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BACKGROUND: Data concerning the long-term risk of heart failure (HF) in patients with takotsubo syndrome (TTS) are sparse. We compared the rates of death and hospitalization due to HF with matched individuals from the background population and patients with ST-segment elevation myocardial infarction (STEMI).METHODS: In this nationwide observational cohort study, all patients with first-time TTS (2011-2018) who were alive at discharge were identified by using data from Danish nationwide registries. These were matched for age and sex with individuals from the background population (1:4 matching) and with patients with STEMI who were alive at discharge (1:3 matching).RESULTS: A total of 881 patients with TTS who were alive at discharge were identified (median age 70 years; 89.4% men). During a mean follow-up of 2.9 years, the incidence rates of death, HF hospitalization, and TTS recurrence in survivors of TTS were 6.9, 0.9 and 1.1 events per 100 person-years. The corresponding absolute 3-year risks were 9.3%, 1.8% and 2.5%, respectively. Survivors of TTS had higher associated rates of death compared with the background population (hazard ratio [HR] 2.05 [95% CI, 1.62-2.60]) and survivors of STEMI (HR 1.69 [1.34-2.13]). Similarly, survivors of TTS had higher associated rates of hospitalization due to HF compared with the background population (HR 4.24 [1.88-9.53]), but lower rates compared with survivors of STEMI (HR 0.34 [0.20-0.56]). Propensity-score matched analyses yielded similar results.CONCLUSIONS: Survivors of TTS had significantly higher associated mortality rates than the background population and survivors of STEMI. Survivors of TTS had lower HF hospitalization rates than survivors of STEMI, but the rates were higher than those of the background population.

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.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.Patients with concomitant HF and DM had a significantly higher economic burden compared to patients with HF but without DM.

AimsWhile clinical trials have suggested that a high ventricular rate is associated with increased risk of heart failure (HF) and mortality, all-comers studies are warranted.ObjectiveTo assess 1-year risk of new-onset diagnosed HF and all-cause mortality among rate-control treated patients presenting with atrial fibrillation (AF) on an electrocardiogram (ECG) according to ventricular rate.Methods and resultsECGs recorded at the Copenhagen General Practitioners Laboratory (2001–15) were used to identify patients with AF. Multivariate Cox proportional hazard regression models were used to compare risk of new-onset HF and all-cause mortality after first ECG presenting with AF according to ventricular rate on ECG [ 110 beats per minute (bpm)]. We identified 7408 patients in treatment with rate control drugs at time of first ECG presenting with AF [median age 78 years (Q1,Q3 = 70–85 years)], 45.8% male, median ventricular rate 83 bpm, (Q1,Q3 = 71–101 bpm)]. During 1-year follow-up, 666 (9.0%) of all patients with AF developed HF and 858 (11.6%) died. Patients with AF ventricular rates 100–110 bpm and >110 bpm had a hazard ratio (HR) of 1.46 (CI: 1.10–1.95) and 2.41 (CI: 1.94–3.00) respectively for new-onset HF, compared with 60–79 bpm. Similarly, patients with AF ventricular rates 100–110 bpm and >110 bpm had a HR of 1.44 (CI: 1.13–1.82) and 1.34 (CI: 1.08–1.65) respectively for all-cause mortality, compared with 60–79 bpm.ConclusionsVentricular rates ≥100 bpm among patients presenting with AF on ECG in treatment with rate control drugs were associated with greater risk of both new-onset HF and all-cause mortality. Aims While clinical trials have suggested that a high ventricular rate is associated with increased risk of heart failure (HF) and mortality, all-comers studies are warranted. Objective To assess 1-year risk of new-onset diagnosed HF and all-cause mortality among rate-control treated patients presenting with atrial fibrillation (AF) on an electrocardiogram (ECG) according to ventricular rate. Methods and results ECGs recorded at the Copenhagen General Practitioners Laboratory (2001-15) were used to identify patients with AF. Multivariate Cox proportional hazard regression models were used to compare risk of new-onset HF and all-cause mortality after first ECG presenting with AF according to ventricular rate on ECG [ 110 beats per minute (bpm)]. We identified 7408 patients in treatment with rate control drugs at time of first ECG presenting with AF [median age 78 years (Q1,Q3 = 70-85 years)], 45.8% male, median ventricular rate 83 bpm, (Q1,Q3 = 71-101 bpm)]. During 1-year follow-up, 666 (9.0%) of all patients with AF developed HF and 858 (11.6%) died. Patients with AF ventricular rates 100-110 bpm and >110 bpm had a hazard ratio (HR) of 1.46 (CI: 1.10-1.95) and 2.41 (CI: 1.94-3.00) respectively for new-onset HF, compared with 60-79 bpm. Similarly, patients with AF ventricular rates 100-110 bpm and >110 bpm had a HR of 1.44 (CI: 1.13-1.82) and 1.34 (CI: 1.08-1.65) respectively for all-cause mortality, compared with 60-79 bpm. Conclusions Ventricular rates >= 100 bpm among patients presenting with AF on ECG in treatment with rate control drugs were associated with greater risk of both new-onset HF and all-cause mortality.

