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Abstract Background Atrial fibrillation (AFib) exists more frequently in patients with aortic stenosis (AS) than in patients without, and AFib may be a sign of progressive deterioration of AS. Echocardiographic assessment of AS in sinus rhythm is well documented, however, little is known about AFib in AS since such patients often are excluded from clinical echocardiographic trials. Aim The purpose of this study was to assess the prognostic importance of AFib in AS. Methods The study was designed as a single-center case-control study. Patients with AS and AFib were enrolled as cases (n = 103) and subsequently matched to controls (103 patients with AS but sinus rhythm). Cases and controls were matched according to age, gender and severity of AS. Primary outcome was all cause mortality and follow-up was 100% complete. Results Compared to controls the group with AFib had lower mean ejection fraction (42% vs. 49%; p Conclusions AFib is an independent risk factor in patients with AS and the prognostic impact of AFib seems to be the same despite the severity of AS.

Background: Global longitudinal strain (GLS) is recognized as a powerful predictor of heart failure (HF). However, the entire strain curve may entail important prognostic information regarding HF risk that might be undiscovered by only focusing on the peak strain value., Objective: The hypothesis of the present study was, that analysis of the entire strain curve using unsupervised machine learning (uML) would reveal novel ventricular deformation patterns capable of predicting incident HF independently of GLS., Methods: Longitudinal strain curves from 3710 subjects from the general population without prevalent HF were analyzed using uML., Results: Mean age was 56 years and 43 % were male. During a median follow-up of 5.3 years, 92 subjects (2.5 %) developed HF. The uML algorithm generated a hierarchical clustering tree (HCT) resulting in 10 different clusters. Generally, the strain curves displayed reduced early diastolic strain to peak-strain ratio with an increasing incidence rate of HF. In multivariable Cox regressions, cluster 9 was significantly associated with increased risk of HF when compared to cluster 2-5, and 7-8 [For cluster 3: HR 8.95, 95 %CI: 2.08;38.48, P = 0.003] even though the subjects of cluster 9 were younger, displayed healthier clinical baseline characteristics, and only had slightly reduced GLS. The mean strain curve of cluster 9 displayed an early systolic lengthening followed by a late and reduced contraction specifically related to the basal lateral segment., Conclusion: The unsupervised machine learning algorithm identified unknown strain patterns beyond GLS presumably related to increased risk of HF., Competing Interests: Declaration of competing interest Nothing to Disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Left atrial (LA) strain by three-dimensional echocardiography (3DE), has been proposed as a more accurate measure of LA function, providing incremental prognostic benefits over traditional two-dimensional approaches., Objectives: Our aim was to evaluate the prognostic value of LA strain by 3DE in predicting incident atrial fibrillation (AF) in the general population., Methods: The study included 4466 participants from a prospective longitudinal cohort study in the general population, among these 3DE LA strain was analysed in 1935 participants. The endpoint was incident AF. Adjustments were made for the CHARGE-AF clinical risk score., Results: Mean age was 54 ± 17 years, 43 % were male. During a median follow-up time of 4.8 years (interquartile range 4.3-5.5 years) 59 participants (3.0 %) developed AF. In univariable analysis, all three parameters were associated with incident AF (p value for all <0.01). After multivariable adjustments, only LA reservoir strain (LASr) and LA contractile strain (LASct) were associated with incident AF (LASr: HR 1.12 (1.07-1.17), p < 0.001, per 1 % decrease; LASct: HR 1.16 (1.09-1.24), p < 0.001, per 1 % decrease), whereas LA conduit strain (LAScd) was not (HR 1.04 (0.98-1.10), p = 0.17, per 1 % decrease). Both LASr (continuous net reclassification index 0.37 ± 0.14; p = 0.003) and LASct (continuous net reclassification index 0.41 ± 0.14; p = 0.002) provided incremental prognostic information beyond the CHARGE-AF risk score., Conclusion: LASr and LASct measured by 3DE are independently associated with incident AF and provided incremental prognostic information beyond existing risk scores., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Aim: The latest guidelines from ACC/AHA define hypertension at systolic blood pressure (SBP) 130-139 mmHg or diastolic blood pressure (DBP) 80-89 mmHg in contrast to guidelines from ESC/ESH defining hypertension at SBP ≥ 140 mmHg or DBP ≥ 90 mmHg. The aim was to determine whether the ACC/AHA definition of hypertension identifies persons at elevated risk for future cardiovascular outcome., Methods: In a Danish prospective cardiovascular study, 19,721 white men and women aged 20-98 years were examined up to five occasions between 1976 and 2015. The population was followed until December 2018. The ACC/AHA definition of the BP levels were applied: Normal: SBP <120 mmHg and DBP <80 mmHg, Elevated: SBP 120-129 mmHg and DBP <80 mmHg, Stage 1: SBP 130-139 mmHg or DBP 80-89 mmHg, Stage 2: SBP ≥140 mmHg or DBP ≥90 mmHg. Absolute 10-year risk was calculated taking repeated examinations, covariates, and competing risk into account., Results: For all outcomes, the 10-year risk in stage 1 hypertension did not differ significantly from risk in subjects with normal BP: The 10-year risk of cardiovascular events in stage 1 hypertension was 14.1% [95% CI 13.2;15.0] and did not differ significantly from the risk in normal BP at 12.8% [95% CI 11.1;14.5] ( p  = 0.19). The risk was highest in stage 2 hypertension 19.4% [95% CI 18.9;20.0] and differed significantly from normal BP, elevated BP, and stage 1 hypertension ( p  < 0.001). The 10-year risk of cardiovascular death was 6.6% [95% CI 5.9;7.4] in stage 1 hypertension and did not differ significantly from the risk in normal BP at 5.7% [95% CI 4.1;7.3] ( p  = 0.33)., Conclusions: Stage 1 hypertension as defined by the ACC/AHA guidelines has the same risk for future cardiovascular events as normal BP. In contrast, the definition of hypertension as suggested by ESC/ESH identifies patients with elevated risk of cardiovascular events.

