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Aims: We aimed to evaluate the effect of acute hyperglycaemia and hypoglycaemia on cardiac function in patients with type 2 diabetes (T2D) and a control group. Materials and methods: In a nonrandomized interventional study, insulin‐treated patients with T2D (N = 21, mean ± SD age 62.8 ± 6.5 years, body mass index [BMI] 29.0 ± 4.2 kg/m2, glycated haemoglobin [HbA1c] 51.0 ± 5.4 mmol/mol [6.8 ± 0.5%]) and matched controls (N = 21, mean ± SD age 62.2 ± 8.3 years, BMI 29.2 ± 3.5 kg/m2, HbA1c 34.3 ± 3.3 mmol/L [5.3 ± 0.3%]) underwent one experimental day with plasma glucose (PG) clamped at three different 30‐minute steady‐state levels: (1) fasting plasma glucose (FPG); (2) hyperglycaemia (FPG + 10 mmol/L); and (3) hyperinsulinaemic hypoglycaemia (PG <3.0 mmol/L). Cardiac function was evaluated during each steady state by echocardiography. Results: Acute hyperglycaemia increased left ventricular (LV) ejection fraction from baseline in patients with T2D (mean [95% confidence interval] 4.5 percentage points [1.1; 7.9]) but not in controls (2.0 percentage points [−1.4; 5.4]). Mitral annular peak systolic velocity (s′) increased during hyperglycaemia in both patients and controls (0.4 m/s [0.2;0.6] and 0.6 m/s [0.4; 0.8], respectively), whereas global longitudinal strain rate only increased in the controls (−0.05 s−1 [−0.12; 0.02] and −0.11 s−1 [−0.18; −0.03], respectively). All measures of LV systolic function increased markedly during hypoglycaemia (P <0.01 for all). No interaction between group and PG level on cardiac function was observed. Conclusions: Acute hyperglycaemia and hypoglycaemia increase LV systolic function, with no difference between patients with T2D and controls. Standardization of PG may improve reproducibility when evaluating LV systolic function in patients with T2D. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. • Dyspnea is common and difficult to assess in patients with type 2 diabetes. • Dyspnea was associated with an increased risk of cardiovascular events. • An echocardiographic substrate for dyspnea identified high risk patients. • No echocardiographic substrate for dyspnea identified low risk patients. • Echocardiography is pivotal in patients with type 2 diabetes complaining of dyspnea. [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]

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]

Patients with type 2 diabetes (T2D) have a markedly altered cardiac metabolism and twice the risk of developing heart failure compared to individuals without diabetes. The effect of acute changes in plasma glucose (PG) on cardiac function is unclear. We evaluated the effect of acute hyperglycemia and hypoglycemia on cardiac function. Insulin-treated patients with T2D (N=21, [mean±SD] age 62.8±6.5 years, BMI 29.0±4.2 kg/m2, HbA1c 51.0±5.4 mmol/mol) and matched controls (N=21, age 62.2±8.3 years, BMI 29.2±3.5, HbA1c 34.3±3.3 mmol/l) with normal glucose tolerance underwent a 3-step glucose clamp day with 30 min of steady-state PG during each step: 1) fasting PG (FPG), 2) hyperglycemia (FPG+10 mmol/l), and 3) hyperinsulinemic hypoglycemia (PG<3.0 mmol/l). Cardiac function was evaluated during steady-state of each step by echocardiography. Acute hyperglycemia increased left ventricular ejection fraction (LVEF) from baseline in T2D patients ([mean±SEM, P-value] 4.5±1.7%, P=0.0108) whereas no change was observed in controls (2.0±1.7%, P=0.2525). Furthermore, left ventricular systolic function measured by s' increased during hyperglycemia in both patients and controls (0.4±0.1 m/s (P=0.0007) and 0.6±0.1 m/s (P <0.0001), respectively) whereas global longitudinal strain rate only increased in the controls (-0.05±0.04 s-1 (P=0.1803) and -0.11±0.04 s-1 (P=0.0053), respectively). All measures of left ventricular systolic function increased markedly during hypoglycemia (P<0.01 for all). No significant interaction between group and PG level on cardiac function was observed. In conclusion, we demonstrate that LVEF increases during acute hyperglycemia in insulin-treated patients with T2D and that acute hypoglycemia markedly increases all measures of left ventricular systolic function. These results point to the importance of glycemia when evaluating left ventricular systolic function by echocardiography in patients with T2D. Disclosure: A. Andersen: None. P.G. Jørgensen: None. J.I. Bagger: Speaker's Bureau; Self; Novo Nordisk A/S. M. Baldassarre: None. M.B. Christensen: None. K.U. Abelin: None. U. Pedersen-Bjergaard: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Research Support; Self; Novo Nordisk A/S. J.J. Holst: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Spouse/Partner; Antag Therapeutics. T.B. Lindhardt: None. F.K. Knop: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk A/S, Sanofi. Consultant; Self; Carmot Therapeutics, Inc., Eli Lilly and Company, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Gubra, Novo Nordisk A/S, Sanofi, Zealand Pharma A/S. Speaker's Bureau; Self; AstraZeneca, Lupin Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Norgine B.V., Novo Nordisk A/S. T. Vilsbøll: Advisory Panel; Self; AstraZeneca, Mundipharma International, Novo Nordisk A/S, Sun Pharmaceutical Industries Ltd. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Medscape, Merck Sharp & Dohme Corp., Sanofi. [ABSTRACT FROM AUTHOR]

