and Narcissistic Self-Sorting from Multicomponent Mixtures in Seed-Initiated Supramolecular Polymerization by Fine-Tuning of Steric Effects.

Supramolecular polymers offer an intriguing possibility to transfer molecular properties from the nano- to the mesoscale. Towards this achievement, seed-initiated supramolecular polymerization has emerged as a powerful tool, as it prevents unlimited growth and enables size control of the assembly outcome. However, the potential application of the seeding method in the context of complex supramolecular systems is hitherto unclear. Herein we demonstrate that minute differences in molecular design in direct proximity to intermolecular recognition sites govern the molecular packing and in turn dictate the efficacy of seeded polymerization processes. We introduce a stepwise increase in steric demand in the central amino acid residue of a diamide system, which gradually increases the rotational displacement within the aggregated state. This fine-tuning of the molecular packing directly affects the propensity of the different aggregates to act as seeds for the other supramolecular synthons. In turn this allows us to selectively target specific trapped monomer states in binary mixtures for social or narcissistic seeded polymerization.

Kinetic Control over Social and Narcissistic Self‐Sorting from Multicomponent Mixtures in Seed‐Initiated Supramolecular Polymerization by Fine‐Tuning of Steric Effects

AbstractSupramolecular polymers offer an intriguing possibility to transfer molecular properties from the nano‐ to the mesoscale. Towards this achievement, seed‐initiated supramolecular polymerization has emerged as a powerful tool, as it prevents unlimited growth and enables size control of the assembly outcome. However, the potential application of the seeding method in the context of complex supramolecular systems is hitherto unclear. Herein we demonstrate that minute differences in molecular design in direct proximity to intermolecular recognition sites govern the molecular packing and in turn dictate the efficacy of seeded polymerization processes. We introduce a stepwise increase in steric demand in the central amino acid residue of a diamide system, which gradually increases the rotational displacement within the aggregated state. This fine‐tuning of the molecular packing directly affects the propensity of the different aggregates to act as seeds for the other supramolecular synthons. In turn this allows us to selectively target specific trapped monomer states in binary mixtures for social or narcissistic seeded polymerization.

Abstract 4137991: Association of the 2022 AHA/ACC/HFSA Heart Failure Staging and Cardiovascular and Kidney Outcomes in Patients with Diabetes and Kidney Disease: A Secondary Analysis of the SCORED Trial

Introduction: The 2022 AHA/ACC/HFSA heart failure (HF) classification newly incorporates cardiac biomarkers to identify patients at risk of HF. Research Question: Given shared risk factors between HF and other cardiorenal events, the HF stages may also guide prognosis and management of cardiovascular (CV) and kidney-related events beyond HF. Aims: Examine the association of HF stage with CV and kidney events. Methods: SCORED was a randomized trial in diabetes with kidney disease comparing sotagliflozin (sota) v. placebo on CV death, hospitalizations for HF, and urgent HF visits. SCORED participants were grouped by HF stage post hoc . Stage A: No HF, normal cardiac biomarkers (NT-proBNP; &lt;125 pg/mL, hs-cTnT; &lt;14 ng/L) and normal cardiac structure/function by echocardiography. Stage B (pre-HF): No HF but elevated NTproBNP, hsTNT or abnormal echocardiography. Stage C/D: symptomatic HF. Endpoints of interest included the primary composite endpoint (CV death and HF-related events), major adverse CV events (MACE), and kidney-related composites (See Figure caption). Using Cox regression, we examined the association between HF stage and these endpoints, and whether the effect of sota v. placebo varied by HF stage. Results: There were 741 patients in stage A, 6560 in stage B (pre-HF) and 3283 in stage C/D (established HF). The mean NTproBNP and hs-cTnT increased with HF stage. Stepwise increases in HF stage were associated with a 2-4 fold higher incidence of the primary, MACE and kidney endpoints in the placebo group, although the incidence of the kidney-specific composite was similar in stage B and C/D (Figure). The relative risk reduction with sota v. placebo for all endpoints was similar irrespective of HF stage (p-interaction&gt;0.05), with higher absolute benefit in each HF stage (Figure). The absolute benefit for the kidney-specific endpoint was comparable for stage B and C/D. Conclusions: Increasing HF stage is associated with higher risk of HF, MACE, and kidney events, but the risk of kidney events is similar in stage B (pre-HF) and stage C/D (established HF). Sota has similar relative benefits for all endpoints, irrespective of HF stage, with a corresponding increase in absolute benefits at higher stages.

