Glycated haemoglobin levels among 3295 hospitalized COVID-19 patients, with and without diabetes, and risk of severe infection, admission to an intensive care unit and all-cause mortality.

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-19 and HbA1c < 48 mmol/mol or HbA1c > 64 mmol/mol had a higher associated risk of the composite outcome. Similarly, among patients without diabetes, varying HbA1c levels were associated with higher risk of the composite outcome.

Direct and indirect costs of heart failure in relation to diabetes status - A nationwide study.

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.

Self-assessed health status and associated mortality in endocarditis: secondary findings from the POET trial.

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.

Heart failure and the prognostic impact and incidence of new-onset of diabetes mellitus: a nationwide cohort study.

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 hospitalization, the incidence of new-onset diabetes was around 2% per year, rising to 3% after 5 years of follow-up. New-onset diabetes was associated with an increased risk of death, compared to HF patients with prevalent diabetes (intermediate risk) and HF patients without diabetes.

The impact of implantable cardioverter-defibrillator implantation on health-related quality of life in the DANISH trial.

AIM: The Danish Study to Assess the Efficacy of Implantable Cardioverter-Defibrillators (ICD) in Patients with Non-ischaemic Systolic Heart Failure (HF) on Mortality (DANISH) found no overall effect on all-cause mortality. The effect of ICD implantation on health-related quality of life (HRQoL) remains to be established as previous trials have demonstrated conflicting results. We investigated the impact of ICD implantation on HRQoL in patients with non-ischaemic systolic HF, a prespecified secondary endpoint in DANISH. METHODS AND RESULTS: In DANISH, a total of 1116 patients with non-ischaemic systolic HF were randomly assigned (1:1) to ICD implantation or usual clinical care (control). Patients completed disease-specific HRQoL as assessed by Minnesota Living with Heart Failure Questionnaire (MLHFQ; 0-105, high indicating worse). Changes in HRQoL 8 months after randomization were assessed with a mixed-effects model. At randomization, MLHFQ was completed by 935 (84%) patients (n = 472 in the ICD group and n = 463 in the control group) and was reassessed in 274 (58%) and 292 (63%) patients, respectively after 8 months for the primary analysis. Patients in the ICD group vs. the control group had similar improvements in MLHFQ after 8 months [least square mean -7.0 vs. -4.2 (P = 0.13)]. A clinically relevant improvement (decrease ≥5) in the MLHFQ overall score at 8 months was observed in 151 patients in the ICD group and 148 patients in the control group [55% vs. 51%, respectively (P = 0.25)]. CONCLUSION: Implantable cardioverter-defibrillator implantation in patients with non-ischaemic systolic HF did not significantly alter HRQoL compared with patients randomized to usual clinical care.

Association between Type D personality and outcomes in patients with non-ischemic heart failure.

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.

Clinical and Echocardiographic Characteristics and Cardiovascular Outcomes According to Diabetes Status in Patients With Heart Failure and Preserved Ejection Fraction: A Report From the I-Preserve Trial (Irbesartan in Heart Failure With Preserved Ejection Fraction).

BACKGROUND: In patients with heart failure and preserved ejection fraction, little is known about the characteristics of, and outcomes in, those with and without diabetes mellitus. METHODS: We examined clinical and echocardiographic characteristics and outcomes in the I-Preserve trial (Irbesartan in Heart Failure With Preserved Ejection Fraction) according to history of diabetes mellitus. Cox regression models were used to estimate hazard ratios for cardiovascular outcomes adjusted for known predictors, including age, sex, natriuretic peptides, and comorbidity. Echocardiographic data were available in 745 patients and were additionally adjusted for in supplementary analyses. RESULTS: Overall, 1134 of 4128 patients (27%) had diabetes mellitus. Compared with those without diabetes mellitus, they were more likely to have a history of myocardial infarction (28% versus 22%), higher body mass index (31 versus 29 kg/m2), worse Minnesota Living With Heart Failure score (48 versus 40), higher median N-terminal pro-B-type natriuretic peptide concentration (403 versus 320 pg/mL; all P<0.01), more signs of congestion, but no significant difference in left ventricular ejection fraction. Patients with diabetes mellitus had a greater left ventricular mass and left atrial area than patients without diabetes mellitus. Doppler E-wave velocity (86 versus 76 cm/s; P<0.0001) and the E/e' ratio (11.7 versus 10.4; P=0.010) were higher in patients with diabetes mellitus. Over a median follow-up of 4.1 years, cardiovascular death or heart failure hospitalization occurred in 34% of patients with diabetes mellitus versus 22% of those without diabetes mellitus (adjusted hazard ratio, 1.75; 95% confidence interval, 1.49-2.05), and 28% versus 19% of patients with and without diabetes mellitus died (adjusted hazard ratio, 1.59; confidence interval, 1.33-1.91). CONCLUSIONS: In heart failure with preserved ejection fraction, patients with diabetes mellitus have more signs of congestion, worse quality of life, higher N-terminal pro-B-type natriuretic peptide levels, and a poorer prognosis. They also display greater structural and functional echocardiographic abnormalities. Further investigation is needed to determine the mediators of the adverse impact of diabetes mellitus on outcomes in heart failure with preserved ejection fraction and whether they are modifiable. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00095238.