Aims: Colour tissue Doppler imaging (TDI) M‐mode through the mitral leaflet is an easy and precise method to obtain cardiac time intervals including isovolumic contraction time (IVCT), isovolumic relaxation time (IVRT) and systolic ejection time (SET). The myocardial performance index (MPI) is defined as [(IVCT + IVRT)/SET]. Whether cardiac time intervals obtained by the TDI M‐mode method can be used to predict outcome in patients with heart failure with reduced ejection fraction (HFrEF) remains unknown. Methods and results: A total of 997 patients with HFrEF (mean age 67 ± 11 years, 74% male) underwent an echocardiographic examination including TDI. During a median follow‐up of 3.4 years (interquartile range 1.9–4.8 years), 165 (17%) patients died. The risk of mortality increased by 9% per 10 ms decrease in SET [per 10 ms decrease: hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.06–1.13; P < 0.001]. The association remained significant even after multivariable adjustment for clinical and echocardiographic parameters (per 10 ms decrease: HR 1.06, 95% CI 1.01–1.11; P = 0.030). The MPI was a significant predictor in an unadjusted model (per 0.1 increase: HR 3.06, 95% CI 1.16–8.06; P = 0.023). However, the association did not remain significant after multivariable adjustment. No significant associations between IVCT or IVRT and mortality were found in unadjusted nor adjusted models. Additionally, SET provided incremental prognostic information with regard to predicting mortality when added to established clinical predictors of mortality in patients with HFrEF. Conclusion: In patients with HFrEF, SET provides independent and incremental prognostic information regarding all‐cause mortality. [ABSTRACT FROM AUTHOR]

Aims. The European Society of Cardiology guidelines on diabetes and cardiovascular disease (CVD) recommend an electrocardiogram (ECG) in patients with diabetes and hypertension or with suspected CVD. We investigated whether ECG abnormalities can be used as a diagnostic and prognostic marker of heart failure (HF) in patients with type-2 diabetes (T2D) in secondary care diabetes-clinics. Methods. We included 722 patients with T2D in sinus rhythm. HF with preserved ejection fraction (HFpEF) was defined according to the European Society of Cardiology guidelines. Heart failure with mid-range ejection fraction (HFmrEF) was patients with dyspnoea and an LVEF 41–49%. Heart failure with reduced ejection fraction (HFrEF) or asymptomatic left ventricular systolic dysfunction (ALVSD) was defined as a LVEF ≤40%. Results. Overall, 24% patients had ECG abnormalities. A total of 15% had HF whereof 48% had ECG abnormalities. A normal ECG had a 99.3% negative predictive value (NPV) of ruling out HFrEF/ALVSD. In a sub-group with 0-1 simple clinical risk markers, the ECG ruled out both HFrEF/ALVSD, HFmrEF, and HFpEF with an NPV of 96.6%. The hazard-ratio (HR) of incident CVD or death in patients with HF and a normal ECG compared with patients without HF was 1.85 [95%CI 1.01–3.39], p =.05, while an abnormal ECG increased the HR to 3.84 [2.33–6.33], p <.001. Conclusion. HFrEF/ALVSD and HFmrEF were rare and HFpEF was frequent in this T2D population. A normal ECG ruled out HFrEF/ALVSD and in a sub-population with 0–1 simple clinical risk markers also both HFrEF/ALVSD, HFmrEF, and HFpEF. What is already known about this subject? In early studies of unselected patients from primary care with suspected chronic heart failure, the presence of a normal ECG was found be useful to rule out heart failure with reduced ejection fraction. What does this study add? This study confirms that a standard electrocardiogram when normal in 722 stable outpatients with type 2 diabetes can be used to rule out HFrEF/ALVSD. Further, it adds knowledge about the risk of incident cardiovascular disease or death as a pathologic electrocardiogram increases the hazard ratio. How might this implicate clinical practice? With this study clinicians in secondary diabetes care clinics can use an electrocardiogram to select patients to undergo echocardiography when suspecting heart failure with reduced ejection fraction, as a normal electrocardiogram will rule out this diagnosis with a negative predictive value of >99%. [ABSTRACT FROM AUTHOR]