Findings regarding the relation between aortic size and risk factors are heterogeneous. This study aimed to generate new insights from a population-based adult cohort on aortic root dimensions and their association with age, anthropometric measures, and cardiac risk factors and evaluate the incidence of acute aortic events. Participants from the fifth examination round of the Copenhagen City Heart study (aged 20 to 98 years) with applicable echocardiograms and no history of aortic disease or valve surgery were included. Aorta diameter was assessed at the annulus, sinus of Valsalva, sinotubular junction, and the tubular part of the ascending aorta. The study population comprised 1,796 men and 2,316 women; mean age: 56.4 ± 17.0 and 56.9 ± 18.1 years, respectively. Men had larger aortic root diameters than women regardless of height indexing (p <0.01). Age, height, weight, systolic and diastolic blood pressure, mean arterial pressure, pulse pressure, hypertension, diabetes, ischemic heart disease, and smoking were positively correlated with aortic sinus diameter in the crude and gender-adjusted analyses. However, after full adjustment, only height, weight, and diastolic blood pressure remained significantly positively correlated with aortic sinus diameter (p <0.001). For systolic blood pressure and pulse pressure, the correlation was inverse (p <0.001). During follow-up (median 5.4 [quartile 1 to quartile 3 4.5 to 6.3] years), the incidence rate of first-time acute aortic events was 13.6 (confidence interval 4.4 to 42.2) per 100,000 person-years. In conclusion, beyond anthropometric measures, age, and gender, diastolic blood pressure was the only cardiac risk factor that was independently correlated with aortic root dimensions. The number of aortic events during follow-up was low., Competing Interests: Declaration of competing interest Dr. Biering-Sørensen is a steering committee member of the Amgen-financed GALACTIC-HF trial, the Boehringer Ingelheim-financed EASi-KIDNEY trial, and “LUX-Dx TRENDS Evaluates Diagnostics Sensors in Heart Failure Patients Receiving Boston Scientific's Investigational ICM System” trial: chief investigator of the Sanofi Pasteur-financed “NUDGE-FLU” trial, the Sanofi Pasteur-financed “DANFLU-1” trial, and the Sanofi Pasteur-financed “DANFLU-2” trial; is on the advisory board for Sanofi Pasteur, Amgen, CSL Seqirus, and GSK; received speaker honoraria from Bayer, Novartis, Sanofi Pasteur, GE Healthcare, and GSK; received research grants from GE Healthcare, AstraZeneca, Novo Nordisk, and Sanofi Pasteur; and is a consultant for Novo Nordisk, IQVIA, and Parexel. The remaining authors have no competing interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: 3D echocardiographic (3DE) assessment of the left atrium (LA) is a new modality of potential clinical value. Age- and sex-based normative values are needed to benchmark these parameters for clinical use., Methods and Results: Of 4466 participants in the 5th Copenhagen City Heart Study, a prospective longitudinal cohort study on the general population, 2082 participants underwent 3DE of the LA. Healthy participants were included to establish normative values for LA strain, volume, and function by 3DE. The effects of age and sex were also evaluated. After excluding participants with comorbidities, 979 healthy participants (median age 44 years, 39.6% males) remained. The median and limits of normality (2.5th and 97.5th percentiles) for functional and volumetric measures were as follows: LA reservoir strain (LASr) 30.8% (18.4-44.2%), LA conduit strain (LAScd) 19.1% (6.8-32.0%), LA contractile strain 11.7% (4.3-22.2%), total LA emptying fraction (LAEF) 61.4% (47.8-71.0%), passive LAEF 37.7% (17.4-53.9%), active LAEF 37.4% (22.2-52.5%), LA minimum volume index (LAVimin) 10.2 (5.9-18.5) mL/m2, and LA maximum volume index (LAVimax) 26.8 (16.5-40.1) mL/m2. All parameters changed significantly with increasing age (P value for all <0.001). Significant sex-specific differences were observed for all parameters except active LAEF and LAVimax. Sex significantly modified the association between age and LASr (P for interaction < 0.001), LAScd (P for interaction < 0.001), LAVimin (P for interaction = 0.037), and total LAEF (P for interaction = 0.034) such that these parameters deteriorated faster with age in females than males., Conclusion: We present age- and sex-specific reference material including limits of normality for LA strain, volume, and function by 3DE., Competing Interests: Conflict of interest: M.Y.: none; F.J.O.: none; K.G.S.: advisory board: Sanofi Pasteur; M.C.H.L.: none; N.D.J.: none; F.L.L.: none; G.B.J.: none; P.Sc.: none; R.M.: none; P.Sø.: advisory board: Biotronik; and T.B.-S.: Steering Committee member of the Amgen-financed GALACTIC-HF trial; Steering Committee member of the Boehringer Ingelheim–financed SHARP3 trial; chief investigator of the Sanofi Pasteur–financed ‘NUDGE-FLU’ trial; chief investigator of the Sanofi Pasteur–financed ‘DANFLU-1’ trial; chief investigator of the Sanofi Pasteur–financed ‘DANFLU-2’ trial; Steering Committee member of ‘LUX-Dx TRENDS Evaluates Diagnostics Sensors in Heart Failure Patients Receiving Boston Scientific’s Investigational ICM System’ trial; advisory board: Sanofi Pasteur, Amgen, and GSK; speaker honorarium: Bayer, Novartis, Sanofi Pasteur, and GSK; and research grants: GE Healthcare, AstraZeneca, Novo Nordisk, and Sanofi Pasteur., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Mitral regurgitation (MR) can be difficult to quantify. We sought to investigate whether the MR jet area to left atrial (LA) area ratio (MR/LA ratio) method for quantifying MRs can be used to predict incident atrial fibrillation (AF) in the general population., Methods and Results: The study included 4466 participants from the 5th Copenhagen City Heart Study, a prospective general population study, who underwent transthoracic echocardiography. MR jet area was measured and indexed to LA area. The endpoint was incident AF. MR was quantified in 4042 participants (mean age: 57 years, 43% men). Of these, 198 (4.9%) developed AF during a median follow-up period of 5.3 years (interquartile range: 4.4-6.1 years). MR was present in 1938 participants (48%) including 1593 (39%) trace/mild MRs (MR/LA ratio ≤ 20% and ≤4 cm2). In unadjusted analysis, MR/LA ratio was associated with incident AF [HR: 1.06 (1.00-1.13), P = 0.042 per 5% increase] but not after adjusting for CHARGE-AF score. However, the association was modified by age (P for interaction = 0.034), such that MR/LA ratio was associated with AF only in participants ≤ 73 years. In these participants, MR/LA ratio 'was' independently associated with AF after adjusting for CHARGE-AF score [HR: 1.14 (1.06-1.24), P = 0.001, per 5% increase]. This finding persisted when restricting the analysis to participants without moderate or severe MR and normal LA size [HR: 1.35 (1.09-1.68), P = 0.005, per 5% increase]., Conclusion: MR, including even trace regurgitations quantified by MR/LA ratio, is independently associated with incident AF in individuals ≤ 73 years of age., Competing Interests: Conflict of interest: M.Y.: none. F.J.O.: none. A.S.: none. K.G.S.: advisory board: Sanofi Pasteur. M.C.H.L.: none. N.D.J.: none. M.T.J.: none. G.B.J.: none. P.S.: none. R.M.: none. T.B.-S.: Steering Committee member of the Amgen financed GALACTIC-HF trial. Chief investigator of the Sanofi Pasteur financed ‘NUDGE-FLU’ trial. Chief investigator of the Sanofi Pasteur financed ‘DANFLU-1’ trial. Chief investigator of the Sanofi Pasteur financed ‘DANFLU-2’ trial. Steering Committee member of ‘LUX-Dx TRENDS Evaluates Diagnostics Sensors in Heart Failure Patients Receiving Boston Scientific’s Investigational ICM System’ trial. Advisory board: Sanofi Pasteur, Amgen, and GSK. Speaker honorarium: Bayer, Novartis, Sanofi Pasteur, and GSK. Research grants: GE Healthcare, Sanofi Pasteur, Novo Nordisk, and AstraZeneca., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: To promote the implementation of right ventricular (RV) longitudinal strain in clinical practice, we sought to propose normal values for RV free wall (RVFWLS) and four-chamber longitudinal strain (RV4CLS) and investigate the association with clinical and echocardiographic parameters in participants from the general population., Methods and Results: Participants from the 5th Copenhagen City Heart Study (2011-2015)-a prospective cohort study-with available RV longitudinal strain measurements were included. RVFWLS and RV4CLS were assessed using two-dimensional speckle-tracking echocardiography. In total, 2951 participants were included. Amongst 1297 participants without cardiovascular disease or risk factors (median age 44, 63% female), mean values of RVFWLS and RV4CLS were - 26.7% ± 5.2 (95% prediction interval (PI) - 36.9, - 16.5) and - 21.7% ± 3.4 (95%PI - 28.4, - 15.0), respectively. Women had significantly higher absolute values of RVFWLS and RV4CLS than men (mean - 27.5 ± 5.5 vs. - 25.4 ± 4.5, p < 0.001 and - 22.3 ± 3.5 vs. - 20.6 ± 3.0, p < 0.001, respectively). Absolute values of RVFWLS but not RV4CLS decreased significantly with increasing age in unadjusted linear regression. Tricuspid annular plane systolic excursion, RV s' and left ventricular global longitudinal strain were the most influential parameters associated with both RVFWLS and RV4CLS in multiple linear regression. Participants with cardiovascular disease (n = 1531) had a higher proportion of abnormal values of RVFWLS and RV4CLS compared to the healthy population (8% vs. 4%, p < 0.001 and 8% vs. 3%, p < 0.001, respectively)., Conclusion: This study proposed normal age- and sex-based values of RVFWLS and RV4CLS in a healthy population sample and showed significant sex differences in both measurements across ages., (© 2023. The Author(s).)

