Long-Term Risk of VTE in Sarcoidosis: A Nationwide Cohort Study.

BACKGROUND: Chronic inflammation is increasingly recognized as a risk factor for VTE, but unlike other inflammatory diseases including systemic lupus erythematosus and rheumatoid arthritis, data on the risk of VTE in patients with sarcoidosis are sparse. RESEARCH QUESTION: Do patients with sarcoidosis have a higher long-term risk of VTE (pulmonary embolism or DVT, and each of these individually) compared with the background population? STUDY DESIGN AND METHODS: Using Danish nationwide registries, patients aged ≥ 18 years with newly diagnosed sarcoidosis (two or more inpatient/outpatient visits, 1996-2020) without prior VTE were matched 1:4 by age, sex, and comorbidities with individuals from the background population. The primary outcome was VTE. RESULTS: We included 14,742 patients with sarcoidosis and 58,968 matched individuals (median age, 44.7 years; 57.2% male). The median follow-up was 8.8 years. Absolute 10-year risks of outcomes for patients with sarcoidosis vs the background population were the following: VTE, 2.9% vs 1.6% (P < .0001), pulmonary embolism, 1.5% vs 0.7% (P < .0001), and DVT, 1.6% vs 1.0% (P < .0001), respectively. In multivariable Cox regression, sarcoidosis was associated with an increased rate of all outcomes in the first year after diagnosis (VTE: hazard ratio [HR], 4.94; 95% CI, 3.61-6.75) and after the first year (VTE: HR, 1.65; 95% CI, 1.45-1.87) compared with the background population. These associations persisted when excluding patients with a history of cancer and censoring patients with incident cancer during follow-up. Three-month mortality was not significantly different between patients with VTE with and without sarcoidosis (adjusted HR, 0.84; 95% CI, 0.61-1.15). INTERPRETATION: In this nationwide cohort study, sarcoidosis was associated with a higher long-term risk of VTE compared with a matched background population.

Hemodialysis and its impact on patient characteristics, microbiology, cardiac surgery, and mortality in infective endocarditis.

BACKGROUND: Patients with chronic renal failure on hemodialysis carry a significant risk of infective endocarditis (IE), but data on whether these patients differ from other patients with IE in terms of comorbidity, microbiology, rates of surgery and mortality are sparse. METHODS: Using Danish nationwide registries, all patients with IE diagnosed between February 1, 2010, and May 14, 2018 were identified and categorized into a "hemodialysis group" and a "non-hemodialysis group." Patient groups were compared by comorbidities, microbiological etiology, cardiac surgery, and mortality. Risk factors associated with mortality were assessed in multivariable Cox regression analysis. RESULTS: In total, 4,366 patients with IE were included with 226 (5.2%) patients in the hemodialysis group. Patients in the hemodialysis group were younger (66.0 years [IQR 53.8-74.9] vs 72.2 years [IQR 62.2-80.0]), had more comorbidities and were surgically treated less often (10.6% vs 20.8%), compared with patients from the nonhemodialysis group. Staphylococcus aureus was more than twice as prevalent (58.0% vs 26.5%). No difference in in-hospital mortality was found between the 2 groups (20.8% vs 18.5%), but 1- and 5-year mortality were significantly higher in the hemodialysis group than in the nonhemodialysis group (37.7% vs 17.7% and 72.1% vs 42.5%, respectively). In adjusted analysis, hemodialysis was associated with higher 1-year (HR = 2.71, 95% CI 2.07-3.55) and 5-year mortality (HR = 2.72, 95% CI 2.22-3.34) CONCLUSIONS: Patients with IE on chronic hemodialysis were younger, had more comorbidity, a higher prevalence of Staphylococcus aureus IE, and a higher mortality than patients without hemodialysis.

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.

Socioeconomic Disparities in Referral for Invasive Hemodynamic Evaluation for Advanced Heart Failure: A Nationwide Cohort Study.

