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Abstract Background In previous studies the authors have found sick leave to be a predictor of future sick leave, unemployment and disability pension. Although sick leave reflects underlying health problems, some studies have suggested that sick leave may have consequences beyond the consequences of the underlying illness. However, few studies have aimed at studying consequences of sick leave while adjusting for ill health. This study aims to explore whether short-term sick leave increases the risk of future long-term sick leave, disability pension, and unemployment. Furthermore, we aim to control for the potentially confounding effects of physical and mental health status. Methods Data were gathered from the Stockholm Public Health Cohort (SPHC), restricted to 11,156 employed individuals (48.6% men) aged 18–59, without long-term sick leave, disability pension or in-patient care the year before inclusion (2002). These were followed-up with regard to unemployment, long-term sick leave, and disability pension in 2006 and 2007. Odds ratios (OR) with corresponding 95% confidence intervals (CI) were estimated by logistic regression, controlling for six different measures of health status (limiting long-standing illness, self-rated health, mental health, somatic disease, musculoskeletal pain and in-patient care) and socio-demographic factors. Results Results from the unadjusted analyses indicated increased risks of long-term sick leave (OR 2.00; CI 1.62-2.46) and short-term unemployment (OR 1.76; CI 1.35-2.29) for individuals exposed to more than one short-term sick-leave spell. There were no increased odds of long-term unemployment (OR 0.54; CI 0.28-1.04) or disability pension (OR 0.72; CI 0.42-1.24). After adjusting for the different measures of health status the odds ratio for short-term unemployment was not statistically significant (OR 1.29; CI 0.97-1.74). The odds ratios for the other outcomes slightly increased after adjustment for the used measures of health status. Conclusions The results support the assumption that short-term sick leave may have consequences for future sick leave beyond the effect of ill health. The results point to the importance of paying attention to short-term sick leave in order to prevent subsequent sickness absence.

Abstract Background Accurate diagnostic and monitoring tools for ulcerative colitis (UC) are missing. Our aim was to describe the proteomic profile of UC and search for markers associated with disease exacerbation. Therefore, we aimed to characterize specific proteins associated with inflamed colon mucosa from patients with acute UC using mass spectrometry-based proteomic analysis. Methods Biopsies were sampled from rectum, sigmoid colon and left colonic flexure from twenty patients with active proctosigmoiditis and from four healthy controls for proteomics and histology. Proteomic profiles of whole colonic biopsies were characterized using 2D-gel electrophoresis, and peptide mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was applied for identification of differently expressed protein spots. Results A total of 597 spots were annotated by image analysis and 222 of these had a statistically different protein level between inflamed and non-inflamed tissue in the patient group. Principal component analysis clearly grouped non-inflamed samples separately from the inflamed samples indicating that the proteomic signature of colon mucosa with acute UC is strong. Totally, 43 individual protein spots were identified, including proteins involved in energy metabolism (triosephosphate isomerase, glycerol-3-phosphate-dehydrogenase, alpha enolase and L-lactate dehydrogenase B-chain) and in oxidative stress (superoxide dismutase, thioredoxins and selenium binding protein). Conclusions A distinct proteomic profile of inflamed tissue in UC patients was found. Specific proteins involved in energy metabolism and oxidative stress were identified as potential candidate markers for UC.

Abstract Background Although illness is an important cause of sick leave, it has also been suggested that non-medical risk factors may influence this association. If such factors impact on the period of decision making, they should be considered as triggers. Yet, there is no empirical support available. The aim was to investigate whether recent exposure to work-related psychosocial events can trigger the decision to report sick when ill. Methods A case-crossover design was applied to 546 sick-leave spells, extracted from a Swedish cohort of 1 430 employees with a 3-12 month follow-up of new sick-leave spells. Exposure in a case period corresponding to an induction period of one or two days was compared with exposure during control periods sampled from workdays during a two-week period prior to sick leave for the same individual. This was done according to the matched-pair interval and the usual frequency approaches. Results are presented as odds ratios (OR) with 95% confidence intervals (CI). Results Most sick-leave spells happened in relation to acute, minor illnesses that substantially reduced work ability. The risk of taking sick leave was increased when individuals had recently been exposed to problems in their relationship with a superior (OR 3.63; CI 1.44-9.14) or colleagues (OR 4.68; CI 1.43-15.29). Individuals were also more inclined to report sick on days when they expected a very stressful work situation than on a day when they were not under such stress (OR 2.27; CI 1.40-3.70). Conclusions Exposure to problems in workplace relationships or a stressful work situation seems to be able to trigger reporting sick. Psychosocial work-environmental factors appear to have a short-term effect on individuals when deciding to report sick.