Manifestations of toxic pulmonary edema during respiratory support in an experiment

BACKGROUND: Currently, respiratory support is successfully used to treat pulmonary edema of non-toxic origin. The manifestations of pulmonary edema of non-toxic origin and toxic pulmonary edema have similar features, so respiratory support can be effective in treating the latter. AIM: To describe the manifestations of toxic pulmonary edema in rabbits and demonstrate the effectiveness of artificial pulmonary ventilation with support of positive end-expiratory pressure (PEEP) in case of severe intoxication with thermal destruction products of fluoroplastic-4. MATERIALS AND METHODS: Three rabbits were used in the study: rabbit N 1 (control), rabbit N 2 (intoxication) and rabbit N 3 (treatment). Rabbits N 2 and 3 were subjected to severe intoxication with thermal destruction products of fluoroplastic-4 (1,5 HLC50, 15 min). For treatment, rabbit N 3 (treatment), an hour after exposure, underwent mechanical ventilation with PEEP (pressure-controlled mode; oxygen fraction — 0,3; starting PEEP — 5 cm H2O, tidal volume — 20–25 ml). At various times, chest radiography was performed, oxygenation index, hemoglobin saturation (SaO2), and partial pressure of carbon dioxide in exhaled air (PetCO2) were determined. Posthumously, pathological changes in lung tissue, pulmonary coefficient were determined, and histological examination was performed. RESULTS: Exposure of rabbit N 2 (intoxication) to the thermal destruction products of fluoroplastic-4 led to the sequential formation of the interstitial and alveolar phases of toxic pulmonary edema, which contributed to its death 13 hours after exposure. As SaO2 decreased and PetCO2 increased (3 and 5 hours after exposure), in rabbit N 3 (treatment), during respiratory support, PEEP was increased twice by 2 cm H2O (maintaining a given respiratory volume), which led to the normalization of the studied parameters. On the 7th day after exposure, the condition of rabbit N 3 (treatment) did not differ from the condition of rabbit N 1 (control); no pathological changes in the respiratory system were detected. CONCLUSION: Carrying out mechanical ventilation with PEEP, started an hour after exposure (with a stepwise increase in PEEP as the condition worsens), is effective for correcting toxic pulmonary edema in rabbits caused by severe intoxication with the thermal destruction products of fluoroplastic-4.

Study on temperature evolution law of coal containing gas under uniaxial loading process with different loading rates

AbstractIn order to investigate the evolution law of coal temperature during the gestation process of coal and gas outburst, laboratory experiments and numerical simulation approaches were employed. Infrared thermal radiation experiments on the surface of outburst coal during uniaxial loading and failure of coal were conducted. A coal and gas thermal‐hydromechanical coupling model considering the endothermic effect of desorption was established. Numerical simulation of uniaxial loading of gas‐containing coal was implemented to study the influences of deformation energy, frictional heat, and adsorption/desorption endothermic effects on coal temperature. The results indicate that the temperature of coal samples during the uniaxial loading and failure process generally exhibits a stepwise temperature increase. In the initial stage, the elastic thermal effect leads to a slow and fluctuating rise in the temperature of coal samples. During the yield and plastic deformation stages, frictional heat causes a rapid increase in the temperature of coal samples. With the increase of the loading rate, the increment of the temperature of coal samples gradually decreases and reaches the peak when the loading stress is 70% of the peak stress. According to the numerical calculation results, with the increase of the loading rate, the temperature reduction caused by gas desorption relatively decreases. By comparing the experimental results and numerical simulation results, it is found that the temperature reduction caused by desorption is greater than the temperature increments caused by deformation energy and frictional heat. The desorption endothermic effect and frictional heat effect are the dominant factors controlling the temperature variation of coal during the gestation process of outburst. The research achievements have significant theoretical significance and practical value for revealing the temperature evolution mechanism during the gestation process of coal and gas outburst, predicting coal and gas outburst, and protecting the atmospheric environment.

Effect of cyclic loading on microstructure and plastic deformation in heat-treated Co–28Cr–6Mo alloy fabricated via laser powder bed fusion: An in situ synchrotron X-ray diffraction study

We present a systematic microstructure-oriented plasticity investigation of an additively manufactured cobalt-based alloy aiming to relate microstructural changes to the fatigue resistance. A load-controlled cyclic test in the low-cycle fatigue regime was utilized to study mechanical response and microstructural changes in the alloy after reverse phase transformation heat treatment. Deformation-induced FCC → HCP phase transformation was followed using in situ synchrotron X-ray diffraction combined with ex situ electron backscatter diffraction and scanning electron microscopy. Scanning transmission electron microscopy provided experimental evidence of the presence of precipitates in the solution annealed sample. It was found, that a stepwise increase in plastic deformation is attributed to nucleation and growth of different martensitic crystallographic variants. These insights into plasticity and microstructural changes suggest that the reverse phase transformation heat treatment is an effective approach for improving the fatigue resistance of low stacking fault energy alloys, that are susceptible to deformation-induced martensitic transformation.