BACKGROUND: Factors determining referral for advanced heart failure (HF) evaluation are poorly studied. We studied the influence of socioeconomic aspects on the referral process in Denmark, which has a taxpayer-funded national health care system. METHODS: We identified all patients aged 18 to 75 years with a first diagnosis of HF during 2010 to 2018. Hospitalized patients had to be discharged alive and were then followed for the outcome of undergoing a right heart catheterization (RHC) used as a surrogate marker of advanced HF work-up. RESULTS: Of 36 637 newly diagnosed patients with HF, 680 (1.9%) underwent RHC during the follow-up period (median time to RHC of 280 days [interquartile range, 73-914]). Factors associated with a higher likelihood of RHC included the highest versus lowest household income quartile (HR, 1.56 [95% CI, 1.19-2.06]; P=0.001), being diagnosed with HF at a tertiary versus nontertiary hospital (HR, 1.68 [95% CI, 1.37-2.05]; P<0.001) and during a hospitalization versus outpatient visit (HR, 1.67 [95% CI, 1.42-1.95]; P<0.001). Level of education, occupational status, and distance to tertiary hospital were not independently associated with RHC. Older age, cancer, and a psychiatric diagnosis were independently associated with a decreased probability of RHC. CONCLUSIONS: Higher household income, HF diagnosis during hospitalization, and first admission at a tertiary hospital were associated with increased likelihood of subsequent referral for RHC independent of other demographic and clinical variables. Greater attention may be required to ensure timely referral for advanced HF therapies in lower income groups.

Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials.

BACKGROUND: GLP-1 receptor agonists reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes. However, uncertainty regarding kidney outcomes persists and whether benefits extend to exendin-4-based GLP-1 receptor remains uncertain. We aimed to meta-analyse the most up-to-date evidence on the cardiovascular benefits and risks of GLP-1 receptor agonists from outcome trials in patients with type 2 diabetes. METHODS: We did a meta-analysis, including new data from AMPLITUDE-O, using a random effects model to estimate overall hazard ratio (HR) for MACE; its components; all-cause mortality; hospital admission for heart failure; a composite kidney outcome consisting of development of macroalbuminuria, doubling of serum creatinine, or at least 40% decline in estimated glomerular filtration rate (eGFR), kidney replacement therapy, or death due to kidney disease; worsening of kidney function, based on eGFR change; and odds ratios for key safety outcomes (severe hypoglycaemia, retinopathy, pancreatitis, and pancreatic cancer). We also examined MACE outcome in patient subgroups on the basis of MACE incidence rates in the placebo group, presence or absence of cardiovascular disease, HbA1c level, trial duration, treatment dosing interval, structural homology to human GLP-1 or exendin-4, BMI, age, and eGFR. We searched PubMed for eligible trials reporting MACE (ie, cardiovascular death, myocardial infarction, or stroke), up to June 9, 2021. We meta-analysed data from published randomised placebo-controlled trials testing either injectable or oral GLP-1 receptor agonists in patients with type 2 diabetes. We restricted the search to trials of more than 500 patients with a primary outcome that included cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. This meta-analysis was registered on PROSPERO, CRD42021259711. FINDINGS: Of 98 articles screened, eight trials comprising 60 080 patients fulfilled the prespecified criteria and were included. Overall, GLP-1 receptor agonists reduced MACE by 14% (HR 0·86 [95% CI 0·80-0·93]; p<0·0001), with no significant heterogeneity across GLP-1 receptor agonist structural homology or eight other examined subgroups (all pinteraction≥0·14). GLP-1 receptor agonists reduced all-cause mortality by 12% (HR 0·88 [95% CI 0·82-0·94]; p=0·0001), hospital admission for heart failure by 11% (HR 0·89 [95% CI 0·82-0·98]; p=0·013), and the composite kidney outcome by 21% (HR 0·79 [95% CI 0·73-0·87]; p<0·0001), with no increase in risk of severe hypoglycaemia, retinopathy, or pancreatic adverse effects. In sensitivity analyses removing the only trial restricted to patients with an acute coronary syndrome (ELIXA), all benefits marginally increased, including the outcome of worsening of kidney function, based on eGFR change (HR 0·82 [95% CI 0·69-0·98]; p=0·030). INTERPRETATION: GLP-1 receptor agonists, regardless of structural homology, reduced the risk of individual MACE components, all-cause mortality, hospital admission for heart failure, and worsening kidney function in patients with type 2 diabetes. FUNDING: None.

