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Aims: We examined the prognostic importance of N-terminal pro B-type natriuretic peptide (NT-proBNP) and troponin T (TnT) in heart failure patients with and without diabetes.Methods and Results: We measured NT-proBNP and TnT in the biomarker substudy of the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF). Of 1907 patients, 759 (40%) had diabetes. Median TnT in patients with diabetes was 18 (interquartile range 11-27) ng/L and 13 (9-21) ng/L in those without (P < 0.001). The TnT frequency-distribution curve was shifted to the right in patients with diabetes, compared to those without diabetes. By contrast, NT-proBNP did not differ between patients with and without diabetes. Diabetes and each biomarker were predictive of worse outcomes. Thus, patients with diabetes, an elevated TnT and a NT-proBNP level in the highest tertile (9% of all patients) had an absolute risk of cardiovascular death or heart failure hospitalization of 265 per 1000 person-years, compared to a rate of 42 per 1000 person-years in those without diabetes, a TnT < 18 ng/L and a NT-proBNP in the lowest tertile (16% of all patients). TnT remained an independent predictor of adverse outcomes in multivariable analyses including NT-proBNP.Conclusion: TnT is elevated to a greater extent in heart failure patients with diabetes compared to those without (whereas NT-proBNP is not). TnT and NT-proBNP are additive in predicting risk and when combined help identify diabetes patients at extremely high absolute risk. [ABSTRACT FROM AUTHOR]

Aims: The role of microvascular complications in the risk conferred by diabetes in heart failure with reduced ejection fraction (HFrEF) is unknown.Methods and Results: We studied 2707 HFrEF patients in the Beta-blocker Evaluation of Survival Trial (BEST), stratified into three groups: no diabetes and diabetes without or with microvascular complications (neuropathy, nephropathy, or retinopathy). The risks of the composite of cardiovascular death or heart failure hospitalization, and all-cause death, were studied using Cox regression analyses adjusted for other prognostic variables. Overall, 964 (36%) patients had diabetes, of which 313 (32%) had microvascular complications. Patients with microvascular complications had more severe symptoms (New York Heart Association class IV 12% vs. 9% diabetes with no complications and 7% no diabetes), and worse quality of life (Minnesota Living with Heart Failure median score 60 vs. 54 and 51 points). In patients with diabetes and complications, the rate of the composite outcome was 50 per 100 person-years of follow-up (compared with 34 and 29 in those with diabetes and no microvascular complications and participants without diabetes, respectively). Compared to patients without diabetes, the adjusted hazard ratio (HR) for the composite outcome was 1.44 [95% confidence interval (CI) 1.22-1.70] and 1.18 (95% CI 1.03-1.35) for patients with diabetes with and without complications, respectively. The risk of all-cause mortality was similarly elevated: adjusted HR 1.42 (95% CI 1.16-1.74) and 1.20 (95% CI 1.01-1.42), respectively.Conclusion: In HFrEF, diabetes with microvascular complications is associated with worse symptoms and outcomes than diabetes without microvascular complications. Prevention of microvascular complications has the potential to improve HFrEF outcomes. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusion Although body mass index (BMI) is the most commonly used anthropometric measure to assess adiposity, alternative indices such as the waist‐to‐height ratio may better reflect the location and amount of ectopic fat as well as the weight of the skeleton.The prognostic value of several alternative anthropometric measures was compared with that of BMI in 1116 patients with non‐ischaemic heart failure with reduced ejection fraction (HFrEF) enrolled in DANISH. The association between anthropometric measures and all‐cause death was adjusted for prognostic variables, including natriuretic peptides. Median follow‐up was 9.5 years (25th–75th percentile, 7.9–10.9). Compared to patients with a BMI 18.5–24.9 kg/m2 (n = 363), those with a BMI ≥25 kg/m2 had a higher risk of all‐cause and cardiovascular death, although this association was only statistically significant for a BMI ≥35 kg/m2 (n = 91) (all‐cause death: hazard ratio [HR] 1.78, 95% confidence interval [CI] 1.28–2.48; cardiovascular death: HR 2.46, 95% CI 1.69–3.58). Compared to a BMI 18.5–24.9 kg/m2, a BMI <18.5 kg/m2 (n = 24) was associated with a numerically, but not a significantly, higher risk of all‐cause and cardiovascular death. Greater waist‐to‐height ratio (as an exemplar of indices not incorporating weight) was also associated with a higher risk of all‐cause and cardiovascular death (HR for the highest vs. the lowest quintile: all‐cause death: HR 2.11, 95% CI 1.53–2.92; cardiovascular death: HR 2.17, 95% CI 1.49–3.15).In patients with non‐ischaemic HFrEF, there was a clear association between greater adiposity and higher long‐term mortality.Clinical Trial Registration: ClinicalTrials.gov NCT00542945. [ABSTRACT FROM AUTHOR]