Clinical efficacy and safety of parenteral nutrition in hematopoietic stem cell transplantation: results of a single-center randomized controlled study

BACKGROUND: Hematopoietic stem cell transplantation frequently necessitates nutritional support. However, the safety and tolerance of parenteral nutrition have not been adequately examined, except for its association with infectious complications. AIM: To evaluate the impact of parenteral nutrition on nutritional status and its correlation with complications during the early period following hematopoietic stem cell transplantation. MATERIALS AND METHODS: From 2019–2020, 125 recipients of autologous (n=38) and allogeneic (n=87) hematopoietic stem cell transplantation were included in the study with a median age of 20 years (2–65). The chosen cohort included patients with leukemia (n=67), solid tumors (n=32), dysplasia (n=15) and lymphoproliferation (n=11). The control group (n=55) was composed of patients who did not depend on nutritional support. Parenteral nutrition was administered to the primary group (n=70) using second-generation (n=22) and third-generation (n=24) fat emulsions. In the event of contraindications, parenteral nutrition was administered without fat emulsions (n=24). To mitigate the risk of side effects, the initial dose of parenteral nutrition was 50%, with the achievement of the complete dose by the third day of therapy. RESULTS: In 95.7% of cases, mucositis was the indication for parenteral nutrition. The duration of parenteral nutrition was 2–31 days (median, 11 days). In 58.6% of cases, parenteral nutrition was initiated against the background of nausea and vomiting. During the escalation of the parenteral nutrition dose, increased nausea was observed in 7.1% of patients. Side effects were noted in 22.9% of cases: hyperglycemia (n=7), vomiting (n=6) and hypertriglyceridemia (n=3). Four patients developed complications associated with parenteral nutrition, and nutritional therapy was discontinued in 20% of cases (n=14). After hematopoietic stem cell transplantation, the primary clinical efficacy criterion, body mass index, was observed to decline in each observation group. However, it recovered by day 28 and did not differ between the comparison groups as follows: the control group — from 22.7±6.4 to 21.7±6.1 kg/m2, (p=0.42); group “2 in 1” — from 23.4±6.1 to 21.6±4 kg/m2, (p=0.56); group provided with parenteral nutrition employing second-generation fat emulsions — from 18,8±4,9 to 18.7±4.4 kg/m2, (p=0.72); group administered parenteral nutrition with third-generation fat emulsions — from 18.6±4.2 to 18.3±3.5 kg/m2, (p=0.84). The febrile neutropenia rate was 75.2% and did not vary in the control and comparison groups (p=0.54). The incidence of sepsis was 24.8% and was not influenced by the use of parenteral nutrition (p=0.07). Furthermore, sepsis risk was higher when administering parenteral nutrition “2 in 1” compared to fat emulsions-containing parenteral nutrition (p=0.002). The overall frequency of acute graft versus host disease was 16.1% and was similar in the comparison groups (p=0.65). CONCLUSION: In the cohort of patients treated with hematopoietic stem cell transplantation, parenteral nutrition regimens supplemented with second- and third-generation fat emulsions with a stepwise dose increase varied in acceptable tolerance, infection-related complications, and immunological safety, as well as effectively maintained nutritional status parameters.

Development and validation of a predictive scoring model for complications following endoscopic endonasal skull base surgery.

The endoscopic endonasal approach (EEA) has evolved into an established technique in skull base surgery. The authors previously examined 1002 EEA procedures and reported factors associated with postoperative complications. Here they report the development and validation of a scoring model based on risk factors to better predict complications following EEA. The authors developed an optimized EEA scoring model for predicting postoperative complications as evidenced by the area under the receiver operating characteristic (AUROC) curve using their previously published data in addition to data collected from the subsequent 292 EEA procedures from years 2010-2020. The model was built systematically by evaluating the contributions that different variables had on the overall predictive ability of the model. The aim was to design a model containing as few variables as possible for practicality and to facilitate calculation and use at the bedside. The Clavien-Dindo grading system was used to classify complications into grades I-V based on the level of intervention that was required to manage the complication, with grades III-V considered to be higher-grade (i.e., those requiring reoperation or ICU-level care or death). The authors identified 1294 EEA operations performed between July 2010 and July 2020 that met their inclusion criteria. Higher-grade complications were identified following 135 EEA operations. The variables that were ultimately included in the model were age, BMI, operative time, meningioma, chordoma, expanded intradural approach, and nasoseptal flap use. The final model yielded an acceptable AUROC curve of 0.72 and predicted a stepwise increase in the rate of higher-grade complications as the score increased. A score of 0-2 (low) on the grading system was associated with an average complication rate of 5.1%. A score of 3-5 (medium) was associated with an average complication rate of 12.6%. A score of 6 or above (high) was associated with an average complication rate of 26%. This EEA complications scoring model accurately categorizes patients into low-, medium-, and high-risk groups with readily obtained variables. A high score in this complications model does not suggest that a patient is ineligible for surgery, but rather highlights the importance of thorough case selection, operating with caution, and appropriate preoperative counseling.

