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Background and aim Heart failure (HF) and diabetes mellitus (DM) are burdensome chronic diseases with high lifetime risks and numerous studies indicate associations between HF and DM. The objective of this study was to investigate the direct and indirect costs of HF patients with and without DM. Methods and results Patients with a first-time diagnosis of HF from 1998 to 2016 were identified through nationwide Danish registries and stratified according to DM status into HF with or without DM. The economic healthcare cost analysis was based on both direct costs, including hospitalization, procedures, medication and indirect costs including social welfare and lost productivity. The economic burden was investigated prior to, at, and following diagnosis of HF. Patients with concomitant HF and DM were younger (median age 74 vs. 77), had more comorbidities and fewer were female as compared to patients with HF but without DM. The socioeconomic burden of concomitant HF and DM compared to HF alone was substantially higher; 45% in direct costs (€16,237 vs. €11,184), 35% in home care costs (€3123 vs. €2320), 8% in social transfer income (€17,257 vs. €15,994) and they had 27% lower income (€10,136 vs. €13,845). The economic burden peaked at year of diagnosis, but the difference became increasingly pronounced in the years following the HF diagnosis. Conclusion Patients with concomitant HF and DM had a significantly higher economic burden compared to patients with HF but without DM., Background and aim: Heart failure (HF) and diabetes mellitus (DM) are burdensome chronic diseases with high lifetime risks and numerous studies indicate associations between HF and DM. The objective of this study was to investigate the direct and indirect costs of HF patients with and without DM. Methods and results: Patients with a first-time diagnosis of HF from 1998 to 2016 were identified through nationwide Danish registries and stratified according to DM status into HF with or without DM. The economic healthcare cost analysis was based on both direct costs, including hospitalization, procedures, medication and indirect costs including social welfare and lost productivity. The economic burden was investigated prior to, at, and following diagnosis of HF. Patients with concomitant HF and DM were younger (median age 74 vs. 77), had more comorbidities and fewer were female as compared to patients with HF but without DM. The socioeconomic burden of concomitant HF and DM compared to HF alone was substantially higher; 45% in direct costs (€16,237 vs. €11,184), 35% in home care costs (€3123 vs. €2320), 8% in social transfer income (€17,257 vs. €15,994) and they had 27% lower income (€10,136 vs. €13,845). The economic burden peaked at year of diagnosis, but the difference became increasingly pronounced in the years following the HF diagnosis. Conclusion: Patients with concomitant HF and DM had a significantly higher economic burden compared to patients with HF but without DM.

Aims Current treatment guidelines recommend implantable cardioverter-defibrillators (ICDs) in eligible patients with an estimated survival beyond 1 year. There is still an unmet need to identify patients who are unlikely to benefit from an ICD. We determined cause-specific 1-year mortality after ICD implantation and identified associated risk factors.Methods and results Using Danish nationwide registries (2000-2017), we identified 14 516 patients undergoing first-time ICD implantation for primary or secondary prevention. Risk factors associated with 1-year mortality were evaluated using multivariable logistic regression. The median age was 66 years, 81.3% were male, and 50.3% received an ICD for secondary prevention. The 1-year mortality rate was 4.8% (694/14 516). ICD recipients who died within 1 year were older and more comorbid compared to those who survived (72 vs. 66 years, P < 0.001). Risk factors associated with increased 1-year mortality included dialysis [odds ratio (OR): 3.26, confidence interval (CI): 2.37-4.49], chronic renal disease (OR: 2.14, CI: 1.66-2.76), cancer (OR: 1.51, CI: 1.15-1.99), age 70-79 years (OR: 1.65, CI: 1.36-2.01), and age >= 80 years (OR: 2.84, CI: 2.15-3.77). The 1-year mortality rates for the specific risk factors were: dialysis (13.8%), chronic renal disease (13.1%), cancer (8.5%), age 70-79 years (6.9%), and age >= 80 years (11.0%). Overall, the most common causes of mortality were related to cardiovascular diseases (62.5%), cancer (10.1%), and endocrine disorders (5.0%). However, the most common cause of death among patients with cancer was cancer-related (45.7%).Conclusion Among ICD recipients, mortality rates were low and could be indicative of relevant patient selection. Important risk factors of increased 1-year mortality included dialysis, chronic renal disease, cancer, and advanced age.