Aims: Pressure-strain loop (PSL) analysis is a novel echocardiographic tool capable of assessing myocardial work non-invasively. In this study, we aim to evaluate the prognostic value of myocardial work indices in the general population., Methods and Results: This was a prospective community-based cohort study (n = 4466). PSL analyses were performed to acquire global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency (GWE). The endpoint was a composite of heart failure or cardiovascular death (HF/CVD). Survival analysis was applied. A total of 3932 participants were included in this analysis (median age: 58 years, 43% men). Of these, 124 (3%) experienced the outcome during a median follow-up period of 3.5 years [interquartile range (IQR): 2.6-4.4 years]. Hypertension significantly modified the association between all work indices and outcome (P for interaction < 0.05), such that work indices posed a higher risk of outcome in non-hypertensive than in hypertensive participants. After adjusting for Atherosclerosis Risk in Communities (ARIC)-HF risk variables, all work indices predicted outcome in non-hypertensive participants, but only GWI, GCW, and GWE predicted outcome in hypertensive participants [GWI: hazard ratio (HR) = 1.12 (1.07-1.16), per 100 mmHg% decrease; GCW: HR = 1.12 (1.08-1.17), per 100 mmHg% decrease; GWE: HR = 1.08 (1.04-1.12), per 1% decrease]. Only GWE significantly increased C-statistics when added to ARIC-HF risk variables in hypertensive participants (C-stat 0.865 vs. 0.877, P for increment = 0.003)., Conclusion: Hypertension modifies the association between myocardial work indices and HF/CVD in the general population. All work indices are associated with outcome in normotensive participants. GWI, GCW, and GWE are independently associated with outcome in hypertension, but only GWE improves risk prediction., Competing Interests: Conflict of interest: T.B.-S.: Steering Committee member of the Amgen financed GALACTIC-HF trial; Steering Committee of the Boston Scientific financed LUX-Dx TRENDS trial; Advisory Board: Sanofi Pasteur. Advisory Board: Amgen; Speaker Honorarium: Novartis; Speaker Honorarium: Sanofi Pasteur; Research grant: GE Healthcare; Research grant: Sanofi Pasteur. O.A.S.: co-inventor of ‘Method for myocardial segment work analysis’, which was used to calculate myocardial work indices. J.H.S.: advisory board member for Medtronic and unrestricted research grants from Medtronic outside this work. The organizations had no role in any aspect of the study. The remaining authors do not have any potential conflicts of interest to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Right ventricular free wall (RVFWLS) and four-chamber longitudinal strain (RV4CLS) are associated with adverse events in various patient populations including patients with heart failure (HF). We sought to investigate the prognostic value of RVFWLS and RV4CLS for the development of incident HF in participants from the general population., Methods and Results: Participants from the 5th Copenhagen City Heart Study (2011-2015) without known chronic ischaemic heart disease or HF at baseline were included. RVFWLS and RV4CLS were obtained using two-dimensional speckle-tracking echocardiography from the right ventricular (RV)-focused apical four-chamber view. The primary endpoint was incident HF. Among 2740 participants (mean age 54 ± 17 years, 42% male), 43 (1.6%) developed HF during a median follow-up of 5.5 years (IQR 4.5-6.3). Both RVFWLS and RV4CLS were associated with an increased risk of incident HF during follow-up independent of age, sex, hypertension, diabetes, body mass index and tricuspid annular plane systolic excursion (TAPSE), (HR 1.06, 95%CI 1.00-1.11, P = 0.034, per 1% absolute decrease and HR 1.14, 95%CI 1.05-1.23, P = 0.001, per 1% absolute decrease, respectively). Left ventricular ejection fraction (LVEF) modified the association between RV4CLS and incident HF (P for interaction = 0.016) such that RV4CLS was only of prognostic importance among those with LVEF < 55% (HR 1.21, 95%CI 1.11-1.33, P < 0.001 vs. HR 0.94, 95%CI 0.80-1.10, P = 0.43 in patients with LVEF ≥ 55%)., Conclusion: In participants from the general population, both RVFWLS and RV4CLS were associated with a greater risk of incident HF independent of important baseline characteristics and TAPSE, and LVEF modified the relationship between RV4CLS and incident HF., Competing Interests: Conflict of interest: T.B.S.: Steering Committee member of the Amgen financed GALACTIC-HF trial, the Boehringer Ingelheim financed EASi-KIDNEY trial, and the ‘LUX-Dx TRENDS Evaluates Diagnostics Sensors in Heart Failure Patients Receiving Boston Scientific’s Investigational ICM System’ trial. Chief investigator of the Sanofi Pasteur financed ‘NUDGE-FLU’ trial, the Sanofi Pasteur financed ‘DANFLU-1’ trial, and the Sanofi Pasteur financed ‘DANFLU-2’ trial, and the Boston Scientific financed “DANLOGIC-HF” trial., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The ratio of transmitral early filling velocity to early diastolic strain rate (E/e'sr) has recently emerged as a measure of left ventricular filling pressure. Reference values are needed for this new parameter for it to be used clinically., Methods: Healthy participants from a prospective general population study, the Fifth Copenhagen City Heart Study, were assessed to establish reference values for E/e'sr derived from two-dimensional speckle-tracking echocardiography. The prevalence of abnormal E/e'sr was assessed in participants with cardiovascular risk factors or specific diseases., Results: The population comprised 1,623 healthy participants (median age, 45; interquartile range, 32-56; 61% female). The upper reference limit for E/e'sr in the population was 79.6 cm. Following multivariable adjustment, male participants exhibited significantly higher E/e'sr than female participants (upper reference limit for male participants, 83.7 cm; for female participants, 76.5 cm). For both sexes, E/e'sr increased in a curvilinear fashion with age such that the largest increases in E/e'sr were observed in participants >45 years. In the entire CCHS5 population with E/e'sr available (n = 3,902), increasing age, body mass index, systolic blood pressure, male sex, estimated glomerular filtration rate, and diabetes were associated with E/e'sr (all P < .05). Total cholesterol was associated with a less steep increase in E/e'sr. Abnormal E/e'sr was seldomly observed in participants with normal diastolic function but became more frequent in participants with increasing grades of diastolic dysfunction (normal, mild, moderate, severe [abnormal E/e'sr for each grade: 4.4% vs 20.0% vs 16.2% vs 55.6%, respectively])., Conclusion: The E/e'sr differs between sexes and is age dependent such that E/e'sr increases with advancing age. Therefore, we established sex- and age-stratified reference values for E/e'sr., (Copyright © 2023 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

(1) Background: To investigate how food intake and preload augmentation affect the cardiac output (CO) and volumes of the left ventricle (LV) and right ventricle (RV) assessed using cardiac magnetic resonance (CMR) and trans-thoracic echocardiography (TTE). (2) Methods: Eighty-two subjects with ( n = 40) and without ( n = 42) cardiac disease were assessed using both CMR and TTE immediately before and after a fast infusion of 2 L isotonic saline. Half of the population had a meal during saline infusion (food/fluid), and the other half were kept fasting (fasting/fluid). We analyzed end-diastolic (EDV) and end-systolic (ESV) volumes and feature tracking (FT) using CMR, LV global longitudinal strain (GLS), and RV longitudinal strain (LS) using TTE. (3) Results: CO assessed using CMR increased significantly in both groups, and the increase was significantly higher in the food/fluid group: LV-CO (ΔLV-CO: +2.6 ± 1.3 vs. +0.7 ± 1.0 p < 0.001), followed by increased heart rate (HR) (ΔHR: +12 ± 8 vs. +1 ± 6 p < 0.001). LV and RV achieved increased stroke volume (SV) through different mechanisms. For the LV, through increased contractility, increased LV-EDV, decreased LV-ESV, increased LV-FT, and GLS were observed. For the RV, increased volumes, increased RV-EDV, increased RV-ESV, and at least for the fasting/fluid group, unchanged RV-FT and RV-LS were reported. (4) Conclusions: Preload augmentation and food intake have a significant impact on hemodynamic and cardiac functional parameters. This advocates for standardized recommendations regarding oral intake of fluid and food before cardiac assessment, for example, TTE, CMR, and right heart catheterization. We also demonstrate different approaches for the LV and RV to increase SV: for the LV by increased contractility, and for the RV by volume expansion.

