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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.)

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.)

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: 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.)

Background: Global longitudinal strain (GLS) is a sensitive marker of myocardial dysfunction and atrial reservoir function. We sought to evaluate its value for predicting atrial fibrillation (AF) in the general population., Methods: Participants from the Copenhagen City Heart Study examined with echocardiography, including speckle tracking analyses, were included. The endpoint was AF obtained through national registries. Proportional hazards Cox regression was applied, including multivariable adjustments made for CHADS 2 and CHARGE-AF risk factors. Abnormal GLS was defined as >-18%., Results: The data from 1,309 participants were analyzed. Of those, 153 (12%) developed AF during a median follow-up time of 15.9 years. The follow-up was 100%. The mean age was 57 years, 38% had hypertension, and GLS was  - 18%. In unadjusted analysis, GLS was a univariable predictor of outcome (1.08 (1.04-1.13), p < 0.001, per 1% absolute decrease), but did not remain an independent predictor after adjusting for neither CHADS 2 nor CHARGE-AF risk factors. However, hypertension modified the relationship between GLS and AF (p for interaction = 0.010), such that GLS only predicted AF in subjects without hypertension. In participants without hypertension, GLS remained an independent predictor of AF after adjusting for CHADS 2 and CHARGE-AF (HR = 1.11 (1.03-1.20) and HR = 1.09 (1.01-1.19), respectively). In these participants, an abnormal GLS was associated with a more than twofold increased risk of AF (HR = 2.16 (1.26-3.72). The incidence rate was 3.17 and 6.81 per 1000 person-years for normal vs. abnormal GLS, respectively., Conclusion: Global longitudinal strain predicts AF in individuals without hypertension from the general population, independently of common risk scores., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: This study sought to investigate whether left atrial (LA) functional measures predict atrial fibrillation (AF) in the general population., Background: Increasing evidence suggests LA functional measures are predictors of AF in several patient groups., Methods: In a community-based cohort study, approximately 2,000 individuals underwent a transthoracic echocardiogram. Conventional echocardiographic measures and extended LA measures, including the minimal and maximal LA volumes (LAV min and LAV max , respectively) and left atrial emptying fraction (LAEF), were performed. The endpoint was incident AF, and participants with known AF were excluded, which left 1,951 for inclusion., Results: Over 11.0 years of follow-up, 184 (9.4%) developed AF. Those who developed AF had significantly larger LA volumes and lower LAEF than participants free of AF. These LA measures were univariable predictors of AF (LAV max hazard ratio [HR]: 1.10 [95% confidence interval (CI): 1.08 to 1.12] per 1-ml increase, p < 0.001; LAV min HR: 1.14 [95% CI: 1.12 to 1.16] per 1-ml increase, p < 0.001; LAEF HR: 1.03 [95% CI: 1.02 to 1.04] per percent decrease, p < 0.001). All LA measures remained predictors independent of clinical risk scores, with LAV min providing the highest C-statistics when added to these risk scores (C-statistic for CHADS 2 0.728 vs. CHADS 2  + LAV min 0.778; C-statistic for CHARGE-AF 0.815 vs. CHARGE-AF + LAV min 0.830). However, hypertension modified the relationship between the measures of LA function (both LAV min and LAEF) and risk of AF (p for interaction < 0.001), which was not the case for LAV max (p = 0.22). The measures of LA function mainly provided prognostic information regarding risk of AF in participants without hypertension. Even when we restricted our analysis to individuals without hypertension and nondilated LA (LAV max <34 ml/m 2 ), the LAV min and LAEF remained significantly independent predictors of AF after multivariable adjustments (LAV min HR: 1.12 [95% CI: 1.01 to 1.24], p = 0.028, and LAEF HR: 1.03 [95% CI: 1.00 to 1.06], p = 0.021, respectively)., Conclusions: LA functional measures predict AF in the general population and provide prognostic information incremental to clinical risk scores. In individuals without hypertension and nondilated LA, these measures indicate an increased risk of AF., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with substantial morbidity and mortality. AF is associated with enlargement of the left atrium (LA), and the LA volume has important prognostic implications for the disease. The objective of the study was to determine how measurements of LA volume and function obtained by transthoracic echocardiography (TTE), cardiac magnetic resonance (CMR), and 320-slice multi-detector computed tomography (MDCT) correlate in patients with permanent AF., Methods and Results: Thirty-four patients with permanent AF participated in the study. TTE, CMR, and 320-slice MDCT imaging procedures were performed within 7 ± 4 days. 320-slice MDCT overestimated maximal LA volume (LAmax) and minimal LA volume (LAmin) compared with CMR (LAmax: 80 vs. 73 mL/m(2), P = 0.0017; LAmin: 69 vs. 64 mL/m(2), P = 0.0217), whereas TTE underestimated these parameters compared with CMR (LAmax: 60 vs. 73 mL/m(2), P < 0.0001; LAmin: 50 vs. 64 mL/m(2), P < 0.0001), and also compared with MDCT (LAmax: 60 vs. 80 mL/m(2), P < 0.0001; LAmin: 50 vs. 69 mL/m(2), P < 0.0001). Measurements of LA volumes by MDCT and CMR closely correlated, and both MDCT and CMR had excellent intra- and inter-observer agreement with correlation coefficients of >0.90. The correlation between TTE-derived measurements and CMR/MDCT was fair to moderate. Intra- and inter-observer agreement for LA volume measurements by TTE were inferior to CMR and MDCT., Conclusion: Measurements of LA volumes by CMR and 320-slice MDCT correlate closely in patients with permanent AF, and both modalities improve the reproducibility of measurements of LA volumes and function compared with 2D TTE.