Long-term prognosis following hospitalization for acute myocarditis - a matched nationwide cohort study.

OBJECTIVE: The aim of this study was to examine the long-term risk of heart failure (HF) and all-cause mortality, in patients discharged alive following hospitalization for myocarditis. Background. Prognosis in patients with apparently uncomplicated myocarditis is in general perceived as good, but data on long-term outcomes are sparse. Methods. From nationwide Danish registries we included patients without prior cardiac disease, discharged alive with a first-time diagnosis of myocarditis 1996-2016. Patients were matched 1:10 by age- and sex, with controls from the general population. Risk of HF hospitalization and death in cases and controls was compared by use of adjusted Cox regression analyses. Results. We identified 1557 patients with a first-time diagnosis of myocarditis, 72% men, median age 39 years. Patients with myocarditis had more hypertension, diabetes, and cancer, and received more pharmacotherapy prior to hospitalization compared to matched controls. During a mean follow-up of 8.5 years, the event rate of HF hospitalization was 8.7 vs. 2.2 per 1000 patient-years (py) in cases and controls; HR 4.59 (95% CI; 3.58-5.88) and for all-cause mortality, event rate 21.9 vs 11.2 per 1000 py; HR 2.10 (95% CI; 1.82-2.43). Among 784 patients with no events or HF medication one year after diagnosis, risk of HF hospitalization (HR 2.15; 95% CI; 1.18-3.92), and all-cause mortality (HR 1.62; 95% CI; 1.21-2.16) remained elevated compared to matched controls. Conclusion. Myocarditis in younger patients without prior cardiac disease was associated with a long-term excess risk of HF hospitalization, and death, even in patients free of events and HF medication 1 year after discharge.HighlightsMyocarditis ranges from chest discomfort to severe heart failure.In most patients, left ventricular ejection fraction recovers but the long-term adverse cardiac risk is unknown.Patients with myocarditis and no prior cardiac disease were at higher risk of death and heart failureRoutine follow-up may be warranted following an episode of acute myocarditis.

Risk Factors for Morbidity and Mortality Following Hospitalization for Pericarditis.

BACKGROUND: Viral or idiopathic pericarditis is a frequent condition, often considered benign, although prior studies have suggested that pericarditis is associated with both cardiovascular and noncardiovascular disease, for example, malignancy. OBJECTIVES: This study sought to assess mortality risk and morbidity patterns in patients with incident viral or idiopathic pericarditis. METHODS: In nationwide Danish registries, we identified patients discharged with a first-time diagnosis of pericarditis from 1996 to 2016. Patients with a severe underlying heart condition were excluded. The patients were matched 1:10 with individuals from the general population by sex and year of birth. We assessed 5-year mortality using Kaplan-Meier and Cox proportional hazards models adjusted for baseline comorbidities and identified subsequent hospital admissions. RESULTS: We identified 7,988 patients with pericarditis and 79,880 matched control individuals. The absolute 5-year survival probability was 92.9% and 95.8% in the pericarditis and control groups, respectively (adjusted hazard ratio: 1.31; 95% confidence interval: 1.13 to 1.52). The greatest difference in mortality was seen the first year, and it was primarily driven by the female part of the population. The incidence rate per 1,000 person-years of new-onset, admission-required diagnosis was higher in the pericarditis group both for cardiovascular and noncardiovascular diseases. CONCLUSIONS: We observed a higher mortality risk over 5 years in the pericarditis group, especially among the female patients, compared to matched control individuals. Furthermore, we observed a higher frequency of both cardiovascular and noncardiovascular hospital admissions, highlighting the need for focus on underlying morbidity in patients presenting with apparent viral or idiopathic pericarditis.

Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials.

BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists differ in their structure and duration of action and have been studied in trials of varying sizes and with different patient populations, with inconsistent effects on cardiovascular outcomes reported. We aimed to synthesise the available evidence by doing a systematic review and meta-analysis of cardiovascular outcome trials of these drugs. METHODS: We searched MEDLINE (via PubMed) and the Cochrane Central Register of Controlled Trials for eligible placebo-controlled trials reporting major adverse cardiovascular events (MACE; ie, cardiovascular death, stroke, or myocardial infarction) up to June 15, 2019. We did a meta-analysis using a random-effects model to estimate overall hazard ratios (HRs) for MACE, its components, death from any cause, hospital admission for heart failure, kidney outcomes, and key safety outcomes (severe hypoglycaemia, pancreatitis, and pancreatic cancer). We also examined MACE in several subgroups based on patient characteristics (history of cardiovascular disease, BMI, age, baseline HbA1c, and baseline estimated glomerular filtration rate), trial duration, treatment dosing interval, and structural homology. FINDINGS: Of 27 publications screened, seven trials, with a combined total of 56 004 participants, were included: ELIXA (lixisenatide), LEADER (liraglutide), SUSTAIN-6 (semaglutide), EXSCEL (exenatide), Harmony Outcomes (albiglutide), REWIND (dulaglutide), and PIONEER 6 (oral semaglutide). Overall, GLP-1 receptor agonist treatment reduced MACE by 12% (HR 0·88, 95% CI 0·82-0·94; p<0·0001). There was no statistically significant heterogeneity across the subgroups examined. HRs were 0·88 (95% CI 0·81-0·96; p=0·003) for death from cardiovascular causes, 0·84 (0·76-0·93; p<0·0001) for fatal or non-fatal stroke, and 0·91 (0·84-1·00; p=0·043) for fatal or non-fatal myocardial infarction. GLP-1 receptor agonist treatment reduced all-cause mortality by 12% (0·88, 0·83-0·95; p=0·001), hospital admission for heart failure by 9% (0·91, 0·83-0·99; p=0·028), and a broad composite kidney outcome (development of new-onset macroalbuminuria, decline in estimated glomerular filtration rate [or increase in creatinine], progression to end-stage kidney disease, or death attributable to kidney causes) by 17% (0·83, 0·78-0·89; p<0·0001), mainly due to a reduction in urinary albumin excretion. There was no increase in risk of severe hypoglycaemia, pancreatitis, or pancreatic cancer. INTERPRETATION: Treatment with GLP-1 receptor agonists has beneficial effects on cardiovascular, mortality, and kidney outcomes in patients with type 2 diabetes. FUNDING: None.

Burden and Causes of Hospital Admissions in Heart Failure During the Last Year of Life.

OBJECTIVES: This study aimed to evaluate the incidence and causes of hospitalization in the year preceding death of patients with heart failure (HF). BACKGROUND: Hospitalizations in HF are common, especially in the last period of the lives of patients with HF, but little is known about hospitalization burden and causes during this phase of the disease. METHODS: From Danish nationwide registries, we identified patients who died in the period 2001-2016 after having experienced HF for at least 1 year, and examined hospitalizations during the last year of life in age- and sex-stratified analyses. RESULTS: We included 32,157 patients. Median age at time of death was 81 years; 39% were women. A total of 26,561 (84%) patients were hospitalized at least once during the last year of life. The patients experienced a median of 2 (1 to 3) hospitalizations and spent 14 (3 to 31) days in the hospital. Of all hospitalizations (n = 80,362), 9,644 (12%) were due to HF, 14,738 (18%) due to other cardiovascular (CV) causes, and 51,696 (64%) due to non-CV causes (p < 0.001). The frequency of hospitalizations increased toward death, but the domination of non-CV causes remained consistent throughout the year, regardless of age and sex. If we included diagnoses covering renal insufficiency in the definition of HF hospitalizations, non-CV hospitalizations remained dominant (58%). CONCLUSIONS: During the last year alive, patients with HF were more often hospitalized due to non-CV causes rather than HF. These findings warrant more focus on a multidisciplinary approach toward end-of-life care in patients with HF.