Aim: To investigate echocardiographic changes during acute hypoglycaemia followed by recovery to hyperglycaemia or euglycaemia in patients with type 1 diabetes. Materials and Methods: In a randomized crossover study, 24 patients with type 1 diabetes took part in two experimental study days, consisting of a hyperinsulinaemic‐euglycaemic phase (5.0‐8.0 mmol/L) for 45 minutes followed by a hyperinsulinemic‐hypoglycaemic phase (2.5 mmol/L) for 60 minutes, and a recovery phase in either hyperglycaemia (20 mmol/L) or euglycaemia (5.0‐8.0 mmol/L) for 60 minutes. Cardiac function was evaluated with echocardiography during each phase. Results: Acute hypoglycaemia increased all markers of left ventricular (LV) systolic function, including LV ejection fraction (LVEF), global longitudinal strain (GLS), GLS rate and peak systolic velocity of mitral annular longitudinal movement (s'; P < 0.001 for all). During the recovery phases, all markers of LV systolic function were increased during hyperglycaemia (P < 0.01 for all), and LVEF and GLS remained increased during euglycaemia (P = 0.0116 and P = 0.0092, respectively). The increment in LVEF during the recovery phase was greater during hyperglycaemia than euglycaemia (P = 0.0046). Conclusions: Hypoglycaemia, recent hypoglycaemia, and overcorrection of hypoglycaemia to rebound hyperglycaemia increased LV systolic function in type 1 diabetes and may imply consideration of plasma glucose when evaluating LV function in patients with type 1 diabetes. An increase in LV systolic function may cause increased strain on the heart and partly explain the link between hypoglycaemia, high glycaemic variability and cardiovascular disease. [ABSTRACT FROM AUTHOR]

Aims: Layer‐specific global longitudinal strain (GLS) has been demonstrated to predict outcome in various patient cohorts. However, little is known regarding the prognostic value of layer‐specific GLS in the general population and whether different layers entail differential prognostic information. The aim of the present study was to investigate the prognostic value of whole wall (GLSWW), endomyocardial (GLSEndo), and epimyocardial (GLSEpi) GLS in the general population. Methods and results: A total of 4013 citizens were included in the present study. All 4013 had two‐dimensional speckle tracking echocardiography performed and analysed. Outcome was a composite endpoint of incident heart failure and/or cardiovascular death. Mean age was 56 years and 57% were female. During a median follow‐up time of 3.5 years, 133 participants (3.3%) reached the composite outcome. Sex modified the relationship between all GLS parameters and outcome. In sex‐stratified analysis, no GLS parameter remained significant predictors of outcome in females. In contrast, GLSWW [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.02–1.31, per 1% decrease] and GLSEpi (HR 1.19, 95% CI 1.04–1.38, per 1% decrease) remained as significant predictors of outcome in males after multivariable adjustment (including demographic, clinical, biochemistry, and echocardiographic parameters). Lastly, only in males did GLS parameters provide incremental prognostic information to general population risk models. Conclusions: In the general population, sex modifies the prognostic value of GLS resulting in GLSEpi being the only layer‐specific prognosticator in males, while no GLS parameter provides independent prognostic information in females. [ABSTRACT FROM AUTHOR]

