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Aims: Vitamin B12 deficiency could be associated with cardiovascular autonomic neuropathy (CAN) in diabetes patients. We aim to investigate the association between serum levels of vitamin B12 and CAN in type 2 diabetes patients.Methods: 469 ambulatory type 2 diabetes patients (mean diabetes duration 10.0years (IQR 5.0;17.0), mean age 59.0years (SD 11.6), 63% men, mean B12 289.0pmol/l (IQR 217;390)) were screened for CAN using three cardiovascular reflex tests, five minute resting heart rate (5min RHR) and heart rate variability indices.Results: Serum levels of vitamin B12 were significantly lower in patients treated with metformin and/or proton pump inhibitors (PPIs) compared with patients not treated (p<0.001). A 25pmol/l higher level of vitamin B12 was associated with an odds ratio of the CAN diagnosis of 0.94 (95% CI 0.88; 1.00, p=0.034), an increase in E/I-ratio of 0.21% (95% CI 0.01; 0.43, p=0.038), and a decrease in 5min RHR of 0.25 beats per minute (95% CI -0.47; -0.03, p=0.025).Conclusion: Vitamin B12 may be inversely associated with CAN in patients with type 2 diabetes. Confirmatory studies investigating a causal role of vitamin B12 for the development of diabetic CAN are warranted. [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]

OBJECTIVE Patients with acute myocardial infarction (MI) have increased risk of developing type 2 diabetes mellitus (T2DM). Adiponectin is an insulin-sensitizing hormone produced in adipose tissue, directly suppressing hepatic gluconeogenesis, stimulating fatty acid oxidation and glucose uptake in skeletal muscle and insulin secretion. In healthy humans, low plasma adiponectin levels associate with increased risk of T2DM; however, the relationship between adiponectin and T2DM in patients with MI has never been investigated. RESEARCH DESIGN AND METHODS We prospectively included 666 patients with ST-segment elevation MI, without diabetes, treated with percutaneous coronary intervention, from September 2006 to December 2008 at a tertiary cardiac center. Blood samples were drawn before intervention, and total plasma adiponectin was measured in all samples. During follow-up (median 5.7 years [interquartile range 5.3-6.1]) 6% (n = 38) developed T2DM. Risk of T2DM was analyzed using a competing risk analysis. RESULTS Low adiponectin levels were associated with increased risk of T2DM (P < 0.001). Even after adjustment for confounding risk factors (age, sex, hypertension, hypercholesterolemia, current smoking, previous MI, BMI, blood glucose, total cholesterol, HDL, LDL, triglyceride, estimated glomerular filtration rate, C-reactive protein, peak troponin I, and proatrial natriuretic peptide), low adiponectin levels remained an independent predictor of T2DM(hazard ratio [HR] 5.8 [2.3-15.0]; P < 0.001). Importantly, plasma adiponectin added to the predictive value of blood glucose, with the combination of high blood glucose and low plasma adiponectin, vastly increasing the risk of developing T2DM (HR 9.6 [3.7-25.3]; P < 0.001). CONCLUSIONS Low plasma adiponectin levels are independently associated with increased risk of T2DM in patients with MI and added significantly to the predictive value of blood glucose. [ABSTRACT FROM AUTHOR]

Background Risk prediction in elderly patients is increasingly relevant due to longer life expectancy. Objectives This study sought to examine whether electrocardiographic (ECG) changes provide prognostic information incremental to current risk models and to the conventional risk factors. Methods In all, 6,991 participants from the Copenhagen Heart Study attending an examination at age ≥65 years were included. ECG changes were defined as Q waves, ST-segment depression, T-wave changes, ventricular conduction defects, and left ventricular hypertrophy based on the Minnesota code. The primary endpoint was fatal cardiovascular disease (CVD) event and the secondary was fatal or nonfatal CVD event. In our study, 2,236 fatal CVD and 3,849 fatal or nonfatal CVD events occurred during a median of 11.9 and 9.8 years of follow-up. Results ECG changes were frequently present (30.6%) and associated with conventional risk factors. All ECG changes except 1 univariably predicted both endpoints. Event rates of ECG changes versus no ECG changes were respectively 41.4% versus 27.8% and 64.6% versus 50.8%. When added to existing risk scores, ECG changes independently increased the risk of both endpoints. Fatal CVD events: hazard ratio (HR): 1.33 (95% confidence interval [CI]: 1.29 to 1.36; p < 0.001) and fatal or nonfatal CVD events: HR: 1.21 (95% CI: 1.19 to 1.24; p < 0.001). When added to conventional risk factors, continuous net reclassification improvement was 42.3% (95% CI: 42.0 to 42.4; p < 0.001) for fatal and 29.2% (95% CI: 28.4 to 29.2; p < 0.001) for fatal or nonfatal events. Categorical net reclassification was 7.1% (95% CI: 6.7 to 9.0; p < 0.001) for fatal and 4.2% (95% CI: 3.5 to 5.6; p < 0.001) for fatal or nonfatal events. Conclusions Simple assessment of the existence of ECG changes improves risk prediction in the general population of persons age ≥65 years. [ABSTRACT FROM AUTHOR]

