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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.)

Background: Dyspnea is a common clinical challenge in patients with type 2 diabetes and may be a sign of heart failure (HF). We sought to evaluate the predictive value dyspnea with and without an echocardiographic substrate in patients with type 2 diabetes without known heart disease., Methods: A total of 724 patients with type 2 diabetes followed at specialized clinics participated in this prospective cohort study. Clinical evaluation, comprehensive echocardiography and follow-up through national registers were performed. An echocardiographic substrate was either left ventricular hypertrophy, increased left atrial size, E/e' > 15, or LV ejection fraction<50%. The end-points were cardiovascular (CVD) events and all-cause mortality., Results: Median follow-up was 4.8 years [Interquartile range: 4.1, 5.3] for CVD event and 77 patients suffered a CVD event. Dyspnea was significantly associated with CVD event: Hazard ratio (HR): 1.58 (95% confidence interval: 1.01-2.48), p = 0.04. Stratifying by evidence of echocardiographic substrate revealed high risk individuals: CVD event: 0.71 (0.35-1.46), p = NS in patients with dyspnea and no echocardiographic substrate and 2.85 (1.74-4.67), p < 0.001 in patients with dyspnea with echocardiographic substrate). This pattern was similar in multivariable analyses. Also, C-statistics improved from 0.66 (0.60-0.72) to 0.69 (0.63-0.75), p < 0.001 and net reclassification index was 27.5%(5.0-50.0), p = 0.01 for CVD event. The results were similar for all-cause mortality except dyspnea was only a borderline significant predictor., Conclusion: In patients with type 2 diabetes complaining of dyspnea, identifying an echocardiographic substrate - thus indicating patients with HF - accurately stratifies patients with increased risk of CV events and all-cause mortality., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims: Albuminuria-a marker of generalized vascular dysfunction-is a strong predictor of heart failure in patients with type 2 diabetes which may be caused by concomitant myocardial dysfunction reflecting the same underlying pathogenesis., Methods and Results: We included 915 patients with type 2 diabetes from two secondary care centres and stratified according to albuminuria status in normo-, micro-, and macroalbuminuria. We performed comprehensive echocardiography including conventional imaging, tissue Doppler imaging, and 2D speckle tracking. Cardiac remodelling occurred in patients with increasing left ventricular (LV) mass index and LV wall thicknesses with increasing severity of albuminuria. Diastolic measures worsened across groups of albuminuria severity (normo-, micro-, and macroalbuminuria, respectively): septal e' velocity [mean: 6.9 cm/s (SD 1.9), 6.4 (1.7), and 5.9 (1.7), P < 0.001], septal E/e' (median: 10.6 [interquartile range: 8.9-13.2], 12.1 [10.3-14.8], and 12.7 [10.4-16.6], P < 0.001), and left atrial volume index (24.3 mL/m2 [19.1-29.9], 25.7 [20.0-31.6], and 29.0 [22.2-34.9], P < 0.001) In contrast, systolic measures were only impaired in patients with macroalbuminuria: global longitudinal strain (GLS): [-14.6% (2.7) in normo- and -13.3 (2.9) in macroalbuminuria, P < 0.001] and GLS rate [mean: -0.79 s-1 (0.17) in normo- and -0.72 (0.16) in macroalbuminuria, P = 0.001]. The findings persisted in subgroup analyses of patients without known coronary heart disease and with normal ejection fraction and in multivariable adjusted analyses., Conclusion: In patients with type 2 diabetes, microalbuminuria is associated with decreased diastolic function whereas decreased systolic function was only associated with macroalbuminuria supporting the notion of similar pathogenic mechanisms of albuminuria and impaired myocardial function.