Background: Delay of atrial electrical conduction measured as prolonged signal-averaged P wave duration (SAPWD) could be due to atrial enlargement. Here, we aimed to compare different atrial size parameters obtained from echocardiography with the SAPWD measured with a signal-averaged electrocardiogram (SAECG)., Methods: In 74 patients scheduled for elective echocardiography, an SAECG was recorded directly after the echocardiogram. We measured the SAPWD and registered clinical characteristics. The correlation between the SAPWD and the left atrial diameter (LAD), left atrial volume (LAV), right atrial volume (RAV), and total atrial volume (TAV) was analyzed by linear regression analyses. The effect of concomitant risk factors on TAV and the SAPWD was examined., Results: Linear regression analysis showed that the correlation between the SAPWD and the LAD was significant (R(2)= 0.11, P = 0.03). However, LAV (R(2)= 0.15, P = 0.009), RAV (R(2)= 0.27, P = 0.0003), and TAV (R(2)= 0.37, P < 0.0001) were more strongly correlated to the SAPWD. The TAV and the SAPWD were not significantly associated with coexisting risk factors., Conclusions: The SAPWD is significantly correlated to the atrial size; most strongly to the TAV. The size of the right atrium, with the sinus node area, appears to affect the SAPWD.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims This study investigated left atrial (LA) parameters as measured on transthoracic echocardiography as predictors of incident heart failure (HF) in a community cohort. Methods and results In a large general population study (n = 2221), participants underwent a health examination with echocardiography. The maximum and minimum LA volumes indexed to body surface area (LAVImax and LAVImin) were measured and the LA emptying fraction (LAEF) and LA expansion index (LAEI) were calculated. Among 1951 participants without atrial fibrillation or significant valve disease, the mean age was 59±16 years and 58% were women. At baseline, 1% (n = 16) had a left ventricular ejection fraction of <50%, 44% had hypertension, and 10% had diabetes. During follow-up (median 15.8 years, interquartile range: 11.3-16.2 years), 187 (10%) participants were diagnosed with incident HF. Participants who were diagnosed with HF during follow-up had a larger LAVImax and LAVImin and a lower LAEF and LAEI compared to participants without HF. In unadjusted analysis, LAVImax, LAVImin, LAEF and LAEI were predictors of incident HF. After multivariable adjustment for clinical and echocardiographic parameters, only LAVImin remained an independent predictor of incident HF (hazard ratio per 1 standard deviation increase: 1.22 [95% confidence interval 1.01-1.47], p = 0.038). Conclusion In the general population, LAVImin is an independent predictor of incident HF. LAVImax, currently the only LA measure in a routine echocardiographic examination, was not an independent predictor of incident HF. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: Layer‐specific global longitudinal strain (GLS) has been demonstrated to predict outcome in various patient cohorts. However, little is known regarding the prognostic value of layer‐specific GLS in the general population and whether different layers entail differential prognostic information. The aim of the present study was to investigate the prognostic value of whole wall (GLSWW), endomyocardial (GLSEndo), and epimyocardial (GLSEpi) GLS in the general population. Methods and results: A total of 4013 citizens were included in the present study. All 4013 had two‐dimensional speckle tracking echocardiography performed and analysed. Outcome was a composite endpoint of incident heart failure and/or cardiovascular death. Mean age was 56 years and 57% were female. During a median follow‐up time of 3.5 years, 133 participants (3.3%) reached the composite outcome. Sex modified the relationship between all GLS parameters and outcome. In sex‐stratified analysis, no GLS parameter remained significant predictors of outcome in females. In contrast, GLSWW [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.02–1.31, per 1% decrease] and GLSEpi (HR 1.19, 95% CI 1.04–1.38, per 1% decrease) remained as significant predictors of outcome in males after multivariable adjustment (including demographic, clinical, biochemistry, and echocardiographic parameters). Lastly, only in males did GLS parameters provide incremental prognostic information to general population risk models. Conclusions: In the general population, sex modifies the prognostic value of GLS resulting in GLSEpi being the only layer‐specific prognosticator in males, while no GLS parameter provides independent prognostic information in females. [ABSTRACT FROM AUTHOR]

