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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 log 2 (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., (© 2021 Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd.)

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., (©2020 World Obesity Federation.)

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.

Aims/hypothesis: Cardiovascular disease is the most common comorbidity in type 1 diabetes. However, current guidelines do not include routine assessment of myocardial function. We investigated whether echocardiography provides incremental prognostic information in individuals with type 1 diabetes without known heart disease., Methods: A prospective cohort of individuals with type 1 diabetes without known heart disease was recruited from the outpatient clinic. Follow-up was performed through Danish national registers. The association of echocardiography with major adverse cardiovascular events (MACE) and the incremental prognostic value when added to the clinical Steno T1D Risk Engine were examined., Results: A total of 1093 individuals were included: median (interquartile range) age 50.2 (39.2-60.3) years and HbA 1c 65 (56-74) mmol/mol; 53% men; and mean (SD) BMI 25.5 (3.9) kg/m 2 and diabetes duration 25.8 (14.6) years. During 7.5 years of follow-up, 145 (13.3%) experienced MACE. Echocardiography significantly and independently predicted MACE: left ventricular ejection fraction (LVEF) <45% (n = 18) vs ≥45% (n = 1075), HR (95% CI) 3.93 (1.91, 8.08), p < 0.001; impaired global longitudinal strain (GLS), 1.65 (1.17, 2.34) (n = 263), p = 0.005; diastolic mitral early velocity (E)/early diastolic tissue Doppler velocity (e') <8 (n = 723) vs E/e' 8-12 (n = 285), 1.59 (1.04, 2.42), p = 0.031; and E/e' <8 vs E/e' ≥12 (n = 85), 2.30 (1.33, 3.97), p = 0.003. In individuals with preserved LVEF (n = 1075), estimates for impaired GLS were 1.49 (1.04, 2.15), p = 0.032; E/e' <8 vs E/e' 8-12, 1.61 (1.04, 2.49), p = 0.033; and E/e' <8 vs E/e' ≥12, 2.49 (1.41, 4.37), p = 0.001. Adding echocardiographic variables to the Steno T1D Risk Engine significantly improved risk prediction: Harrell's C statistic, 0.791 (0.757, 0.824) vs 0.780 (0.746, 0.815), p = 0.027; and net reclassification index, 52%, p < 0.001., Conclusions/interpretation: In individuals with type 1 diabetes without known heart disease, echocardiography significantly improves risk prediction over and above guideline-recommended clinical risk factors alone and could have a role in clinical care.

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 (HbA 1c ) (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.

Aims: Echocardiography is suggested in the diagnostic work-up of patients with Type 2 diabetes (T2D). We investigated which echocardiographic parameters that best predicted cardiovascular disease (CVD) and whether this was persistent in both genders in a large cohort of outpatients with T2D., Methods and Results: We performed comprehensive echocardiography in 933 patients with T2D followed at specialized out-patients clinics in Copenhagen, Denmark. Follow-up was performed using national registries and included admission with future CVD events and non-CVD death as competing risk. Median follow-up was 4.8 years and 138 CVD events occurred. In univariable and multivariable analyses, a wide range of structural, diastolic, and systolic measurements predicted CVD including mean E/e' [hazard ratio (HR) 1.06, 95% confidence interval: (1.03-1.10), P < 0.001, C-statistics 0.74 (0.70-0.78)] and global longitudinal strain (GLS) [1.10 (1.01-1.20), P = 0.03, C-statistics 0.73 (0.69-0.77)]. However, this was modified by gender. In men, mean E/e' remained the strongest predictor in multivariable analyses and performed best measured by highest C-statistics [HR 1.15, 95% confidence interval: (1.08-1.21), P < 0.001, C-statistics 0.75 (0.71-0.80)] whereas in women this was GLS [1.39 (1.14-1.70), P = 0.001, C-statistics 0.79 (0.70-0.87)]. These findings persisted when excluding patients with known heart disease and when regarding all-cause mortality as a competing risk., Conclusion: A range of echocardiographic parameters predicted CVD in patients with Type 2 diabetes, however, in multivariable analyses, mean E/e' was the strongest predictor and had the highest model performance. Importantly, this study identifies a hitherto undescribed gender interaction as mean E/e' performed best in men, whereas in women this was GLS., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

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]

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]