Interplay between strain pattern-based classification of dyssynchrony and myocardial scar in CRT patients

Abstract Introduction Echocardiography-derived septal strain patterns are valuable for predicting volumetric reverse remodelling and survival in patients undergoing cardiac resynchronization therapy (CRT). Nevertheless, presence of myocardial scarring in the left ventricle (LV) is known to attenuate CRT treatment response. Purpose This study aims to investigate the interplay between septal strain patterns and myocardial scarring in CRT candidates, and how they link to outcome after CRT. Methods In this prospective multicentre study, CRT candidates from five European institutions underwent pre-implantation assessments using speckle-tracking strain analysis on echocardiography and cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement (LGE). Dyssynchrony was graded through analysis of septal strain curves, categorizing patients into five distinct patterns, denoted as strain Stage-0 through strain Stage-4 (Fig. A). LGE of the LV wall was quantitatively assessed using CMR (as a percentage). The study endpoints were volumetric reverse remodelling (volume responder = more than 15% decrease LV end-systolic volume) after one year, and all-time all-cause mortality. Results A total of 267 patients, with a mean age of 66±11 years (69% males, 90% left bundle branch block [LBBB]) presented with an average LV ejection fraction (EF) of 30±7%. With each stepwise increase in strain stage, global LV scarring decreased (p&amp;lt;0.01; Fig. B) and the proportion of volume responders increased (all p&amp;lt;0.0001; Fig. C). ROC curves demonstrated that the predictive power of strain stages for CRT volumetric response was not significantly improved when scarring percentage was added (AUC 0.78 [95% CI: 0.69-0.83] vs. 0.81 [95% CI: 0.71-0.90]; p&amp;gt;0.05; Fig. D). In a multivariate cox regression model – including clinical characteristics that were significantly related to survival in univariate analysis – a patients’ strain stage was the only significant predictor of survival, also outperforming scar burden as determinant of outcome (HR 0.68; p=0.041; Fig. E). Conclusions Septal strain patterns show a strong association with the extent of reverse remodelling and outcome in CRT-treated patients. An inverse relationship is observed between pre-implant strain stages and the extent of myocardial scarring. However, scar burden did not provide incremental predictive value over the strain stages. Strain-pattern-based dyssynchrony assessment is a meaningful predictive marker which integrates information on myocardial dysfunction due to dyssynchrony as well as scar burden.

Periprocedural changes in systolic pulmonary artery pressure in transcatheter aortic valve implantation

Abstract Background Pulmonary hypertension (PH) is common in patients with aortic stenosis and associated with increased mortality following transcatheter aortic valve replacement (TAVR). PH often improves after TAVR and systolic pulmonary artery pressure (sPAP) can change, but to what extent these changes in sPAP following TAVR affect long-term prognosis is unclear. Purpose To investigate the association between periprocedural changes in sPAP and long-term prognosis after TAVR. Methods Patients undergoing TAVR between 2012-2021 from the Swedish Transcatheter Cardiac Intervention Registry (SWENTRY) were included. sPAP was estimated from echocardiography before and after TAVR and categorized as: (1) No PH before and unchanged (≤5 mmHg change) after, (2) No PH before and worsened (&amp;gt;5 mmHg increase) after, (3) PH before and improved (&amp;gt;5 mmHg decrease) after, (4) PH before and unchanged after and (5) PH before and worsened after. An sPAP cutoff at &amp;gt;50 mmHg was applied for PH. Patients were followed for a median of 3.1 years for the primary endpoint heart failure hospitalizations (HFH) and the secondary endpoint all-cause mortality. Cox regression analyses were performed and adjusted for age, sex, body mass index, atrial fibrillation, eGFR class, diabetes, frailty, left ventricular ejection fraction and chronic obstructive pulmonary disease. Results In total, 4926 patients were included (mean age 82 years, 50% female) among whom 2596 (53%) patients had no PH and unchanged, 864 (18%) had no PH and worsened after, 912 (19%) had PH and improved after, 401 (8%) had PH and unchanged after and 153 (3%) had PH and worsened after. The mean sPAP levels preoperatively in each group were 36, 31, 60, 58, 57 mmHg respectively. Mean change in patients with no PH and worsened was +16 mmHg, in patients with PH and improved -20 mmHg and in patients with PH and worsened +14 mmHg. Cumulative incidence rates of HFH at 5 years among the five groups were 18%, 25%, 32%, 41%, and 52%, respectively (p&amp;lt;0.001). In adjusted analyses, there was a stepwise increase in the risk of HFH (Figure 1A) and all-cause mortality (Figure 1B) for no PH and worsened, PH and improved, PH and unchanged and PH and worsened as compared with no PH and unchanged. Conclusion Increase of periprocedural sPAP in patients with and without known PH before TAVR was associated with worse prognosis whereas reduction of sPAP was associated with improved outcomes.