Abstract Background Young car drivers run a higher risk of road traffic crash and injury not only because of their lack of experience but also because of their young age and their greater propensity for adopting unsafe driving practices. Also, low family socioeconomic position increases the risk of crash and of severe crash in particular. Whether this holds true for young unlicensed drivers as well is not known. Increasing attention is being drawn to the prevalence and practice of unlicensed driving among young people as an important contributor to road traffic fatalities. Methods This is a population-based cohort study linking Swedish national register data for a cohort of 1 616 621 individuals born between 1977 and 1991. Crash circumstances for first-time road traffic crash (RTC) were compared considering licensed and unlicensed drivers. The socioeconomic distribution of injury was assessed considering household socioeconomic position, social welfare benefits, and level of urbanicity of the living area. The main outcome measure is relative risk of RTC. Results RTCs involving unlicensed drivers were over-represented among male drivers, suspected impaired drivers, severe injuries, crashes occurring in higher speed limit areas, and in fair road conditions. Unlicensed drivers from families in a lower socioeconomic position showed increased relative risks for RTC in the range of 1.75 to 3.25. Those living in rural areas had an increased relative risk for a severe RTC of 3.29 (95% CI 2.47 - 4.39) compared to those living in metropolitan areas. Conclusions At the time of the crash, young unlicensed drivers display more risky driving practices than their licensed counterparts. Just as licensed drivers, unlicensed young people from low socioeconomic positions are over-represented in the most severe injury crashes. Whether the mechanisms lying behind those similarities compare between these groups remains to be determined.

Abstract Background The role of HNF4α has been extensively studied in hepatocytes and pancreatic β-cells, and HNF4α is also regarded as a key regulator of intestinal epithelial cell differentiation. The aim of the present work is to identify novel HNF4α target genes in the human intestinal epithelial cells in order to elucidate the role of HNF4α in the intestinal differentiation progress. Methods We have performed a ChIP-chip analysis of the human intestinal cell line Caco-2 in order to make a genome-wide identification of HNF4α binding to promoter regions. The HNF4α ChIP-chip data was matched with gene expression and histone H3 acetylation status of the promoters in order to identify HNF4α binding to actively transcribed genes with an open chromatin structure. Results 1,541 genes were identified as potential HNF4α targets, many of which have not previously been described as being regulated by HNF4α. The 1,541 genes contributed significantly to gene ontology (GO) pathways categorized by lipid and amino acid transport and metabolism. An analysis of the homeodomain transcription factor Cdx-2 (CDX2), the disaccharidase trehalase (TREH), and the tight junction protein cingulin (CGN) promoters verified that these genes are bound by HNF4α in Caco2 cells. For the Cdx-2 and trehalase promoters the HNF4α binding was verified in mouse small intestine epithelium. Conclusion The HNF4α regulation of the Cdx-2 promoter unravels a transcription factor network also including HNF1α, all of which are transcription factors involved in intestinal development and gene expression.

Abstract Background Sudden emotions may interfere with mechanisms for keeping balance among the elderly. The aim of this study is to analyse if emotional stress and specifically feelings of anger, sadness, worries, anxiety or stress, can trigger falls leading to hip or pelvic fracture among autonomous older people. Methods The study applied the case-crossover design and was based on data gathered by face to face interviews carried out in Stockholm between November 2004 and January 2006 at the emergency wards of two hospitals. Cases (n = 137) were defined as persons aged 65 and older admitted for at least one night due to a fall-related hip or pelvic fracture (ICD10: S72 or S32) and meeting a series of selection criteria. Results are presented as relative risks with 95% confidence intervals. Results There was an increased risk for fall and subsequent hip or pelvic fracture for up to one hour after emotional stress. For anger there was an increased relative risk of 12.2 (95% CI 2.7–54.7), for sadness of 5.7 (95% CI 1.1–28.7), and for stress 20.6 (95% CI 4.5–93.5) compared to periods with no such feelings. Conclusion Emotional stress seems to have the potential to trigger falls and subsequent hip or pelvic fracture among autonomous older people. Further studies are needed to clarify how robust the findings are – as the number of exposed cases is small – and the mechanisms behind them – presumably balance and vision impairment in stress situation.