Background: The cardiac time intervals include the isovolumic contraction time (IVCT), the left ventricular ejection time (LVET), the isovolumic relaxation time (IVRT) and the combination of all the cardiac time intervals in the myocardial performance index (MPI) (defined as [(IVCT+IVRT)/LVET)]. Whether the cardiac time intervals change over time and which clinical factors that accelerate these changes is not well-established. Additionally, whether these changes are associated with subsequent heart failure (HF), remains unknown., Methods: We investigated participants from the general population (n = 1064) who had an echocardiographic examination including color tissue Doppler imaging performed in both the 4th and 5th Copenhagen City Heart Study. The examinations were performed 10.5 years apart., Results: The IVCT, LVET, IVRT and MPI increased significantly over time. None of the investigated clinical factors were associated with increase in IVCT. Systolic blood pressure (standardized β= - 0.09) and male sex (standardized β= - 0.08) were associated with an accelerated decrease in LVET. Age (standardized β=0.26), male sex (standardized β=0.06), diastolic blood pressure (standardized β=0.08), and smoking (standardized β=0.08) were associated with an increase in IVRT, while HbA1c (standardized β= - 0.06) was associated with a decrease in IVRT. Increasing IVRT over a decade was associated with an increased risk of subsequent HF in participants aged <65 years (per 10 ms increase: HR 1.33; 95%CI (1.02-1.72), p = 0.034)., Conclusion: The cardiac time increased significantly over time. Several clinical factors accelerated these changes. An increase in IVRT was associated with an increased risk of subsequent HF in participants aged <65 years., Competing Interests: Declaration of Competing Interest Tor Biering-Sørensen reports receiving research grants from Sanofi Pasteur and GE Healthcare, being a Steering Committee member of an Amgen financed and a Boston Scientific financed trial, on advisory boards for Sanofi Pasteur and Amgen, and speaker honorariums from Novartis, Sanofi Pasteur, and GSK. The remaining authors have nothing to disclose., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Color tissue Doppler imaging (TDI) M-mode can be used to measure the cardiac time intervals including the isovolumic contraction time (IVCT), the left ventricular ejection time (LVET), the isovolumic relaxation time (IVRT), and the combination of all the cardiac time intervals in the myocardial performance index (MPI) defined as [(IVCT + IVRT)/LVET]. The aim of this study was to establish normal age- and sex-based reference ranges for the cardiac time intervals., Methods and Results: A total of 1969 participants free of cardiovascular diseases and risk factors from the general population with limited age range underwent an echocardiographic examination including TDI. The median age was 46 years (25th-75th percentile: 33-58 years), and 61.5% were females. In the entire study population, the IVCT was observed to be 40 ± 10 ms [95% prediction interval (PI) 20-59 ms], the LVET 292 ± 23 ms (95% PI 248-336 ms), the IVRT 96 ± 19 ms (95% PI 59-134 ms) and MPI 0.47 ± 0.09 (95% PI 0.29-0.65). All the cardiac time intervals differed significantly between females and males. With increasing age, the IVCT increased in females, but not in males. The LVET did not change with age in both sexes, while the IVRT increased in both sexes with increasing age. Furthermore, we developed regression equations relating the heart rate to the cardiac time intervals and age- and sex-based normal reference ranges corrected for heart rate., Conclusion: In this study, we established normal age- and sex-based reference ranges for the cardiac time intervals. These normal reference ranges differed significantly with sex., (© 2023. The Author(s).)

Aims: Left ventricular (LV) systolic deformation is altered early in the ventricular disease process despite normal LV ejection fraction (LVEF). These alterations seem to be characterized by decreased global longitudinal strain (GLS) and augmented global circumferential strain (GCS). This study aimed to investigate the link between myocardial deformation phenotyping using longitudinal and circumferential strain and risk of incident heart failure (HF) and cardiovascular death (CD)., Methods and Results: The study sample was based on the prospective cohort study the 5th Copenhagen City Heart Study (2011-15). All participants were examined with echocardiography following a pre-defined protocol. A total of 2874 participants were included. Mean age was 53±18 years and 60% were female. During a median follow-up of 3.5 years, a total of 73 developed HF/CD. A U-shaped relationship between GCS and HF/CD was observed. LVEF significantly modified the association between GCS and HF/CD (P for interaction <0.001). The optimal transition point for the effect modification was LVEF < 50%. In multivariable Cox regressions, increasing GCS was significantly associated with HF/CD in participants with LVEF ≥ 50% (hazard ratio [HR]=1.12 [95% confidence interval (CI): 1.02; 1.23] per 1% increase), while decreasing GCS was associated with a higher risk of HF/CD in individuals with LVEF < 50% [HR=1.18 (95% CI: 1.05; 1.31) per 1% decrease]., Conclusions: The prognostic utility of GCS is modified by LVEF. In participants with normal LVEF, higher GCS was associated with increased risk of HF/CD, while the opposite was observed in participants with abnormal LVEF. This observation adds important information to our understanding of the pathophysiological evolution of myocardial deformation in cardiac disease progression., Competing Interests: Conflict of interest: K.G.S is a member of an advisory board in Sanofi Pasteur. T.B.S. is a steering committee member of the Amgen-financed GALACTIC-HF trial, chief investigator and steering committee chair of the Sanofi Pasteur–financed ‘NUDGE-FLU’ trial, chief investigator and steering committee chair of the Sanofi Pasteur–financed ‘DANFLU-1’ trial, chief investigator and steering committee chair of the Sanofi Pasteur–financed ‘DANFLU-2’ trial, and steering committee member of the ‘LUX-Dx TRENDS Evaluates Diagnostics Sensors in Heart Failure Patients Receiving Boston Scientific’s Investigational ICM System’ trial. He is a member of an advisory board in Sanofi Pasteur, Amgen, and GSK and has received speaker honorarium from Novartis, Sanofi Pasteur, and GSK and research grants from GE Healthcare and Sanofi Pasteur. The remaining authors have nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia following coronary artery bypass grafting (CABG). We hypothesized that measures of left atrial (LA) function would be useful in predicting AF in patients undergoing CABG., Methods and Results: In the study, 611 patients were included after CABG. All patients had echocardiograms performed preoperatively and LA functional measurements were assessed. These measurements were LA maximum volume index (LAVmax), LA minimum volume index (LAVmin) and LA emptying fraction (LAEF). The endpoint was AF occurring >14 days after surgery. During the follow-up period of a median of 3.7 years, 52 (9%) developed AF. The mean age was 67 years, 84% were male and the average left ventricle ejection fraction was 50%. Patients who developed AF had a lower CCS class and lower LAEF (40 vs. 45%), otherwise no clinical differences were observed between outcome groups. No functional LA measurements were significant predictors of AF in the whole CABG population. However, in patients with normal-sized LA (n = 532, events: 49), both LAEF and LAVmin were univariable predictors of AF. When the functional measurements were adjusted for the CHADS 2 score, both LAVmin (HR = 1.07 [1.01-1.13], p = .014) and LAEF (HR: 1.02 [1.00-1.03], p = .023), remained significant predictors., Conclusion: No echocardiographic measurements were significant predictors of AF after CABG. In patients with a normal LA size, LAVmin as well as LAEF were significant predictors of AF., (© 2023 The Authors. Echocardiography published by Wiley Periodicals LLC.)