The impact of escape mapping for roof line completion during BOX isolation for atrial fibrillation

Abstract Background and Aim The creation of complete roof line (RL) is often challenging due to the presence of epicardial myocardial bundle or fat interposition. The disconnecting the septopulmonary bundle from the Buchmann bundle arrays requires for RL completion. Therefore, the conduction time to the left atrial appendage (LAA) and the high right atrium (HRA) potentials under left superior pulmonary vein pacing (LSPVp), so-called •escape mapping•, should be significantly prolonged after the creation of the transmural RL. This study investigates whether the changes conduction times from LSPVp to LAA and HRA (∆LSPVp-LAA and ∆LSPVp-HRA) between before and after the creation of the line as the assessment of bi-directional RL block. Methods 76 de-novo non-paroxysmal atrial fibrillation (nPAF) patients underwent BOXI strategy ablation. We initially intended single ring protocol BOXI for all patients. The activation times were measured at LAA and HRA under LSPV pacing at baseline and after application for the RL. Then we compared the change of activation time at LAA (∆LSPVp-LAA) and at HRA (∆LSPVp-HRA) between 2 groups; the group that completed BOXI with the first-pass roof line (fp-RL group) and the other group (Nfp-RL group). Results In 47 patients, the first-pass roof line was successfully obtained and in patients was done with additional application for gap(s) on the roof line to complete BOXI. There was a stepwise increase in mean ∆LSPVp-HRA not ∆LSPVp-LAA. Increased LA diameter, lower LVEF, and thinner LA wall were associated with the first-pass roof line. ∆LSPVp-HRA ≥33ms predict roof line block with high specificity and sensitivity. Conclusions Our findings suggest that the changes conduction times between LSPV and HRA during LSPV pacing help in the assessment of RL block.

Biomarkers of cardiohepatic syndrome in the cardiac intensive care unit

Abstract Introduction Non-cardiovascular end-organ dysfunction is an important determinant of outcomes in cardiac intensive care unit (CICU) patients. We examined the association between in-hospital mortality with the severity and extent of admission liver function test (LFT) abnormalities in a heterogeneous CICU population. Purpose We hypothesized that a greater severity or extent of LFT abnormalities would be associated with higher in-hospital mortality. Methods We included consecutive unique adult CICU patients with available data for one or more of the admission LFT values of interest. Admission laboratory values were defined as those closest to CICU admission. We used the NIH Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 to categorize the severity of each LFT abnormality from Grade 0 (normal) to Grade 4 (life-threatening). We defined the extent of LFT abnormality as the number of individual LFTs meeting criteria for CTCAE Grade 1 or greater. The primary outcome of interest was all-cause in-hospital mortality. Odds ratio (OR) and 95% confidence interval (CI) values for in-hospital mortality were estimated using logistic regression, before and after multivariable adjustment. Results Of 12,428 unique CICU patients, 5,144 were excluded due to a lack of available data for any admission LFT values. The remaining 7,284 patients comprised the final study population. Among patients with available data for each individual LFT, abnormal values were present in: AST, 2,743/5,733 (47.8%); ALT 1,576/5,512 (28.6%); ALK 611/3,684 (16.6%); and TB 898/5,155 (17.4%). A total of 864 (11.9%) patients died during hospitalization. In-hospital mortality was higher for patients with one or more LFTs meeting criteria for CTCAE Grade 1 or greater (17.9% vs. 6.4%, adjusted OR 1.54 [1.27-1.86], p &amp;lt;0.001). A stepwise increase in in-hospital mortality was observed with increasing CTCAE grade, both overall (adjusted OR 1.25 per each higher CTCAE grade [1.16-1.34], p &amp;lt;0.001); (Figure 1A), and for each individual LFT (Figure 1B). Conclusion Cardiohepatic syndrome is an important predictor of prognosis in CICU patients, as the extent and severity of LFT abnormalities are strongly associated with in-hospital mortality. This is the first large-scale study to examine the association between the magnitude of hepatic biomarker derangement with in-hospital mortality in unselected CICU patients. Patients with markedly elevated LFT values exhibited the highest risk of in-hospital mortality. This analysis advocates for the inclusion of commonly obtained LFTs in future risk-prediction tools for enhanced prognostication.

