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Gas plays an important role in many processes in galaxy formation and evolution, but quantifying the importance of gas has been hindered by the challenge to measure gas masses for large samples of galaxies. Datasets of direct atomic and molecular gas measurements are sufficient to establish simple scaling relations, but often not large enough to quantify three-parameter relations, or second order dependencies. As an alternative approach, we derive here indirect cold gas measurements from optical emission lines using photoionization models for galaxies in the SDSS main galaxy sample and the PHANGS-MUSE survey. We calibrate the gas surface density measurements using xCOLD GASS and PHANGS-ALMA molecular gas measurements to ensure our measurements are reliable. We demonstrate the importance of taking into account the scale-dependence of the relation between optical depth ($\tau_V$) and gas surface density ($\Sigma_{gas}$) and provide a general prescription to estimate $\Sigma_{gas}$ from $\tau_V$, metallicity and the dust-to-metal ratio, at any arbitrary physical resolution. To demonstrate that the indirect cold gas masses are accurate enough to quantify the role of gas in galaxy evolution, we study the mass-metallicity relation (MZR) of SDSS galaxies and show that as a third parameter, gas mass is better than SFR at reducing the scatter of the relation, as predicted by models and simulations., Comment: 15 pages, 12 figures, 3 tables, submitted to MNRAS

Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Amsterdam UMC. Background Maintenance of muscle strength and muscle mass is important for long-term health. Periods of physical inactivity and poor dietary intake (e.g. waiting for a medical procedure) can provoke loss of muscle strength and muscle mass. Purpose We aim to determine the course of muscle strength and muscle mass in patients with severe aortic stenosis from before until six months after an elective transcatheter aortic valve implantation (TAVI). Moreover, we aim to explore baseline characteristics associated with change. Methods All patients undergoing an elective TAVI in our high-volume tertiary center were asked to participate. Included patients received three home visits (pre-procedural and 30 days and 6 months post-procedural). During these home visits, handgrip strength was measured with a handheld dynamometer. Muscle mass was determined as skeletal muscle index with a bioelectrical impedance (BIA) measurement. Multivariate mixed linear models were used to determine changes over time. A linear model adjusted for age and sex was performed to explore baseline characteristics associated with changes in muscle strength or muscle mass. Results In total 112 patients were included, mean age of the participants was 81 ± 5 years and 58% were male. The preprocedural measurement took place on a median of 48 [IQR: 19 – 79] days before the TAVI. Preprocedural handgrip strength was on average 36 kg for male and 24 kg for female patients and decreased after the TAVI (-0.12 [95% CI: -0.21, -0.02] kg/month, p=0.02). Living alone and lower hemoglobin level were predictive for a higher decrease in strength (β -2.20 [95% CI: -3.98, -0.42], p=0.02 and β 0.14 [95% CI: 0.02, 0.27] per mmol/l, p=0.03, respectively). Appendicular skeletal muscle index was 7.2 kg/m2 for males and 6.1 kg/m2 for females and did not change after TAVI (0.00 [95%CI: -0.01, 0.01] kg/m2/month, p=0.95). No baseline characteristics were associated with a change in muscle mass. Conclusion Muscle strength significantly declines and muscle mass remains the same from before until six months after the TAVI procedure. Patients living alone or patients with low hemoglobin levels are at increased risk to lose muscle strength. Future studies should focus on the prevention of strength loss, for instance with interventions focusing on nutrition and exercise around the TAVI procedure.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): EPIC Norfolk was supported by the Medical Research Council UK (programme grants numbers MRC G0401527, MRC G0701863, MRC G1000143) and Cancer Research UK (programme grant number CRUK 8257). Introduction The Systematic COronary Risk Evaluation 2 – Older Persons (SCORE2-OP) algorithm is developed to assess 10-year risk of fatal and non-fatal cardiovascular disease (CVD) in apparently healthy individuals aged ≥70 years. We evaluated the performance of SCORE2-OP in the European Prospective Investigation of Cancer Norfolk (EPIC-Norfolk) prospective population cohort. Purpose To validate the SCORE2-OP model in men and women aged 70-80 years without prior myocardial infarction or stroke. Methods We included individuals aged 70-80 without prior myocardial infarction or stroke. We compared SCORE2-OP (low-risk algorithm) calculated 10-year risk with 10-year observed event rates in the EPIC-Norfolk cohort. SCORE2-OP was calculated using baseline EPIC-Norfolk data (1993-1997). Cardiovascular events were defined as a composite outcome of (i) death due to ischemic heart disease, cardiac failure, cerebrovascular disease or peripheral-artery disease, (ii) non-fatal myocardial infarction or (iii) non-fatal stroke. Observed rates were adjusted for competing fatal events. We evaluated discriminative power using C-statistic and calibration by plotting predicted versus observed event rates and calculating the observed/predicted ratios. Results SCORE2-OP was evaluated in 3,712 individuals (54% women) with a median (IQR) age of 73 (72-75) years. Ten-year SCORE2-OP was 10.3% (95% confidence interval (CI) 10.2-10.4) versus observed CVD of 16.8% (95% CI 15.6-18.0), yielding a ratio of 1.6 (95% CI 1.5-1.7). Observed events consisted of 9.4% (95% CI 8.4-10.3) fatal CVD events, 10.6% (95% CI 9.6-11.5) non-fatal myocardial infarctions, 10.5% (95% CI 9.5-11.5) non-fatal strokes, adjusted for 68.9% (95% CI 67.4-70.4) competing mortality events. C-statistic was 0.60 (95% CI 0.58-0.63), with a calibration plot demonstrating underestimation of risk across sex and risk groups.(Figure). Conclusion SCORE2-OP underestimates risk in individuals aged 70-80 years, and demonstrates suboptimal discriminative ability. However some underestimation of risk is to be expected given the EPIC-Norfolk baseline between 1993-1997, a low SCORE2-OP calculated risk should not be used as a standalone argument to withhold preventive efforts in older individuals.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): EPIC-Norfolk is supported by programme grants from the Medical Research Council UK (MRC G0401527, MRC G0701863, MRC G1000143) and Cancer Research UK (CRUK 8257). Introduction The latest European guidelines recommend the use of the Systematic COronary Risk Evaluation 2 (SCORE2) to assess 10-year risk of fatal and non-fatal cardiovascular disease (CVD) in individuals aged 40-70 years. Therefore, validation of the SCORE2 algorithm in a large population is needed. Purpose To assess the predictive performance of SCORE2 in individuals without prior myocardial infarction, stroke or diabetes mellitus. Methods Individuals aged 40-70 without prior myocardial infarction, stroke or diabetes mellitus were included from the European Prospective Investigation of Cancer Norfolk (EPIC-Norfolk) prospective population cohort. We assessed discriminative power using the C-statistic; calibration was assessed by plotting calculated SCORE2 (low-risk algorithm) 10-year risks against observed CVD event rates. We defined the composite cardiovascular outcome as death due to ischemic heart disease, cardiac failure, cerebrovascular disease or peripheral-artery disease, or non-fatal myocardial infarction or non-fatal stroke. Observed probabilities were adjusted for competing mortality events. Results We included 20,318 individuals (56% women) with a median (IQR) age of 56 (50-63) years, with baseline measures between 1993-1997. Mean predicted 10-year risk was 3.7% (95% confidence interval (CI) 3.7-3.8) versus adjusted observed 4.2% (95% CI 3.9-4.5) 10-year CVD incidence, yielding a ratio of 1.1 (95% CI 1.1-1.2).(Figure) Observed events consisted of 1.5% (95% CI 1.3-1.7) fatal CVD events, 1.8% (95% CI 1.6-2.0) non-fatal myocardial infarctions, 1.5% (95% CI 1.3-1.6) non-fatal strokes and 23.4% (95% CI 22.1-23.2) competing mortality events. Overall C-statistic was 0.75 (95% CI 0.73-0.77). Conclusion SCORE2 demonstrates reasonable discriminative ability and accurate risk estimations in low-risk individuals in a large, prospective population cohort. However, as actual CVD incidence is expected to be lower given the baseline between 1993-1997, these findings do not indicate that SCORE2 is suitable for current use for risk assessment in individuals from the United Kingdom.