The use of temporary mechanical circulatory support (tMCS) in cardiogenic shock patients has increased during the last decades with most management strategies relying on observational studies and expert opinion, including hemodynamic monitoring, device selection and timing of support institution/duration. In this context, imaging has a pivotal role throughout the patient pathway, from identification to initiation, monitoring and weaning. This manuscript summarizes the consensus of an expert panel from the European Society of Cardiology Association for Acute CardioVascular Care, the European Association of CardioVascular Imaging and the European Extracorporeal Life Support Organization, providing the rationale for and practical guidance of imaging to tMCS based on existing evidence and consensus on best current practice., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The relationship between speckle tracking assessed global longitudinal strain (GLS) and Doppler-based echocardiography with basic physiological markers of cardiac function derived from pressure-volume loops is poorly elucidated., Objective: We aimed to describe the association between LS and Doppler-based echocardiography and direct measurements of central haemodynamic parameters from conductance catheter-based pressure-volume loops in an animal model with increasing left ventricular (LV) dysfunction., Methods: 12 Danish landrace female pigs (75-80 kg) were used. All instrumentations were performed percutaneously, including the conductance catheter in the LV. Progressive LV dysfunction was induced by embolisation through the left main coronary artery with microspheres every 3 min until a >50% reduction in cardiac output (CO) or mixed venous saturation (SvO 2 ), compared with baseline, or SvO 2 <30%. Echocardiography was performed at baseline and 90 s after each injection., Results: With progressive LV dysfunction, mean CO decreased from 5.6±0.9 L/min to 2.1±0.9 L/min, and mean SvO 2 deteriorated from 61.1±7.9% to 35.3±6.1%. Mean LS and LV outflow tract velocity time integral (LVOT VTI) declined from -13.8±3.0% to -6.1±2.0% and 16.9±2.6 cm to 7.8±1.8 cm, respectively. LS and LVOT VTI showed the strongest correlation to stroke work in unadjusted linear regression (r 2 =0.53 and r 2 =0.49, respectively). LS correlated significantly with stroke volume, end-systolic elastance, systolic blood pressure, ventriculo-arterial coupling and arterial elastance., Conclusion: In an animal model of acute progressive LV dysfunction, echocardiographic and conductance catheter-based measurements changed significantly. LS and LVOT VTI displayed the earliest and the largest alterations with increased myocardial damage and both correlated strongest with stroke work., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Heart failure with preserved ejection fraction (HFpEF) is associated with an array of central and peripheral haemodynamic and metabolic changes. The exact pathogenesis of exercise limitation in HFpEF remains uncertain. Our aim was to compare lactate accumulation and central haemodynamic responses to exercise in patients with HFpEF, non-cardiac dyspnoea (NCD), and healthy volunteers., Methods and Results: Right heart catheterization with mixed venous blood gas and lactate measurements was performed at rest and during symptom-limited supine exercise. Multivariable analyses were conducted to determine the relationship between haemodynamic and biochemical parameters and their association with exercise capacity. Of 362 subjects, 198 (55%) had HFpEF, 103 (28%) had NCD, and 61 (17%) were healthy volunteers. This included 139 (70%) females with HFpEF, 77 (75%) in NCD (P = 0.41 HFpEF vs. NCD), and 31 (51%) in healthy volunteers (P < 0.001 HFpEF vs. volunteers). The median age was 71 (65, 75) years in HFpEF, 66 (57, 72) years in NCD, and 49 (38, 65) years in healthy volunteers (HFpEF vs. NCD or volunteer, both P < 0.001). Peak workload was lower in HFpEF compared with healthy volunteers [52 W (interquartile range 31-73), 150 W (125-175), P < 0.001], but not NCD [53 W (33, 75), P = 0.85]. Exercise lactate indexed to workload was higher in HFpEF at 0.08 mmol/L/W (0.05-0.11), 0.06 mmol/L/W (0.05-0.08; P = 0.016) in NCD, and 0.04 mmol/L/W (0.03-0.05; P < 0.001) in volunteers. Exercise cardiac index was 4.5 L/min/m 2 (3.7-5.5) in HFpEF, 5.2 L/min/m 2 (4.3-6.2; P < 0.001) in NCD, and 9.1 L/min/m 2 (8.0-9.9; P < 0.001) in volunteers. Oxygen delivery in HFpEF was lower at 1553 mL/min (1175-1986) vs. 1758 mL/min (1361-2282; P = 0.024) in NCD and 3117 mL/min (2667-3502; P < 0.001) in the volunteer group during exercise. Predictors of higher exercise lactate levels in HFpEF following adjustment included female sex and chronic kidney disease (both P < 0.001)., Conclusions: HFpEF is associated with reduced exercise capacity secondary to both central and peripheral factors that alter oxygen utilization. This results in hyperlactataemia. In HFpEF, plasma lactate responses to exercise may be a marker of haemodynamic and cardiometabolic derangements and represent an important target for future potential therapies., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Randomized studies attempting to prove benefit of mechanical circulatory support in cardiogenic shock have failed to reduce the risk of death. Further, both registry and randomized data suggest increased rates of serious complications associated with these devices. This last review in the supplement discusses current evidence and provides a perspective on how the scientific community could advance cardiogenic shock research focused on mechanical circulatory support., Competing Interests: Conflict of interest: J.M. received grant funding from Abiomed and Novo Nordic Foundation, honoraria for lectures Abiomed, Boehringer Ingelheim, Abbott, and Orion and travel support from Abiomed. N.M. received grant funding from Abiomed and Boston Scientific, consulting fees from Abiomed, B. Braun, Boston Scientific, Pfizer, and Sanofi