Neutrophil gelatinase-associated lipocalin (NGAL) is an inflammatory biomarker related to acute kidney injury (AKI). Including 1892 consecutive patients with ST-elevation myocardial infarction (STEMI), in which NGAL was measured in 1624 (86%) on admission and in a consecutive subgroup at 6-12 h (n = 163) and 12-24 h (n = 222) after admission, this study aimed to evaluate the prognostic value of NGAL in predicting AKI and mortality. Patients were stratified based on whether their admission NGAL plasma concentration was greater than or equal to/less than the median. The primary endpoint was a composite of the first occurrence of AKI or all-cause death within 30 days. AKI was classified by the maximal plasma creatinine increase from baseline during index admission as KDIGO1 (<200% increase) or KDIGO23 (≥200% increase) according to the Kidney Disease Improving Global Outcomes (KDIGO) system. Admission NGAL > the median was independently associated with a higher risk of severe AKI (KDIGO2-3) and 30-day all-cause mortality when adjusted for age, admission systolic blood pressure and high-sensitivity C-reactive protein, left-ventricular ejection fraction, known kidney dysfunction, and cardiogenic shock with an odds ratio (95% confidence interval) of 2.26 (1.18-4.51), p = 0.014. Finally, we observed increasing predictive values in a subgroup during the first day of hospitalization suggesting that assessment of NGAL should be delayed for optimal prognostic purposes.

Aims: Measures of left atrial (LA) function are known to predict both ischaemic stroke and atrial fibrillation in specific patient groups. The aim of this study was to investigate the value of LA reservoir strain for predicting ischaemic stroke in patients undergoing coronary artery bypass grafting (CABG) and investigate whether the presence of postoperative atrial fibrillation (POAF) modified this relationship., Methods and Results: Patients undergoing isolated CABG were included. The primary endpoint was ischaemic stroke. The association between LA reservoir strain and ischaemic stroke was investigated in uni- and multivariable Cox proportional hazards regression models including adjustment for POAF.We included 542 patients (mean age 67.3±8.9 years, 16.4% female). During a median follow-up period of 3.9 years, 21 patients (3.9%) experienced an ischaemic stroke. In total, 96 patients (17.7%) developed POAF during the index hospitalization. In a multivariable-adjusted Cox proportional hazards regression model, LA reservoir strain was significantly associated with the development of ischaemic stroke [HR (hazard ratio) 1.09 (95% CI 1.02-1.17) per 1% decrease, P = 0.011]. The presence of POAF did not modify this association ( p for interaction = 0.07). The predictive value of the LA reservoir strain persisted in multiple sensitivity analyses including restricting the analysis to patients with normal left atrial volumes (LAV<34 ml/m 2 ), patients without POAF, patients without prior stroke, and when excluding patients who developed atrial fibrillation at any time during follow-up., Conclusion: LA reservoir strain was independently associated with ischaemic stroke in CABG patients. The predictive value of LA reservoir strain was unaffected by the presence of POAF. Prospective studies are warranted to validate the potential usefulness of LA reservoir strain to predict postoperative ischaemic stroke in the setting of CABG., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Valvular event timing is an integral part of echocardiographic pressure-strain loop (PSL) analyses. The impact that different event timing modalities may have on myocardial work indices is unknown., Methods and Results: A methodological study was performed on 200 subjects, including 50 healthy subjects, 50 with aortic valve sclerosis, 50 with atrial fibrillation, and 50 with reduced left ventricular ejection fraction. Valvular event timing was estimated by visual assessment, spectral Doppler, and colour tissue Doppler imaging (TDI) M-mode. These valvular event timings were added to the same PSL analyses sequentially to acquire myocardial work indices, including global work index (GWI). For the 200 participants, the median age was 72 years, 50% were men, and mean blood pressure was 143/80 mmHg. Valvular event timings differed between all three modalities and so did all myocardial work indices. Compared with visual assessment, spectral Doppler resulted in a significantly higher GWI (mean difference: 114 ± 93 mmHg%, P < 0.001), and so did TDI (mean difference: 83 ± 90 mmHg%, P < 0.001). A higher GWI by spectral Doppler than by TDI was also observed (mean difference: 30 ± 53 mmHg%, P < 0.001). In the healthy subgroup, a systematic bias was observed for spectral Doppler compared with visual assessment (mean difference: 160 ± 77 mmHg%, P < 0.001), and a similar trend was noted for TDI vs. visual assessment (mean difference: 124 ± 74 mmHg%, P < 0.001)., Conclusion: Myocardial work indices differ depending on the event timing modality used, with visual assessment yielding lower GWI values compared with Doppler-based methods. Serial PSL analyses should apply the same event timing method., Competing Interests: Conflict of interest: B.-S.: Steering Committee: Amgen financed GALACTIC-HF trial; the Boston Scientific financed LUX-Dx TRENDS trial; Advisory Board: Sanofi Pasteur; Amgen; Speaker Honorarium: Novartis; Sanofi Pasteur; GSK; research grant: GE Healthcare; Sanofi Pasteur. J.H.S.: advisory board, speaker fee, and research grant: Medtronic. P.S.: consulting fees and speaker honoraria for Biotronic. Remaining others: none., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: A pattern of reduced basal longitudinal strain (BLS) is often observed with left ventricular (LV) hypertrophy (LVH). Whether this pattern is associated with poor outcome is unclear. We aimed to evaluate the prognostic value of regional longitudinal strain according to LV geometry., Methods and Results: We investigated participants in the 4th Copenhagen City Heart Study who had an echocardiogram with speckle tracking performed. Participants were stratified according to the presence of LVH (LV mass index ≥116 g/m2 for men and ≥96 g/m2 for women). The outcome was major adverse cardiovascular events (MACE) defined as a composite of myocardial infarction, heart failure, and/or cardiovascular death. The study population consisted of 1090 participants. Mean LVEF was 60% and 160 (15%) had LVH. During a median follow-up of 14.7 years, there were 137 events. Both BLS and midventricular strain, but not apical strain, became incrementally impaired in the spectrum from normal to hypertensives subjects without LVH, and to participants with hypertension and LVH. After multivariable adjustment, BLS and midventricular strain were independently associated with MACE in participants with LVH (BLS: HR 1.08, 95% CI 1.00-1.17, P = 0.041; midventricular strain: HR 1.10, 95% CI 1.00-1.21, P = 0.041) but not in participants without LVH (BLS: HR 0.96, 95% CI 0.90-1.01, P = 0.13; midventricular strain: HR 0.97, 95% CI 0.91-1.03, P = 0.36)., Conclusion: BLS and midventricular strain, but not apical strain, become incrementally impaired in the spectrum from normal geometry to LVH, and are independently associated with MACE in participants with LVH., Competing Interests: Conflict of interest: K.E.F.-M. was supported by a travel grant from the William Demant Foundation. F.J.O was funded by a research grant from the Danish Heart Foundation (Grant no.: 18-R125-A8534-22083). T.B.-S. was supported by grants from the Fondsbørsvekselerer Henry Hansen og Hustrus Hovedlegat and the Lundbeck Foundation. All other authors declared no conflict of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Assessment of the left ventricular (LV) function by three-dimensional echocardiography (3DE) is potentially superior to 2D echo echocardiography (2DE) for LV performance assessment. However, intra- and interobserver variation needs further investigation. We examined the intra- and interobserver variability between 2 and 3DE in a general population. In total, 150 participants from the Copenhagen City Heart Study were randomly chosen. Two observers assessed left ventricular ejection fraction (LVEF), end-diastolic (EDV) and end-systolic volumes (ESV) by 2DE and 3DE. Inter-, intraobserver and intermodality variabilities are presented as means of difference (MD), limits of agreement (LoA), coefficient of correlation (r), intraclass correlation coefficients (ICC). The lowest MD and LoA and highest r- and ICC-values was generally seen among the 3D acquisitions, with the 3D EDV interobserver as the best performing estimate (r = 0.95, ICC = 0.94). The largest MD, LoA and lowest r- and ICC-values was found in the interobserver 2D LVEF (r = 0.76, ICC = 0.63. For the intraobserver analysis, there were statistically significant differences between observations for all but 3DE EDV (p = 0.06). For interobserver analysis, there were statistically significant differences between observers for all estimates but 2DE EDV (p = 0.11), 3D ejection fraction (p = 0.9), 3DE EDV (p = 0.11) and 3D ESV (p = 0.15). Three-dimensional echocardiography is more robust and reproducible than 2DE and should be preferred for assessment of LV function., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background Left atrial (LA) volumes and emptying fraction in the general population may address structural and functional aspects of atrial cardiomyopathy associated with long-term risk of ischemic stroke in the absence of atrial fibrillation or prior stroke. We investigated the association between LA volumes and function and ischemic stroke. Methods and Results In a community-based cohort, we measured LA minimal volume, LA maximal volume, and LA emptying fraction by transthoracic echocardiography. The primary end point was ischemic stroke. Participants with known atrial fibrillation or prior ischemic stroke were excluded, which resulted in 1866 participants. The mean age was 58±16 years, and 57% were women. During a median follow-up of 16.5 years (interquartile range: 11.4-16.8 years), 176 (9.4%) ischemic strokes occurred. In multivariable cause-specific regression models and competing risk models with death as a competing risk, LA emptying fraction was associated with ischemic stroke (hazard ratio [HR], 1.14 per 10% decrease [95% CI, 1.02-1.28]) and (subdistribution HR, 1.14 [95% CI, 1.01-1.29]). This association remained when adjusting for participants who developed atrial fibrillation during follow-up (HR, 1.12 per 10% decrease [95% CI, 1.00-1.26]). Indexed LA volumes were not associated with ischemic stroke in the same models. LA emptying fraction and indexed LA volumes were not associated with all-cause mortality. Conclusions Lower LA emptying fraction measured by transthoracic echocardiography was associated with future ischemic stroke independently of incident atrial fibrillation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02993172.