Sacubitril/valsartan reduces serum uric acid concentration, an independent predictor of adverse outcomes in PARADIGM-HF.

AIMS: Elevated serum uric acid concentration (SUA) has been associated with an increased risk of cardiovascular disease, but this may be due to unmeasured confounders. We examined the association between SUA and outcomes as well as the effect of sacubitril/valsartan on SUA in patients with heart failure with reduced ejection fraction (HFrEF) in PARADIGM-HF. METHODS AND RESULTS: The association between SUA and the primary composite outcome of cardiovascular death or heart failure (HF) hospitalization, its components, and all-cause mortality was examined using Cox regression analyses among 8213 patients using quintiles (Q1-Q5) of SUA adjusted for baseline prognostic variables including estimated glomerular filtration rate (eGFR), diuretic dose, and log N-terminal pro-brain natriuretic peptide. Change in SUA from baseline over 12 months was also evaluated in each treatment group. Patients in Q5 (SUA ≥8.6 mg/dL) compared with Q1 (<5.4 mg/dL) were younger (62.8 vs. 64.2 years), more often male (88.7% vs. 63.1%), had lower systolic blood pressure (119 vs. 123 mmHg), lower eGFR (57.4 vs. 76.6 mL/min/1.73 m2 ), and greater diuretic use. Higher SUA was associated with a higher risk of the primary outcome (adjusted hazard ratios) Q5 vs. Q1 = 1.28 [95% confidence intervals (1.09-1.50), P = 0.003], cardiovascular death [1.44 (1.11-1.77), P = 0.001], HF hospitalization [1.37 (1.11-1.70), P = 0.004], and all-cause mortality [1.36 (1.13-1.64), P = 0.001]. Compared with enalapril, sacubitril/valsartan reduced SUA by 0.24 (0.17-0.32) mg/dL over 12 months (P < 0.0001). Sacubitril/valsartan improved outcomes, irrespective of SUA concentration. CONCLUSION: Serum uric acid concentration was an independent predictor of worse outcomes after multivariable adjustment in patients with HFrEF. Compared with enalapril, sacubitril/valsartan reduced SUA and improved outcomes irrespective of SUA.

Return to the workforce following infective endocarditis-A nationwide cohort study.

BACKGROUND: The ability to return to work after infective endocarditis (IE) holds important socioeconomic consequences for both patients and society, yet data on this issue are sparse. We examined return to the workforce and associated factors in IE patients of working age. METHODS: Using Danish nationwide registries, we identified 1,065 patients aged 18-60 years with a first-time diagnosis of IE (1996-2013) who were part of the workforce prior to admission and alive at discharge. RESULTS: One year after discharge, 765 (71.8%) patients had returned to the workforce, 130 (12.2%) were on paid sick leave, 76 (7.1%) received disability pension, 23 (2.2%) were on early retirement, 65 (6.1%) had died, and 6 (0.6%) had emigrated. Factors associated with return to the workforce were identified using multivariable logistic regression. Younger age (18-40 vs 56-60 years; odds ratio, 2.85; 95% CI, 1.71-4.76) and higher level of education (higher educational level vs basic school; 5.47, 2.05-14.6) and income (highest quartile vs lowest; 3.17, 1.85-5.46) were associated with return to the workforce. Longer length of hospital stay (>90 vs 14-30 days; 0.16, 0.07-0.38); stroke during IE admission (0.38, 0.21-0.71); and a history of chronic kidney disease (0.29, 0.11-0.75), chronic obstructive pulmonary disease (0.31, 0.13-0.71), and malignancy (0.39, 0.22-0.69) were associated with a lower likelihood of returning to the workforce. CONCLUSIONS: Seven of 10 patients who were part of the workforce prior to IE and alive at discharge were part of the workforce 1 year later. Younger age, higher socioeconomic status, and absence of major comorbidities were associated with return to the workforce.