Aims Telemonitoring modalities in heart failure (HF) have been proposed as being essential for future organization and transition of HF care, however, efficacy has not been proven. A comprehensive meta-analysis of studies on home telemonitoring systems (hTMS) in HF and the effect on clinical outcomes are provided. Methods and results A systematic literature search was performed in four bibliographic databases, including randomized trials and observational studies that were published during January 1996–July 2022. A random-effects meta-analysis was carried out comparing hTMS with standard of care. All-cause mortality, first HF hospitalization, and total HF hospitalizations were evaluated as study endpoints. Sixty-five non-invasive hTMS studies and 27 invasive hTMS studies enrolled 36 549 HF patients, with a mean follow-up of 11.5 months. In patients using hTMS compared with standard of care, a significant 16% reduction in all-cause mortality was observed [pooled odds ratio (OR): 0.84, 95% confidence interval (CI): 0.77–0.93, I2: 24%], as well as a significant 19% reduction in first HF hospitalization (OR: 0.81, 95% CI 0.74–0.88, I2: 22%) and a 15% reduction in total HF hospitalizations (pooled incidence rate ratio: 0.85, 95% CI 0.76–0.96, I2: 70%). Conclusion These results are an advocacy for the use of hTMS in HF patients to reduce all-cause mortality and HF-related hospitalizations. Still, the methods of hTMS remain diverse, so future research should strive to standardize modes of effective hTMS.

