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

Aims: Retinopathy and heart disease in Type 1 Diabetes Mellitus (Type 1 DM) may be associated; however previous results have been conflicting. Tissue Doppler Imaging (TDI) and speckle-tracking echocardiography (STE) quantify myocardial function not assessable by conventional echocardiography. We investigated the association between severity of retinopathy and early myocardial dysfunction using conventional echocardiography, TDI and STE in Type 1 DM patients., Methods: Type 1 Diabetes Mellitus patients without known heart disease were included from the Steno Diabetes Center. The cross sectional association between retinopathy and myocardial function was analyzed in uni-and multivariable models. Retinopathy was categorized as nil-, simplex- or proliferative retinopathy., Results: A total of 1090 Type 1 Diabetes Mellitus patients were included, mean age was 49.6years and 53% were males. Left ventricular ejection fraction did not differ between groups of retinopathy. Global longitudinal strain (GLS) by STE decreased significantly with increasing degrees of retinopathy (nil; -18.6%, simplex; -18.2% (p=0.024), proliferative; -17.7% (p<0.001)), however differences attenuated in multivariable models (p⩾0.05). In univariable models, myocardial tissue velocities differed in relation to retinopathy: s' (nil; 6.9, simplex; 6.5, proliferative; 5.9 (p=0.001), e' (nil; 10.4, simplex; 9.2, proliferative; 7.9, p<0.001), a' (nil; 6.1, simplex; 6.7, proliferative; 7.0, p<0.001) and E/e' (nil; 6.7, simplex; 7.5, proliferative; 9.5, p<0.001). In multivariable models, differences persisted between nil and proliferative retinopathy for s', e' and E/e'., Conclusion: Proliferative retinopathy is independently associated with decreased myocardial function assessed by Tissue Doppler Imaging in patients with Type 1 Diabetes Mellitus without history of heart disease., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Aims: Two‐dimensional speckle tracking echocardiography (2DSTE) detects early signs of left ventricular dysfunction; however, it is unknown whether layer‐specific global longitudinal strain (GLS) has incremental value in diagnosis of patients with reversible ischemia assessed by single photon emission computed tomography (SPECT). Methods and Results: Eighty patients with stable angina pectoris (SAP), normal left ventricular ejection fraction (LVEF), and no history of ischemic heart disease were retrospectively identified to have been examined by 2DSTE, SPECT, and coronary angiography (CAG). Patients with a normal SPECT constituted the control group, and patients with a positive SPECT were divided into patients with or without (true‐ or false‐ positive SPECT) significant stenosis assessed by CAG. GLS was measured for two myocardial layers (endocardial and epicardial) and as well as mid‐myocardial GLS. Patients with reversible ischemia had significantly lower GLS compared to the control group (GLSEndocardial: −19.0 ± 4.4% vs −21.4 ± 3.7%, P = .011; GLSEpicardial: −14.3 ± 2.9% vs −16.3 ± 2.9%, P = .004); GLSMid‐myocardial: −16.5 ± 3.6% vs −18.6 ± 3.2%, P = .006. This difference was even more evident in patients with a true‐positive SPECT (GLSEndocardial: −18.0 ± 4.4% vs −21.4 ± 3.7%, P < .001; GLSEpicardial: −13.6 ± 3.0% vs −16.3 ± 2.9%, P < .001); GLSMid‐myocardial: −15.6 ± 3.6% vs −18.6 ± 3.2%, P < .001. Notably, no significant differences existed in patients with a false‐positive SPECT. GLSEpicardial was the only independent predictor of coronary artery disease. In conclusion: In patients with SAP and preserved LVEF, layer‐specific GLS at rest identifies patients with reversible ischemia. This seems to be evident only in patients with a true‐positive SPECT, thus, 2DSTE at rest might improve the diagnostic accuracy of a positive SPECT. [ABSTRACT FROM AUTHOR]