Background: Diagnostic tests including echocardiography, albuminuria, electrocardiogram (ECG), high‐sensitivity troponin I (hs‐TnI), and N‐terminal prohormone brain natriuretic peptide (NT‐proBNP) have been suggested as cardiovascular (CV) risk predictors in type 2 diabetes. We studied the separate and combined prognostic yield of these risk markers. Methods: In all, 1030 patients with type 2 diabetes were recruited from specialized clinics in this prospective cohort study. Full echocardiographic evaluation was feasible in 886 patients in sinus rhythm with adequate image quality. ECG was performed in 998 patients. Albuminuria was measured in 1009 and NT‐proBNP/hs‐TnI in 933 patients. The end point was a composite of CV events. Results: The median follow‐up was 4.7 years (interquartile range: 4.0‐5.3), and 174 patients experienced a CV disease event. All considered markers, except hs‐TnI, were significantly (P <.001) associated with the outcome: abnormal echocardiogram (hazard ratio 2.40 [1.70‐3.39]), albuminuria 2.01 (1.47‐2.76), abnormal ECG (2.27 [1.66‐3.08]), high NT‐proBNP (>150 pg/mL) 3.05 (2.11‐4.40), and hs‐TnI 1.12 (0.79‐1.59). After adjusting for clinical variables, all remained significantly associated with the end point. However, after adjusting for each other, only NT‐proBNP >150 pg/mL remained significantly associated with the end point (2.07 [1.28‐3.34], P <.001). Measured by C‐statistics, model performance was highest with log2 (NT‐proBNP) (0.70 [0.65‐0.75]) and similar to clinical variables alone (0.71 [0.67‐0.76]). Combining all risk markers only resulted in a very limited increase in C‐statistics (0.69 [0.64‐0.74]). Conclusions: This study identified NT‐proBNP over echocardiography, ECG, and albuminuria in risk prediction in patients with type 2 diabetes. The diagnostic yield in considering more than one risk marker was limited in this population. [ABSTRACT FROM AUTHOR]

Summary: Epicardial adipose tissue (EAT) and pericardial adipose tissue (PAT) are metabolically active fat depots implicated in cardiovascular disease, and EAT has potential as a novel cardiac risk factor, suitable as a target for interventions. The objective of this systematic review and meta‐analysis was to investigate the evidence whether EAT and PAT volume can be reduced by weight‐loss interventions (exercise, diet, bariatric surgery or pharmaceutical interventions). A systematic literature search identified 34 studies that were included in the qualitative synthesis (exercise, n = 10, diet, n = 5, bariatric surgery, n = 9 and pharmaceutical interventions, n = 10). Of the 34 studies, 10 reported sufficient data to be included in the meta‐analysis. The meta‐analysis was only conducted for changes in EAT volume, since only few controlled studies reported changes in PAT (n = 3) or total cardiac adipose tissue volume (n = 1). A significant pooled effect size (ES) for reduction in EAT volume was observed following weight‐loss interventions as compared with control interventions (ES = −0.89, 95% CI: −1.23 to −0.55, P < 0.001). When comparing the effect of exercise training versus control on EAT volume reduction, there was a significant pooled ES favouring exercise training (ES: −1.11, 95% CI: −1.57 to −0.65, P < 0.001). Similarly, the ES of pharmaceutical versus control interventions on EAT volume reduction was significant, favouring pharmaceutical interventions (ES: −0.79, 95% CI: −1.37 to −0.21, P < 0.0072). In conclusion, this systematic review and meta‐analysis provides evidence that exercise, diet, bariatric surgery and pharmaceutical interventions can reduce cardiac adipose tissue volume. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the association of epicardial (EAT) and pericardial (PAT) adipose tissues with myocardial function in type 2 diabetes (T2D). EAT and PAT were measured by ultrasound in 770 patients with T2D and 234 age‐ and sex‐matched non‐diabetic controls. Echocardiography was performed, including tissue Doppler imaging and 2D speckle tracking. Patients with T2D versus controls had increased EAT (4.6 ± 1.8 mm vs. 3.4 ± 1.2 mm, P < 0.0001) and PAT (6.3 ± 2.8 mm vs. 5.3 ± 2.4 mm, P < 0.0001). EAT and PAT were associated with structural cardiac measures both in T2D patients and controls (all P < 0.043), but only in T2D patients with functional measures: PAT was associated with impaired global longitudinal strain [beta coefficient (SE)] [0.11% (0.04), P = 0.002], while EAT was associated with reduced diastolic function by lateral early diastolic myocardial velocity (e'lat) [−0.31 (0.05) cm/s, P = 0.001], mitral inflow velocities: peak early (E)/peak atrial (A) ratio [−0.02 (0.01), P = 0.001] and lateral E/e'lat [0.36 (0.10), P < 0.001]. However, no interaction was found between diabetes status and PAT (P = 0.75) or EAT (P = 0.45). Adipose tissue in intimate relation to the myocardium is higher in patients with T2D versus controls and is associated with functional myocardial measures in T2D. [ABSTRACT FROM AUTHOR]