Background: The ratio of transmitral early filling velocity to early diastolic strain rate (E/e'sr) may be a more accurate measure of LV filling pressure then ratio of early filling pressure to early tissue velocity. The aim of the study was to investigate the impact of age, sex, obesity, smoking, hypertension, hypercholesterolemia, diabetes, physical activity level, socioeconomic, and psychosocial status on E/e'sr over a decade. Additionally, the predictive value of ΔE/e'sr on future major adverse cardiovascular events (MACE) has never been explored. Method: The study included 623 participants from the general population, who participated in the 4th and 5th Copenhagen City Heart Study (CCHS4 and CCHS5). Examinations were median 10 years apart. MACE was the composite endpoint of heart failure, myocardial infarction, and all‐cause death. Results: Follow‐up time was median 5.7 years, and 43 (7%) experienced MACE. Mean age was 51 ± 14 years, and 43% were male. Mean ΔE/e'sr was 2.1 ± 23.0 cm. After multivariable adjustment for demographic, clinical, and biochemistry variables, high age (stand. β‐coef. =.24, P <.001) and mean arterial blood pressure (MAP) (stand. β‐coef. =.17, P <.001) were significantly associated with an accelerated increase in E/e'sr In multivariable Cox regression, E/e'sr at CCHS5 and ΔE/e'sr were independent predictors of MACE (HR = 1.20, 95% CI [1.01; 1.42] per 10 cm increase for both). ΔE/e'sr did only provide incremental prognostic value to change in left atrial volume index of the conventional diastolic measurements. Conclusion: In the general population, age and MAP were predictors of an accelerated increase in E/e'sr over a decade. E/e'sr at CCHS5 and ΔE/e'sr were independent predictors of future MACE. [ABSTRACT FROM AUTHOR]

Aims Colour tissue Doppler imaging (TDI) M-mode through the mitral leaflet is an easy and precise method to obtain cardiac time intervals including the isovolumic contraction time (IVCT), isovolumic relaxation time (IVRT), and ejection time (ET). The myocardial performance index (MPI) was defined as [(IVCT + IVRT)/ET]. Our aim was to investigate if cardiac time intervals can be used to predict atrial fibrillation (AF) in the general population. Methods and results A total of 1915 participants from the general population underwent a health examination including TDI echocardiography. The primary endpoint was AF, and the secondary endpoint was complicated AF as assessed by the occurrence of either stroke or heart failure (HF) after the diagnosis of AF. Participants with known AF were excluded (n  = 54). During a median follow-up of 11 years, 166 participants (9%) were diagnosed with AF and of these 44 participants (27%) developed HF or stroke. Assessing the association between IVCT and incident AF, the risk increased with 27% per 10 ms increase in IVCT [per 10 ms increase: hazard ratio (HR) 1.27, 95% confidence interval (CI) (1.17–1.38); P  < 0.001]. The association remained significant after multivariable adjustment [per 10 ms increase: HR 1.22, 95% CI (1.09–1.35); P  < 0.001]. No associations between the IVRT, ET, MPI, and AF remained significant after multivariable adjustment. The IVCT also predicted complicated AF and the association remained significant even after multivariable adjustment [per 10 ms increase: HR 1.39, 95% CI (1.06–1.81); P  = 0.015]. Conclusion In the general population, the IVCT provides novel and independent prognostic information on the long-term risk of AF. Additionally, the IVCT can identify persons in risk of complicated AF. [ABSTRACT FROM AUTHOR]