Aim To determine the risk of adverse outcomes across the spectrum of glycated haemoglobin (HbA1c) levels among hospitalized COVID-19 patients with and without diabetes. Materials and methods Danish nationwide registries were used to study the association between HbA1c levels and 30-day risk of all-cause mortality and the composite of severe COVID-19 infection, intensive care unit (ICU) admission and all-cause mortality. The study population comprised patients hospitalized with COVID-19 (3 March 2020 to 31 December 2020) with a positive polymerase chain reaction (PCR) test and an available HbA1c ≤ 6 months before the first positive PCR test. All patients had at least 30 days of follow-up. Among patients with diabetes, HbA1c was categorized as <48 mmol/mol, 48 to 53 mmol/mol, 54 to 58 mmol/mol, 59 to 64 mmol/mol (reference) and >64 mmol/mol. Among patients without diabetes, HbA1c was stratified into <31 mmol/mol, 31 to 36 mmol/mol (reference), 37 to 41 mmol/mol and 42 to 47 mmol/mol. Thirty-day standardized absolute risks and standardized absolute risk differences are reported. Results We identified 3295 hospitalized COVID-19 patients with an available HbA1c (56.2% male, median age 73.9 years), of whom 35.8% had diabetes. The median HbA1c was 54 and 37 mmol/mol among patients with and without diabetes, respectively. Among patients with diabetes, the standardized absolute risk difference of the composite outcome was higher with HbA1c < 48 mmol/mol (12.0% [95% confidence interval {CI} 3.3% to 20.8%]) and HbA1c > 64 mmol/mol (15.1% [95% CI 6.2% to 24.0%]), compared with HbA1c 59 to 64 mmol/mol (reference). Among patients without diabetes, the standardized absolute risk difference of the composite outcome was greater with HbA1c < 31 mmol/mol (8.5% [95% CI 0.5% to 16.5%]) and HbA1c 42 to 47 mmol/mol (6.7% [95% CI 1.3% to 12.1%]), compared with HbA1c 31 to 36 mmol/mol (reference). Conclusions Patients with COVID-1

Purpose: Self-assessed poor health status is associated with increased risk of mortality in several cardiovascular conditions, but has not been investigated in patients with endocarditis. We examined health status and mortality in patients with endocarditis. Methods: This is a re-specified substudy of the randomized POET endocarditis trial, which included 400 patients. Patients completed the single-question self-assessed health status from the Short-Form 36 questionnaire at time of randomization and were categorized as having poor or non-poor (excellent/very good, good, or fair) health status. Self-assessed health status and all-cause mortality were examined by a Cox regression model. Results: Self-assessed health status was completed by 266 (67%) patients with a mean age of 68.0 years (± 11.8), 54 (20%) were females, and 86 (32%) had one or more major concurrent medical conditions besides endocarditis. The self-assessed health status distribution was poor (n = 21, 8%) and non-poor (n = 245, 92%). The median follow-up was 3.3 years and death occurred in 9 (43%) and 48 (20%) patients reporting poor and non-poor health status, respectively, and mortality rates [mortality/100 person-years, 95% confidence interval (CI)] were 18.1 (95% CI 9.4–34.8) and 5.4 (95% CI 4.1–7.2), i.e., the crude hazard ratio for death was 3.4 (95% CI: 1.7–7.0, p < 0.01). Conclusion: Self-assessed poor health status compared with non-poor health status as assessed by a single question was associated with a threefold increased long-term mortality in patients with endocarditis. POET ClinicalTrials.gov number, NCT01375257. Trial registry: POET ClinicalTrials.gov number, NCT01375257.