Return to the Workforce After First Hospitalization for Heart Failure: A Danish Nationwide Cohort Study.

BACKGROUND: Return to work is important financially, as a marker of functional status and for self-esteem in patients developing chronic illness. We examined return to work after first heart failure (HF) hospitalization. METHODS: By individual-level linkage of nationwide Danish registries, we identified 21 455 patients of working age (18-60 years) with a first HF hospitalization in the period from 1997 to 2012. Of these patients, 11 880 (55%) were in the workforce before HF hospitalization and comprised the study population. We applied logistic regression to estimate odds ratios for associations between age, sex, length of hospital stay, level of education, income, comorbidity, and return to work. RESULTS: One year after first HF hospitalization, 8040 (67.7%) returned to the workforce, 2981 (25.1%) did not, 805 (6.7%) died, and 54 (0.5%) emigrated. Predictors of return to work included younger age (18-30 versus 51-60 years; odds ratio [OR], 3.12; 95% confidence interval [CI], 2.42-4.03), male sex (OR, 1.22; 95% CI, 1.12-1.34), and level of education (long-higher versus basic school; OR, 2.06; 95% CI, 1.63-2.60). Conversely, hospital stay >7 days (OR, 0.56; 95% CI, 0.51-0.62) and comorbidity including history of stroke (OR, 0.55; 95% CI, 0.45-0.69), chronic kidney disease (OR, 0.46; 95% CI, 0.36-0.59), chronic obstructive pulmonary disease (OR, 0.62; 95% CI, 0.52-0.75), diabetes mellitus (OR 0.76; 95% CI, 0.68-0.85), and cancer (OR, 0.49; 95% CI, 0.40-0.61) were all significantly associated with lower chance of return to work. CONCLUSIONS: Patients in the workforce before HF hospitalization had low mortality but high risk of detachment from the workforce 1 year later. Young age, male sex, and a higher level of education were predictors of return to work.

The effects of sacubitril/valsartan on coronary outcomes in PARADIGM-HF.

BACKGROUND: Angiotensin converting enzyme inhibitors (ACE-I), are beneficial both in heart failure with reduced ejection fraction (HF-REF) and after myocardial infarction (MI). We examined the effects of the angiotensin-receptor neprilysin inhibitor sacubitril/valsartan, compared with the ACE-I enalapril, on coronary outcomes in PARADIGM-HF. METHODS AND RESULTS: We examined the effect of sacubitril/valsartan compared with enalapril on the following outcomes: i) the primary composite endpoint of cardiovascular (CV) death or HF hospitalization, ii) a pre-defined broader composite including, in addition, MI, stroke, and resuscitated sudden death, and iii) a post hoc coronary composite of CV-death, non-fatal MI, angina hospitalization or coronary revascularization. At baseline, of 8399 patients, 3634 (43.3%) had a prior MI and 4796 (57.1%) had a history of any coronary artery disease. Among all patients, compared with enalapril, sacubitril/valsartan reduced the risk of the primary outcome (HR 0.80 [0.73-0.87], P<.001), the broader composite (HR 0.83 [0.76-0.90], P<.001) and the coronary composite (HR 0.83 [0.75-0.92], P<.001). Although each of the components of the coronary composite occurred less frequently in the sacubitril/valsartan group, compared with the enalapril group, only CV death was reduced significantly. CONCLUSIONS: Compared with enalapril, sacubitril/valsartan reduced the risk of both the primary endpoint and a coronary composite outcome in PARADIGM-HF. Additional studies on the effect of sacubitril/valsartan on atherothrombotic outcomes in high-risk patients are merited.