Aims: Diabetes is associated with higher arterial stiffness—an early marker of cardiovascular disease. The coupling between arterial stiffness and myocardial function is still unresolved. We investigate associations between arterial stiffness and early myocardial impairment assessed with advanced echocardiography.Methods: In 305 type 1 diabetes (T1D) patients without known heart disease and with normal left ventricular ejection fraction (LVEF) (biplane LVEF > 45%), we measured arterial stiffness as pulse wave velocity (PWV) and performed conventional and speckle-tracking echocardiography assessing global longitudinal strain (GLS) as a measure of systolic myocardial function. Associations between PWV and myocardial function were reported as standardized beta values from adjusted regression models including age, sex, mean arterial pressure, body mass index, HbA1c, diabetes duration, estimated glomerular filtration rate, degree of albuminuria, total cholesterol, heart rate and smoking.Results: Patients were 54 (12) years [mean (SD)], 152 (50%) females, diabetes duration 31 (16) years, HbA1c 65 (12) mmol/mol, LVEF 58 (5) %, GLS −18.2 (2.6) % and PWV 10.2 (3.4) m/s. There was no association between PWV and LVEF (p = 0.93). Conversely, there was a highly significant association between PWV and GLS in crude and multivariable models (standardized β-coefficient 0.25, p < 0.001 and 0.16, p = 0.036, respectively). Also, diastolic function measured as E/e′ was highly associated with PWV in crude and multivariable models (standardized β-coefficient 0.43, p < 0.001 and 0.17, p = 0.016, respectively).Conclusions: In T1D patients with normal LVEF and without known heart disease, higher arterial stiffness is independently associated with early systolic and diastolic myocardial impairment detectable by advanced echocardiography. Although unable to demonstrate causality, we display a relationship between diabetic angiopathy and diabetic cardiomyopathy (H-3-2009-139 and PROFIL-H-B-2009-056). [ABSTRACT FROM AUTHOR]

Objectives: We aimed to determine the prevalence of echocardiographic abnormalities and their relation to clinical characteristics and cardiac symptoms in a large, contemporary cohort of patients with type 2 diabetes. Results: A total of 1030 patients with type 2 diabetes participated. Echocardiographic abnormalities were present in 513 (49.8%) patients, mainly driven by a high prevalence of diastolic dysfunction 178 (19.4%), left ventricular hypertrophy 213 (21.0%) and left atrial enlargement, 200 (19.6%). The prevalence increased markedly with age from 31.1% in the youngest group (<55 years) to 73.9% in the oldest group (>75 years) (p < 0.001) and was equally distributed among the sexes (p = 0.76). In univariate analyses, electrocardiographic abnormalities, age, body mass index, known coronary heart disease, hypertension, albuminuria, diabetes duration and creatinine were associated with abnormal echocardiography along with dyspnoea and characteristic chest pain (p < 0.05 for all). Neither of the cardiac symptoms nor clinical characteristics had sufficient sensitivity and specificity to accurately identify patients with abnormal echocardiography. Conclusion: Echocardiographic abnormalities are very common in outpatients with type 2 diabetes, but neither cardiac symptoms nor clinical characteristics are effective to identify patients with echocardiographic abnormalities. [ABSTRACT FROM AUTHOR]

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

Background: Despite 5-7 months of physical inactivity during hibernation, brown bears (Ursus arctos) are able to cope with physiological conditions that would be detrimental to humans. During hibernation, the tissue metabolic demands fall to 25% of the active state. Our objective was to assess cardiac function associated with metabolic depression in the hibernating vs. active states in free-ranging Scandinavian brown bears. Methods: We performed echocardiography on seven free-ranging brown bears in Dalarna, Sweden, anesthetized with medetomidine-zolazepam-tiletamine-ketamine during winter hibernation in February 2013 and with medetomidine-zolazepam-tiletamine during active state in June 2013. We measured cardiac output noninvasively using estimates of hemodynamics obtained by pulsed wave Doppler echocardiography and 2D imaging. Comparisons were made using paired T-tests. Results: During hibernation, all hemodynamic indices were significantly decreased (hibernating vs. active state): mean heart rate was 26.0 (standard deviation (SD): 5.6) beats per min vs. 75.0 (SD: 17.1) per min (P = 0.002), mean stroke volume 32.3 (SD: 5.2) ml vs. 47.1 (SD: 7.9) ml (P = 0.008), mean cardiac output 0.86 (SD: 0.31) l/min vs. 3.54 (SD: 1.04) l/min (P = 0.003), and mean cardiac index 0.63 (SD: 0.21) l/min/kg vs. 2.45 (SD: 0.52) l/min/m2 (P < 0.001). Spontaneous echo contrast was present in all cardiac chambers in all seven bears during hibernation, despite the absence of atrial arrhythmias and valvular disease. Conclusion: Free-ranging brown bears demonstrate hemodynamics comparable to humans during active state, whereas during hibernation, we documented extremely low-flow hemodynamics. Understanding these physiological changes in bears may help to gain insight into the mechanisms of cardiogenic shock and heart failure in humans. [ABSTRACT FROM AUTHOR]

