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

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

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

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

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

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

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., (© 2021 European Society of Cardiology.)

Aims: The degree of cardiovascular sequelae following COVID-19 remains unknown. The aim of this study was to investigate whether cardiac function recovers following COVID-19., Methods and Results: A consecutive sample of patients hospitalized with COVID-19 was prospectively included in this longitudinal study. All patients underwent an echocardiographic examination during hospitalization and 2 months later. All participants were successfully matched 1:1 with COVID-19-free controls by age and sex. A total of 91 patients were included (mean age 63 ± 12 years, 59% male). A median of 77 days (interquartile range: 72-92) passed between the two examinations. Right ventricular (RV) function improved following resolution of COVID-19: tricuspid annular plane systolic excursion (TAPSE) (2.28 ± 0.40 cm vs. 2.11 ± 0.38 cm, P < 0.001) and RV longitudinal strain (RVLS) (25.3 ± 5.5% vs. 19.9 ± 5.8%, P < 0.001). In contrast, left ventricular (LV) systolic function assessed by global longitudinal strain (GLS) did not significantly improve (17.4 ± 2.9% vs. 17.6 ± 3.3%, P = 0.6). N-terminal pro-B-type natriuretic peptide decreased between the two examinations [177.6 (80.3-408.0) ng/L vs. 11.7 (5.7-24.0) ng/L, P < 0.001]. None of the participants had elevated troponins at follow-up compared to 18 (27.7%) during hospitalization. Recovered COVID-19 patients had significantly lower GLS (17.4 ± 2.9% vs. 18.8 ± 2.9%, P < 0.001 and adjusted P = 0.004), TAPSE (2.28 ± 0.40 cm vs. 2.67 ± 0.44 cm, P < 0.001 and adjusted P < 0.001), and RVLS (25.3 ± 5.5% vs. 26.6 ± 5.8%, P = 0.50 and adjusted P < 0.001) compared to matched controls., Conclusion: Acute COVID-19 affected negatively RV function and cardiac biomarkers but recovered following resolution of COVID-19. In contrast, the observed reduced LV function during acute COVID-19 did not improve post-COVID-19. Compared to the matched controls, both LV and RV function remained impaired., (© 2021 European Society of Cardiology.)

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 (GLS WW ), endomyocardial (GLS Endo ), and epimyocardial (GLS Epi ) 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, GLS WW [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.02-1.31, per 1% decrease] and GLS Epi (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 GLS Epi being the only layer-specific prognosticator in males, while no GLS parameter provides independent prognostic information in females., (© 2021 European Society of Cardiology.)

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., (© 2021 Wiley Periodicals LLC.)

Background: Elevated resting heart rate (RHR) is associated with cardiovascular mortality and morbidity. Assessment of heart rate (HR) from Holter recording may afford a more precise estimate of the effect of RHR on cardiovascular risk, as compared to casual RHR. Comparative analysis was carried out in an age-stratified subsample of 131 subjects in the Copenhagen City Heart Study (CCHS)., Methods: Casual RHR was assessed from electrocardiograms recorded during clinical assessment. Hourly daytime HRs were mapped by Holter recording. Holter RHR was defined as the average of the lowest 3 hourly HRs recorded and mean HR calculated from all daytime HRs. Follow-up was recorded from public registers. Outcome measure was hazard rate for the combined endpoint of cardiovascular mortality, non-fatal heart failure and non-fatal acute myocardial infarction. Comparison of casual RHR, Holter RHR and mean HR by Multivariate Cox regression was performed., Results: A total of 57 composite endpoints occurred during 17.1 years of follow-up. Regression analysis suggests correlation between Casual RHR and Holter RHR. Multivariate Cox regression analysis adjusted for gender and age demonstrated hazard rates of 1.02 (p = 0.079) for casual RHR, 1.04 (p = 0.036*) for Holter RHR, and 1.03 (p = 0.093) for mean HR for each 10 beat increment in HR., Conclusions: In a comparative analysis on the correlation and significance of differing RHR measurement modalities RHR measured by 24-hour Holter recording was found to be marginally superior as a predictor of cardiovascular morbidity and mortality. The results presented here do not however warrant the abandonment of a tested epidemiological variable.

Aims: To investigate levels of vitamin D and parathyroid hormone (PTH) in a population of heart failure (HF) patients, and to evaluate whether vitamin D and PTH are related to prognosis., Methods and Results: This was a prospective study of 148 HF outpatients (mean age 68 years, 102 men) with follow-up for mortality after 3½ years. Levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), PTH, 25-hydroxyvitamin D (25-OHD), and several other biomarkers were examined. Mortality and cardiovascular mortality were analysed in multivariable regression analyses adjusting for other independent prognostic variables. Vitamin D deficiency (≤50 nmol/L) was prevalent in 43% of the population; 26% had elevated PTH levels; none had primary hyperparathyroidism. We found a strong and independent significant association of both PTH and vitamin D to mortality, which was independent of other clinically important parameters [NT-proBNP, estimated glomerular filtration rate (eGFR), age, and left ventricular ejection fraction (LVEF)]. Both PTH and vitamin D were also significantly associated with all cause mortality. In an adjusted model, we found a hazard ratio of 1.9 (confidence interval 1.1-3.4) for vitamin D deficiency and 2.0 (1.0-3.8) for the upper median of PTH, respectively., Conclusion: In this relatively small prospective study, PTH and vitamin D were independently associated with all cause and cardiovascular mortality in patients with HF. This was independent of other known risk factors such as eGFR, LVEF, NT-proBNP, and age.