Patients undergoing coronary artery bypass grafting (CABG) face an elevated risk of heart failure (HF) and cardiovascular (CV) death. Detailed myocardial tissue analyses of the right ventricle are now possible and may hold prognostic value in these patients. Accordingly, we aimed to evaluate the usefulness of right ventricular (RV) layer-specific RV free wall strain (RVFWS) for predicting HF and/or CV death. Patients undergoing CABG at Gentofte Hospital from 2006 to 2011 with a preoperative echocardiogram underwent RVWFS analysis. RVFWS was obtained by speckle tracking. The outcome was defined as a composite of HF and/or CV death. Cox proportional hazards regression, Harrell's C-statistics, and competing risk regression were used to assess the prognostic value of RVFWS. Of 317 patients, 30 (9.5%) reached the endpoint at a median follow-up of 3.5 years. The mean age was 67 years, 83% were men, and the mean LVEF was 50%. In univariable analyses, endo-RVFWS (HR 1.08, P < 0.001), mid-RVFWS (HR 1.07, P = 0.002), and epi-RVFWS (HR 1.07, P = 0.004, per 1% absolute decrease) were associated with a higher risk of HF or/and CV death. Furthermore, all three layers remained independently associated with the outcome after multivariable adjustment for baseline clinical and echocardiographic measurements. Low endo-RVFWS was associated with a more than threefold increased risk of the outcome (HR = 3.04 (1.45-6.38) P = 0.003). The same was observed for mid-RVFWS (HR = 3.16 (1.45-6.91) P = 0.004), and epi-RVFWS (HR = 3.00 (1.46-6.17) P = 0.003). In patients undergoing CABG, RVFWS assessed by speckle-tracking is a predictor of adverse outcomes., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The purpose of this study was to assess whether influenza vaccination has an impact on the risk of coronavirus disease 2019 (COVID-19)., Methods: A cohort of 46 112 healthcare workers were tested for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and filled in a survey on COVID-19 symptoms, hospitalization, and influenza vaccination., Results: The risk ratio of hospitalization due to SARS-CoV-2 for influenza vaccinated compared with unvaccinated participants was 1.00 for the seasonal vaccination in 2019/2020 (confidence interval, .56-1.78, P = 1.00). Likewise, no clinical effect of influenza vaccination on development of antibodies against SARS-CoV-2 was found., Conclusions: The present findings indicate that influenza vaccination does not affect the risk of SARS-CoV-2 infection or COVID-19., Competing Interests: Potential conflicts of interest. H. B. received lecture fee from BMS. F. F. received research grants from the Novo Nordisk Foundation and the Laerdal Foundation. M. G.-B. reports working as an unpaid chairman for the Committee for Transfusion Medicine, Danish Society for Clinical Immunology. A. D. K. received a research grant from the Danish Heart Foundation. T. B. reports grants for his institution from the Novo Nordisk Foundation, Simonsen Foundation, Lundbeck Foundation, Kai Foundation, and Erik and Susanna Olesen’s Charitable Fund. T. B. also reports the following: an unrestricted grant for his institution and working on the advisory board for GSK; an unrestricted grant for his institution, working as a principal investigator for a clinical trial, and working on the advisory board for Pfizer; working as a principal investigator for a clinical trial for Boehringer Ingelheim; an unrestricted grant for his institution, working as a principal investigator for a clinical trial, and working on the advisory board for Gilead Sciences; an unrestricted grant for his institution, working as a principal investigator, and working on the advisory board for MSD; working as a board member for Pentabase; working as a principal investigator for clinical trials for Roche, Novartis, and Kancera AB; and working on the advisory board for Janssen and Astra Zeneca. T. B. received consulting fees from GSK and Pfizer. T. B. held lectures for GSK, Pfizer, Gilead Sciences, Boehringer Ingelheim, Abbvie, and Astra Zeneca. T. B. received a donation of trial medication from Eli Lilly. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Wall Motion Score Index (WMSI) is a simple method to quantify global and regional systolic function on echocardiography. We sought to investigate the prognostic importance of global and regional WMSI for the development of incident heart failure (HF) in the general population., Methods: We included adults without HF or ischemic heart disease from the 4th Copenhagen City Heart Study (2001-2003). At baseline, participants underwent an echocardiography and physical examination and completed a self-administered health questionnaire. WMSI was assessed by conventional echocardiography using a 16-segment model obtaining WMSI assessments for the anterior, lateral, inferior, septal, and posterior left ventricular (LV) walls and calculating a global WMSI. The primary endpoint was incident HF., Results: Among 3415 participants (mean age 58 years, 42% male, 45% with hypertension), 83 (2.4%) had hypo-, a-, or dyskinesia of at least one LV wall segment at baseline. During a median follow-up of 15.4 years, 297 (8.7%) participants developed HF. After adjusting for important clinical variables, LV ejection fraction and E/A, hypo-, a- or dyskinesia of at least one segment in any of the LV regional walls was associated with a higher risk of incident HF (HR 3.63, 95% CI 2.15-6.12, p < 0.001). Similarly, global WMSI was independently associated with a higher risk of HF (HR 1.38 per 0.1 increase, 95%CI 1.22-1.56, p < 0.001)., Conclusion: Wall motion abnormalities in any regional LV wall and global WMSI were associated with incident HF in this general population cohort independent of various baseline clinical data, LV ejection fraction and E/A., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: Antibodies to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are a key factor in protecting against coronavirus disease 2019 (COVID-19). We examined longitudinal changes in seroprevalence in healthcare workers (HCWs) in Copenhagen and the protective effect of antibodies against SARS-CoV-2., Methods: In this prospective study, screening for antibodies against SARS-CoV-2 (ELISA) was offered to HCWs three times over 6 months. HCW characteristics were obtained by questionnaires. The study was registered at ClinicalTrials.gov, NCT04346186., Results: From April to October 2020 we screened 44 698 HCWs, of whom 2811 were seropositive at least once. The seroprevalence increased from 4.0% (1501/37 452) to 7.4% (2022/27 457) during the period (p < 0.001) and was significantly higher than in non-HCWs. Frontline HCWs had a significantly increased risk of seropositivity compared to non-frontline HCWs, with risk ratios (RRs) at the three rounds of 1.49 (95%CI 1.34-1.65, p < 0.001), 1.52 (1.39-1.68, p < 0.001) and 1.50 (1.38-1.64, p < 0.001). The seroprevalence was 1.42- to 2.25-fold higher (p < 0.001) in HCWs from dedicated COVID-19 wards than in other frontline HCWs. Seropositive HCWs had an RR of 0.35 (0.15-0.85, p 0.012) of reinfection during the following 6 months, and 2115 out of 2248 (95%) of those who were seropositive during rounds one or two remained seropositive after 4-6 months. The 133 of 2248 participants (5.0%) who seroreverted were slightly older and reported fewer symptoms than other seropositive participants., Conclusions: HCWs remained at increased risk of infection with SARS-CoV-2 during the 6-month period. Seropositivity against SARS-CoV-2 persisted for at least 6 months in the vast majority of HCWs and was associated with a significantly lower risk of reinfection., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Pressure-strain loop analyses is a noninvasive technique capable of evaluating myocardial work. Reference values are needed to benchmark these myocardial work indices for clinical practice., Methods: Healthy participants from a general population study were used to establish reference values for