Early risk stratification of patients with acute myocardial infarction complicated by severe cardiogenic shock - The ECLS-SHOCK Risk Score

Abstract Background Prognosis after acute myocardial infarction complicated by cardiogenic shock (AMI-CS) remains dismal. Timely risk stratification is crucial to make adequate treatment decisions. Existing CS scores are limited to either registry data, included not readily available parameters (such as coronary flow after revascularisation, cystatin C or interleukin-6), or are not tailored to patients with AMI-CS. Purpose The aim of this study was to develop a readily available and easy-to-use risk prediction tool for 30-day mortality in patients with severe AMI-CS derived from the ECLS-SHOCK (Extracorporeal Life Support in Infarct-Related Cardiogenic Shock) trial. Methods Backward stepwise regression analysis was used to develop the risk score across 43 centres in two countries. Results Five variables emerged as independent predictors for 30-day mortality and were used as risk score parameters: age ≥69 years, female sex, ≥3 known cardiovascular risk factors (i.e., hypertension, dyslipidaemia, diabetes, smoking or known vascular disease), baseline arterial lactate ≥7.1 mmol/L and performed resuscitation. Between 1 and 7 points were attributed to each variable, resulting in a score with three risk categories: low (0 to 1), intermediate (2 to 3) and high (4 to 7) (Figure). The observed 30-day mortality rates were 23%, 50% and 80% in each risk category (p&amp;lt;0.001) with a good discrimination at an area under the curve of 0.75. A stepwise increase in mortality between the different risk score categories was observed in Kaplan-Meier analyses (p&amp;lt;0.001 for low vs. intermediate, intermediate vs. high and low vs. high; see Figure). Conclusion The ECLS-SHOCK risk score can be easily and promptly calculated in daily clinical practice and correlated with mortality in patients with severe AMI-CS. It may help stratify patient risk for short-term mortality and facilitate early clinical decision making.

Progression of myocardial fibrosis is the major determinant of heart failure hospitalization in patients undergoing transcatheter aortic valve implantation

Abstract Background Patient who are hospitalized for heart failure (HF) prior to transcatheter aortic valve implantation (TAVI) are associated with poor prognosis. In this study, we aimed to assess whether myocardial fibrosis (MF) in TAVI patients is strongly involved in prior heart failure hospitalization. Methods We performed a retrospective single-center study, including 93 patients who underwent cardiac biopsies before TAVI from December 2022 to December 2023. The extent of MF was assessed on Masson’s trichrome-stained tissue specimens, using a validated software "ImageJ". Results Prior hospitalization had significant association with BNP (HF hospitalization (+): 461.9[130.4-987.7] vs. HF hospitalization (-):125.3[78.2-228.6], p=0.0014) , aortic valve area index (AVAi) (0.43±0.02 vs. 0.51±0.01, p=0.002), left ventricular ejection fraction (LVEF) (54.4±2.8 vs. 67.2±1.6, p=0.0002), E/e’ (23.4±1.9 vs. 19.1±1.0, p=0.045), left atrial volume index (LAVI)(59.0±3.5 vs. 46.1±1.6, p=0.0013), global longitudinal strain (GLS) (13.2±1.0 vs. 15.7±0.5), and percent area of myocardial fibrosis(7.0[4.8-14.2] vs. 3.3[2.2-7.3], p=0.0002) Moreover, percent area of MF was the most reliable indicator (area under the curve: AUC= 0.75, p=0.0009) of prior heart failure hospitalization (figure 1) among HF parameters which include BNP (AUC=0.73, p&amp;lt;0.0001), AVAi (AUC=0.69, p=0.0024), LVEF(AUC=0.68,p=0.0005), E/e’ (AUC=0.63, p=0.051), LAVI (AUC=0.72, p=0.0022), GLS (AUC=0.65, p=0.035). Furthermore, the ROC curve analyses demonstrated that the best thresholds of LVEF and percent area of MF were 64.9% (60.9% sensitivity and 68.1% specificity) and 4.1% (91.7% sensitivity and 56.5% specificity) for heart failure hospitalization, respectively. When patients were divided into 4 groups according to LVEF 65% and percent area of myocardial fibrosis 4%, a stepwise increase in the proportion of heart failure hospitalization was found in the 4 groups (figure 2). Conclusions This study illustrates that extensive myocardial fibrosis was strongly associated with prior heart failure hospitalization in TAVI patients. Patients with advanced myocardial fibrosis due to aortic stenosis may benefit from earlier treatment with TAVI to prevent further progression of myocardial fibrosis.