Hypertension may be the most significant cardiovascular risk factor. Few studies have assessed the prognostic value of echocardiography in hypertensive individuals. This study examines the incremental prognostic value of adding echocardiographic parameters to established risk factors in individuals from the general population with and without hypertension. A total of 1294 individuals from the general population underwent a health examination and an echocardiogram including 2-dimensional speckle tracking. Outcome was a composite of ischemic heart disease and heart failure. The prevalence of hypertension was 38.3%. During a median follow-up of 12.5 years (interquartile range, 9.4-12.8 years), 222 participants (17.2%) developed the outcome. Out of these 222 events, 145 (65%) occurred in hypertensive participants, whereas 77 (35%) occurred in nonhypertensive individuals, corresponding to an incidence rate of 32/(1000×person-years) and 8/(1000×person-years), respectively. Follow-up was 100%. After multivariable adjustment, only left ventricular mass index predicted the outcome in hypertensive individuals, whereas only global longitudinal strain predicted the outcome in nonhypertensive individuals. In hypertensive individuals the prognostic value of left ventricular mass index was incremental to SCORE and abnormal ECG status. In nonhypertensive individuals the prognostic value of global longitudinal strain was incremental to SCORE and abnormal ECG status. The prognostic value of echocardiography in predicting cardiovascular outcomes in the general population is altered by hypertension. In hypertensive individuals, left ventricular mass index added incremental prognostic value in addition to established risk factors. In nonhypertensive individuals, global longitudinal strain added incremental prognostic value in addition to established risk factors., (© 2018 American Heart Association, Inc.)

Background: Echocardiographic classification of DDF has been widely discussed. The aim of this study was to investigate the independent prognostic value of established echocardiographic measures in a community-based population and create a new classification of DDF., Methods: Within the Copenhagen City Heart Study, a prospective, community-based study, 1851 participants were examined by echocardiography including Tissue Doppler Imaging (TDI) in 2001 to 2003 and followed with regard to MACE (median, 10.9 years)., Results: We found that persons with impaired myocardial relaxation as defined by low peak early diastolic mitral annular velocity e' by TDI had higher incidence of clinical and echocardiographic markers of cardiac dysfunction and increased risk of MACE. Among persons with impaired relaxation, only echocardiographic indices of increased filling pressures such as LAVi≥34 mL/m 2 (HR 1.97 (1.13-3.45, P=.017), E/e' ≥ 17 (HR 1.89 (1.34-2.65), P<.001), and E/A>2 (HR 5.24 (1.91-14.42), P=.001) provided additional and independent prognostic information on MACE. Based on these findings, we created a new classification of DDF where all grades were significant predictors of MACE independently of age, sex, and cardiac clinical risk markers (Mild DDF: HR 1.99 (1.23-3.21), P=.005; Moderate DDF: HR 3.11 (1.81-5.34), P<.001; Severe DDF: HR 4.20 (1.81-9.73), P<.001). Increasing severity of DDF was linearly associated with increasing plasma proBNP concentrations., Conclusions: In the general population, the presence of echocardiographic markers of elevated filling pressures in persons with impaired relaxation increased the risk of MACE significantly. Based on this, we present a new, feasible, and unambiguous classification of DDF capable of accurate risk prediction in the community., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aims: To improve risk prediction of cardiovascular morbidity and mortality, we need sensitive markers of cardiac dysfunction; Echocardiographic Tissue Doppler Imaging (TDI) is feasible and harmless and may be ideal for this purpose., Methods and Results: Within the community-based Copenhagen City Heart Study, 2064 participants were examined by echocardiography including TDI and followed (median 10.9 years) with regard to cardiovascular death, heart failure, or acute myocardial infarction (n = 277). Impaired systolic (s') and diastolic (e' and a') function according to age and sex as assessed by TDI was associated with increased risk of the combined end point, even in the subgroup of persons with a normal conventional echocardiographic examination [per 1 cm/s decrease: s': HR 1.32 (1.12-1.57), P < 0.001; e': HR 1.17(1.04-1.31), P < 0.01; a': HR 