Background Patients with chronic diseases are at higher risk of requiring domiciliary and nursing home care, but how different chronic diseases compare in terms of risk is not known. We examined initiation of domiciliary care and nursing home admission among patients with heart failure (HF), stroke, COPD and cancer. Methods Patients with a first-time hospitalization for HF, stroke, COPD or cancer from 2008–2016 were identified. Patients were matched on age and sex and followed for five years. Results 111,144 patients, 27,786 with each disease, were identified. The median age was 69 years and two thirds of the patients were men. The 5-year risk of receiving domiciliary care was; HF 20.9%, stroke 25.2%, COPD 24.6% and cancer 19.3%. The corresponding adjusted hazard ratios (HRs), with HF patients used as reference, were: stroke 1.35[1.30–1.40]; COPD 1.29[1.25–1.34]; and cancer 1.19[1.14–1.23]. The five-year incidence of nursing home admission was 6.6% for stroke, and substantially lower in patients with HF(2.6%), COPD(2.6%) and cancer (1.5%). The adjusted HRs were (HF reference): stroke, 2.44 [2.23–2.68]; COPD 1.01 [0.91–1.13] and cancer 0.76 [0.67–0.86]. Living alone, older age, diabetes, chronic kidney disease, depression and dementia predicted a higher likelihood of both types of care. Conclusions In patients with HF, stroke, COPD or cancer 5-year risk of domiciliary care and nursing home admission, ranged from 19–25% and 1–7%, respectively. Patients with stroke had the highest rate of domiciliary care and were more than twice as likely to be admitted to a nursing home, compared to patients with the other conditions.

OBJECTIVE: To examine the gradual association between self-reported health status and mortality in patients with heart failure (HF) as current research has focused on poor health status and increased risk of mortality.METHOD: This is a substudy of the DANISH (Defibrillator Implantation in Patients with Nonischemic Systolic HF) trial in which 1116 patients were randomized to receive or not receive an implantable cardioverter-defibrillator. Health status was assessed by a single question of the Short-Form 36. Patients were classified as having excellent/very good, good, fair (reference) or poor health status. We assessed the association between health status and mortality using multivariable Cox proportional hazard models.RESULTS: Self-reported health status was completed by 943 (84%) patients at randomization with a median follow-up of 67 months and a health status distribution of; excellent/very good (n = 79, 8%), good (n = 369, 39%), fair (n = 409, 43%), and poor (n = 86, 9%). All-cause mortality (death events/ 100 person-years) occurred with gradual differences according to health status from excellent/ very good (2.14), good (3.74), fair (5.21) to poor health status (5.57). The gradual difference yielded a crude hazard ratio (HR) of 0.40, 95% CI 0.20-0.80 (adjusted HR 0.47 (95% CI 0.23-0.95) for excellent/ very good health status, HR 0.71, 95% CI 0.52-0.97 (adjusted HR 0.78 (95% CI 0.56-1.08) for good health status. Poor being worse than fair health status yielded a crude HR of 1.07, 95% CI 0.67-1.69.CONCLUSION: Excellent/very good self-reported health status as assessed by a single question was associated with lower long-term mortality in patients with HF.

Objectives: To examine the association between health-related quality of life (HRQoL) and mortality in patients with heart failure (HF). Background: The potential association of HRQoL and mortality in patients with HF is unclear. We investigated this association in The Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators (ICD) in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH). Methods: In DANISH, a total of 1116 patients with non-ischemic systolic HF on guideline-recommended therapy were randomized to ICD therapy or usual clinical care. HRQoL was assessed at randomization using the disease-specific Minnesota Living with Heart Failure Questionnaire (MLHFQ, 0–105, high score indicating worse HRQoL). Multivariable Cox proportional hazard models were used to compare hazard ratios (HR) for all-cause mortality according to MLHFQ above or below 45, as recommended by a recent meta-analysis, to identify patients with poor HRQoL. Results: HRQoL was completed by 935 (84%) patients at baseline with a median follow-up of 67 months (IQR 47–83). Patients with poor HRQoL (MLHFQ score > 45, median 60 (IQR 53–71), n = 350) had a higher incidence of all-cause mortality than patients with moderate/good HRQoL (MLHFQ ≤45, median 23 (IQR 13–33), n = 585), respectively 26% vs. 18% with an unadjusted HR of 1.57 (95% CI 1.19–2.08, p =.002), and an adjusted HR of 1.39 (95% CI 1.01–1.91, p =.04). Conclusion: Poor HRQoL was associated with an increased risk of all-cause mortality after adjustment for traditional risk factors. Clinical trial registration: https: //clinicaltrials.gov/ct2/show/NCT00542945 (DANISH).