An elevated urinary albumin excretion (UAE) in non-diabetic subjects without renal or cardiovascular disease has been shown to be predictive of ischaemic heart disease. An insertion (I)/deletion (D) polymorphism in the angiotensin I-converting enzyme (ACE) gene has been identified and the D allele may be associated with cardiovascular disease. The aim of this study was to find a potential linkage between this polymorphism and elevated UAE. For studies of UAE and cardiovascular pathophysiology, a highly selected population sample has been identified comprising all clinically healthy subjects aged 40-65 years with elevated UAE in a dipstick negative urinary sample (n = 27) from The Copenhagen City Heart Study. Neither the ACE genotype distribution (p = 0.12) nor the D and I allele frequencies (p = 0.69) differed significantly between subjects with elevated UAE and a matched normoalbuminuric control group (n = 46). Elevated UAE in clinically healthy subjects is not linked to the ACE gene polymorphism. [ABSTRACT FROM AUTHOR]

Objectives. To assess prevalence of positive urinary dipstick analysis for leucocyte esterase, nitrite, haemoglobin, or glucose in the general population and measure the urinary albumin excretion rate (UAER) in subjects with or without a positive dipstick analysis. Design. A cross-sectional study of 3645 subjects. Setting. An unselected urban population study. Main outcome measures. Prevalence data of positive dipstick analyses and UAER values. Results. Prevalence data of a positive dipstick analysis were 12%, 4%, 3% and 6%, respectively, for leucocyte esterase, nitrite, haemoglobin, and glucose. Subjects with any positive dipstick analysis had significantly higher UAER than subjects with a negative analysis: 4.9 (4.4-5.3) (geometric mean (95% confidence interval)) vs 3.0 (2.9-3.1) mg 24 h[sup -1] (p < 0.001). Conclusions. Prevalence data of positive urinary dipstick analyses in a large population based study are provided. Subjects with any positive finding had higher UAER than controls. Exclusion of subjects with a positive finding is recommended in studies of UAER as a cardiovascular risk factor in non-diabetic subjects. [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]

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. [ABSTRACT FROM AUTHOR]

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]

Introduction Supraventricular ectopic complexes (SVEC) are known risk factors of recurrent atrial fibrillation (AF). However, the impact of SVEC in different age groups is unknown. We aimed to investigate the risk of AF recurrence with higher SVEC burden in patients ± 57 years, respectively, after treatment with antiarrhythmic medication (AAD) or catheter ablation (CA). Methods In total, 260 patients with LVEF > 40% and age ≤ 70 years were randomized to AAD (N = 132) or CA (N = 128) as first-line treatment for paroxysmal AF. All patients underwent 7-day Holter monitoring at baseline, and after 3, 6, 12, 18 and 24 months and were categorized according to median age ± 57 years. We used multivariate Cox regression analyses and we defined high SVEC burden at 3 months of follow-up as the upper 75th percentile > 195 SVEC/day. AF recurrence was defined as AF ≥ 1 min, AF-related cardioversion or hospitalization. Results Age > 57 years were significantly associated with higher AF recurrence rate after CA (58% vs 36%, p = 0.02). After CA, we observed a higher SVEC burden during follow-up in patients > 57 years which was not observed in the younger age group treated with CA (p = 0.006). High SVEC burden at 3 months after CA was associated with AF recurrence in older patients but not in younger patients (> 57 years: HR 3.4 [1.4–7.9], p = 0.005). We did not find any age-related differences after AAD. Conclusion We found that younger and older patients respond differently to CA and that SVEC burden was only associated with AF recurrence in older patients. [ABSTRACT FROM AUTHOR]