Aims Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with substantial morbidity and mortality. AF is associated with enlargement of the left atrium (LA), and the LA volume has important prognostic implications for the disease. The objective of the study was to determine how measurements of LA volume and function obtained by transthoracic echocardiography (TTE), cardiac magnetic resonance (CMR), and 320-slice multi-detector computed tomography (MDCT) correlate in patients with permanent AF. Methods and results Thirty-four patients with permanent AF participated in the study. TTE, CMR, and 320-slice MDCT imaging procedures were performed within 7 ± 4 days. 320-slice MDCT overestimated maximal LA volume (LAmax) and minimal LA volume (LAmin) compared with CMR (LAmax: 80 vs. 73 mL/m2, P = 0.0017; LAmin: 69 vs. 64 mL/m2, P = 0.0217), whereas TTE underestimated these parameters compared with CMR (LAmax: 60 vs. 73 mL/m2, P < 0.0001; LAmin: 50 vs. 64 mL/m2, P < 0.0001), and also compared with MDCT (LAmax: 60 vs. 80 mL/m2, P < 0.0001; LAmin: 50 vs. 69 mL/m2, P < 0.0001). Measurements of LA volumes by MDCT and CMR closely correlated, and both MDCT and CMR had excellent intra- and inter-observer agreement with correlation coefficients of >0.90. The correlation between TTE-derived measurements and CMR/MDCT was fair to moderate. Intra- and inter-observer agreement for LA volume measurements by TTE were inferior to CMR and MDCT. Conclusion Measurements of LA volumes by CMR and 320-slice MDCT correlate closely in patients with permanent AF, and both modalities improve the reproducibility of measurements of LA volumes and function compared with 2D TTE. [ABSTRACT FROM PUBLISHER]

Background. Atrial fibrillation (AF) is associated with significant morbidity and mortality. To test the effect of interventions, knowledge of cardiac output (CO) is important. However, the irregular heart rate might cause some methods for determination of CO to have inherent weaknesses. Objective. To assess the validity of these methods in AF, a new inert gas rebreathing device and impedance cardiography was tested with echocardiography as reference. Methods. Using a cross-sectional design, 127 patients with AF and 24 in SR were consecutively recruited. Resting CO was measured using inert gas rebreathing ( n == 62) or impedance measurement of intrathoracic blood flow ( n == 89) in separate studies with echocardiographic measurement as reference. Results. CO determined with impedance cardiography was mean 4.77 L/min ±± 2.24(SD) compared to 4.93 L/min ±± 1.17 by echocardiography ( n == 89, n.s.) in patients with AF. CO by inert gas rebreathing was 4.98 L/min ±± 2.49(SD) compared to 5.70 L/min ±± 2.49 by echocardiography ( n == 62, n.s.) in patients with AF and SR (AF 5.42 ±± 2.9 vs. 6.27, n.s. and SR 4.09 ±± 1.08 vs. 4.35 ±± 0.86, n.s.). Mean bias between impedance cardiography and echocardiography was 0.14 ±± 0.95 L/min and −−0.13 ±± 0.98 L/min between inert gas rebreathing and echocardiography. Inert gas rebreathing showed larger intra-patient variation than impedance cardiography (0.11 vs. 0.054). Correlation between inert gas rebreathing and echocardiography was r == −−0.060 and between impedance cardiography and echocardiography was r == 0.128. Impedance cardiography and inert gas rebreathing both underestimated CO compared to echocardiography. Conclusion. Variation between the inert gas rebreathing and the reference method for AF patients was less than desired. Impedance cardiography was superior to inert gas rebreathing and showed acceptable agreement with echocardiography and variability similar to echocardiography. [ABSTRACT FROM AUTHOR]