Background: QT dispersion is considered an index of spatial inhomogeneity of repolarization duration and increased dispersion of ventricular repolarization is supposed to increase the risk of ventricular arrhythmia. Circadian variation in QT dispersion was investigated., Methods: Three different modes of lead selection was used: all 12-leads (QTdisp 12), only precordial leads (QTdisp 6), and one pair of preselected leads (QTdisp 2) in a 24-hour Holter recording every fourth hour each comprising 10 consecutive measurements in 54 healthy subjects, 29 patients with coronary artery disease (CAD), and 29 patients with heart failure (HF)., Results: A significant circadian variation was observed in healthy subjects when modes QTdisp 12 and QTdisp 6 were used (Mean +/- SD 35.58 +/- 16.48 ms; P < 0.0001; and 28.82 +/- 16.02 ms; P < 0.0001, respectively), and in patients with CAD (Mean +/- SD 37.86 +/- 17.87 ms; P < 0.01; and 28.72 +/- 17.06 ms; P < 0.0001, respectively), whereas no circadian variation was observed in QTdisp 2. No circadian variation was observed in patients with HF irrespectively of lead selection. Patients with CAD without myocardial infarction (MI) had a circadian variation in QTdisp 12 (Mean +/- SD 33.13 +/- 14.86 ms; P < 0.05), whereas no circadian variation was observed in patients with MI (Mean +/- SD 40.35 +/- 18.80 ms; P = NS)., Conclusions: Circadian variation of QT dispersion was detected in healthy subjects and in patients with uncomplicated CAD, but not in those who had suffered a previous MI and in patients with HF. The number of leads among which selection of the longest and shortest QT intervals took place was critical for the disclosure of circadian variation of QT dispersion.

Objective: To evaluate the prognostic roles of prolonged signal-averaged P wave duration (SAPWD), raised levels of natriuretic peptides, and clinical characteristics in patients with stable congestive heart failure (CHF)., Design: The SAPWD was assessed from a signal-averaged electrocardiogram (SAECG), and the plasma levels of N-terminal pro-atrial natriuretic peptide (Nt-proANP) and N-terminal pro-brain natriuretic peptide (Nt-proBNP) were measured in 43 consecutive patients with stable CHF without prior supraventricular arrhythmia. Echocardiographic and clinical data were also recorded. Time to death, hospitalization due to deteriorated CHF, or ECG-documented atrial fibrillation (AF) was recorded over a 438-day median follow-up., Results: During follow-up, 17 patients met an endpoint defined as death, AF, or hospitalization due to deteriorated CHF. Proportional hazard regression including the variables high age, prolonged SAPWD, raised levels of Nt-proANP and Nt-proBNP, and low ejection fraction (EF) showed that only prolonged SAPWD > or =149 ms was associated with an increased risk of meeting an early endpoint; the hazard ratio 3.94 with 95% confidence interval 1.50-10.42; p = 0.006., Conclusion: Prolonged SAPWD appears to predict early death, AF development, or hospitalization due to deterioration of CHF in patients with stable CHF.

Unlabelled: 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 < or =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.

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 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 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]

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]

Background: Atrial fibrillation (AF) is the most common aberrant cardiac arrhythmia. Many AF patients present with symptoms of dyspnea and fatigue, but have normal left ventricular ejection fraction (LVEF). Purpose: To determine the reproducibility of measurements of global longitudinal strain (GLS) and strain rate in patients with AF and examine if the arrhythmia is associated with abnormal LV strain and strain rate independent of age, sex, heart rate, LVEF and LV mass. We hypothesized that AF independently reduces ventricular systolic performance. Methods: The study was conducted as a retrospective analysis of images from 150 randomly selected patients with AF compared to an equal number of subjects with sinus rhythm (SR) matched for age, sex, heart rate, LVEF and LV mass. Half of the patients had normal LVEF (LVEF > 50%) and half had reduced LVEF (LVEF < 50%). GLS and strain rate were measured in each group, as were quantitative LV volumes and standard systolic and diastolic parameters. Results: GLS was significantly impaired in patients with AF compared to subjects with SR, both in the overall population (-12.25 ± 4.1% vs. –16.13 ± 4.7%, p<0.0001), in patients with normal LVEF (-14.41 ± 3.9% vs. –19.42 ± 3.1%, p<0.0001) and in patients with reduced LVEF (-10.10 ± 3.1% vs. –12.85 ± 3.5%, p<0.0001). Linear regression and Bland Altman analyses demonstrated good intraobserver and interobserver agreement for measurements of GLS and strain rate parameters even in patients with AF. Conclusions: Measurements of GLS and strain rate parameters are reproducible in patients with AF. Patients with AF have significantly impaired values of GLS when compared to similar patients with SR independent of age, sex, heart rate, LVEF and LV mass. [ABSTRACT FROM AUTHOR]