Background Supraventricular ectopic complexes (SVEC) originating in the pulmonary veins are known triggers of atrial fibrillation (AF) which led to the development of pulmonary vein isolation for AF. However, the long-term prevalence of SVEC after catheter ablation (CA) as compared to antiarrhythmic medication (AAD) is unknown. Our aims were to compare the prevalence of SVEC after AAD and CA and to estimate the association between baseline SVEC burden and AF burden during 24 months of follow-up. Methods Patients with paroxysmal AF ( N = 260) enrolled in the MANTRA PAF trial were treated with AAD ( N = 132) or CA ( N = 128). At baseline and 3, 6, 12, 18 and 24 months follow-up patients underwent 7-day Holter monitoring to assess SVEC and AF burden. We compared SVEC burden between treatments with Wilcoxon sum rank test. Results Patients treated with AAD had significantly lower daily SVEC burden during follow-up as compared to CA (AAD: 19 [6–58] versus CA: 39 [14–125], p = 0.003). SVEC burden increased post-procedurally followed by a decrease after CA whereas after AAD SVEC burden decreased and stabilized after 3 months of follow-up. Patients with low SVEC burden had low AF burden after both treatments albeit this was more pronounced after CA at 24 months of follow-up. Conclusion AAD was superior to CA in suppressing SVEC burden after treatment of paroxysmal AF. After CA SVEC burden increased immediately post-procedural followed by a decrease whereas after AAD an early decrease was observed. Lower SVEC burden was highly associated with lower AF burden during follow-up especially after CA. [ABSTRACT FROM AUTHOR]

In patients with type 2 diabetes, both supervised exercise and treatment with the glucagon-like peptide-1 ( GLP-1) receptor agonist ( GLP-1RA) liraglutide may improve cardiac function. We evaluated cardiac function before and after 16 weeks of treatment with the GLP-1RA liraglutide or placebo, combined with supervised exercise, in 33 dysregulated patients with type 2 diabetes on diet and/or metformin. Early diastolic myocardial tissue velocity was improved by exercise in the placebo group (mean ± standard deviation [s.d.] −7.1 ± 1.6 to −7.7 ± 1.8 cm/s, P = .01), but not in the liraglutide group (−7.1 ± 1.4 to −7.0 ± 1.4 cm/s, P = .60; between groups, P = .02). Similarly, the mean ± s.d. ratio of early and atrial mitral annular tissue velocities improved in the placebo group (1.0 ± 0.4 to 1.2 ± 0.4, P = .003), but not in the liraglutide group (1.0 ± 0.3 to 1.0 ± 0.3, P = .87; between groups, P = .03). We found no significant differences in heart rate, left ventricular ( LV) structure or function within or between the groups. In conclusion, the addition of liraglutide to exercise in sedentary patients with dysregulated type 2 diabetes may blunt the suggested beneficial effect of exercise on LV diastolic function. [ABSTRACT FROM AUTHOR]

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 Circulating levels of pregnancy-associated plasma protein-A (PAPP-A) predict outcome in patients with acute coronary syndrome (ACS). Unfortunately, administration of heparin to patients with ACS increases circulating PAPP-A, probably by a detachment of PAPP-A from cell surfaces, inducing a considerable bias when using PAPP-A as a biomarker. It remains unknown whether PAPP-A-derived N- and C-terminal fragments of insulin-like growth factor binding protein-4 (NT-IGFBP-4/CT-IGFBP-4) are acutely affected by the increase in PAPP-A. Methods We prospectively included 78 patients with ST-segment elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI). Prior to PCI, patients were injected with 10,000 IU of unfractionated heparin (UFH). Blood samples were collected immediately before PCI, but after UFH-injection, immediately after PCI and on day 1 and day 2. Plasma IGFBP-4, CT-IGFBP-4 and NT-IGFBP-4 levels were determined by specific, novel immunoassays, and PAPP-A and IGF-I by commercial immunoassays. Results Plasma PAPP-A was strongly elevated upon STEMI, UFH-administration and PCI with mean concentrations (95%-confidence interval) pre-PCI, post-PCI, day 1, and day 2 of 13.0 (11.2;15.2), 14.8 (13.1;16.8), 1.03 (0.90;1.18), and 1.08 (0.92;1.28) μg/L, respectively ( p < 0.0001). Pre-PCI concentrations of IGFBP-4, CT-IGFBP-4 and NT-IGFBP-4 were 154 (142;166), 53 (47;60) and 136 (122;150) μg/L, and levels were unaltered post-PCI. Concentrations increased on day 1 by 63 (43;87)%, 69 (36;110)%, and 47 (21;79)%, respectively ( p < 0.0001), i.e. at a time point when PAPP-A levels had normalized. Conclusion Plasma IGFBP-4-fragment levels are not acutely altered in patients with STEMI treated with UFH and PCI. Thus, they possess potentials as prognostic markers in ACS patients. [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]