Objective. To assess the long-term risk of developing permanent AF in relation to the signal-averaged P wave duration (SAPWD) and clinical and echocardiographic characteristics. Design. In an observational study design we studied 131 patients with earlier ECG-documented AF and successfully restored sinus rhythm attending a long-term, follow-up visit at hospital or at home. Established permanent AF was examined in relation to primary clinical, echocardiographic, and electrophysiological parameters. Results. Only prolonged SAPWD (p =0.006) was associated with an increased risk of development of permanent AF. The risk of permanent AF after 3 years follow-up was 0.72 with an SAPWD equal to 180 ms versus 0.39 with a normal SAPWD (130 ms). We found no prognostic effect of age, gender, dilated left atrium, long duration of AF history, or long duration of the most recent episode of AF. Co-existing hypertension reduced the risk of permanent AF; this could be explained by concomitant treatment with angiotensin-converting-enzyme-inhibitors. Conclusion. Prolonged SAPWD (a marker of atrial remodelling) appears to be a risk factor for long-term development of permanent AF. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the efficacy of adding the beta-blocker bucindolol to standard therapy shortly after a myocardial infarction in a high-risk population with reduced left ventricular function. Methods: The study was planned to include 2000 patients with an enzyme confirmed myocardial infarction and severely reduced left ventricular function determined by echocardiography (corresponding to ejection fraction &les;0.35). The primary endpoint was all cause mortality and the secondary endpoints were time to first event of death, progression of heart failure or reinfarction—and the components. The study was closed early due to discontinuation of development of bucindolol by the manufacturer. Therefore, 170 patients were randomised to receive bucindolol and 173 to receive placebo. Results: There were 27 deaths in the bucindolol group and 30 in the placebo group, hazard ratio of bucindolol 0.88 (95% confidence limits 0.5–1.5; P=0.6). There were 9/4 (bucindolol/placebo, P=0.16) heart failure events and 5/17 (P=0.01) reinfarctions in the bucindolol/placebo groups. Conclusion: Due to early closure it is unknown whether bucindolol changes mortality in high-risk post myocardial infarct patients when added to best medical therapy. The frequency of reinfarction was significantly reduced. [Copyright &y& Elsevier]

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. 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. 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). 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. [Display omitted] • 3,415 participants from the general population without heart failure or ischemic heart disease were included. • Wall motion score index was assessed by echocardiography at baseline using a 16 segment model. • 83 participants (2.4%) had hypo-, a-, or dyskinesia of at least one left ventricular segment at baseline. • During a median follow-up of 15.4 years (IQR 11.9-16.0), 297 participants (8.7%) developed incident heart failure. • Hypo-, a-, or dyskinesia of ≥1 segment in any left ventricular wall was associated with a higher risk of incident heart failure. [ABSTRACT FROM AUTHOR]

Background Though the electrocardiogram(ECG) and plasma pro-brain-natriuretic-peptide (pro-BNP) are widely used markers of subclinical cardiac injury and can be used to predict future cardiovascular disease(CVD), they could merely be markers of the same underlying pathology. We aimed to determine if ECG changes and pro-BNP are independent predictors of CVD and if the combination improves risk prediction in persons without known heart disease. Methods Pro-BNP and ECG were obtained on 5454 persons without known heart disease from the 4th round of the Copenhagen City Heart Study, a prospective cohort study. Median follow-up was 10.4 years. High pro-BNP was defined as above 90th percentile of age and sex adjusted levels. The end-points were all-cause mortality and the combination of admission with ischemic heart disease, heart failure or CVD death. Results ECG changes were present in 907 persons and were associated with high levels of pro-BNP. In a fully adjusted model both high pro-BNP and ECG changes remained significant predictors: all-cause mortality(high pro-BNP, no ECG changes: HR: 1.43(1.12–1.82);P = 0.005, low pro-BNP, ECG changes: HR: 1.22(1.05–1.42);P = 0.009, and both high pro-BNP and ECG changes: HR: 1.99(1.54–2.59);P < 0.001), CVD event(high pro-BNP, no ECG changes: HR: 1.94(1.45–2.58);P < 0.001, low pro-BNP, ECG changes: HR: 1.55(1.29–1.87);P < 0.001, and both high pro-BNP and ECG changes: HR: 3.86(2.94–5.08);P < 0.001). Adding the combination of pro-BNP and ECG changes to a fully adjusted model correctly reclassified 33.9%(26.5–41.3);P < 0.001 on the continuous net reclassification scale for all-cause mortality and 49.7%(41.1–58.4);P < 0.001 for CVD event. Conclusion Combining ECG changes and pro-BNP improves risk prediction in persons without known heart disease. [ABSTRACT FROM AUTHOR]