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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.

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., BACKGROUND: Three-dimensional 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, 2,082 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: LA reservoir strain (LASr) 30.8% (18.4-44.2%), LA conduit strain (LAScd) 19.1% (6.8-32.0%), LA contractile strain (LASct) 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, 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.

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., 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 ag

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 Participants from the 5th Copenhagen City Heart Study (2011–2015) without known chronic ischaemic heart disease or HF and results 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.

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., 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.

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., 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.

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 CHADS2 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.

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/m2), 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.

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.

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.

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.

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.

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.

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

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.

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 (GLS(WW.Sys)), endomycardial (GLS(Endo.Sys)), and epimyocardial (GLS(Epi.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 (GCS(WW.Sys)), was 21.6 +/- 3.7% (PI: 14.3-28.9%), endomyocardial (GCS(Endo.Sys)) was 31.9 +/- 4.7% (PI: 22.7-41.1%), and epimyocardial (GCS(Epi.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.

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.

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.

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.

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 (LAVmax) and minimal LA volume (LAVmin). 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 LAVmax and LAVmin, respectively. Upper reference values were determined to be LAVmax > 22.1 mL/m1.72 and LAVmin > 12.7 mL/m1.56. In the validation cohort, 41 patients (8%) developed AF during follow-up (median, 14.7 years). In unadjusted analyses, both isometric and allometric indexed LAVmax 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/m1.72 increase, respectively) with equal C statistics of 0.63. Height-indexed LAVmin was also associated with AF, with higher C statistics than for LAVmax. All findings were consistent after multivariable adjustment. LAVmax > 22.1 mL/m1.72 posed an increased risk for AF (hazard ratio, 4.65; 95% CI, 1.83-11.86), but LAVmin > 12.7 mL/m1.56 carried a higher risk (

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.

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/eʹ 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/eʹ and Duke Score.