Data de publicació electrònica: 04-04-2022 Pathogenic variants in A Disintegrin And Metalloproteinase (ADAM) 22, the postsynaptic cell membrane receptor for the glycoprotein leucine-rich repeat glioma-inactivated protein 1 (LGI1), have been recently associated with recessive developmental and epileptic encephalopathy. However, so far, only two affected individuals have been described and many features of this disorder are unknown. We refine the phenotype and report 19 additional individuals harboring compound heterozygous or homozygous inactivating ADAM22 variants, of whom 18 had clinical data available. Additionally, we provide follow-up data from two previously reported cases. All affected individuals exhibited infantile-onset, treatment-resistant epilepsy. Additional clinical features included moderate to profound global developmental delay/intellectual disability (20/20), hypotonia (12/20), delayed motor development (19/20). Brain MRI findings included cerebral atrophy (13/20), supported by post-mortem histological examination in patient-derived brain tissue, cerebellar vermis atrophy (5/20), and callosal hypoplasia (4/20). Functional studies in transfected cell lines confirmed the deleteriousness of all identified variants and indicated at least three distinct pathological mechanisms: defective cell membrane expression (1), impaired LGI1-binding (2), and/or impaired interaction with the postsynaptic density protein PSD-95 (3). We reveal novel clinical and molecular hallmarks of ADAM22 deficiency and provide knowledge that might inform clinical management and early diagnostics. Funding: most families were collected as part of the SYNaPS Study Group collaboration funded by the Wellcome Trust and strategic award (Synaptopathies) funding (WT093205 MA and WT104033AIA). This study was also supported by JSPS/MEXT KAKENHI (Grants 19H03331, 19K22439 and 21K19390 to Y.F., Grant 19K16269 to Y.M., and Grants 20H00459 and 20H04915 to M.F.) and Japan Agency for Medical Research and Development (21wm0525022h0001 to Y.F.); intramural funding (fortüne) from the University of Tübingen (Grant 2545-1-0) and the Ministry of Science, Research and Art Baden-Württemberg to B.V. P.S. contributed to this work within the framework of the DINOGMI Department of Excellence of MIUR 2018-2022 (legge 232 del 2016). T.B.H. was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – 418081722, 433158657. I.S.P., V.Y.V. are supported by the Government Assignment of the Russian Ministry of Health (#121061500066-2). HL receives support from the Canadian Institutes of Health Research (Foundation Grant FDN-167281), the Canadian Institutes of Health Research and Muscular Dystrophy Canada (Network Catalyst Grant for NMD4C), the Canada Foundation for Innovation (CFI-JELF 38412), and the Canada Research Chairs program (Canada Research Chair in Neuromuscular Genomics and Health, 950-232279). S.H. is funded by TUBITAK (Turkish Scientific and Technological Research Council) Project number 216S771. R.H. is a Wellcome Trust Investigator (109915/Z/15/Z), who received support from the Medical Research Council (UK) (MR/N025431/1 and MR/V009346/1), the European Research Council (309548), the Newton Fund (UK/Turkey, MR/N027302/1), the Addenbrookes Charitable Trust (G100142), the Evelyn Trust, the Stoneygate Trust, the Lily Foundation and an MRC strategic award to establish an International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD) MR/S005021/1. This research was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014)

Lassa virus (LASV) causes mild to severe hemorrhagic fever disease in humans. Strain 13/N guinea pigs are highly susceptible to infection with LASV strain Josiah (clade IV), providing a critical model system for therapeutics and vaccine development. To develop additional models of disease, we detail the clinical course in guinea pigs infected with 5 geographically and genetically diverse LASV strains. Two of the developed models (LASV clades II and III) were then used to evaluate efficacy of a virus replicon particle vaccine against heterologous LASV challenge, demonstrating complete protection against clinical disease after a single vaccination dose.

Aims Patients with cardiac disease are considered high risk for poor outcomes following hospitalization with COVID-19. The primary aim of this study was to evaluate heterogeneity in associations between various heart disease subtypes and in-hospital mortality. Methods and results We used data from the CAPACITY-COVID registry and LEOSS study. Multivariable Poisson regression models were fitted to assess the association between different types of pre-existing heart disease and in-hospital mortality. A total of 16 511 patients with COVID-19 were included (21.1% aged 66–75 years; 40.2% female) and 31.5% had a history of heart disease. Patients with heart disease were older, predominantly male, and often had other comorbid conditions when compared with those without. Mortality was higher in patients with cardiac disease (29.7%; n = 1545 vs. 15.9%; n = 1797). However, following multivariable adjustment, this difference was not significant [adjusted risk ratio (aRR) 1.08, 95% confidence interval (CI) 1.02–1.15; P = 0.12 (corrected for multiple testing)]. Associations with in-hospital mortality by heart disease subtypes differed considerably, with the strongest association for heart failure (aRR 1.19, 95% CI 1.10–1.30; P Conclusion Considerable heterogeneity exists in the strength of association between heart disease subtypes and in-hospital mortality. Of all patients with heart disease, those with heart failure are at greatest risk of death when hospitalized with COVID-19. Serious cardiac complications are rare during hospitalization.