Measures of insulin resistance and aortic valve calcification in the general population

Abstract Background Insulin resistance (IR) is a key component in several cardiovascular risk factors. The triglyceride-glucose index (TyG index), triglyceride to high density lipoprotein-cholesterol ratio (TG/HDL-C) and visceral adiposity index (VAI) are easily accessible surrogate measures of IR and have been associated with coronary artery calcification and other cardiovascular diseases. Less is known about IR and aortic valve calcification (AVC). Purpose To investigate the association between different measures of IR (TyG index, TG/HDL-C, VAI) and AVC. Method The Swedish Cardiopulmonary Bioimage Study (SCAPIS) recruited 30 154 randomly selected individuals aged 50 to 64 years from the general population in Sweden between 2013 to 2018. AVC was assessed visually on cardiac computed tomography and categorized as present or absent. TyG index was calculated based on triglyceride and glucose levels, TG/HDL-C ratio using triglyceride and HDL-C levels and VAI using waist circumference, triglyceride and HDL-C levels. The association between IR indexes (as continuous variables by 1 unit increment and categorical variables by quartiles) and AVC was assessed using multivariable logistic regression models. Results In total, measures of IR were available in 29 268 participants of whom 2118 (7%) had AVC. Mean IR index levels were higher in participants with compared to without AVC (TyG index: 8.65 vs. 8.49; p&amp;lt;0.01; TG/HDL-C: 1.11 vs. 0.91; p&amp;lt;0.01 and VAI: 1.73 vs. 1.48; p&amp;lt;0.01). All three indices of IR were associated with AVC in continuous analyses. Subsequently, in multivariable logistic regressions adjusted for age, sex, study site and smoking, there was a stepwise increase in the risk of AVC with increasing quartiles of TyG index, TG/HDL-C and VAI (Figure 1). Conclusion Three different surrogate measures of IR (TyG index, TG/HDL-C and VAI) were all associated with AVC in a middle-aged general population suggesting that they could all be used as risk markers in clinical practice.

Temporal trends in mitral valve surgery in Denmark: changes in patient characteristics and outcomes from 1996 to 2021

Abstract Background Mitral valve regurgitation (MR) is associated with increased morbidity and mortality. Mitral valve surgery (MVS) is recommended in severe MR, which is the second most common cause of heart valve surgery in the Western world. Data on national practice patterns are lacking and are essential for the continuous epidemiologic surveillance of the disease. Purpose To investigate temporal trends in patient characteristics, incidence and mortality in patients undergoing MVS for MR in Denmark from 1996 to 2021. Methods Using Danish nationwide registries, we identified all patients ≥18 years undergoing MVS for MR. Patients operated due to infective endocarditis were excluded. The study population was grouped into one 6-year and four 5-year calendar bands and type of MVS (mitral valve repair, mechanical or biological valve replacement and transcatheter-edge-to-edge repair (TEER)). Temporal trends in patient characteristics were computed. Annual incidence rates were calculated while considering the total Danish population ≥18 years at risk. For one-year postoperative mortality analysis, the reverse Kaplan-Meier estimator and a multivariable Cox proportional hazard analysis were used. Results We identified 7,813 patients (median age 67.3 years, 65.6% males) undergoing MVS. Over calendar time, burden of comorbidities decreased while median age increased, Table 1. From 1996 to 2021, a stepwise increase was seen in the overall incidence rate for MVS from 3.87 [95% CI 3.32-4.51] to 7.06 [95% CI 6.34-7.58] per 100,000 person-years (p&amp;lt;0.001). The incidence of mechanical valve replacement statistically significantly decreased (p&amp;lt;0.001), while the incidence of mitral valve repair (p=0.004), biological replacement (p≤0.001) and TEER statistically increased (p=0.015), Figure 1. For the overall study period, one-year mortality was 5.0% for mitral valve repair, 12.7% for mechanical valve replacement, 15.7% for biological valve replacement and 19.0% for TEER. Demographics and one-year mortality stratified by calendar period are shown in Table 1. In the mitral valve repair group, adjusted analysis showed a stepwise statistically significant decrease in one-year mortality with HR 0.30 (95% CI 0.17-0.53, p≤0.001) in 2017-2021 as compared to 1996-2001. In the remaining surgical groups, trends were towards decreasing one-year mortality over calendar periods but did not reach statistical significance. Conclusion(s) In this Danish nationwide cohort study, we observed an increase in the incidence of overall mitral valve surgery from 1996 to 2021. The incidence of mechanical valve replacement decreased, while the incidence of mitral valve repair, biological replacement and TEER increased. Mortality rates significantly improved for mitral valve repair patients over calendar time. Continuous epidemiological surveillance of this patient group is required in an era of development in treatment guidelines, surgical methods and patient demographics.Table 1Figure 1