1.17 (1.06-1.30), P < 0.005]. Interestingly, reduced early diastolic myocardial velocity (e') was associated with risk of acute myocardial infarction, whereas reduced systolic (s') or late diastolic function (a') was associated with heart failure and cardiovascular death independently of traditional risk factors, plasma proBNP, and conventional echocardiographic measures. Combining information on early and late diastolic function by TDI provided incremental prognostic information and improved risk classification (net reclassification improvement: 27%; P < 0.001) and remained a significant predictor of the combined end point even in the subgroup with a normal conventional echocardiographic examination [per cm/s decrease: HR 1.18 (1.08-1.28), P < 0.001]., Conclusion: In the general population, TDI identifies individuals with cardiac dysfunction and high risk of cardiovascular morbidity and mortality independently of traditional risk factors, even in persons with a normal conventional echocardiographic examination., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Aims: There is increasing evidence of cross-talk between the heart, body metabolism, and adipose tissue, but the precise mechanisms are poorly understood. Natriuretic peptides (NPs) have recently emerged as the prime candidate for a mediator. In patients with heart failure (HF), infusion of NPs increases adiponectin secretion, indicating that NPs may improve adipose tissue function and in this way function as a cardio-protective agent in HF. Accordingly we investigated the interplay between plasma adiponectin, plasma proBNP, and development of HF., Methods and Results: We prospectively followed 5574 randomly selected men and women from the community without ischaemic heart disease or HF. Plasma adiponectin and proBNP were measured at study entry. Median follow-up time was 8.5 years (interquartile range 8.0-9.1 years). During follow-up 271 participants developed symptomatic HF. Plasma adiponectin and proBNP were strongly associated (P < 0.001). Participants with increasing adiponectin had increased risk of incident HF (P < 0.001). After adjustment for confounding risk factors (including age, gender, smoking status, body mass ratio, waist-hip ratio, glucose, glycated haemoglobin, systolic and diastolic blood pressure, lipid profile, high sensitivity C-reactive protein, estimated glomerular filtration rate, and physical activity) by Cox regression analysis, adiponectin remained an independent predictor of HF: the hazard ratio (HR) per 1 standard deviation (SD) increase in adiponectin was 1.20 [95% confidence interval (CI) 1.06-1.30; P = 0.003]. However, the association vanished when plasma proBNP was included in the analysis, HR 1.08 (95% CI 0.95-1.23; P = 0.26)., Conclusions: In conclusion, plasma adiponectin and proBNP are strongly associated. Increasing plasma adiponectin is associated with increased risk of HF. However, concomitantly elevated proBNP levels appear to explain the positive association between adiponectin and risk of HF., (© 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.)

Background: Osteoprotegerin (OPG) is a glycoprotein with a regulatory role in immune, skeletal and vascular systems. Data suggest that high circulating OPG levels are associated with an increased risk of cardiovascular disease. We analyzed the association between OPG and long-term outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI)., Methods: We included 716 consecutive STEMI patients admitted to a single high-volume invasive heart center from September 2006 to December 2008. Endpoints were all-cause mortality, repeat myocardial infarction, admission due to heart failure and combinations thereof. Median follow-up lasted 27 months (interquartile range: 22-33)., Results: OPG levels exhibited a non-Gaussian distribution and were therefore divided into quartiles. High levels of OPG were significantly associated with a worse outcome. After adjustment for conventional risk factors (e.g. C-reactive protein, estimated glomerular filtration rate, symptom-to-balloon time and troponin I) using Cox regression, OPG remained a significantly independent predictor of death (HR per increase in OPG quartile: 1.28; CI: 1.03-1.59; p = 0.03), repeat myocardial infarction (HR: 1.30; CI: 1.00-1.68; p = 0.05) and admission with heart failure (HR: 1.50; CI: 1.18-1.90; p = 0.001)., Conclusion: This study shows that OPG independently predicts long-term outcome in STEMI patients treated with pPCI. Eventually, this knowledge could improve risk stratification and overall outcome., (Copyright © 2012 S. Karger AG, Basel.)