Abstract: Background: Heart failure is a major public health problem. To improve its grave prognosis, early identification of cardiac dysfunction is mandatory. Conventional echocardiography is not suitable for this. Tissue Doppler imaging (TDI), however, could be so. Methods and Results: Within a large community-based population-study (n = 1012), cardiac function was evaluated by conventional echocardiography (left ventricular hypertrophy, dilatation, systolic, and severe diastolic dysfunction), TDI, and plasma proBNP. 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′ × s′). Compared with controls, persons with elevated plasma proBNP concentrations (n = 100) displayed lower systolic and diastolic performance by TDI, in terms of lower s′ (P = 0.017) and a′ (P < .001), and higher e′/a′ (P = .002) and eas-index (P < .001). This pattern remained significant after multivariable adjustment for age, sex, body mass index, heart rate, estimated glomerular filtration rate, hypertension, diabetes, ischemic heart disease, and conventional echocardiography. Furthermore, TDI provided incremental information over conventional echocardiography in predicting elevated plasma proBNP concentrations. Conclusions: Preclinical systolic and diastolic dysfunction by TDI is associated with elevated plasma proBNP levels, even when conventional echocardiography is normal. [Copyright &y& Elsevier]

Background Contemporary treatment of type 2 diabetes (T2D) has improved patient outcome and may also have affected myocardial structure and function. We aimed to describe the effect of T2D and T2D duration on cardiac structure and function in a large outpatient population. Methods We performed comprehensive echocardiography on a representative sample of 1004 persons including a representative sample of 770 patients with T2D without known heart disease and 234 age- and sex-matched controls. Results T2D was associated with increased left ventricular (LV) wall thicknesses and decreased LV internal diameter and the changes were pronounced with increasing diabetes duration ( P < 0.01 for all) but not with increased LV mass ( P = 0.74). It was also significantly associated with the prevalence of diastolic dysfunction (16.5% vs. 4.0%; P < 0.001), with indices of LV relaxation and elevated filling pressures expressed as e ' septal (mean: 6.9 (SD: 1.9) cm/s vs. 7.5 (2.4); P < 0.001) and E / e ' septal (median: 10.8 (interquartile range (IQR): 9.1–13.3) vs. 9.1 (7.2–11.1); P < 0.001) and global longitudinal strain (mean: − 14.1 (SD: 2.4) vs. − 15.0 (2.0), P < 0.001) but not with LV ejection fraction (median: 60.8 (IQR: 56.5–65.1) vs. 62.1 (57.9–65.4), P = 0.28). With the exception of global longitudinal strain, this was pronounced with increasing diabetes duration for all measures including increasing diastolic dysfunction (< 10 years: 10.8%, 10–20 years: 18.5%, > 20 years: 24.8%; P < 0.001). The increased risk of diastolic dysfunction persisted after multivariable adjustment ( P = 0.013). Conclusions In patients with T2D, LV structural and functional alterations persist and are accentuated with increasing diabetes duration despite reductions in overall risk of cardiovascular disease in this patient population. [ABSTRACT FROM AUTHOR]