The prevalence of heart failure (HF) in patients with type 2 diabetes (T2DM) is debatable and no data exist concerning the diagnostic value of mid‐regional pro‐atrial natriuretic peptide (MR‐proANP). We aimed to identify HF prevalence and evaluate the diagnostic value of MR‐proANP in outpatients followed in two specialized diabetes clinics. HF was pre‐defined as HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). The prevalence of HFrEF and HFpEF was 2.4% and 17.5%, respectively. An MR‐proANP <60 pmol/L ruled out HFrEF in the total population (n = 806) and in patients reporting dyspnea (n = 311) with a sensitivity of 94.7% and 87.5%, a negative predictive value of 99.7% and 99.0%, a specificity of 39.5% and 33.0%, and a positive predictive value of 3.6% and 3.3%, respectively. In a multivariable model including age, sex, T2DM duration, albuminuria, uncontrolled systolic blood pressure, abnormal electrocardiogram and ischaemic heart disease for diagnosis of HF in patients reporting dyspnea, adding MR‐proANP increased the area under the curve from 0.69 to 0.78 (P < 0.001). In conclusion, HFrEF was rare among outpatients with T2DM. MR‐proANP rules out HFrEF and contributes independent information relevant to diagnosis of HF in patients reporting dyspnea. [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]

Insulin treatment in patients with type 1 diabetes (T1D) causes rapid and large fluctuations in plasma glucose (PG) concentrations, and patients with T1D and poor glycemic control have an increased risk of cardiovascular disease including heart failure. We evaluated echocardiographic changes in cardiac function during experimental hypoglycemia and rebound hyperglycemia in patients with T1D. Patients with T1D (age 52.8±11.4 years, HbA1c 7.5±0.8% [57.6±8.9 mmol/mol], BMI 25.7±3.1 kg/m2) underwent two clamp days in random order. Both clamp days included three steady-state phases: 1) a 45-min hyperinsulinemic euglycemic phase (PG=6 mmol/L); 2) a 60-min hyperinsulinemic hypoglycemic phase (PG=2.5 mmol/L), and 3) a 60-min recovery phase in either hyperglycemia or euglycaemia (Clamp A: PG: 20 mmol/L; Clamp B: PG: 6 mmol/L). Cardiac function was evaluated with echocardiography at each phase by a blinded observer. Acute hypoglycemia increased left ventricular ejection fraction (LVEF) (absolute change, Clamp A: 6.5% [5.0;8.1], P=0.0001; Clamp B: 6.2% [4.6;7.9], P<0.0001) and global longitudinal strain (GLS) (absolute change, Clamp A: -3.1% (-4.5;-1.6), P<0.001; Clamp B: -3.5% (-4.6;-2.3), P<0.0001) from baseline. In Clamp A during hyperglycemia, LVEF and GLS were increased compared to baseline euglycemia (5.0% [3.2;6.8] (P<0.0001) and 2.1% [-3.7;-0.6] (P<0.01), respectively). An increase in LVEF was also observed in the recovery phase in Clamp B despite normalization of PG for 60 min (2.1% [0.5;3.8], P<0.05). In the recovery phase, LVEF was greater during hyperglycemia in Clamp A (2.9% [1.0;4.7], P<0.01) compared to euglycaemia in Clamp B. In conclusion, our findings suggest that acute fluctuations in PG affect echocardiographic-derived measures of systolic function in patients with T1D. Disclosure: C. R. Andreasen: None. F. K. Knop: Advisory Panel; Self; MSD Corporation, Novo Nordisk A/S, Sanofi, Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S, Pharmacosmos, Zealand Pharma A/S, Research Support; Self; Novo Nordisk A/S, Zealand Pharma A/S, Speaker's Bureau; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MSD Corporation, Novo Nordisk A/S. T. Vilsbøll: Consultant; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Gilead Sciences, Inc., Lilly Diabetes, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk, Sanofi, Sun Pharmaceutical Industries Ltd. A. Andersen: None. P. G. Hagelqvist: None. K. U. Abelin: None. J. V. Lauritsen: None. P. G. Jørgensen: Speaker's Bureau; Self; AstraZeneca. S. Engberg: None. J. J. Holst: Consultant; Self; Novo Nordisk, Other Relationship; Self; Antag Therapeutics, Bainan Biotech, MSD Corporation, Novo Nordisk, Other Relationship; Spouse/Partner; Antag Therapeutics, Bainan Biotech, Synklino ApS. U. Pedersen-bjergaard: Advisory Panel; Self; Novo Nordisk A/S, Sanofi-Aventis, Consultant; Self; Abbott, Speaker's Bureau; Self; Novo Nordisk A/S. Funding: Novo Nordisk Foundation (NNF17SA0031406) [ABSTRACT FROM AUTHOR]