The prevalence and prognostic importance of possible familial hypercholesterolemia in patients with myocardial infarction.

AIMS: Familial hypercholesterolemia (FH) is a common genetic disorder causing accelerated atherosclerosis and premature cardiovascular disease. The aim of this study was to examine the prevalence and prognostic significance of possible FH in patients with myocardial infarction (MI). METHODS AND RESULTS: By individual-level linkage of data from the Eastern Danish Heart Registry and national administrative registries, a study population of patients referred for coronary angiography due to MI was selected. The study population was divided into "unlikely FH" and "possible FH" based on the Dutch Lipid Clinic Network criteria, which included a plasma low-density lipoprotein cholesterol (LDL-C) and age for onset of cardiac disease. A score of ≥3 points was used as the cutpoint between the 2 groups. Among the study population of 13,174 MI patients, 1,281 (9.7%) had possible FH. These patients were younger (59.1 vs 65.7 years, P ≤ .0001), had similar levels of comorbidities, and were treated more aggressively with cholesterol-lowering drugs compared with patients with unlikely FH. During a median of 3.3 years of follow-up, the unadjusted and adjusted event rates of recurrent MI were higher in patients with possible FH compared with unlikely FH (16% vs 11%, adjusted hazard ratio 1.28, 95% CI 1.09-1.51, P = .003.). Differences in adjusted all-cause mortality were not statistically significant (17% vs 23%, adjusted hazard ratio 0.89 [0.74-1.04], P = .1). CONCLUSION: We found that MI patients with possible FH have higher risk of recurrent MI but similar risk of mortality compared with unlikely FH patients. Further studies on secondary prevention are warranted.

Sulfonylurea in combination with insulin is associated with increased mortality compared with a combination of insulin and metformin in a retrospective Danish nationwide study.

AIMS/HYPOTHESIS: Individual sulfonylureas (SUs) and metformin have, in some studies, been associated with unequal hypoglycaemic, cardiovascular and mortality risks when used as monotherapy in type 2 diabetes. We investigated the outcomes in patients treated with different combinations of SUs and insulin vs a combination of metformin and insulin in a retrospective nationwide study. METHODS: All Danish individuals using dual therapy with SU + insulin or metformin + insulin without prior myocardial infarction (MI) or stroke were followed from 1 January 1997 to 31 December 2009 in nationwide registries. Risks of all-cause mortality, cardiovascular death, hypoglycaemia and a composite endpoint of MI, stroke and cardiovascular death were compared. Rate ratios (RR) [95% CIs] were calculated using time-dependent multivariable Poisson regression analysis. RESULTS: A total of 11,081 patients used SU + insulin and 16,910 used metformin + insulin. Patients receiving metformin + insulin were younger and had less comorbidity and a longer history of glucose-lowering treatment. SU + insulin was associated with higher mortality rates compared with metformin + insulin (76-126 vs 23 per 1,000 person-years). In adjusted analyses, SU + insulin was associated with increased all-cause mortality (RR 1.81 [1.63, 2.01]), cardiovascular death (RR 1.35 [1.14, 1.60]) and the composite endpoint (RR 1.25 [1.09, 1.42]) compared with metformin + insulin. Hypoglycaemia was more frequent with SU + insulin than with metformin + insulin (17-23 vs six events per 1,000 person-years) and was associated with increased mortality (RR 2.13 [1.97, 2.37]). There were no significant differences in risk between individual SUs in combination with insulin. CONCLUSIONS/INTERPRETATION: In combination with insulin, the use of SUs was associated with increased mortality compared with metformin. There were no significant risk differences between SUs.

Early diastolic strain rate in relation to systolic and diastolic function and prognosis in acute myocardial infarction: a two-dimensional speckle-tracking study.