Aims: With increasing socioeconomic disparity in cardiovascular risk factors, there is a need to assess the role of socioeconomic factors in chronic heart failure (CHF) and to what extent this is caused by modifiable risk factors., Methods and Results: In a prospective cohort of 18 616 men and women without known myocardial infarction or CHF examined in 1976-78, 1981-83, 1991-94, and 2001-03 in the Copenhagen City Heart Study, we studied the effect of education on CHF incidence. During a median follow-up of 21 years (range 0-31), 2190 participants were admitted to hospital for CHF. Age-adjusted hazard ratio (HR) for intermediary (8-10 years) and high level of education (>10 years) with low (< 8 years) as reference was 0.69 (0.62-0.78) and 0.52 (0.43-0.63), respectively, with similar associations in men and women. After adjusting for updated cardiovascular risk factors, corresponding HRs were 0.75 (0.67-0.85) and 0.61 (0.50-0.73). In a random subset of the population examined with echocardiography in 2001-03 (n = 3589), education was associated with left ventricular (LV) hypertrophy, LV dilatation, reduced LV ejection fraction, and severe diastolic dysfunction (P for trend, all <0.05), whereas no association was found for mild diastolic dysfunction (P for trend, 0.61). With the exception of LV hypertrophy, significant associations persisted after adjustment for potential mediating factors., Conclusion: In this cohort study, the level of education was associated with cardiac dysfunction and predicted future hospital admission for CHF. Only a minor part of the excess risk was mediated through traditional cardiovascular risk factors. Strategies to reduce this inequality should be strengthened.

Background: In studies showing benefits of cardiac resynchronization therapy (CRT), individual atrioventricular (AV) delays have been optimized using echocardiography. However, the method for AV delay optimization remains controversial., Methods: In 100 consecutive patients with CRT device implantation, AV delay was optimized using echocardiography. The optimal AV delay was determined by changing the interval in 20-ms increments while measuring displacement in 6 basal left ventricular segments (averaged and reported as left ventricular displacement [D(LV)]) and other echocardiographic measures., Results: A single optimal AV delay existed for each patient, and the associated highest D(LV) corresponded with the maximal velocity-time integral (VTI) in the left ventricular outflow tract (VTI(LVOT)) and the E/e' ratio. Significant increases in D(LV) and the VTI(LVOT) from before to after implantation with standard settings and from standard to optimal AV delay by displacement were found. Diastolic filling time corresponded poorly with D(LV) and the VTI(LVOT)., Conclusion: Individual optimal AV delay programming provides significant improvement in left ventricular performance and hemodynamics. Displacement analysis and the VTI(LVOT) are interchangeable, whereas diastolic filling time cannot be recommended., (Copyright 2010 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Background: Tissue Doppler imaging (TDI) detects left ventricular dysfunction in patients with heart failure and normal ejection fraction, but the prognostic significance of left ventricular dysfunction by TDI in the general population is unknown., Methods and Results: Within the Copenhagen City Heart Study, a large community-based population study, cardiac function was evaluated in 1036 participants by both conventional echocardiography and TDI. Averages of peak systolic (s'), early diastolic (e'), and late diastolic (a') velocities from 6 mitral annular sites were used. TDI was furthermore quantified by a combined index (eas index) of diastolic and systolic performance: e'/(a' x s'). During follow-up (median, 5.3 years), 90 participants died. Left ventricular dysfunction by TDI, in terms of low s' (hazard ratio, 1.23 per 1-cm/s decrease; P<0.05) and a' (hazard ratio, 1.20 per 1-cm/s decrease; P=0.001), were significant predictors of death in Cox proportional-hazards models adjusted for clinical variables (age, sex, body mass index, heart rate, hypertension, diabetes mellitus, and ischemic heart disease) and conventional echocardiography. The adjusted hazard ratio for death in the third tertile compared with the first tertile of the combined index of systolic and diastolic performance by TDI was 2.5 (P<0.005)., Conclusions: In the general population, in which most are free of left ventricular systolic dysfunction and restrictive diastolic filling using conventional echocardiographic parameters, left ventricular dysfunction by TDI is a powerful and independent predictor of death, especially when systolic performance and diastolic performance are considered together, recognizing their interdependency and their complex relation to deteriorating cardiac function.