PURPOSE: The "distressed" (Type D) personality trait has been reported to be over-represented in patients with heart failure (HF) compared to the background population and may provide prognostic information for mortality. We examined the association between Type D personality and outcomes in the DANISH trial (The Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart Failure on Mortality).METHODS: The DANISH trial included a total of 1116 patients with non-ischemic HF on guideline-recommended therapy. Type D personality was assessed with the Type D Scale (DS14) at baseline and investigated through follow-up accordingly. Multivariable Cox proportional hazard models were used to compare hazard ratios (HR) of cardiovascular and all-cause mortality.RESULTS: Type D personality assessment was completed by 873 (78%) patients at baseline and Type D personality was found in 120 (14%) patients. The median follow-up was 67 months (interquartile range [IQR] 48-83). Among patients with versus without Type D personality, 22% versus 19% died from all-cause yielding similar incidence rates of 4.62 (95% CI 3.14-6.87) versus 3.95 (95% CI 3.37-4.66) per 100 person-years. The adjusted risk of all-cause mortality was not significantly different in patients with versus without Type D personality with an adjusted HR of 1.31 (95% CI 0.84-2.03, p = 0.23) with similar results for cardiovascular death (HR 1.46 (95% CI 0.88-2.44, p = 0.15).CONCLUSION: Type D personality was not significantly associated with increased risk of all-cause mortality or cardiovascular death in patients with non-ischemic HF.

BACKGROUND: Heart failure (HF) imposes a large burden on both the individual and the society. The aim of this study was to investigate the economic burden (either direct or indirect costs) attributed to patients with HF before, at, and after time of diagnosis.METHODS AND RESULTS: Using Danish nationwide registries we identified all patients > 18 years with a first-time diagnosis of HF from 1998-2016 and matched them 1:1 with a control group from the background population on age, gender, marital status, and educational level. The economic analysis of the total costs after diagnosis was based on direct costs including hospitalization, procedures, medication, and indirect costs including social welfare and lost productivity to estimate the annual cost of HF. A total of 176 067 HF patients with a median age of 76 (interquartile range 67-84) years and 55% male were included. Patients with HF incurred an average of €17 039 in total annual direct (€11 926) and indirect (€5113) healthcare costs peaking at year of diagnosis compared to €5936 in the control group with the majority attributable to inpatient admissions. The total annual net costs including public transfer after index HF were €11 957 higher in patients with HF compared to controls and the economic consequences were evident more than 2 years prior to the diagnosis of HF.CONCLUSION: Patients with HF impose significantly higher total annual healthcare costs compared to a matched control group with findings evident more than 2 years prior to HF diagnosis.

AIMS: Type 1 diabetes is associated with increased cardiovascular (CV) morbidity and mortality, and cardiovascular autonomic neuropathy (CAN) is an important CV risk factor. The study aimed to explore associations between CAN and altered cardiac chamber sizes in persons with type 1 diabetes.METHODS: This was a cross-sectional study of 71 asymptomatic, normoalbuminuric participants with long-term type 1 diabetes (39 with CAN, determined by >1 abnormal autonomic function test) examined with cardiac multi detector computed tomography scans, which allowed measurements of left ventricular mass and all four cardiac chamber volumes. Cardiac chambers were indexed according to body surface area (ml/m2 or g/m2).RESULTS: Persons with and without CAN had mean ± SD age of 57 ± 7 and 50 ± 8 years (p < 0.001) and diabetes duration of 36 ± 11 and 32 ± 9 years (p < 0.05), respectively. Increasing autonomic dysfunction, evaluated by decrease in heart rate variability during deep breathing (in beats per minute), was associated with larger right (-0.5, 95% CI -1.0 to -0.0, p < 0.05) and trend towards larger left (-0.4, 95% CI -0.8-0.0, p < 0.1) ventricular volumes in multivariable linear regression.CONCLUSIONS: Our results suggest that impaired autonomic function may be associated with modest enlargement of ventricular volumes; this might be an early sign of progression towards heart failure.