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 STEMl 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; Cl: 1.03-1.59; p = 0.03), repeat myocardial infarction (HR: 1.30; Cl: 1.00-1.68; p = 0.05) and admission with heart failure (HR: 1.50; Cl: 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. [ABSTRACT FROM AUTHOR]

Atherosclerosis is the main cause of cardiovascular disease, but the extent of atherosclerosis in individual patients is difficult to estimate. A biomarker of the atherosclerotic burden would be very valuable. The aim of the present study was to evaluate the association of plasma osteoprotegerin (OPG) to clinical and subclinical atherosclerotic disease in a large community-based, cross-sectional population study. In the Copenhagen City Heart Study, OPG concentrations were measured in 5,863 men and women. A total of 494 participants had been hospitalized for ischemic heart disease or ischemic stroke, and compared to controls, this group with clinical atherosclerosis had higher mean OPG (1,773 vs 1,337 ng/L, p <0.001) and high-sensitivity C-reactive protein (2.3 vs 1.6 mg/L, p <0.001). In a multivariate model with age, gender, body mass index, hypertension, diabetes, hypercholesterolemia, smoking status, estimated glomerular filtration rate, high-sensitivity C-reactive protein, and OPG, OPG remained significantly associated with clinical atherosclerosis (p <0.01); high-sensitivity C-reactive protein, in contrast, did not (p = 0.74). In the control group without clinical atherosclerosis, OPG was independently associated with hypertension, diabetes, hypercholesterolemia, smoking, and subclinical peripheral atherosclerosis as measured by ankle brachial index. For each doubling of the plasma OPG concentration, the risk for subclinical peripheral atherosclerosis increased by 50% (p <0.001) after multivariate adjustment. In conclusion, OPG appears to be a promising biomarker of atherosclerosis that is independently associated with traditional risk factors of atherosclerosis, subclinical peripheral atherosclerosis, and clinical atherosclerotic disease such as ischemic heart disease and ischemic stroke. [ABSTRACT FROM AUTHOR]

Objective. The mechanisms by which overweight and physical inactivity lead to hypertension are complex. Leptin, an adipocyte-derived hormone, has been linked with hypertension. We wanted to investigate the relationship between leptin, physical activity and new-onset hypertension. Methods. The study was a prospective cohort study of 744 women and 367 men, who were normotensive in the third Copenhagen City Heart Study (CCHS) examination, performed 1991-94. Based on questionnaire items, the participants were divided into two groups with low ( n == 674) and high ( n == 437) levels of leisure-time physical activity, respectively. Results. Between the third and the fourth CCHS examination, performed 2001-03, 304 had developed hypertension, defined as systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg or use of antihypertensive medication. In a logistic regression model, including age, sex, body mass index, SBP, DBP, level of physical activity and leptin, we found a significant interaction between leptin and level of physical activity with new-onset hypertension as outcome variable ( p == 0.012). When we entered the interaction variables, effect of leptin with low level of physical activity and with high level of physical activity, respectively, in the original model, leptin predicted new-onset hypertension in participants with low level of physical activity [odds ratio (95% confidence interval): 1.16 (1.01-1.33) for one unit increase in log-transformed leptin levels, p == 0.038], but not in participants with high level of physical activity [0.88 (0.74-1.05), p == 0.15]. Conclusion. We found that leptin predicted new-onset hypertension but only in participants with low level of physical activity. [ABSTRACT FROM AUTHOR]