Return to the workforce following coronary artery bypass grafting: A Danish nationwide cohort study.

BACKGROUND: Returning to the workforce after coronary artery bypass grafting (CABG) holds important socioeconomic consequences not only for patients, but the society as well. Yet data on this issue are limited. We examined return to the workforce and associated factors in patients of working age undergoing CABG. METHODS AND RESULTS: Using Danish nationwide administrative registries, we identified 6031 patients of working age (18-60years) undergoing isolated CABG (1998-2011) who were part of the workforce 30days prior to admission and alive at discharge. One year after discharge for CABG, 4827 (80.0%) patients had returned to the workforce, 614 (10.2%) were on paid sick leave, 267 (4.4%) received disability pension, 250 (4.1%) were on early retirement, 57 (0.9%) had died, and 16 (0.3%) had emigrated. Factors associated with return to the workforce were identified using multivariable logistic regression. Younger age (18-45 versus 56-60years; odds ratio, 1.89; 95% confidence interval, 1.48-2.42), male sex (1.51, 1.24-1.84), and higher level of education (higher educational level versus basic school; 1.53, 1.05-2.23) and income (highest quartile versus lowest; 3.01, 2.42-3.75) were associated with return to the workforce. Urgency of surgery (emergency versus elective; 0.65, 0.49-0.88), cardiovascular comorbidity, a history of chronic kidney disease (0.49, 0.29-0.84) and liver disease (0.47, 0.28-0.80), as well as additional hospital admissions within the first year post-discharge (>2 versus none; 0.25, 0.19-0.32) were associated with a lower likelihood of returning to the workforce. CONCLUSION: One year after discharge for CABG, four out of five patients were part of the workforce and mortality was low. Younger age, male sex, higher socioeconomic status, and absence of major comorbidities were associated with return to the workforce.

Dementia-related adverse events in PARADIGM-HF and other trials in heart failure with reduced ejection fraction.

AIMS: Inhibition of neprilysin, an enzyme degrading natriuretic and other vasoactive peptides, is beneficial in heart failure with reduced ejection fraction (HFrEF), as shown in PARADIGM-HF which compared the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan with enalapril. As neprilysin is also one of many enzymes clearing amyloid-ß peptides from the brain, there is a theoretical concern about the long-term effects of sacubitril/valsartan on cognition. Therefore, we have examined dementia-related adverse effects (AEs) in PARADIGM-HF and placed these findings in the context of other recently conducted HFrEF trials. METHODS AND RESULTS: In PARADIGM-HF, patients with symptomatic HFrEF were randomized to sacubitril/valsartan 97/103 mg b.i.d. or enalapril 10 mg b.i.d. in a 1:1 ratio. We systematically searched AE reports, coded using the Medical Dictionary for Regulatory Activities (MedDRA), using Standardized MedDRA Queries (SMQs) with 'broad' and 'narrow' preferred terms related to dementia. In PARADIGM-HF, 8399 patients aged 18-96 years were randomized and followed for a median of 2.25 years (up to 4.3 years). The narrow SMQ search identified 27 dementia-related AEs: 15 (0.36%) on enalapril and 12 (0.29%) on sacubitril/valsartan [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.33-1.59]. The broad search identified 97 (2.30%) and 104 (2.48%) AEs (HR 1.01, 95% CI 0.75-1.37), respectively. The rates of dementia-related AEs in both treatment groups in PARADIGM-HF were similar to those in three other recent trials in HFrEF. CONCLUSION: We found no evidence that sacubitril/valsartan, compared with enalapril, increased dementia-related AEs, although longer follow-up may be necessary to detect such a signal and more sensitive tools are needed to detect lesser degrees of cognitive impairment. Further studies to address this question are warranted.

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.