Background: Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a useful biomarker in outpatients with type 2 diabetes (T2D) to diagnose heart failure (HF). Elevated B-type natriuretic peptides are included in the definition of HF with preserved ejection fraction (HFpEF) but little is known about the prognostic value of including A-type natriuretic peptides (MR-proANP) in the evaluation of patients with T2D. Methods: We prospectively evaluated the risk of incident cardiovascular (CV) events in outpatients with T2D (n = 806, mean ± standard deviation age 64 ± 10 years, 65% male, median [interquartile range] duration of diabetes 12 [6–17] years, 17.5% with symptomatic HFpEF) according to MR-proANP levels and stratified according to HF-status including further stratification according to a prespecified cut-off level of MR-proANP. Results: A total of 126 CV events occurred (median follow-up 4.8 [4.1–5.3] years). An elevated MR-proANP, with a cut-off of 60 pmol/l or as a continuous variable, was associated with incident CV events (p < 0.001). Compared to patients without HF, patients with HFpEF and high MR-proANP (≥ 60 pmol/l; median 124 [89–202] pmol/l) and patients with HF and reduced ejection fraction (HFrEF) had a higher risk of CV events (multivariable model; hazard ratio (HR) 2.56 [95% CI 1.64–4.00] and 3.32 [1.64–6.74], respectively). Conversely, patients with HFpEF and low MR-proANP (< 60 pmol/l; median 46 [32–56] pmol/l) did not have an increased risk (HR 2.18 [0.78–6.14]). Conclusions: Patients with T2D and HFpEF with high MR-proANP levels had an increased risk for CV events compared to patients with HFpEF without elevated MR-proANP and compared to patients without HF, supporting the use of MR-proANP in the definition of HFpEF from a prognostic point-of-view. [ABSTRACT FROM AUTHOR]

Background: Cardiac fat is a cardiovascular biomarker but its importance in patients with type 2 diabetes is not clear. The aim was to evaluate the predictive potential of epicardial (EAT), pericardial (PAT) and total cardiac (CAT) fat in type 2 diabetes and elucidate sex differences. Methods: EAT and PAT were measured by echocardiography in 1030 patients with type 2 diabetes. Follow-up was performed through national registries. The end-point was the composite of incident cardiovascular disease (CVD) and all-cause mortality. Analyses were unadjusted (model 1), adjusted for age and sex (model 2), plus systolic blood pressure, body mass index (BMI), low-density lipoprotein (LDL), smoking, diabetes duration and glycated hemoglobin (HbA1c) (model 3). Results: Median follow-up was 4.7 years and 248 patients (191 men vs. 57 women) experienced the composite end-point. Patients with high EAT (> median level) had increased risk of the composite end-point in model 1 [Hazard ratio (HR): 1.46 (1.13; 1.88), p = 0.004], model 2 [HR: 1.31 (1.01; 1.69), p = 0.038], and borderline in model 3 [HR: 1.32 (0.99; 1.77), p = 0.058]. For men, but not women, high EAT was associated with a 41% increased risk of CVD and mortality in model 3 (p = 0.041). Net reclassification index improved when high EAT was added to model 3 (19.6%, p = 0.035). PAT or CAT were not associated with the end-point. Conclusion: High levels of EAT were associated with the composite of incident CVD and mortality in patients with type 2 diabetes, particularly in men, after adjusting for CVD risk factors. EAT modestly improved risk prediction over CVD risk factors. [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]