Aims: Type 1 diabetes entails increased cardiovascular morbidity and cardiac chamber sizes are associated with cardiovascular disease. The aim of this study was to compare cardiac chamber sizes in normoalbuminuric persons with type 1 diabetes to a background population without diabetes. Methods: In a cross-sectional study, we examined 71 normoalbuminuric persons with long-term type 1 diabetes without known cardiovascular disease using cardiac multi-detector computed tomography. Cardiac chamber sizes and left ventricular remodelling were compared to persons without diabetes from the Copenhagen General Population Study. Results: Participants were median (interquartile range) 54 (48–60) (type 1 diabetes) and 57 (50–64) (without diabetes) years old and 59% were men (both groups). Participants with type 1 diabetes had smaller left ventricular mass (−3.5 g/m2, 95% confidence interval −5.8 to −1.3) and left (−4.0 mL/m2, 95% confidence interval −6.9 to −1.0) and right (−11.7 mL/m2, 95% confidence interval −15.4 to −7.9) ventricular volumes in multivariable analyses (adjusted for age, sex, body composition, blood pressure and antihypertensive medication), but no differences in atrial volumes. Conclusion: Persons with long-term type 1 diabetes had smaller left ventricular mass and biventricular volumes, yet similar atrial sizes, compared to a background population without diabetes. These findings may reflect subclinical development of diabetic cardiomyopathy.

BACKGROUND: Long duration of diabetes mellitus (DM) is associated with an increased risk of infection, however no studies have yet focused on the duration of DM and the associated risk of infective endocarditis (IE).METHODS: Patients with DM were identified through the Danish Prescription Registry, 1996-2015. Duration of DM was split in follow-up periods of: 0-5 years, 5-10 years, 10-15 years, and >15 years. Multivariable adjusted Poisson regression was used to calculate incidence rate ratios (IRR) according to study groups. DM late-stage complications and the associated risk of IE were investigated as time-varying covariates using the validated Diabetes Complications Severity Index (DCSI).RESULTS: We included 299,551 patients with DM. In patients with DM duration of 0-5 years, 5-10 years, 10-15 years, and >15 years, the incidence rates of IE were 0.24, 0.33, 0.58, and 0.96 cases of IE/1000 person years, respectively. Patients with DM duration 5-10 years, 10-15 years, and >15 years were associated with a higher risk of IE with an IRR of 1.24 (95% CI: 1.02-1.51), 1.92 (95% CI: 1.52-2.43) and 3.05 (95% CI: 2.11-4.40), respectively, compared with DM duration 0-5 years. Patients with a DCSI score of 2, 3 and >3 were associated with a higher risk of IE compared with patients with a DCSI score of 0, IRR = 1.78 (95% CI: 1.34-2.36), IRR = 2.34 (95% CI: 1.73-3.16), and IRR = 2.59 (95% CI: 1.92-3.48), respectively.CONCLUSION: This study shows a stepwise increase in the risk of IE with DM duration and severity independent of age and known comorbidity.

Background: Prevalent diabetes at the time of heart failure (HF) diagnosis is associated with a higher risk of death, but the incidence and prognostic importance of new-onset diabetes in patients with established HF remains unknown. Methods: Patients with a first hospitalization for HF in the period 2003-2014 were included and stratified according to history of diabetes. Annual incidence rates of new-onset diabetes were calculated and time-dependent multivariable Cox regression models were used to compare the risk of death in patients with prevalent and new-onset diabetes with patients without diabetes as reference. The model was adjusted for age, sex, duration of HF, educational level and comorbidity. Covariates were continuously updated throughout follow-up. Results: A total of 104,522 HF patients were included in the study, of which 21,216 (19%) patients had diabetes at baseline, and 8164 (10%) developed new-onset diabetes during a mean follow-up of 3.9 years. Patients with new-onset diabetes and prevalent diabetes were slightly younger than patients without diabetes (70 vs. 74 and 77, respectively), more likely to be men (62% vs. 60% and 54%), and had more comorbidities expect for ischemic heart disease, hypertension and chronic kidney disease which were more prevalent among patients with prevalent diabetes. Incidence rates of new-onset diabetes increased from around 2 per 100 person-years in the first years following HF hospitalization up to 3 per 100 person-years after 5 years of follow-up. A total of 61,424 (59%) patients died during the study period with event rates per 100 person-years of 21.5 for new-onset diabetes, 17.9 for prevalent diabetes and 13.9 for patients without diabetes. Compared to patients without diabetes, new-onset diabetes was associated with a higher risk of death (adjusted HR 1.47; 95% CI 1.42-1.52) and prevalent diabetes was associated with an intermediate risk (HR 1.19; 95% CI, 1.16-1.21). Conclusion: Following the first HF hospital