Background: Pleural effusion is present in 50% to 80% of patients with acute heart failure, depending on image modality. We aim to describe the association between the presence and size of pleural effusion and central hemodynamics, including pulmonary capillary wedge pressure (PCWP) in an advanced heart failure population., Methods: An observational, cross-sectional study in a cohort of patients with advanced heart failure (left ventricular ejection fraction ≤45%) who underwent right heart catheterization at The Department of Cardiology at Copenhagen University Hospital, Rigshospitalet, Denmark, between January 1, 2002 and October 31, 2020. The presence and size of pleural effusion were determined by a semiquantitative score of chest x -rays or computed tomography scans performed within 2 days of right heart catheterization., Results: In 346 patients (50±13 years; 78% males) with median left ventricular ejection fraction of 20% (15-25), we identified 162 (47%) with pleural effusion. The pleural effusion size was medium in 38 (24%) and large in 30 (19%). Patients with pleural effusion had a 4.3 mm Hg (2.5-6.1) higher PCWP and 2.4 mm Hg (1.2-3.6) higher central venous pressure ( P <0.001 for both). Patients with a medium/large pleural effusion had statistically significantly higher filling pressures than patients with a small effusion. Higher PCWP (odds ratio [OR], 1.06 [1.03-1.10]) and central venous pressure (OR, 1.09 [1.05-1.15]) were associated with pleural effusion in multivariable logistic regression adjusted for age, sex, and heart failure medications ( P <0.001 for both). In a subgroup of 204 (63%) patients with serum albumin data, PCWP (OR, 1.06 [1.01-1.11]; P =0.032), central venous pressure (OR, 1.14 [1.06-1.23]; P <0.001) and serum albumin level (OR, 0.89 [0.83-0.95]; P <0.001) were independently associated with the presence of a medium/large-sized pleural effusion., Conclusions: In patients with left ventricular ejection fraction ≤45% undergoing right heart catheterization as part of advanced heart failure work-up, pleural effusion was associated with higher PCWP and central venous pressure and lower serum albumin.

Aims: Myocardial infarction (MI) with cardiogenic shock (CS) and/or out-of-hospital cardiac arrest (OHCA) are conditions with potential loss of autonomy. In patients with MI, the association between CS and OHCA and need for home care or nursing home admission was examined., Methods and Results: Danish nationwide registries identified patients with MI (2008-19), who prior to the event lived at home without home care and discharged alive. One-year cumulative incidences and hazard ratios (HRs) were reported for home care need or nursing home admission, a composite proxy for disability in activities of daily living (ADL), along with all-cause mortality. The study population consisted of 67 109 patients with MI (by groups: -OHCA/-CS: 63 644; -OHCA/+CS: 1776; +OHCA/-CS: 968; and +OHCA/+CS: 721). The 1-year cumulative incidences of home care/nursing home were 7.1% for patients who survived to discharge with -OHCA/-CS, 20.9% for -OHCA/+CS, 5.4% for +OHCA/-CS, and 8.2% for those with +OHCA/+CS. The composite outcome was driven by home care. With the -OHCA/-CS as reference, the adjusted HRs for home care/nursing home were 2.86 (95% CI: 2.57-3.19) for patients with -OHCA/+CS; 1.31 (95% CI: 1.00-1.73) for + OHCA/-CS; and 2.18 (95% CI: 1.68-2.82) for those with +OHCA/+CS. The 1-year cumulative mortality were 5.1% for patients with -OHCA/-CS, 9.8% for -OHCA/+CS, 3.0% for +OHCA/-CS, and 3.4% for those with +OHCA/+CS., Conclusion: In patients discharged alive after a MI, CS, and to a lesser degree OHCA were associated with impaired ADL with a two-fold higher 1-year incidence of home care or nursing home admission compared with MI patients without CS or OHCA., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The mineralocorticoid receptor antagonists (MRAs) eplerenone and spironolactone are beneficial in heart failure with reduced ejection fraction (HFrEF), but have not been prospectively compared. We compared clinical outcomes, daily dosages, and discontinuation rates for the two drugs in a nationwide cohort., Methods: We identified all patients with HFrEF in the period 2016-2020, who were alive and had initiated MRA treatment at study start, 180 days after HF diagnosis. We estimated the 2-year risk of a composite of death and HF hospitalization, as well as each component separately, using Kaplan-Meier, cumulative incidence functions, and Cox proportional hazards models adjusted for age, sex, and comorbidities. Secondly, we assessed