Background: An increasing proportion of patients with acute coronary syndrome (ACS) requiring percutaneous coronary intervention (PCI) are classified as elderly (aged ≥ 70 years). The glycoprotein IIb/IIIa inhibitor abciximab is known to reduce adverse outcomes in patients aged <70 years with high-risk ACS undergoing PCI, but conflicting findings relating to its effects in the elderly have been reported. Objective: The aim of this study was to evaluate the effect of abciximab in elderly high-risk ACS patients undergoing PCI. Methods: From our dedicated PCI registry we identified 2068 ACS patients with high-risk lesions that were treated with PCI. Baseline data were collected prospectively. All-cause mortality, target vessel revascularization (TVR), myocardial infarction (MI), and the combination of these were primary study endpoints. All endpoints within 1 year after PCI were registered and validated. The population was subsequently stratified according to age and use of abciximab. Results: Elderly patients constituted 42% of the total population. They presented with more co-morbidities, were less frequently treated with abciximab and had a higher risk of reaching the combined endpoint and higher all-cause mortality than younger patients. The age/abciximab stratified analysis revealed no effect of abciximab on any of the endpoints in elderly patients (combined endpoint: no abciximab 22.6% vs abciximab 23.4%, p = 0.85; all-cause mortality: no abciximab 15.4% vs abciximab 15.9%, p = 0.91; TVR: no abciximab 3.4% vs abciximab 5.5%, p = 0.21; MI: no abciximab 7.0% vs abciximab 8.5%, p = 0.54), whereas all-cause mortality and the risk of reaching the combined endpoint were significantly reduced in younger patients (combined endpoint: no abciximab 14.0% vs abciximab 9.4%, p = 0.03; all-cause mortality: no abciximab 4.5% vs abciximab 1.7%, p = 0.02; TVR: no abciximab 5.5% vs abciximab 4.3%, p = 0.39; MI: no abciximab 7.2% vs abciximab 6.6%, p = 0.80). These findings were confirmed in our adjusted analyses. Conclusions: In this large observational study we found no benefit of abciximab treatment in elderly high-risk ACS patients who underwent PCI. These findings should be taken into consideration when deciding on the treatment strategy for elderly ACS patients undergoing PCI. [ABSTRACT FROM AUTHOR]

Abciximab is beneficial in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) . However, the optimal administration route of the initial bolus of abciximab, that is, intravenous (IV) versus intracoronary (IC), has been questioned. Preliminary studies suggest that IC-bolus is superior, probably due to high local concentration. In this study, we assess the short-term efficacy and safety of IC compared to IV bolus of abciximab in patients with STEMI during pPCI. In 2006-2008, we randomized 355 STEMI patients who underwent pPCI and had indication for abciximab to either IV or IC bolus followed by a 12-hour IV infusion. Primary end-points at 30 days were target vessel revascularization (TVR), recurrent myocardial infarction (MI) or death, and the composite of the three. Secondary end-points were bleeding complications. The two groups (IV n = 170;IC n = 185) were similar with respect to baseline characteristics. Mortality at 30 days was 5.3% in the IV group compared to only 1.1% in the IC group (P = 0.02). TVR was performed in 9.4% in the IV group compared to 3.8% in the IC group (P = 0.03). No significant difference in MI rates was seen (IV 4.7% vs. IC 2.7%; P = 0.32). We found a significant reduction in the composite end-point (IV 19.4% vs. IC 7.6%; P = 0.001) in favor of IC use. Major bleeding complications were similar (IV 2.4% vs. IC 1.6%; P = 0.62). Neither difference was observed in minor bleedings (IV 14.1% vs. IC 9.7%; P = 0.20). IC administration of bolus abciximab in STEMI patients undergoing pPCI reduces 30-day mortality and TVR and tends to reduce MI, compared to IV-bolus. (J Interven Cardiol 2011;24:105-111) [ABSTRACT FROM AUTHOR]

Abstract: A microbiological study was carried out on Baobab fermented seeds (Maari) obtained from 4 different production sites in Burkina Faso (Mansila, Toulfé, Ouagadougou and Gorgadji). A total of 390 representative isolates comprising 251 aerobic mesophilic bacteria (AMB) and 139 lactic acid bacteria (LAB) were isolated and identified to species level using a combination of pheno- and genotypic methods including conventional morphological analysis, carbohydrate fermentation profiling, rep-PCR ((GTG)5-fingerprinting) and 16S rRNA gene sequencing. The fermentation of Baobab seeds was initiated by the AMB identified as Bacillus subtilis (82% of AMB isolates) and Staphylococcus sciuri (18% of AMB isolates). No lactic acid bacteria were isolated at the beginning of the process. After 24h fermentation time, Enterococcus faecium appeared in the fermenting seeds and remained until the end of the fermentation, as the predominant LAB. In Maari collected from retail outlets the AMB count ranged from 6.7log10CFU/g to 10log10CFU/g while the LAB load ranged from 4.4log10CFU/g to 9.9log10CFU/g. The AMB were identified as belonging to genus Bacillus (12 species), Staphylococcus (3 species) and one species of Aerococcus, Macrococcus, Leifsonia, Kurthia, Proteus, Acinetobacter and Globicatella, respectively. A putatively novel, previously undescribed Corynebacterium sp. was also found. E. faecium was the dominant LAB in all investigated retail samples except one sample dominated by Pediococcus acidilactici. [ABSTRACT FROM AUTHOR]