Genzyme; and honoraria from Abbott, Abiomed, AstraZeneca, Bayer, B. Braun, Boston Scientific, Edwards Life Science, Medtronic, Novartis, Pfizer, and Sanofi Genzyme. F.P. received manuscript support from Abiomed, consulting fees from Abiomed, honoraria from Abiomed, and advisory board for Abiomed. H.T. declares a leadership role for German Cardiac Society (President)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: To describe characteristics of patients admitted with refractory cardiac arrest for possible extracorporeal cardiopulmonary resuscitation (ECPR) and gain insight into the reasons for refraining from treatment in some., Methods: Nationwide retrospective cohort study involving all tertiary centres providing ECPR in Denmark. Consecutive patients admitted with ongoing chest compression for evaluation for ECPR treatment were enrolled. Presenting characteristics, duration of no-flow and low-flow time, end-tidal carbon dioxide (ETCO 2 ), lactate and pH, and recording of reasons for refraining from ECPR documented by the treating team were recorded. Outcomes were survival to intensive care unit admission and survival to hospital discharge., Results: Of 579 patients admitted with refractory cardiac arrest for possible ECPR, 221 patients (38%) proceeded to ECPR and 358 patients (62%) were not considered candidates. Median prehospital low-flow time was 70 min (IQR 56 to 85) in ECPR patients and 62 min (48 to 81) in no-ECPR patients, p<0.001. Intra-arrest transport was more than 50 km in 92 (42%) ECPR patients and 135 in no-ECPR patients (38%), p=0.25. The leading causes for not initiating ECPR stated by the treating team were duration of low-flow time in 39%, severe metabolic derangement in 35%, and in 31% low ETCO 2 . The prevailing combination of contributing factors were non-shockable rhythm, low ETCO 2 , and metabolic derangement or prehospital low-flow time combined with low ETCO 2 . Survival to discharge was only achieved in six patients (1.7%) in the no-ECPR group., Conclusions: In this large nationwide study of patients admitted for possible ECPR, two-thirds of patients were not treated with ECPR. The most frequent reasons to abstain from ECPR were long duration of prehospital low-flow time, metabolic derangement and low ETCO 2 ., Competing Interests: Competing interests: JEM reports speaker fees and grants from Abiomed and served at the scientific advisory board for Boehringer Ingelheim, outside the submitted work. CH reports grants from the Lundbeck Foundation and speaker’s honoraria from Abiomed, outside the submitted work. JK reports non-financial participation in the advisory board for the CoCa Trial. CJT is supported by an unrestricted research grant from the Danish Heart Foundation. The remaining authors have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Haemodynamic exercise testing is important for evaluating patients with dyspnoea on exertion and preserved ejection fraction. Despite very different pathologies, patients with pressure (aortic stenosis (AS)) and volume (mitral regurgitation (MR)) overload and diastolic dysfunction after recent acute myocardial infarction (AMI) reach similar filling pressure levels with exercise. The pressure-flow relationships (the association between change in cardiac output (∆CO) and change in pulmonary arterial wedge pressure (∆PAWP) may provide insight into haemodynamic adaptation to exercise in these groups., Methods and Results: One hundred sixty-eight subjects aged >50 years with a left ventricular ejection fraction of ≥50% underwent invasive exercise testing. They were enrolled in four different studies: AS (40 patients), AMI (52 patients), MR (43 patients) and 33 healthy subjects. Haemodynamic data were measured at rest, at 25 W, 75 W and at peak exercise. In all groups, PAWP increased with exercise. The greatest increase was observed in patients with AMI (from 12.7±3.9 mm Hg to 33.1±8.2 mm Hg, p<0.0001) and patients with AS (from 11.8±3.9 mm Hg to 31.4±6.1 mm Hg, p<0.0001), and the smallest was observed in healthy subjects (from 8.3±2.4 mm Hg to 21.1±7.5 mm Hg, p<0.0001). In all groups, the relative pressure increase was greatest at the beginning of the exercise. CO increased most in healthy patients (from 5.3±1.1 to 16.0±3.0 L/min, p<0.0001) and least in patients with AS (from 5.3±1.2 L/min to 12.4±2.6 L/min, p<0.0001). The pressure-flow relationships (∆PAWP/∆CO) and differed among groups (p = 0.02). In all groups, the pressure-flow relationship was steepest in the initial phase of the exercise test. The AMI and AS groups (2.3±1.2 mm Hg/L/min and 3.0±1.3 mm Hg/L/min, AMI and AS, respectively) had the largest overall pressure-flow relationship; the healthy group had the smallest initially and at peak exercise (1.3±1.1 mm Hg/L/min) followed by MR group (1.9±1.4 mm Hg/L/min)., Conclusion: The pressure-flow relationship was steepest in the initial phase of the exercise test in all groups. The pressure-flow relationship differs between groups., Trial Registration Numbers: NCT01974557, NCT01046838, NCT02961647 and NCT02395107., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To describe the occurrence of significant pericardial effusion, and to investigate characteristics associated with pericardial effusion within three months following heart valve surgery., Methods: A retrospective, observational cohort study including adult patients undergoing heart valve surgery at Odense University Hospital from August 2013 to November 2017. Data were gathered from The Western Denmark Heart Registry and electronic patient records.Cox proportional hazard models were used to investigate the associations between characteristics associated with significant pericardial effusion during index admission and within 3 months. Results are presented as HR with 95% CI., Results: In total, 1460 patients were included (70% men, median age 71 years (IQR 63-76)) and of those, n=230 patients (16%) developed significant pericardial effusion.EuroScore II was significantly associated