Background Computed Tomography Coronary Angiography (CTCA) is an effective non-invasive imaging modality for anatomo-functional assessment of coronary artery disease (CAD). Radiomics features have been used for diagnosis or outcome prediction, however, their potential value for characterizing flow limiting coronary lesions has not been explored. Purpose To assess whether application of novel radiomics and machine learning (ML) techniques on CTCA derived datasets improves characterization of functionally significant coronary lesions. Methods Consecutive patients with stable chest pain and intermediate pre-test likelihood for CAD, who underwent CTCA and PET-or SPECT-Myocardial Perfusion Imaging (MPI) respectively, were prospectively evaluated and included in the analysis. PET-MPI was considered abnormal when >1 contiguous segments showed both stress Myocardial Blood Flow ≤2.3mL/g/min and Myocardial Flow Reserve (MFR) ≤2.5 for 15O-water or Results A total of 292 coronary vessels (140 with corresponding PET-MPI data and 152 with SPECT MPI data) were analysed. Plaque burden and stenosis severity were the only independent predictors of impaired myocardial perfusion on PET-MPI, with an AUC = 0.749, (95% CI: 0.658–0.826). Stenosis severity, kurtosis, contrast, interquartile range and entropy were predictors of an abnormal PET-MPI result and their combination resulted in an AUC = 0.854, (95% CI: 0.775–0.914). The difference between the 2 models was statistically significant (p-diff: 0.02, 95% CI: 0.0165–0.194). Stenosis severity was the only predictor of a DR on SPECT-MPI, AUC = 0.624 (95% CI: 0.542–0.702). Small Dependence High Gray Level Emphasis, Cluster Prominence, Region Length, wavelet Median and square Median were predictors of a positive SPECT result, with AUC = 0.816, (95% CI: 0.745–0.875). The difference between the two models was statistically significant (p-diff: 0.006, 95% CI: 0.152–0.329) Conclusion Radiomic futures can be combined with anatomical and morphological characteristics of coronary lesions in CTCA imaging and provide valuable complementary information for characterizing functionally significant coronary lesions. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work was supported from European Regional Development Fund, Operational Programme “Competitiveness, Entrepreneurship and Innovation 2014-2022 (EPAnEK)”, titled: The Greek Research Infrastructure for Personalized Medicine (pMED-GR)

Introduction Use of serial coronary computed tomography angiography (CCTA) allows for the early assessment of coronary plaque progression which may aid in the prevention of major adverse cardiac events (MACE). However, assessment of serial CCTA is done by using anatomical landmarks for matching baseline and follow-up scans. Recently, a tool has been developed allowing for automatic quantification of plaque progression dynamics in serial CCTA utilizing plaque delineation. Purpose The aim of this study was to determine the thresholds that define whether there is plaque progression and/or regression. These thresholds depend on the contrast to noise ratio (CNR) which is an objective marker for scan quality as the latter impacts the plaque delineation. Methods Thresholds and CNR ratios were determined on 50 patients referred for a CCTA due to thoracic complaints. Two scan phases were selected from each patient in which maximum and minimum differences in plaque delineation were measured. Also, CNR was calculated separately for all three major epicardial coronary vessels. A total of 100 scans were analyzed in the current analysis accounting for a total of 300 coronary vessels. First, vessel and lumen wall delineation was done semi-automatically for all major epicardial coronary vessels. Secondly, manual drawings of 7 regions of interest (ROI) per scan were used to quantify scan quality which was defined using the CNR and calculated for each vessel separately. As plaque differences of two scans at the same moment in time should always be zero, the minimum and maximum difference in plaque delineation was used in these scans along with the CNR in order to create calibration graphs on which a linear regression analysis was performed (Figure 1, charts A & B). Inter-observer measurements were calculated using Pearson's correlation coefficient. Results A total of 300 coronary vessels were assessed at CCTA. Semi-automatic vessel and lumen wall delineation as well as CNR calculation was successful in all cases. Subsequent linear regression analysis performed on the CNR and maximal and minimal plaque delineation differences and taking into account the standard error of the estimate revealed the following formulas for minimum and maximum cut-off values: Max = [(0.660 − (002 × CNR)] + 0.349 Min = [(−1.028 + (0.012 × CNR)) − 0.61 The average CNR values was 13.4±3.6. Average maximum and minimum difference in plaque delineation was 0.7±0.3mm and −0.9±0.6mm respectively. The inter-observer correlation for CNR values was excellent yielding a correlation coefficient of 0.872 (p Conclusion Development of vessel-specific quality-based thresholds for the quantification and visualization of plaque progression dynamics as assessed by serial CCTA seems feasible and may aid in the early detection of atherosclerosis progression. Funding Acknowledgement Type of funding sources: None.