Objectives Soluble receptor of advanced glycation end-products (sRAGE) may be a predictive biomarker in coronary artery disease (CAD). Patients with acute myocardial infarction (AMI) have higher sRAGE levels compared to healthy subjects. Accordingly, the aim of this study was to investigate the dynamic changes in sRAGE levels during AMI and relationship with cardiac dysfunction. Design and methods We prospectively included 80 patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). sRAGE concentrations were measured before pPCI, immediately after pPCI and again on the first and second following days. Left ventricular ejection fraction (LVEF) was evaluated 1–3 days after the pPCI and again at a median of 7 months by echocardiography, and infarct size was measured by cardiac magnetic resonance. Results sRAGE levels were high in the early phase of AMI; sRAGE levels significantly increased after pPCI compared with sRAGE before pPCI (median ratio: 1.25, 95% CI: 1.15–1.35, P < 0.001), and the increase was observed prior to Troponin I (TnI). sRAGE levels decreased notably the first day after pPCI (median ratio: 0.34, 95% CI: 0.30–0.39, P < 0.001). Peak sRAGE independently associated with long-term cardiac dysfunction estimated by LVEF (P = 0.008). Furthermore, sRAGE measured after pPCI associated with infarct size (P = 0.038). Conclusions sRAGE levels were high in the early phase rather than in the days after AMI and pPCI. The increase in sRAGE was seen before detectable changes in TnI. In addition, sRAGE was independently associated with long-term cardiac dysfunction. [ABSTRACT FROM AUTHOR]

Objectives: This study was designed to determine whether measurement of plasma pro-B-type natriuretic peptide (proBNP) could be used in discriminating between cardiac and pulmonary dyspnea in the general population. Background: Natriuretic peptides are useful markers in ruling out acute cardiac dyspnea in the emergency department, but their diagnostic significance in evaluating chronic dyspnea in the general population is unknown. Methods: Within the Copenhagen City Heart Study, a large, community-based population study, dyspnea was evaluated by spirometry, oxygen saturation, echocardiography, and plasma proBNP. Results: Of 2,929 participants, 959 reported dyspnea. The plasma proBNP concentration was higher in the group with dyspnea (mean 17.8 pmol/l; 95% confidence interval [CI] 16.3 to 19.4 pmol/l) than in the group without (10.6 pmol/l; 95% CI 10.0 to 11.4 pmol/l; p < 0.001). In the group with dyspnea, left ventricular hypertrophy and/or systolic dysfunction was associated with a 2.6-fold increase in plasma proBNP concentration (p < 0.001), whereas pulmonary dysfunction was not associated with increased plasma proBNP (p = 0.66). Using multivariable regression analysis, a model to estimate the expected concentration of plasma proBNP based on age and gender was established for dyspneic subjects: an actual plasma proBNP concentration below half of the expected value ruled out left ventricular systolic and diastolic dysfunction (sensitivity 100%, 95% CI 100% to 100%; specificity 15%, 95% CI 12% to 17%). Conclusions: In the general population with dyspnea, plasma proBNP concentrations are increased in left ventricular dilatation, hypertrophy, systolic dysfunction, or diastolic dysfunction, but are unaffected by pulmonary dysfunction. [Copyright &y& Elsevier]

Background: Post-systolic shortening (PSS) has been proposed as a marker of myocardial ischemia. We sought to determine if PSS is associated with coronary artery calcium (CAC) score in patients with suspected stable angina. Methods: We retrospectively studied 522 patients with suspected stable angina pectoris (mean age 60±11 years, 44% male) who underwent speckle tracking echocardiography and assessment of the Agatston CAC score by computed tomography. The post-systolic index (PSI) was defined as follows: [(peak systolic strain - maximum strain in cardiac cycle)/maximum strain in cardiac cycle] x 100. PSS was present if PSI≥20% in one myocardial wall segment. Patients were divided into categories of CAC score: no coronary artery disease (0), minimal (1-10), mild (11-100), moderate (101-400) and severe (>400). We assessed the CAC score continuously using negative binomial regression models for highly dispersed count data, and categorically using Spearman's correlation. Results: Each 1% absolute increase in the PSI was associated with a 7% relative increase in CAC score (95%CI: +0% to +15%, P=0.037, figure 1a), while each wall displaying PSS was associated with a 37% relative increase in CAC score (+8% to +74%, P=0.010, figure 1b). After adjustment for age, sex, hypertension, dyslipidemia and E/A-ratio, both PSI (+10%, 95%CI +1% to +21%, P=0.038) and number of walls with PSS (+60% [+23% to +112%], P<0.001) remained independently associated with the CAC score. Both PSI (Rho 0.12, P=0.006) and walls with PSS (Rho 0.13, P=0.001, figure 1c) increased significantly with increasing categories of CAC score. Conclusion: PSS is independently associated with CAC score in patients with suspected stable angina pectoris and may aid in the identification of patients with an increased CAC score. [ABSTRACT FROM AUTHOR]