global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) measured by pressure-strain loop analyses. The relation to age and sex was examined. We furthermore examined the proportion of abnormal work indices according to low, intermediate, and high cardiovascular risk by the Framingham risk score., Results: The healthy sample consisted of 1827 participants (median age, 45 years; 39% men). Lower reference values were GWI, 1576 mm Hg%; GCW, 1708 mm Hg%; and GWE, 93.0% and upper reference value for GWW was 159 mm Hg%. Women exhibited significantly higher GWI, GCW, and GWW and lower GWE. Sex significantly modified the association between all indices and age ( P for interaction: 0.001 for GWI, 0.009 for GCW, 0.003 for GWW, and 0.009 for GWE). For men, only GCW increased with age, whereas the other indices did not change with age. For women, GCW increased linearly with increasing age, whereas GWI, GWW, and GWE changed in a curvilinear fashion with age such that GWI increased in younger participants, GWW increased in elderly, and GWE declined concordantly. Abnormalities in myocardial work indices became more frequent with increasing Framingham risk score category (abnormal GWI: 2% versus 4% versus 5%, P =0.001; abnormal GCW: 2% versus 3% versus 4%, P =0.006; abnormal GWW: 3% versus 6% versus 11%, P <0.001; abnormal GWE: 3% versus 4% versus 11%, P <0.001)., Conclusions: Myocardial work indices differ between sexes and change with age in a sex-dependent manner. Accordingly, we established age- and sex-specific reference values from a general population sample. Abnormal work indices become more frequent with higher clinical risk., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02993172.

Aims: Technical advancements in 2D-speckle tracking echocardiography (2DSTE) have allowed for quantification of layer-specific global longitudinal strain (GLS) and circumferential strain (GCS) of the left ventricle (LV). The aim of this study was to establish age- and sex-based reference ranges of peak systolic layer-specific GLS and GCS and to assess normal values of regional strain., Methods and Results: We performed 2DSTE analysis of 1997 members of the general population from the fifth round of the Copenhagen City Heart Study, who were free of cardiovascular disease and risk factors. The mean age was 46 ± 16 years (range 21-97) and 62% were female. Mean values for peak systolic whole wall GLS (GLSWW.Sys), endomycardial (GLSEndo.Sys), and epimyocardial (GLSEpi.Sys) were 19.9 ± 2.1% (prediction interval [PI]: 15.8-24.0%), 23.5 ± 2.5% (PI: 18.6-28.4%), and 17.3 ± 1.9% (PI: 13.6-21.1%), respectively. Mean peak systolic whole wall GCS (GCSWW.Sys), was 21.6 ± 3.7% (PI: 14.3-28.9%), endomyocardial (GCSEndo.Sys) was 31.9 ± 4.7% (PI: 22.7-41.1%), and epimyocardial (GCSEpi.Sys) was 14.3 ± 3.8% (PI: 6.8-21.8%). A significant discrepancy in normal strain values between males and females was observed. Men had lower mean values and lower reference limits for all strain parameters. Furthermore, GLS and GCS changed differently with age in males and females. Finally, regional LS decreased from the apical to the basal LV region in both sexes, and regional CS varied significantly by LV segment., Conclusion: In this study, we reported age- and sex-based reference ranges of layer-specific GLS and GCS. These reference ranges varied significantly with sex and age., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Aims: Left atrial enlargement predicts incident atrial fibrillation (AF). However, the prognostic value of peak atrial longitudinal strain (PALS) for predicting incident AF in participants from the general population is currently unknown. Our aim was to investigate if PALS can be used to predict AF and ischaemic stroke in the general population., Methods and Results: A total of 400 participants from the general population underwent a health examination, including two-dimensional speckle tracking echocardiography of the left atrium. The primary endpoint was incident AF at follow-up. All participants with known AF and prior stroke at baseline were excluded (n = 54). The secondary endpoint consisted of the composite of AF and ischaemic stroke. During a median follow-up of 16 years, 36 participants (9%) were diagnosed with incident AF and 30 (7%) experienced an ischaemic stroke, resulting in 66 (16%) experiencing the composite outcome. PALS was a univariable predictor of AF [per 5% decrease: hazard ratio (HR) 1.42; 95% confidence interval (CI) (1.19-1.69), P < 0.001]. However, the prognostic value of PALS was modified by age (P = 0.002 for interaction). After multivariable adjustment PALS predicted AF in participants aged <65 years [per 5% decrease: HR 1.46; 95% CI (1.06-2.02), P = 0.021]. In contrast, PALS did not predict AF in participants aged ≥65 years after multivariable adjustment [per 5% decrease: HR 1.05; 95% CI (0.81-1.35), P = 0.72]. PALS also predicted the secondary endpoint in participants aged <65 years and the association remained significant after multivariable adjustment., Conclusion: In a low-risk general population, PALS provides novel prognostic information on the long-term risk of AF and ischaemic stroke in participants aged <65 years., (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: Height-based indexations for the evaluation of left atrial (LA) volumes have been proposed as an alternative method to account for body stature when body composition is abnormal. The aim of this study was to derive reference values for these indexation methods and to examine their association with atrial fibrillation (AF)., Methods: A healthy population was randomly split into derivation and validation cohorts (n = 493 each). The derivation cohort was used to derive reference values for iso- and allometric height-indexed LA volumes. Echocardiography included measurement of maximal LA volume (LAV max ) and minimal LA volume (LAV min ). Associations between these measures and AF were investigated in the validation cohort. Cox proportional-hazards regression was performed, adjusting for CHARGE-AF (Cohorts for Heart and Aging Research in Genomic Epidemiology Atrial Fibrillation) risk score., Results: From 986 healthy subjects, allometric height-indexed exponents were determined to 1.72 and 1.56 for LAV max and LAV min , respectively. Upper reference values were determined to be LAV max > 22.1 mL/m 1.72 and LAV min > 12.7 mL/m 1.56 . In the validation cohort, 41 patients (8%) developed AF during follow-up (median, 14.7 years). In unadjusted analyses, both isometric and allometric indexed LAV max were associated with AF (hazard ratio, 1.07 [95% CI, 1.03-1.11; P < .001] and 1.11 [95% CI, 1.05-1.18; P < .001] per 1 mL/m and 1 mL/m 1.72 increase, respectively) with equal C statistics of 0.63. Height-indexed LAV min was also associated with AF, with higher C statistics than for LAV max . All findings were consistent after multivariable adjustment. LAV max > 22.1 mL/m 1.72 posed an increased risk for AF (hazard ratio, 4.65; 95% CI, 1.83-11.86), but LAV min > 12.7 mL/m 1.56 carried a higher risk (hazard ratio, 6.33; 95% CI, 2.66-15.07)., Conclusions: Both isometric and allometric height-indexed LA volumes are associated with AF in the general population. LAV min is more strongly associated with AF than LAV max regardless of indexation., (Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Global longitudinal strain (GLS) has proven to be a powerful prognostic marker in various patient populations, but the prognostic value of layer-specific GLS has not yet been investigated in patients with suspected stable angina pectoris (SAP). We sought to investigate the prognostic value of layer-specific and whole wall GLS in patients with suspected SAP. From September 2008 to March 2011, 296 consecutive patients with clinically suspected SAP, normal ejection fraction, and no previous cardiac history were enrolled in a prospective cohort study. Patients underwent echocardiography including two-dimensional speckle tracking at rest, exercise