with an increased risk of pericardial effusion during index admission and associated with a lower risk following discharge (index admission HR 1.05, 95% CI 1.02 to 1.08, after discharge HR 0.80, 95% CI 0.69 to 0.92). Increasing age (HR 0.97, 95% CI 0.95 to 0.98 per year) and concomitant coronary artery bypass grafting versus isolated valve surgery (HR 0.58, 95% CI 0.35 to 0.97) were significantly associated with a reduced risk of pericardial effusions in both periods. Being a man (HR 2.30, 95% CI 1.32 to 4.01) and aortic valve disease versus mitral valve disease (HR 2.16, 95% CI 1.20 to 3.90) were significantly associated with an increased risk after discharge., Conclusion: Significant pericardial effusions requiring drainage were present in 16% of cases following heart valve surgery, and different clinical characteristics were associated with the development of effusion., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background Although a rapid rise in left atrial pressure during exertion is considered pathognomonic of heart failure with preserved ejection fraction (HFpEF), the fundamental circulatory determinants of this response are not clear, impacting upon the development of more effective therapies. We aimed to comprehensively describe the circulatory mechanics of patients with HFpEF at rest and during exercise in comparison with controls. Methods and Results We performed simultaneous right-heart catheterization and echocardiography at rest and during exercise in 22 healthy control volunteers and 60 patients with confirmed HFpEF. Using detailed individual patient-level hemodynamic and left ventricular ejection fraction data we performed computer simulations to evaluate the circulatory parameters including the estimated stressed blood volumethat contribute to the resting and exercise pulmonary capillary pressure. At rest and during exercise, left ventricular stiffness (V 30 , the end-diastolic pressure-volume relationship at a filling pressure of 30 mm Hg), left ventricular elastance, and arterial elastance were all significantly greater in HFpEF than in controls. Stressed blood volume was significantly greater in HFpEF (26.9±5.4 versus 20.2±4.7 mL/kg, P <0.001), becoming even more pronounced during exercise (40.9±3.7 versus 27.5±7.0 mL per 70 kg, P <0.001). During exercise, the magnitude of the change in stressed blood volume ( r =0.67, P <0.001) and left ventricular stiffness ( r =-0.44, P <0.001) were key determinants of the rise in pulmonary capillary wedge pressure. Further detailed modeling studies showed that the hemodynamic response to exercise results from a complex non-linear interaction between circulatory parameters. Conclusions The circulatory determinants of HFpEF physiology are complex. We identified stressed blood volume at rest and during exercise is a novel, key factor, therebyrepresenting an important potential therapeutic target.

Aims: More patients survive myocardial infarction (MI) with cardiogenic shock (CS), but long-term outcome data are sparse. We aimed to examine rates of heart failure hospitalization and mortality in MI hospital survivors., Methods and Results: First-time MI patients with and without CS alive until discharge were identified using Danish nationwide registries between 2005 and 2017. One-, 5-, and 1- to 5-year rates of heart failure hospitalization and mortality were compared using landmark cumulative incidence curves and Cox regression models. We identified 85 865 MI patients of whom 2865 had CS (3%). Cardiogenic shock patients were of similar age as patients without CS (median age years: 68 vs. 67), and more were men (70% vs. 65%). Cardiogenic shock was associated with a higher 5-year rate of heart failure hospitalization compared with patients without CS [40% vs. 20%, adjusted hazard ratio (HR) 2.90 (95% confidence interval (CI) 2.67-3.12)]. The increased rate of heart failure hospitalization was evident after 1 year and in the 1- to 5-year landmark analysis among 1-year survivors. All-cause mortality was higher at 1 year among CS patients compared with patients without CS [18% vs. 8%, adjusted HR 3.23 (95% CI 2.95-3.54)]. However, beyond the first year, the mortality for CS was not markedly different compared with patients without CS [12% vs. 13%, adjusted HR 1.15 (95% CI 1.00-1.33)]., Conclusion: Among MI hospital survivors, CS was associated with a markedly higher rate of heart failure hospitalization and 1-year mortality compared with patients without CS. However, among 1-year survivors, the remaining 5-year mortality was similar for MI patients with and without CS., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: First-phase ejection fraction (EF1), the left ventricular (LV) ejection fraction (EF) until the time of peak transaortic velocity, is a novel marker of subclinical LV dysfunction able to predict adverse events in aortic stenosis (AS). This study investigated the association between end-systolic wall stress (ESWS) and EF1 in severe AS, as well as the prognostic value of EF1 in severe asymptomatic AS., Methods: Two prospectively gathered cohorts of 94 asymptomatic patients and 108 symptomatic patients scheduled for aortic valve replacement (AVR), all with severe AS (aortic valve area <1 cm 2 ) were stratified according to the median value of EF1 (33%). EF1 was defined as the EF at peak transaortic velocity. Asymptomatic patients were followed up for 3 years for the combined end-point of death, AVR or admission with heart failure., Results: EF1 correlated with EF and was inversely associated with ESWS. In multivariate regression analysis, ESWS (p<0.001) and replacement fibrosis measured by MRI (p=0.02) were associated with EF1. Among asymptomatic patients, EF1 above the median was associated with the combined primary endpoint (HR=0.53 (95% CI 0.33 to 0.87)), while global longitudinal strain and EF were not. Among 42 patients with discordant AS (mean gradient <40 mm Hg), EF1 above median was associated with the primary endpoint (HR 0.28 (95% CI 