AIMS: Diastolic dysfunction in acute myocardial infarction (MI) is associated with adverse outcome. Recently, the ratio of early mitral inflow velocity (E) to global diastolic strain rate (e'sr) has been proposed as a marker of elevated LV filling pressure. However, the prognostic value of this measure has not been demonstrated in a large-scale setting when existing parameters of diastolic function are known. We hypothesized that the E/e'sr ratio would be independently associated with an adverse outcome in patients with MI. METHODS AND RESULTS: We prospectively included patients with MI and performed echocardiography with comprehensive diastolic evaluation including E/e'sr. The relationship between E/e'sr and the primary composite endpoint (all-cause mortality, hospitalization for heart failure (HF), stroke, and new onset atrial fibrillation) was analysed with Cox models. A total of 1048 patients (mean age 63 ± 12, 73% male) were included and 142 patients (13.5%) reached the primary endpoint (median follow-up 29 months). A significant prognostic value was found for E/e'sr [hazard ratio (HR) per 1 unit change: 2.36, 95% confidence interval (CI): 2.02-2.75, P < 0.0001]. After multivariable adjustment E/e'sr remained independently related to the combined endpoint (HR per 1 unit change, 1.50; CI: 1.05-2.13, P = 0.02). The prognostic value of E/e'sr was driven by mortality (HR per 1 unit change, 2.52; CI: 2.09-3.04, P < 0.0001) and HF admissions (HR per 1 unit change, 2.79; CI: 2.23-3.48, P < 0.0001). CONCLUSION: Deformation-based E/e'sr contributes important information about global myocardial relaxation superior to velocity-based analysis and is independently associated with the outcome in acute MI.

Dapagliflozin and Days of Full Health Lost in the DAPA-HF Trial.

BACKGROUND: Conventional time-to-first-event analyses cannot incorporate recurrent hospitalizations and patient well-being in a single outcome. OBJECTIVES: To overcome this limitation, we tested an integrated measure that includes days lost from death and hospitalization, and additional days of full health lost through diminished well-being. METHODS: The effect of dapagliflozin on this integrated measure was assessed in the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial, which examined the efficacy of dapagliflozin, compared with placebo, in patients with NYHA functional class II to IV heart failure and a left ventricular ejection fraction ≤40%. RESULTS: Over 360 days, patients in the dapagliflozin group (n = 2,127) lost 10.6 ± 1.0 (2.9%) of potential follow-up days through cardiovascular death and heart failure hospitalization, compared with 14.4 ± 1.0 days (4.0%) in the placebo group (n = 2,108), and this component of all measures of days lost accounted for the greatest between-treatment difference (-3.8 days [95% CI: -6.6 to -1.0 days]). Patients receiving dapagliflozin also had fewer days lost to death and hospitalization from all causes vs placebo (15.5 ± 1.1 days [4.3%] vs 20.3 ± 1.1 days [5.6%]). When additional days of full health lost (ie, adjusted for Kansas City Cardiomyopathy Questionnaire-overall summary score) were added, total days lost were 110.6 ± 1.6 days (30.7%) with dapagliflozin vs 116.9 ± 1.6 days (32.5%) with placebo. The difference in all measures between the 2 groups increased over time (ie, days lost by death and hospitalization -0.9 days [-0.7%] at 120 days, -2.3 days [-1.0%] at 240 days, and -4.8 days [-1.3%] at 360 days). CONCLUSIONS: Dapagliflozin reduced the total days of potential full health lost due to death, hospitalizations, and impaired well-being, and this benefit increased over time during the first year. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure; NCT03036124).

Cause-specific death and risk factors of 1-year mortality after implantable cardioverter-defibrillator implantation: a nationwide study.

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.

The impact of partial-oral endocarditis treatment on anxiety and depression in the POET trial.

BACKGROUND: The Partial-Oral versus Intravenous Antibiotic Treatment of Endocarditis Trial (POET) found that partial-oral outpatient treatment was non-inferior to conventional in-hospital intravenous treatment in patients with left-sided infective endocarditis. We examined the impact of treatment strategy on levels of anxiety and depression. METHODS: Patients completed the Hospital Anxiety and Depression Scale (HADS) at randomization, at antibiotic completion, and after month 3 and month 6. Changes in anxiety and depression (each subdimension 0-21, high scores indicating worse) were calculated using a repeated measure analysis of covariance model with primary assessment after 6 months. Change in score of 1.7 represented a minimal clinical important difference (MCID). RESULTS: Among the 400 patients enrolled in the POET trial, 263 (66%) completed HADS at randomization with reassessment rates of 86-87% at the three subsequent timepoints. Patients in the partial-oral group and the intravenous group had similar improvements after 6 months in levels of anxiety (-1.8 versus -1.6, P = 0.62) and depression (-2.1 versus -1.9, P = 0.63), although patients in the partial-oral group had numerically lower levels of anxiety and depression throughout. An improvement in MCID scores after 6 months was reported by 47% versus 45% (p = 0.80) patients for anxiety and by 51% versus 54% (p = 0.70) for depression. CONCLUSION: Patients with endocarditis receiving partial-oral outpatient treatment reported similar significant improvements in anxiety and depression at 6 months, as compared to conventionally treated, but numerically lower levels throughout. These findings support the usefulness of partial-oral treatment.