Background Previous studies have demonstrated that MMP-9 may be a predictor of atherosclerotic plaque instability and future adverse cardiovascular events, but longitudinal data on the association between MMP9 and coronary disease progression are lacking. Purpose This study is aimed at investigating whether MMP9 is associated with atherosclerotic plaque progression. Methods MMP9 serum levels were measured in stable patients with chronic coronary syndrome (CCS) undergoing coronary computed tomography angiography at baseline and after a period of 6.5±1.1 years of follow up to assess progression of Total, Fibrous, Fibro-fatty, Necrotic Core, and Dense Calcium plaque volume (PV). The relationship of serum MMP9 with plaque progression was assessed using linear regression analysis, adjusting for clinical variables including, age, sex, risk factors, medical therapy, LDL-C, TG/HDL-C ratio, hs-CRP, and the presence of obstructive CAD (>50% coronary stenosis in at least one major coronary vessels). Results A total of 157 patients (58±8 years of age; 66% males) were included in the analysis, with median MMP9 values of 135±186 mg/dL (mean ± SD). Annual changes of Total, Fibrous-Fatty and Necrotic Core PV were significantly different across MMP9 tertiles (Figure 1). Multivariable linear regression analysis demonstrated a positive association between serum levels of MMP9 and annual change of Total and Necrotic Core PV (Figure 1). Conclusion Among patients with CCS, MMP9 serum levels were an independent predictor of progression of coronary plaque burden and, in particular, of adverse plaque features, such as Necrotic Core PV. This association was robust and independent from baseline traditional cardiovascular risk factors and medications, supporting for MMP9 a role as a novel marker of residual coronary risk. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Horizon 2020 - Project “Simulation Modeling of coronary ARTery disease: a tool for clinical decision support–SMARTool”

Introduction Current primary prevention strategies in cardiovascular (CV) disease focus on initiating preventive interventions in people at high 10-year risk of CV mortality. However, initiating such strategies should be beneficial not only in the first 10 years, but throughout life. Established risk algorithms estimate the risk of 10-year CV mortality, but limited evidence is available about the relationship between 10-year and longer-term CV mortality. Purpose To compare cumulative incidence of CV mortality in a population cohort at 10- and 20-years follow-up, stratified by sex. Methods We analysed CV mortality at 10-years and 20-years follow-up using Kaplan-Meier estimates among men and women aged 39–70 years without baseline CV disease or diabetes mellitus in the large, prospective population-based EPIC-Norfolk cohort. CV mortality included death with as underlying or contributing cause ischaemic heart disease, heart failure, cerebrovascular disease or peripheral artery disease. Results We analysed data from 20,453 participants (56% women), with a mean age of 56±8 years, and median (IQR) follow-up of 22 (21–23) years. At baseline, there were no clinically relevant differences in CV risk factors between men and women. Overall cumulative CV mortality rate was 1.9% (384 deaths) in the first 10 years, and 7.3% (995 deaths) at 20 years follow-up (ratio 3.8). Among men, 10-year CV mortality was 2.9% (249 deaths), and 9.6% (785 deaths) at 20 years follow-up (ratio 3.3). Among women, CV mortality was 1.2% (135 deaths) at 10 year and 5.5% (594 deaths) at 20 years follow-up (ratio 4.6). Conclusion We observed an incremental increase in CV mortality beyond the 10-year scope of current established CV risk algorithms. At 20 years follow-up, CV mortality rates were 3–5 times higher compared with the first decade, indicating that 20-year CV mortality risk for both men and women cannot simply be estimated based on extrapolation of 10-year risk. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): EPIC-Norfolk is supported by programme grants from the Medical Research Council UK (MRC G0401527, MRC G0701863, MRC G1000143) and Cancer Research UK (CRUK 8257).

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NWO-grant Title (Dutch): Het centraal stellen van behandelvoorkeuren van de individuele patiënt met een chronische hartziekte. Subtitle: Persoonsgerichte zorg voor hartpatiënten Introduction Motivated patients are more likely to successfully improve unhealthy lifestyles. How patients perceive their risk factors and their willingness to improve is an integral part of this motivation. However, such preferences, and how they align with clinicians’ risk perception are seldom systematically assessed in patients with coronary artery disease (CAD). Purpose We aimed to investigate preferences in risk factor treatment in patients with CAD, and to compare this with clinicians’ perception of patients’ risks. Methods We administered a 10-item questionnaire on patients’ preferences on risk factor treatment in secondary prevention which was developed in consultation with end-users. We sent the questionnaire to approximately 450 patients who were referred to cardiac rehabilitation after recent ( Results A total of 296 patients completed the survey (66% of eligible respondents) at mean (SD) age 64 (10) years on median (IQR) 38 (25-53) days after discharge. Physical activity was much more frequently reported as risk factor by patients (P 55%) compared to clinicians (C 31%), followed by other disparities such as for high cholesterol (P 48% vs. C 36%) and overweight (P 46% vs. C 59%) (Figure 1). Patients were asked which of their perceived risk factors on Q1 was most important to improve (Q2) and for which they wanted help (Q3). Top-3 risk factors chosen for improvement were overweight (87%), physical inactivity (81%), and stress (79%), for which 75% required help with any risk factor, again most frequently with increasing physical activity (64%), overweight (59%) and stress (51%) (Figure 2). Motivation and confidence for improvement of risk factors were high: 87% were willing to adapt their lifestyles, with motivation rates of median (IQR) 8 (7-9) out of 10, and estimated chance for successful improvement of median (IQR) 7 (6-8) out of 10. Conclusion(s) Patients who recently suffered from coronary event are highly motivated to lose weight and increase physical inactivity. The use of these patient preferences by the clinician will enable compliance and outcomes with respect to weight loss and improved physical activity.