0.12 to 0.61))., Conclusion: EF1 is an afterload-dependent measure that is associated with events in patients with asymptomatic severe AS. The afterload dependency of EF1 may be useful in timing of risk stratification in patients with discordant AS., Trial Registration Numbers: NCT02395107 and NCT02316587., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To describe the contemporary trends in the use of mechanical circulatory support (MCS) in patients with acute myocardial infarction and cardiogenic shock (AMICS). To evaluate survival benefit with early application of intra-aortic balloon pump (IABP) or Impella CP., Methods: A cohort study of all consecutive patients with AMICS undergoing percutaneous coronary intervention (PCI) <24 hours of symptom onset (early PCI) in southeastern Denmark from 2010 to 2017. A matched case-control study comparing 30-day mortality between patients receiving early-IABP or early-Impella CP and their respective control group. Controls were matched on age, left ventricular ejection fraction, arterial lactate, estimated glomerular filtration rate and cardiac arrest before PCI. Early-IABP/Impella CP was defined as applied before PCI if shock developed pre-PCI, or immediately after PCI if shock developed during PCI., Results: 903 patients with AMICS undergoing early PCI were identified. Use of MCS decreased from 50% in 2010 to 25% in 2017, p for trend of <0.001. The IABP was abandoned in 2012 and replaced mostly by Impella CP. Patients receiving MCS in 2013-2017 had more compromised haemodynamics compared with patients receiving MCS in 2010-2012. 40 patients received early IABP, and 40 patients received early Impella CP. Only the group receiving early Impella CP was associated with lower 30-day mortality compared with their matched control group (30-day mortality 40% vs 77.5%, plog-rank of<0.001)., Conclusion: Use of MCS decreased by 50% from 2010 to 2017. Patients receiving MCS had more compromised haemodynamics in recent years. Early application of Impella CP was associated with reduced 30-day mortality compared with a matched control group., Competing Interests: Competing interests: OKLH and NLJU received travel compensation from Abiomed. JEM received research grants and speaker’s fee from Abiomed., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: In aortic stenosis (AS), there is poor association between symptoms and conventional markers of AS severity or left ventricular (LV) systolic function. This may reflect that symptoms arise from LV diastolic dysfunction or that aortic valve area (AVA) and transvalvular gradient do not reflect afterload. We aimed to study the impact of afterload (end-systolic wall stress [ESWS]) on the presence of symptoms in AS and to test whether symptoms are related to increased ESWS or LV remodelling., Methods and Results: In a prospective study, ESWS was estimated by measuring LV wall thickness from MRI and estimated LV end systolic pressure from echocardiographic mean gradient and systolic blood pressure in 78 patients with severe AS scheduled for aortic valve replacement and 91 patients with asymptomatic severe AS. Symptomatic patients had lower indexed AVA (0.40±0.11 vs 0.45±0.09 cm 2 /m 2 , p=0.009). They had undergone more extensive remodelling (MRI LV mass index [LVMi]: 85±24 vs 69±17 g/m 2 , p<0.0001), had higher tricuspid regurgitant gradient (24±8 mm Hg vs 19 ± 7 mm Hg, p=0.0001) and poorer global longitudinal strain (-15.6±3.8 vs -19.9±3.2%, p<0.0001). ESWS was higher among symptomatic patients (96±51 vs 76±25 kdynes/cm 2 , p=0.003). Multivariate logistic regression identified echocardiographic relative wall thickness, tricuspid gradient, mitral deceleration time, early diastolic strain rate, MRI LVMi, MRI LV end-diastolic volume index and ESWS as independently associated with being symptomatic., Conclusion: ESWS can be estimated from multimodality imaging combining MRI and echocardiography. It is correlated with LV remodelling and neurohormonal activation and is independently associated with symptomatic status in AS., Competing Interests: Competing interests: None declared.

Objective: To assess the association between cardiac morphology and function assessed with cardiac MRI (CMRI) and haemodynamics at rest and during exercise in patients with primary mitral regurgitation (MR)., Methods: In an observational study, subjects with significant primary MR (N = 46) with effective regurgitant orifice ≥ 0.30 cm 2 and left ventricular (LV) ejection fraction > 60% were examined with right heart catheterisation during rest and exercise and CMRI at rest. End-diastolic pressure volume relationship (EDPVR) was assessed using a single beat method using pulmonary capillary wedge pressure (PCWP) and end-diastolic volume. Patients were divided according to normal PCWP at rest (> 12 mm Hg) and with exercise (> 28 mm Hg). Results: Resting regurgitant volume correlated positively with resting PCWP, (r = 0.42, p = 0.002). However, with exercise no association between PCWP and regurgitant volume was seen (r = 0.09, p = 0.55). At rest left atrial (LA) maximal, minimal and volume index at atrial contraction correlated positively with PCWP (r = 0.60; r = 0.55; r = 0.58, all p < 0.001); in contrast none of these correlated with exercise PCWP (all p > 0.2). EDPVR in patients with high PCWP at rest was shifted towards higher volumes for the same pressures. The opposite was seen for patients with high PCWP during exercise where estimated volumes were smaller for the same pressure than patients with normal exercise PCWP., Conclusion: In patients with significant MR the degree of regurgitation and LA dilatation is associated with resting PCWP. However, with exercise this association disappears. Estimation of EDPVR suggests lower LV compliance in patients where PCWP is increased with exercise., Clinical Trial Registration: URL: https://clinicaltrials.gov/ct2/show/NCT02961647?term=HEMI&rank=1. ID: NCT02961647., Competing Interests: Competing interests: None declared.