stress test, and coronary angiography. The end-point was a composite of incident heart failure, acute myocardial infarction, and cardiovascular death (MACE). Out of the 285 included patients (mean age 61 years, 50% male), 24 (8%) developed MACE during a median follow-up of 3.5 years. Both endocardial [hazard ratio (HR) 1.21, 95% CI 1.08-1.35, p = 0.001], epicardial (HR 1.29, 95% CI 1.12-1.50, p = 0.001) and whole wall GLS (HR 1.25, 1.10-1.42, p = 0.001) were significantly associated with an increased risk of developing MACE during follow-up in univariable Cox regression analysis. In multivariable analysis, only epicardial (HR 1.23, 95% CI 1.00-1.51, p = 0.046) and whole wall GLS (HR 1.20, 95% CI 1.00-1.43, p = 0.049) remained significantly associated with an increased risk of MACE independent of various baseline clinical variables, left ventricular ejection fraction (LVEF), E/e' and Duke Score. Layer-specific and whole wall GLS were significant predictors of MACE in this cohort of patients with suspected SAP independent of various baseline clinical variables, LVEF, E/e' and Duke Score., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Left atrial (LA) strain parameters have been demonstrated to be valuable predictors of atrial fibrillation (AF) in several patient cohorts. The purpose of this study was to investigate whether LA strain, assessed by two-dimensional speckle-tracking echocardiography, can be used to predict the development of AF in the general population., Methods and Results: This prospective longitudinal study included 4466 participants from the fifth Copenhagen City Heart Study. All participants underwent a health examination, including echocardiographic measurements of LA strain. Participants with prevalent AF at baseline were excluded. The primary endpoint was incident AF. During a median follow-up period of 5.3 years, 154 (4.3%) participants developed AF. In univariable analysis, peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS), and LA strain during the conduit phase were significantly associated with the development of AF. PALS [hazard ratio (HR) 1.05, 95% confidence interval (CI) (1.03-1.07), P < 0.001, per 1% decrease] and PACS (HR 1.08, 95% CI (1.05-1.12), P < 0.001, per 1% decrease] remained independent predictors of AF in multivariable analysis. In addition, PALS and PACS remained significantly associated with AF development even in participants with normal-sized atria and normal left ventricular (LV) systolic function., Conclusion: In the general population, PALS and PACS independently predict incident AF. These findings remained consistent even in participants with normal-sized LA and normal LV systolic function., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Aims: Assessing left atrial (LA) size and function is an important part of the echocardiographic examination. We sought to assess how LA size and function develop over time, and which clinical characteristics promote atrial remodelling., Methods and Results: We examined longitudinal changes of the LA between two visits in the Copenhagen City Heart Study (n = 1065). The median time between the examinations was 10.4 years. LA measurements included: maximal LA volume (LAVmax), minimal LA volume (LAVmin), and LA emptying fraction (LAEF). Clinical and echocardiographic accelerators were determined from linear regression. The value of LA remodelling for predicting incident atrial fibrillation (AF) and heart failure (HF) was examined by Cox proportional hazards regressions. During follow-up, LAVmax and LAVmin significantly increased by 8.3 and 3.5 mL/m2, respectively. LAEF did not change. Age and AF were the most impactful clinical accelerators of LA remodelling with standardized beta-coefficients of 0.17 and 0.28 for changes in LAVmax, and 0.18 and 0.38 for changes in LAVmin, respectively. Left ventricular (LV) systolic function, diameter, and mass were also significant accelerators of LA remodelling. Changes in both LAVmax and LAVmin were significantly associated with incident AF [n = 46, ΔLAVmax: HR = 1.06 (1.03-1.09), P < 0.001 and ΔLAVmin: HR = 1.14 (1.10-1.18), P < 0.001, per 1 mL/m2 increase] and HF [n = 27, ΔLAVmax: HR = 1.08 (1.04-1.12), P < 0.001 and ΔLAVmin: HR = 1.13 (1.09-1.18), P < 0.001, per 1 mL/m2 increase]., Conclusion: Both maximal and minimal LA volume increase over time. Clinical accelerators included age and AF. LV structure and systolic function also accelerate LA remodelling. LA remodelling poses an increased risk of clinical outcomes., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Aims: Left atrial (LA) function assessed by two-dimensional speckle-tracking echocardiography has shown increasing clinical and prognostic significance. We sought to establish age- and sex-based normative values of LA strain in the general population and to assess the prognostic yield of lower limits of normality of LA strain in relation to future atrial fibrillation (AF)., Methods and Results: We determined normative values of peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS), and LA strain during the conduit phase (LACS) in 1641 healthy participants included in the fifth Copenhagen City Heart Study. In a secondary analysis, a validation cohort of 2016 participants, regardless of health status, were included to assess the prognostic value of the established reference values. In the healthy cohort, median age was 46 years (interquartile range 32-57), 62% were female. Median PALS, PACS, and LACS and corresponding limits of normality in the healthy participants were 39.4% (23.0-67.6%), 15.5% (6.4-28.0%), and 23.7% (8.8-44.8%), respectively. There was a tendency of lower values of PALS and LACS in males and older participants, while PACS tended to increase with advancing age. The established lower limits of normality showed high specificity (range 93-94%) regarding future AF, implying a low risk of developing AF in participants with LA strain above the lower limits of normality in their respective sex and age group., Conclusion: We report normal values for LA strain stratified by sex and age. The lower limits of normality showed high specificity regarding future AF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: The ratio of early mitral inflow velocity to early diastolic strain rate (E/e'sr) is a novel echocardiographic measure to estimate early left ventricular (LV) filling pressure. We hypothesize that E/e'sr is a predictor of outcome following coronary artery bypass grafting (CABG) and that it is superior to the conventionally used E/e'., Methods & Results: Consecutive patients undergoing isolated CABG at Gentofte Hospital (n = 652) were included. The mean age of the study population was 67 ± 9 years, 84% were male, mean LVEF was 50 ± 11%. Prior to surgery, all patients underwent an extensive echocardiographic examination. The outcome was all-cause mortality. During follow-up (median 3.8 years [IQR: 2.7; 4.9 years]), a total of 73 (11.2%) died. Both E/e' and E/e'sr were significant predictors in univariable models. In a multivariable model, E/e'sr remained an independent predictor of outcome (HR:1.05 [1.01-1.10], p = 0.049, per 10 cm increase) whereas E/e' did not (HR:1.05 [0.99-1.11], p = 0.053, per 1-unit increase). The relationship between E/e'sr, and the outcome was significantly modified by GLS (p for interaction = 0.043). In the multivariable model, E/e'sr was still significantly associated with the outcome in patients with high GLS (≥13.6%) (HR:1.18 [1.02-1.36], p = 0.029) but not in patients with low GLS (HR 1.04 CI95%: [0.99-1.10], p = 0.14). E/e' was not a significant predictor of all-cause mortality after multivariable adjustment in neither of the groups. E/e'sr improved net reclassification with 33% when added to EuroSCOREII., Conclusion: Following CABG, preoperative E/e'sr is an independent predictor of all-cause mortality, especially in patients with preserved systolic function and superior to E/e'., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)