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Commission in the H2020 program: Project SMARTool, “Simulation Modeling of coronary ARTery disease: a tool for clinical decision support—SMARTool” Background and aims The coexistence of elevated plasma triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) may contribute to the residual cardiometabolic risk of coronary artery disease (CAD) independently of total cholesterol and low-density lipoprotein cholesterol (LDL-C) absolute plasma levels [1]. Aim of this study is to assess whether a high TG/HDL-C ratio is characterized by a specific lipidomics signature in statin users and its relationship with the coronary risk score defined by coronary computed tomography angiography (CTA). Methods TG/HDL-C ratio was calculated in 132 patients (68.8±7.7 years, 85 males) with suspected or known CAD referred to coronary CTA and receiving statins treatment in the last 6.3 ± 1.4 years before enrolment. Patients were grouped according to TG/HDL-C ratio quartiles: IQ (≤1.694), IIQ (1.695-2.399), IIIQ (2.400-3.281), and IVQ (>3.282). Coronary CTA exams were analysed according to the modified 17-segment American Heart Association classification [2] and interpretable segments were visually assessed for degree of stenosis and plaque composition. A comprehensive coronary risk score (CTA score) [3], previously validated as predictor of adverse outcome, was calculated in each patient. Except for subjects with normal arteries (CTA score = 0), all patients were classified into 3 groups of CTA score severity: low (score < 5), intermediate (score 5-20) and high (score > 20) risk [4]. Patient-specific plasma targeted lipidomics was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This approach allowed to quantify 69 circulating lipids encompassing six lipid classes (triacylglycerol [TG], phosphatidylcholine [PC], phosphatidylethanolamine [PE], ceramide [Cer], sphingomyelin [SM], cholesterol ester [CE]). Differential analysis was performed using TG/HDL-C and CTA score annotation. Results 18 altered lipid species in the group with higher TG/HDL-C ratio were also altered in the group with higher CTA risk score. This common set of lipids is composed of CE(16:0), CE(18:0), PC(38:2), 8 SM [SM(34:2), SM(38:2), SM(41:2), SM(41:1), SM(42:4), SM(42:3), SM(42:1), SM(43:3)], TG(52:1) and 6 PE [PE(34:0), PE(34:1), PE(34:2), PE(36:1), PE(36:2), PE(36:3)], and represents the lipidomics signature associating elevated plasma TG/HDL-C ratio with high CTA risk score in statin users. Conclusion In patients with stable CAD under statin treatment, a specific pattern of altered lipids, characterized by reduced plasma levels of cholesterol esters and sphingomyelins and increased levels of triacylglicerols and phosphatidylethanolamines, is associated with high TG/HDL-C ratio and high CTA score. This specific lipidomic signature identifies patients with higher residual cardiometabolic and coronary risk, not tackled by current lipid lowering therapy, unveiling possible new molecular targets of treatment.

Funding Acknowledgements Type of funding sources: None. Introduction Most risk models for patients with established atherosclerotic cardiovascular disease (ASCVD) calculate short-term risk of recurrent events and death, typically for a duration of 10 years. However, lifetime risk estimates may better support the healthcare professional in selecting patients for intensified preventive treatment (1). Also, a cross-sectional study suggested that communicating lifetime risk to ASCVD patients enhances risk perception and willingness for therapy (2). In the new ESC prevention guideline, however, 10-year risk estimates remain standard for ASCVD patients but the additional use of lifetime risk is recommended for communication in the shared decision-making process (3). Purpose We therefore aimed to compare estimates of 10-year with lifetime risk of recurrent ASCVD events or death, stratified by age. Methods We pooled individual-level data on risk factors from six large, recent prospective studies (RESPONSE 1 and 2, OPTICARE, EUROASPIRE IV and V and HELIUS). We included Dutch patients aged ≥45 years with a follow-up of ≥6 months after acute coronary syndrome or revascularisation. The SMART-REACH models were used to estimate the difference between 10-year and lifetime risk of recurrent myocardial infarction, stroke, or cardiovascular death, stratified by age ( Results In 3,230 ASCVD patients (24% women), mean age 61±8 years, at median follow-up 1.1 (IQR 1.0-1.8) years after index event, SMART-REACH 10-year risk was 23±11% versus lifetime 56±11%. (Figure 1) We found a considerable difference between 10-year and lifetime risk in patients aged 45-55 years (18±8% vs. 61±10%). Discrepancies decreased with increasing age, with similar estimates in the highest (75-85) age group. (Figure 2). Conclusion Lifetime risk of a limited set of cardiovascular outcomes rather than 10-year risk may provide a more complete estimate of future ASCVD disease burden, as especially in younger patients 10-year risk is usually low, even in the presence of risk factors.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Dutch Heart Foundation and ZonMw Goal setting within cardiac care: the effect of linking life goals to health goals on intention to change lifestyle in patients. Background Initiating and maintaining a healthy lifestyle is difficult and often needs several attempts. Reaching health goals may become easier if linked to life goals (see Fig.1). Life goals, also described as abstract, long-term goals, reflect objectives that matter to people personally. Guidelines recommend goal setting to realise behaviour change in patients with cardiovascular disease (CVD). However, research is inconclusive about whether positive effects of lifestyle interventions can be attributed to linking life goals to health goals or to other intervention elements. Purpose This experimental study examines the effect of linking a life goal to a health goal on intention to change lifestyle in patients with CVD. Methods Research panel members of a CVD patient association were recruited for the online study via advertisement on the association’s website. Patients were randomised and controlled into two groups: setting a health goal (HG) and setting a health goal linked to a life goal (+LG). Based on the Theory of Planned Behavior (see Fig.2) and previous research, main outcome measure ‘intention to change lifestyle’ was assessed using a visual analogue scale ranging 0-10 (low to high). Effect of group (HG vs +LG) on intention to change lifestyle (high vs low) was analysed using logistic regression. Gender, age, education level, and type of CVD were entered as possible effect modifiers. Results Patients (N=628) were mostly male (61%), with a mean age of 69±35 years, and medium (33%) or high (47%) education level. In both groups, HG and +LG, 47% of the patients expressed high intention to change lifestyle. Logistic regression showed no effect of group (HG vs +LG) on intention, OR:0.98 (95%CI: 0.72–1.35, p=0.92). Only education level appeared to be an effect modifier, X²(2):8.2, p=0.02; showing that linking a life goal to a health goal was effective in patients with a high education level. Contrary to this, setting a life goal negatively affected intention in patients with a low education level. Among patients with a high education level, percentage of 'high intention' was higher in the +LG group (57%) than in the HG group (45%). In contrast, among patients with a low education level, percentage of 'high intention' was higher in the HG group (48%) than in the +LG group (36%). Conclusions This study showed no main effect of linking a life goal to a health goal on patients’ intention to change lifestyle. Education level was found to be a significant effect modifier. Patients with a high education level significantly benefitted from linking a life goal to a health goal. Patients with lower education levels benefitted most from setting only a health goal. In conclusion, within practice, health care providers may personalise their approach towards goal setting based on patients’ education level.