We present two cases of females in their 40s presenting with biventricular heart failure being the consequence of a large arteriovenous fistula. Both patients had undergone abdominal surgery several years prior to the heart failure event with the initial finding of moderate pulmonary hypertension and high-output heart failure. CT revealed a large arteriovenous fistula between the common iliac artery and vein which subsequently was closed percutaneously., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Management of patients requiring temporary, mechanical hemodynamic support during high- risk percutaneous coronary intervention (PCI) or in cardiogenic shock is rapidly evolving. With the availability of the Impella 2.5, CP, 5.0, LD, and RP percutaneous mechanical circulatory support devices, there is a need for continued surveillance of outcomes. Three factors underline the importance of a registry for these populations. First, large randomized trials of hemodynamic support, involving cardiogenic shock, are challenging to conduct. Second, there is increasing interest in the use of registries to provide "real-world" experience and to allow the flexibility to evaluate individual patient uses and outcomes. Third, current, large databases have not captured the specific impact of mechanical support treatment of cardiogenic shock. The predecessor to the catheter-based ventricular assist devices registry, known as USpella, began in 2009 with paper data acquisition but beginning in 2011 transferred to electronic data capture, enrolling 3,339 patients through 2016. Throughout, registry data have been used to assess the outcomes of Impella therapy, leading to 8 publications and 4 Food and Drug Administration premarket approvals covering multiple indications and Impella devices. Going forward, the registry will continue to assess not only in-hospital outcomes but long-term follow-up to 1 year. In addition, data management will be enhanced to assess quality and clinical experiences. The registry will also provide a mechanism for postmarketing surveillance. This manuscript reviews the ongoing catheter-based ventricular assist devices registry design, management, and contributions of the registry data. The upgraded registry will provide a more robust opportunity to assess acute and late outcomes of current and future device use worldwide., Condensed Abstract: The current catheter-based ventricular assist devices registry is an international database documenting outcomes with temporary Impella hemodynamic support. The registry has supported 8 publications and 4 Food and Drug Administration premarket approvals since its inception in 2009. The current registry is more robust containing outcomes up to 1 year postprocedure., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We report a case of a 66-year-old man with known ischaemic heart disease, diabetes mellitus and stage 4 kidney disease who was admitted to our tertiary centre with shortness of breath and atrial flutter. Transoesophageal echocardiography (TOE) was without suspicion of endocarditis. During hospitalisation, the patient suffered a nosocomial infection in a peripheral vascular catheter caused by Staphylococcus aureus. TOE after positive blood cultures revealed a new vegetation on the pulmonary valve that resolved after antibiotic treatment., (2015 BMJ Publishing Group Ltd.)

Background: Renal dysfunction is associated with a variety of cardiac alterations including left ventricular (LV) hypertrophy, LV dilation, and reduction in systolic and diastolic function. It is common and associated with an increased mortality risk in heart failure (HF) patients. This study was designed to evaluate whether severe diastolic dysfunction contribute to the increased mortality risk observed in HF patients with renal dysfunction., Methods: Using Cox Proportional Hazard Models on data (N = 669) from the EchoCardiography and Heart Outcome Study (ECHOS) study we evaluated whether estimated glomerular filtration rate (eGFR) was associated with mortality risk before and after adjustment for severe diastolic dysfunction. Severe diastolic dysfunction was defined by a restrictive left ventricular filling pattern (RF) (=deceleration time < 140 ms) by Doppler echocardiography., Results: Median eGFR was 58 ml/min/1.73 m², left ventricular ejection fraction was 33% and RF was observed in 48%. During the 7 year follow up period 432 patients died. Multivariable adjusted eGFR was associated with similar mortality risk before (Hazard Ratio(HR)(eGFR 10 ml increase): 0.94 (95% CI: 0.89-0.99, P = 0.024) and after (HR(eGFR 10 ml increase): 0.93 (0.89-0.99), P = 0.012) adjustment for RF (HR: 1.57 (1.28-1.93), P < 0.001)., Conclusions: In patients admitted with HF RF does not contribute to the increased mortality risk observed in patients with a decreased eGFR. Factors other than severe diastolic dysfunction may explain the association between renal function and mortality risk in HF patients.