Left ventricular ejection fraction and clinical outcomes after transcatheter aortic valve implantation

Abstract Background Reduced left ventricular ejection fraction (LVEF ≤50%) has been associated with poor prognosis in patients with severe aortic stenosis treated medically or with aortic valve replacement. However, less is known regarding the impact of different degrees of LVEF including moderately to severely reduced LVEF after transcatheter aortic valve replacement (TAVR). Purpose To examine the association between baseline LVEF and clinical outcomes after TAVR. Methods Patients undergoing TAVR between 2008-2021 from the Swedish Transcatheter Cardiac Intervention Registry (SWENTRY) were included. LVEF was estimated from echocardiography before TAVR and categorized as ≥50%, 40-49%, 30-39% and &amp;lt;30%. SWENTRY was linked to the National Patient Registry and Cause of Death Registry for outcome variables. Patients were followed for a median of 3.2 years for the primary outcome heart failure hospitalizations and the secondary outcome all-cause mortality. Cox regression analyses adjusted for age, sex, BMI, atrial fibrillation, eGFR class, diabetes, hypertension, frailty, chronic pulmonary disease and coronary artery disease were performed for the association between LVEF groups and outcome. Results In total, 8686 patients were included (mean age 81 years, 47% female) of whom 5904 (68%) patients had LVEF ≥50%, 1342 (15%) had LVEF 40-49%, 906 (10%) had LVEF 30-39% and 534 (6%) had LVEF &amp;lt;30%. Significant differences were observed across the LVEF groups in the cumulative incidence rates of heart failure hospitalizations (19, 30, 37 and 43%; p&amp;lt;0.001) and all-cause mortality (41, 54, 55, 57%; p&amp;lt;0.001) at five years. In adjusted analyses there was a stepwise increase in the risks of heart failure hospitalizations (Figure 1A) and all-cause mortality (Figure 1B) for each respective LVEF category. Conclusion Reduced LVEF, especially LVEF &amp;lt;30%, was associated with a dramatically increased long-term risk of heart failure hospitalizations and all-cause mortality in patients undergoing TAVR. LVEF should be considered in risk stratification and patient selection for TAVR.

External validation of the CA-AKI score in patients with acute coronary syndrome: A real-world cohort analysis from Asia

Abstract Background Contrast-associated acute kidney injury (CA-AKI) is associated with long-term impairment of kidney function, the need for renal replacement therapy, and subsequent all-cause deaths. A practical risk score, the CA-AKI risk score is derived for the prediction of contrast-associated acute kidney injury. However, this novel score has not received sufficient evidence of external validation in real-world studies, especially in Asian individuals. Methods Short-term endpoints and long-term endpoints were assessed in 8,816 patients with acute coronary syndrome enrolled in a large Asia registry. Discrimination was assessed by Harrell’s C statistic, and calibration was assessed by calibration plots. The ability of the CA-AKI score to predict short-term and long-term prognosis was assessed. Results CA-AKI occurred in 5.3% of the patients, with a stepwise increase of CA-AKI rates from the lowest to the highest of the 4 risk categories. When predicting the risk of CA-AKI, both discrimination and calibration were helpful in model 2 (C-index: 0.72; slope: 0.97) and in model 1(C-index: 0.69; slope: 1.02). The risks of 1-year all-cause mortality and 1-year bleeding were higher in CA-AKI patients (HR: 2.70 [95% CI: 2.22-3.30] and HR: 1.76 [95% CI: 1.41-2.46]; respectively). Conclusion The updated CA-AKI risk score could accurately identify patients with contrast-associated acute kidney injury, the occurrence of which is strongly associated with long-term mortality and bleeding.