Room for improvement: initiation of lipid-lowering treatment and achievement of lipid target levels-a Danish registry-based study.

AIMS: Prevention of adverse outcomes in individuals with high cholesterol levels may be improved by intensified lipid-lowering treatment (LLT). We studied whether treatment goals of low-density lipoprotein cholesterol (LDL-C) were reached within 1 year from baseline (defined as first LDL-C measurement) in a Danish population. METHODS AND RESULTS: Danish registries were used to identify all persons in the Northern Region of Denmark who had LDL-C measured between 1997 and 2012 and who were naïve to LLT. Patients were categorized in LDL-C <5 or ≥5 mmol/L and further subdivided into low, high, and very high predicted cardiovascular (CV) risk as suggested by European guidelines for risk stratification. Initiation of LLT and lipid target levels were assessed after 1 year (3.0, 2.5, and 1.8 mmol/L, respectively). In this study, we examined the intensity of LLT and whether treatment goals were reached. More patients with LDL-C ≥5 mmol/L, regardless of the CV risk, initiated LLT compared with patients who had a very high CV risk and LDL-C <5 mmol/L. In total, 37.7% (n = 32 581) of all patients with a follow-up LDL-C, and 25.1% (n = 3229) of patients with LDL-C ≥5 mmol/L, had achieved their target levels after 1 year. Only 45.2% (n = 4545) of the LDL-C ≥5 mmol/L high-risk patients with a follow-up LDL-C had started LLT 12 months after baseline. CONCLUSION: Less than half of patients presenting with an LDL-C ≥5 mmol/L start LLT within 1 year, representing a missed opportunity for both primary and secondary prevention of CV disease.

Initiation of domiciliary care and nursing home admission following first hospitalization for heart failure, stroke, chronic obstructive pulmonary disease or cancer.

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.

Serum potassium in the PARADIGM-HF trial.

AIMS: The associations between potassium level and outcomes, the effect of sacubitril-valsartan on potassium level, and whether potassium level modified the effect of sacubitril-valsartan in patients with heart failure and a reduced ejection fraction were studied in PARADIGM-HF. Several outcomes, including cardiovascular death, sudden death, pump failure death, non-cardiovascular death and heart failure hospitalization, were examined. METHODS AND RESULTS: A total of 8399 patients were randomized to either enalapril or sacubitril-valsartan. Potassium level at randomization and follow-up was examined as a continuous and categorical variable (≤3.5, 3.6-4.0, 4.1-4.9, 5.0-5.4 and ≥5.5 mmol/L) in various statistical models. Hyperkalaemia was defined as K+ ≥5.5 mmol/L and hypokalaemia as K+ ≤3.5 mmol/L. Compared with potassium 4.1-4.9 mmol/L, both hypokalaemia [hazard ratio (HR) 2.40, 95% confidence interval (CI) 1.84-3.14] and hyperkalaemia (HR 1.42, 95% CI 1.10-1.83) were associated with a higher risk for cardiovascular death. However, potassium abnormalities were similarly associated with sudden death and pump failure death, as well as non-cardiovascular death and heart failure hospitalization. Sacubitril-valsartan had no effect on potassium overall. The benefit of sacubitril-valsartan over enalapril was consistent across the range of baseline potassium levels. CONCLUSIONS: Although both higher and lower potassium levels were independent predictors of cardiovascular death, potassium abnormalities may mainly be markers rather than mediators of risk for death.

Self-reported health status and the associated risk of mortality in heart failure: The DANISH trial.

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.

Quality of life and the associated risk of all-cause mortality in nonischemic heart failure.

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).