Background: When the left ventricle (LV) pressure rises during early systole, impaired myocardial fibers may lengthen instead of shorten. This is known as early systolic lengthening (ESL). We sought to investigate if ESL provides prognostic information on cardiovascular events. Methods: In this prospective cohort study we included 1,260 participants from a low risk general population who underwent speckle tracking echocardiography (men 42%, mean age 57 years, SD 16). Primary endpoints were incident heart failure (HF), myocardial infarction (MI) and cardiovascular death (CVD). We assessed duration of ESL defined as time from onset of Q wave to maximum systolic lengthening and the early systolic index defined as: [(duration of ESL / time from Q wave to aortic valve closure) x 100]. Results: During median follow-up of 11 years, 73 (6%) developed HF, 40 (3%) had MI and 69 suffered from CVD (5%). Per 1 unit increase in ln ESL was associated with HF (HR 1.45 95%CI 1.03-2.04, P=0.035, figure 1a) but not MI (HR 1.55 95%CI 0.96-2.51, P=0.07) or CVD (HR 0.91 95%CI 0.66-1.26, P=0.58). Likewise, the ESI was associated with HF (HR 1.46 95%CI 1.02-2.08, P=0.038 per 1 unit increase in ln ESI, figure 1b). After adjusting for echocardiographic and clinical parameters, including afterload, all associations with HF remained significant. Hypertension modified the relationship with HF such that both duration of ESL (P interaction = 0.018) and the ESI (P interaction = 0.020) were significant predictors of HF in non-hypertensive participants but not in those with hypertension. Conclusion: Early systolic lengthening in the general population provides independent and novel prognostic information on the risk of HF but is not associated with MI or CVD. [ABSTRACT FROM AUTHOR]

Background: Color Tissue Doppler imaging M-mode through the mitral leaflet is an easy and precise method to obtain the cardiac time intervals including the left ventricular ejection time (LVET). The aim of this study was to investigate whether the LVET can be used to predict cardiovascular morbidity and mortality following acute coronary syndrome (ACS). Methods: We retrospectively studied 390 patients with ACS (mean age 64 ±12 years, men 74%, STEMI 81%, mean LVEF 41±11%, mean LVET 256±35ms) who underwent echocardiography, following percutaneous coronary intervention. The LVET was measured. The primary endpoint was major adverse cardiac events (MACE) and consisted of heart failure, myocardial infarction and cardiovascular death. The secondary endpoint was all-cause mortality. Patients with prevalent HF were excluded. Results: During a median follow-up of 3 years, 180 patients (46%) reached the composite endpoint MACE, and 77 (20%) suffered from all-cause mortality. LVET was significantly associated with risk of MACE (HR 1.13; 95% CI (1.08-1.18), p<0.001) with a 13% increase in risk per 10ms decrease in LVET (figure). The association remained significant after adjusting for age, sex, hypertension, diabetes, body mass index, previous ischemic heart disease, STEMI, multivessel culprit lesions, left ventricular ejection fraction, left ventricular mass index, E/e', E/A and deceleration time (HR 1.10; 95% CI (1.03-1.17), p=0.002 per 10ms decrease). Additionally, the LVET predicted all-cause mortality and the association remained significant even after multivariable adjustment (HR 1.11; 95% CI (1.01-1.21), p=0.032 per 10ms decrease). Conclusion: In patients with ACS the LVET provides novel and independent prognostic information on the risk of cardiovascular morbidity and mortality. [ABSTRACT FROM AUTHOR]