Funding Acknowledgements Type of funding sources: None. Introduction New risk prediction models estimate and employ individual ‘treatment benefit’, which can be used to motivate patients with atherosclerotic cardiovascular disease (ASCVD) to quit smoking and to adhere to beneficial pharmacological interventions. However, this treatment benefit is usually calculated for a limited set of cardiovascular outcomes, i.e. years gained without myocardial infarction or stroke, while ignoring non-cardiovascular health benefits and pharmacological side- and adverse effects. Importantly, treatment effect size of medication is smaller in persistent smokers compared to non-smokers, because of the higher overall mortality of the smokers. By disregarding non-cardiovascular outcomes, the overall benefit of smoking cessation will be underestimated. Purpose We estimated and compared the treatment benefits – expressed as ‘gain in years without major cardiovascular events’ – of smoking cessation versus persistent smoking with targeted pharmaceutical interventions in patients with established ASCVD treated with anti-platelet agents, statins and anti-hypertensive drugs. Methods We pooled individual-level risk factors data from six large, recent prospective studies: RESPONSE 1 and 2, OPTICARE, EUROASPIRE IV and V and HELIUS. We included patients aged ≥45 years who persisted in smoking ≥6 months after acute coronary syndrome or revascularisation. The primary outcome was SMART-REACH estimated treatment benefit expressed as gain in years without a myocardial infarction or stroke. We compared the cardiovascular treatment benefit of smoking cessation versus the use of one or more pharmaceutical treatments: bempedoic acid, colchicine and PCSK9 inhibitors. Results We included 989 smokers with established ASCVD (23% female), with mean age of 60 (SD 8) years at median 1.2 (IQR 1.0-2.0) years post-index event. A mean of 4.81 (95%CI 4.73-4.89) event-free years would be gained through smoking cessation. Persistent smoking with maximal pharmaceutical treatment resulted in a comparable gain of 4.83 (95% CI 4.72-4.93) event-free years.(Figure) Conclusion The estimated lifetime treatment benefit of smoking cessation appeared to be comparable to the use of several pharmaceutical treatments combined, even when the analysis was limited to major cardiovascular events. This substantial health benefit underscores smoking cessation to be one of the most important actions to improve the overall health of patients with established ASCVD. To accurately compare treatment options, overall benefits and harms should be considered, in addition to the patients’ preferences, in a shared decision making process.