Objectives: We evaluated the independent impact of field triage on treatment delay and long-term clinical outcome in a large contemporary, consecutive population of ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (pPCI). Background: Reduction of treatment delay is crucial for patients with STEMI. Methods: From January 2005 to July 2008, 1,437 STEMI patients were treated with pPCI at a single high-volume invasive center. We present the 1-year outcome in this observational registry study. Results: A total of 616 patients were admitted by field triage and 821 by emergency departments. Baseline and angiographic variables were similar in the 2 populations. Patients admitted by field triage had a significantly shorter median door-to-balloon time compared with patients admitted by emergency department triage (83 min, interquartile range 67 to 100 min vs. 103 min, interquartile range 80 to 135 min; p < 0.001). Door-to-balloon times of less than the recommended 90 min were achieved in 61% of field triage patients, but only in 36% of nonfield-triage patients (p < 0.001). After adjustment for relevant baseline variables, patients admitted by field triage had a reduced risk of reaching the combined end point of all-cause mortality or nonfatal myocardial infarction (hazard ratio: 0.67; 95% confidence interval: 0.46 to 0.97; p = 0.035). Conclusions: This study shows that field triage of STEMI patients to pPCI significantly reduces treatment delay and improves outcome. These results emphasize the value of field triage as an important tool in the quest to improve clinical outcomes in STEMI patients undergoing pPCI. [Copyright &y& Elsevier]

Alkaline-fermented food condiments play an important role in the diets of many people in developing and a few developed countries. The rise in pH during production of these foods is due to the ability of the dominant microorganisms, Bacillus spp., to hydrolyze proteins into amino acids and ammonia. Studies have been undertaken which have investigated a number of these products like dawadawa, ugba, bikalga, kinema, natto, and thua- nao. In this review, current knowledge about the principal microbiological activities and biochemical modifications which occur during the processing of the alkaline condiments including nutritional, antimicrobial, and probiotic aspects are discussed. The current use of molecular biology methods in microbiological research has allowed unambiguous and more reliable identification of microorganisms involved in these fermentations generating sufficient knowledge for the selection of potential starter cultures for controlled and better production procedures for alkaline-fermented seeds condiments. [ABSTRACT FROM AUTHOR]

This article presents the results of a clinical trial that compared two drug-eluting stents used in heart patients. Stent implantation has reduced the mortality rate of patients with coronary artery obstructions and the goal of drug-eluting stents is to reduce neointima formation by using antiprofilerative drugs built into the stent. This study chose to compare stents that are sirolimus-eluting to those that are paclitaxel-eluting. The study did not find a significant difference in adverse cardiac events between the two stents nor did they differ much in thrombosis rates.

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]

Microalbuminuria, a subclinical rise in the urinary albumin excretion, is a risk indicator of atherosclerotic cardiovascular disease. The aim of this study was to measure the urinary albumin excretion in patients with acute myocardial infarction, and to correlate this with known atherosclerotic risk factors. One-hundred-and-twenty-six patients and 56 healthy controls matched for age and sex were studied. The albumin/creatinine concentration ratio in morning urine specimens was calculated as an index of the albumin excretion. Microalbuminuria was defined as a urinary albumin/creatinine concentration ratio above 1 mg/mmol. Urinary albumin excretion (0.88 [95% confidence interval 0.69-1.11] versus 0.51 [0.40-0.63] mg/mmol; p = 0.001) and frequency of microalbuminuria (33 [95% confidence interval 25-41] versus 16 [9-23]%; p = 0.03) were higher in patients than controls. This difference was independent of blood pressure, body weight, smoking, diabetes mellitus, renal disease, and thrombolytic treatment. There was a positive correlation between urinary albumin excretion and thickness of the left ventricle wall (R = 0.28; p = 0.001) which was independent of blood pressure. Follow-up examination of the patients will reveal whether microalbuminuria increases the risk for recurrence of acute myocardial infarction. [ABSTRACT FROM AUTHOR]