Aims: This study investigated the association between invasive and non-invasive estimates of left ventricular (LV) filling pressure and exercise capacity, in order to find new potential candidates for risk markers in severe aortic valve stenosis (AS)., Methods and Results: Twenty-nine patients with AS, aortic valve area (AVA) < 1 cm(2), performed a symptom-limited multistage supine bicycle exercise test. Immediately before the exercise test, the pulmonary capillary wedge pressure (PCWP), Doppler index for LV filling (E/e'), and left atrial (LA) volume were measured. Symptomatic status was determined by senior staff doctors blinded to the results of this study. All patients terminated the exercise test because of dyspnoea. There were no significant differences in AVA between asymptomatic patients (n = 9) and symptomatic patients (n = 20), and AVA did not correlate with exercise capacity (r = -0.16, P = NS). In contrast, PCWP, LA volume, and E/e' were significantly increased in the symptomatic group and they all correlated with exercise capacity (r = -0.66, -0.75, and -0.62, respectively, P < 0.001). Receiver operating characteristic curve analysis confirmed that PCWP, LA volume index, and E/e' all provided incremental information [area under the curve (AUC) = 0.90, 0.92, and 0.90, respectively, P < 0.05] over AVA index (AUC = 0.66, NS) in predicting symptomatic status., Conclusion: PCWP, LA volume, or E/e' is closely related to exercise capacity and symptomatic status, and may therefore be important markers of disease severity in AS. Clinical Trials.gov Identifier: NCT00252317 (http://clinicaltrials.gov/ct2/results?term=NCT00252317).

Background: The Doppler index of left ventricular (LV) filling (E/e') is recognized as a noninvasive measure for LV filling pressure at rest but has also been suggested as a reliable measure of exercise-induced changes. The aim of this study was to investigate changes in LV filling pressure, measured invasively as pulmonary capillary wedge pressure (PCWP), at rest and during exercise to describe the relation with E/e' in patients with severe aortic stenosis., Methods: Twenty-eight patients with an aortic valve areas<1 cm(2) performed a multistage supine bicycle exercise test until exhaustion. PCWP, E/e'(septal), and E/e'(lateral) were determined simultaneously by echocardiography at rest and at maximal tolerated workload., Results: PCWP increased significantly from 18+/-8 mm Hg at rest to 39+/-10 mm Hg at peak exercise (P < .0001). E, e'(septal), and e'(lateral) increased with exercise, whereas E/e'(septal) remained unchanged (19+/-6 vs 19+/-6; P=NS), and only minimal changes were observed in E/e'(lateral) (14+/-4 vs 15+/-4; P=.05). E/e'(septal) and E/e'(lateral) were significantly correlated with PCWP at rest (r=0.72, P < .0001, and r=0.67, P < .0001, respectively) as well as at peak exercise (r=0.66, P=.0003, and r=0.47, P=.02, respectively), with nearly similar slopes of the linear regression lines. The intercepts, however, increased by 18 mm Hg (P=.01) and by 19 mm Hg (P=.01) at peak exercise, respectively. Changes in E/e'(septal) and E/e'(lateral) were not related to changes in PCWP with exercise (P=NS). Instead, the ratio of E velocity during exercise to e'(septal) at rest (E(exercise)/e'(septal, rest)) was correlated with PCWP during exercise (r=0.61, P=.001), and furthermore, E(exercise)-E(rest)/e'(septal, rest) was related to changes in PCWP (r=0.45, P=.02). The results for the lateral side were r=0.50 (P=.01) and r=0.44 (P=.03), respectively., Conclusions: E/e' is well correlated with PCWP at rest. However, E/e' cannot be used to detect exercise-induced changes in PCWP in patients with severe aortic stenosis. Using the ratio of E during exercise to e' at rest may result in a better estimate of the increase in PCWP during exercise.

We report a case of severe systolic anterior motion (SAM) and dynamic left ventricular outflow obstruction after repair of a flail posterior leaflet of the mitral valve. The reason for SAM was found to be due to traction on the pericardial stay sutures placed to expose the surgical field. The SAM and the outflow obstruction were completely resolved by cutting these sutures. Our case demonstrates the contribution of geometric factors in the development of SAM and left ventricular outflow obstruction and emphasizes the need to evaluate the heart in its natural position within the mediastinum.

Background: After acute myocardial infarction (AMI), diastolic function assessed by Doppler echocardiography provides important prognostic information that is incremental to systolic function. However, Doppler variables are affected by multiple factors and may change rapidly. In contrast, left atrial (LA) volume is less influenced by acute changes and reflects subacute or chronic diastolic function. This may be of importance when one assesses risk in patients with AMI., Methods and Results: Three hundred fourteen patients with AMI who had a transthoracic echocardiogram with assessment of left ventricular (LV) systolic and diastolic function and measurement of LA volume during admission were identified. The LA volume was corrected for body surface area, and the population was divided according to LA volume index of 32 mL/m2 (2 SDs above normal). LA volume index was >32 mL/m2 in 142 (45%). The primary study end point was all-cause mortality. During follow-up of 15 (range 0 to 33) months, 46 patients (15%) died. LA volume index was a powerful predictor of mortality and remained an independent predictor (hazard ratio 1.05 per 1-mL/m2 change, 95% CI 1.03 to 1.06, P<0.001) after adjustment for clinical factors, LV systolic function, and Doppler-derived parameters of diastolic function., Conclusions: Increased LA volume index is a powerful predictor of mortality after AMI and provides prognostic information incremental to clinical data and conventional measures of LV systolic and diastolic function.