treatment withdrawal, cross-over, and daily drug dosage., Results: We included 7479 patients; 653 (9%) on eplerenone and 6840 (91%) on spironolactone. Patients in the eplerenone group were younger (median age 65 vs. 69 years), and more often men (91% vs. 68%), both P < 0.001. In adjusted analyses, with spironolactone as reference, there were no differences in the risk of the composite of all-cause death and HF hospitalization (HR 1.02, 95% CI 0.82-1.27), all-cause death (HR 0.93, 95% CI 0.67-1.30), or HF hospitalization (HR 1.10, 95% CI 0.84-1.42). Treatment withdrawal occurred in 34% in the eplerenone group and 53% in the spironolactone group (P < 0.001), treatment cross-over in 3%, and 10%, respectively. Daily dose >25 mg at 12 months, was observed in 230 patients (37%) in the eplerenone group and 771 patients (12%) in the spironolactone (P < 0.001)., Conclusions: In a contemporary nationwide cohort of patients with new-onset HFrEF who initiated MRA, we found no differences in clinical outcomes associated with initiation of eplerenone vs. spironolactone. Treatment was more frequently withdrawn, and daily drug dosage was lower among patients treated with spironolactone., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Implantable cardioverter-defibrillator (ICD) implantation reduce the risk of sudden cardiac death, but not all-cause death in patients with non-ischaemic systolic heart failure (HF). Whether co-existence of diabetes affects ICD treatment effects is unclear., Methods and Results: We examined the effect of ICD implantation on risk of all-cause death, cardiovascular death, and sudden cardiac death (SCD) according to diabetes status at baseline in the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischaemic Systolic Heart Failure on Mortality (DANISH) trial. Outcomes were analysed by use of cumulative incidence curves and Cox regressions models. Of the 1116 patients enrolled, 211 (19%) had diabetes at baseline. Patients with diabetes were more obese, had worse kidney function and more were in New York Heart Association Class III/IV. The risk of device infections and other complications in the ICD group was similar among patients with and without diabetes (6.1% vs. 4.6% P = 0.54). Irrespective of treatment group, diabetes was associated with higher risk of all-cause death, cardiovascular death, and SCD. The treatment effect of ICD in patients with diabetes vs. patients without diabetes was hazard ratio (HR) = 0.92 (0.57-1.50) vs. HR = 0.85 (0.63-1.13); Pinteraction = 0.60 for all-cause mortality, HR = 0.99 (0.58-1.70) vs. HR = 0.70 (0.48-1.01); Pinteraction = 0.25 for cardiovascular death, and HR = 0.81 (0.35-1.88) vs. HR = 0.40 (0.22-0.76); Pinteraction = 0.16 for sudden cardiac death., Conclusion: Among patients with non-ischaemic systolic HF, diabetes was associated with higher incidence of all-cause mortality, primarily driven by cardiovascular mortality including SCD. Treatment effect of ICD therapy was not significantly modified by diabetes which might be due to lack of power., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: To investigate the prognostic significance of hospitalization for worsening heart failure (WHF), myocardial infarction (MI), and stroke in patients with chronic heart failure (HF)., Methods and Results: We studied 5011 patients with HF and reduced EF (HF-REF) in the CORONA trial and 4128 patients with HF and preserved EF (HF-PEF) in the I-Preserve trial. Adjusted hazard ratios (HRs) for death were estimated for 0-30 days and ≥31 days after first post-randomization WHF, MI, or stroke used as a time-dependent variable, compared with patients with none of these events. In CORONA, 1616 patients (32%) had post-randomization first events (1223 WHF, 216 MI, 177 stroke), and the adjusted HR for mortality ≤30 days after an event was: WHF 7.21 [95% confidence interval (CI) 2.05-25.40], MI 23.08 (95% CI 6.44-82.71), and stroke 32.15 (95% CI 8.93-115.83). The HR for mortality at >30 days was: WHF 3.62 (95% CI 3.11-4.21), MI 4.41 (95% CI 3.23-6.02), and stroke 3.19 (95% CI 2.21-4.61). In I-Preserve, 896 patients (22%) experienced a post-randomization event (638 WHF, 111 MI, 147 stroke). The HR for mortality ≤30 days was WHF 31.77 (95% CI 7.60-132.81), MI 154.77 (95% CI 34.21-700.17), and stroke 223.30 (95% CI 51.42-969.78); for >30 days it was WHF 3.36 (95% CI 2.79-4.05), MI 3.29 (95% CI 2.14-5.06), and stroke 5.13 (95% CI 3.61-7.29)., Conclusions: In patients with both HF-REF and HF-PEF, hospitalization for WHF was associated with high early and late mortality. The early relative risk of death was not as great as following MI or stroke, but the longer term relative risk of death was similar following all three types of event. Numerically, more deaths occurred following WHF because it was a much more common event., (© 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.)