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]

Introduction: Patients with type 2 diabetes (T2D) have high levels of epicardial (EAT) and pericardial (PAT) adipose tissue, which due to their intimate proximities to the myocardium, are believed to impact cardiac structure and function in a paracrine manner. EAT is known to secrete inflammatory and sympathetic factors, and apply mechanical stress on the cardiac muscle that could contribute to heart failure. Hypothesis: We hypothesize that EAT and PAT are associated with reduced diastolic and systolic function in a large population of T2D. Methods: 1030 patients with T2D were included in this cross-sectional study. 260 were excluded due to atrial fibrillation (n=62), heart valve disease (n=34) or known ischemic heart disease (n=164). The final study population comprised 770 patients. A comprehensive baseline echocardiography was performed including conventional imaging, tissue Doppler imaging, and 2D speckle tracking. Total cardiac fat (CAT) including EAT and PAT were measured from the parasternal long axis view. Results: 465 (60%) were men, with an age average (SD) of 63±10 years, and known diabetes duration of 12±8 years. Mean total cardiac fat was 11.9±3.6 mm with a mean EAT of 4.6±1.8 mm and mean PAT of 6.3±2.8 mm. Total cardiac fat was associated with measures of decreased diastolic function including peak A velocity (SE) (0.64 cm/s (0.20), p =0.001), lateral E'(-0.13 cm/s (0.03), p <0.001), E/A ratio (-0.01 (0.03), p <0.001), and lateral E/E' (0.13, (0.05), p =0.002). The associations remained after adjusting for age, sex, systolic blood pressure, LDL, HbA1c, and were mainly driven by EAT (all p<0.04 in adjusted models) and not PAT (all p>0.05). Split by the median, patients with high vs. low EAT levels had significantly higher mean E/E'(11.4 (0.25) vs. 10.1 (0.2) p <0.001). In contrast, CAT was only associated with increasing global longitudinal strain (0.08% (0.03) p =0.01), and no other systolic parameters. Conclusion: In patients with T2D, total cardiac adipose tissue was associated with measures of decreased diastolic function primarily driven by epicardial and not pericardial adipose tissue. These results indicate that epicardial and total cardiac adipose tissue may be biomarkers of diastolic dysfunction. [ABSTRACT FROM AUTHOR]

Introduction: The ratio of early mitral inflow velocity to global diastolic strain rate (E/e'sr) has recently emerged as a novel measure of left ventricular (LV) filling pressure. This new measure has demonstrated to have prognostic value in specific patient populations and to be superior to E/e'. Objectives: This study sought to investigate the prognostic value of E/e'sr in a large cohort of patients with heart failure with reduced ejection fraction (HFrEF) in relation to all-cause mortality. Methods: We retrospectively studied 897 HFrEF (mean age 66 ± 12 years, 73% male, 59% ischemic cardiomyopathy) patients who underwent speckle tracking echocardiography where E/e'sr along with novel and conventional echocardiographic parameters were obtained. The primary endpoint was defined as all-cause mortality. Results: During follow-up (median: 40 months IQR: 22-57), 137 (15.3%) patients died. Both E/e'sr and E/e' were significantly associated with all-cause mortality (E/e'sr: HR 1.03 95%CI [1.02-1.04], p<0.001, per 0.10 m increase) and (E/e': HR 1.04 95%CI [1.02-1.06], p=0.001, per 1 unit increase) (Figure 1). E/e'sr remained an independent predictor of mortality in a multivariable model after adjusting for age, gender, BMI, mean arterial pressure, total cholesterol, LV mass index, heart rate, percutaneous transluminal coronary angioplasty, noninsulin dependent diabetes mellitus, and left ventricular ejection fraction (HR 1.02 95%CI [1.01-1.03], p=0.006) whereas E/e' did not (HR 1.02 95%CI [0.97-1.06], p=0.49). Furthermore, E/e'sr provided incremental prognostic information beyond a model including known risk factors: age, gender, total cholesterol, mean arterial pressure, heart rate, BMI, smoking status and E/e' (Harrell's C-statistics: 0.72 (0.68-0.77) vs 0.70 (0.66-0.75), p = 0.043). Conclusions: In HFrEF patients, E/e'sr provides independent and incremental prognostic information regarding all-cause mortality superior to E/e'. [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]

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]