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Amsterdam UMC Background Despite a technically successful procedure, not all patients with severe aortic valve stenosis benefit from Transcatheter Aortic Valve Implantation (TAVI). Screening of patients at increased risk of adverse outcomes can improve treatment decisions. Studies in healthy older adults show that fat density on a Computed Tomography scan (CT) scan is a possible risk factor associated with weight loss and mortality. The association of fat density with mortality after TAVI is unknown. Objectives The aim of this study is to investigate the association of subcutaneous and visceral fat density with long-term mortality after TAVI, in addition to known risk factors. Methods Patients undergoing TAVI from January 2010 to January 2020 were included. Computed-tomography (CT) scans were made in all patients as work-up for the procedure. Deep-learning-based software was used to automatically determine subcutaneous and visceral fat density on available fat tissue at the transversal slice at the height of lumbar vertebra 3 (L3), see figure 1. Association with all-cause long-term mortality was determined with Kaplan-Meier curves, log-rank tests, and adjusted Cox regression models. In all analyses, patients in the highest tertile of fat density were compared to patients in the middle and lowest tertile. Two Cox regression models were made, model one adjusted for relevant confounders: age, sex, EuroSCORE-II, New York Heart Association score, chronic obstructive pulmonary disease, left ventricular ejection fraction, transfemoral access route, body mass index, and chronic kidney disease; and model two additionally including muscle mass and muscle density. Results In total, 1,404 patients were included, mean age was 80 ± 7 years and 53% were female. Median long-term follow up was 1,093 [IQR: 639 – 1,602] days. Unadjusted Kaplan-Meier curves showed that both subcutaneous fat density (Figure 2, log rank p Conclusion High subcutaneous and visceral fat density determined on the procedural CT-scan before the TAVI are independently associated with long-term mortality. These results show that future risk models in TAVI patients should take fat density into account.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Dutch Research Council (NWO) RAAK-PRO grant Background Fear of movement (kinesiophobia) after cardiac hospitalization is associated with low physical activity levels and reduced quality of life. Participation in cardiac rehabilitation (CR) improves psychological wellbeing and relieves kinesiophobia. However, little is known about the predictors of kinesiophobia and the impact of kinesiophobia on participation in CR. Purpose To identify predictors of kinesiophobia after (acute) cardiac hospitalization and to assess the impact of kinesiophobia on participation in CR. Methods We performed a longitudinal study in patients with coronary artery disease, acute heart failure or atrial fibrillation. At hospital discharge we collected demographic variables, cardiac disease history and administered questionnaires about kinesiophobia, cardiac anxiety, depression and psychological complexity (severity of psychological problems). Kinesiophobia was measured with the Tampa Scale for Kinesiophobia (TSK), scores >28 are considered `high levels of kinesiophobia’. At 3 months patients were followed up to evaluate participation in CR. We investigated (1) predictors of kinesiophobia at hospital discharge and (2) the impact of kinesiophobia on participation in CR at 3-months follow up, using two multivariable logistic regression models with backward elimination to identify predictors. Results In 149 patients (22% women), mean age 64.1 (±10.1) high levels of kinesiophobia were measured in 61 patients (40,9%). Higher age decreased the odds for kinesiophobia: OR: 0.95 (95%CI:0.89 – 0.99). Two variables increased the odds for kinesiophobia: higher levels of psychological complexity: OR: 1.27 (95%CI 1.01- 1.60) and cardiac anxiety: OR: 1.10 (95%CI: 1.02 – 1.19). The odds for participating in CR were decreased by kinesiophobia: OR: 0.91 (95%CI: 0.84 – 0.99) and higher age: OR: 0.92 (95%CI:0.86-0.98). Conclusion(s) Kinesiophobia at hospital discharge is associated with psychological complexity and negatively impacts participation in CR. This study emphasizes the need for early screening to identify those who are at risk of developing kinesiophobia which in turn can lead to non-adherence to CR.

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Amsterdam UMC - location AMC Background Physical activity is crucial to preserve muscle mass and muscle function, which is hard to regain at older age. Therefore, even short periods of physical inactivity can be harmful for older adults. Due to symptoms of aortic stenosis patients planned for an elective Transcatheter Aortic Valve Implantation (TAVI) treatment could be at risk of physical inactivity. Specifically, because many of these patients are already older and frail, this could be harmful for physical functioning and even mortality at the long-term. Purpose To determine physical activity in patients planned for TAVI, using a wearable. Methods Consecutive patients undergoing TAVI from January 2020 to September 2021 were included. All patients were asked to wear a Stepwatch activity monitor to objectively measure physical activity in the period before the TAVI. The Stepwatch is a valid tool to determine physical activity in frail and older adults, because it is able to detect slow or irregular movement. Patients were asked to wear the Stepwatch for seven consecutive days during every awake hour. By three complete days of at least 10 hours of wear time the data were included in the analysis. Two parameters were collected: the number of steps per day and activity time at moderate intensity. For number of steps per day patients were classified as extremely inactive (7500). For time at moderate intensity, it was determined how many patients did meet the activity guidelines (>150 min of moderate activity per week). Results In total 89 patients were included; mean age was 81 ± 5 years and 54% was male. Average number of steps per day were 6249 ± 2999. In total 19% (n=17) of the patients were extreme inactive, 67% (n=59) were inactive, and 15% (n=13) were active. Patients were moderate active for a median of 8 [IQR: 0 – 43] minutes per week. In total 6% (n=5) of the patients met the recommended guidelines of at least 150 minutes of moderate physical activity per week. Conclusion Older and frail patients with severe aortic stenosis planned for TAVI are mainly inactive. Most patients only moved at low intensity and a very small number of patients (6%) met the activity guidelines. The extremely low physical activity in patients waiting for TAVI, make them at high risk for muscle breakdown and adverse health outcomes at the longer term. (P)rehabilitation interventions should be developed to encourage patients with severe aortic stenosis to become more active during waiting time before TAVI.