Background Employment is important for physical and mental health and self-esteem and provides financial independence. However, little is known on the prognostic value of employment status prior to admission with acute myocardial infarction (MI). Methods and results Using Danish nationwide registries, all patients between 18 and 60 years with a first-time MI admission (2010–2018) and alive at discharge were included. Rates of all-cause mortality and recurrent MI according to workforce attachment at the time of the event was compared using multivariable Cox regression. Of the 16 060 patients included in the study, 3520 (21.9%) patients were not part of the workforce. Patients who were not part of the workforce were older (52 vs. 51 years), less often men (63% vs. 77%), less likely to have higher education, more often living alone (47% vs. 29%), and more often had comorbidities, including heart failure, atrial fibrillation, hypertension, diabetes, chronic kidney disease, and chronic obstructive pulmonary disease. The absolute 5-year risk of death was 3.3% and 12.8% in the workforce and non-workforce group, respectively. The corresponding rates of recurrent MI were 7.5% and 10.9%, respectively. In adjusted analyses, not being part of the workforce was associated with a significantly higher rate of all-cause mortality [HR: 2.39 (95% CI: 2.01–2.83)] and recurrent MI [1.36 (1.18–1.57)]. Conclusion Among patients of working age who were admitted with MI and alive at discharge, not being part of the workforce was associated with a higher long-term rate of all-cause mortality and recurrent MI.

Aim: There is an association between heart failure with preserved ejection fraction (HFpEF) and insulin resistance, but less is known about the diabetic continuum, and in particular about pre-diabetes, in HFpEF. We examined characteristics and outcomes of participants with diabetes or pre-diabetes in PARAGON-HF.Methods and results: Patients aged ≥50 years with left ventricular ejection fraction ≥45%, structural heart disease and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) were eligible. Patients were classified according to glycated haemoglobin (HbA1c): (i) normal HbA1c, Conclusion: Pre-diabetes is common in patients with HFpEF and is associated with worse clinical status and greater risk of HFH. Clinical Trial Registration: ClinicalTrials.gov Identifier NCT01920711.

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.

Background Diabetes is a risk factor for atrial fibrillation (AF), and increases the risk of thromboembolic events in persons with AF. However, the link between the two conditions is not fully elucidated. Few studies have investigated the association of dysglycemia and incident AF. We investigated the risk of incident AF and prognosis according to diabetes status. Methods The Copenhagen Primary Care Laboratory Database was merged with data on medical prescriptions, in- and outpatient contacts and vital status. The risk of AF according to diabetes status was investigated by use of Cox regression models. Results Of 354.807 individuals with a hemoglobin A1c (HbA1c) measurement, 28.541(8%) had known diabetes, 13.038(4%) had new onset diabetes and 27.754(8%) had prediabetes (HbA1c 42-47mmol/mol). Persons with dysglycemia (HbA1c > 42mmol/mol) and diabetes were older, more were men, they had lower level of education and were more likely to be living alone. We observed a gradual increase in risk of developing AF from HbA1c levels of 40 to 60 mmol/mol. In adjusted analyses we found a stepwise increase in hazard of AF from normoglycemia over prediabetes to persons with diabetes (No diabetes:1.00 [ref.]; Prediabetes:1.12[1.08–1.16]; New-onset diabetes:1.16[1.10–1.22]); Known diabetes:1.15[1.11–1.20]). Persons with known diabetes had a significant higher hazard of stroke, cardiovascular and all-cause mortality. Conclusion Increasing levels of HbA1c were associated with an increased hazard of developing AF. Persons with new onset of diabetes and those with known diabetes had similar hazard of developing AF, however persons with known diabetes had a significant higher hazard of stroke, cardiovascular- and all-cause mortality.

AimsThyroid dysfunction is considered the most frequent complication to amiodarone treatment, but data on its occurrence outside clinical trials are sparse. The present study aimed to examine the incidence of thyroid dysfunction following initiation of amiodarone treatment in a nationwide cohort of patients with and without heart failure (HF).Methods and resultsIn Danish registries, we identified all patients with first-time amiodarone treatment during the period 2000–18, without prior thyroid disease or medication. The primary outcome was a composite of thyroid diagnoses and initiation of thyroid drugs. Outcomes were assessed at 1-year follow-up, and for patients free of events in the first year, in a landmark analysis for the subsequent 5 years. We included 43 724 patients with first-time amiodarone treatment, of whom 16 939 (38%) had HF. At 1-year follow-up, the cumulative incidence and adjusted hazard ratio (HR) of the primary outcome were 5.3% and 1.37 (95% confidence interval 1.25–1.50) in patients with a history of HF and 4.2% in those without HF (reference). In the 1-year landmark analysis, the subsequent 5-year cumulative incidences and adjusted HRs of the primary outcome were 5.3% (reference) in patients with 1-year accumulated dose 63.88 g (ADD >175 mg).ConclusionAmong patients who initiated amiodarone treatment, around 5% had thyroid dysfunction at 1-year follow-up, with a slightly higher incidence in those with HF. A dose–response relationship was observed between the 1-year accumulated amiodarone dose and the subsequent 5-year cumulative incidence of thyroid dysfunction.

Background Physical and mental well-being after critical illness may be objectified by the ability to work. We examined return to work among patients with myocardial infarction (MI) by cardiogenic shock (CS) status. Methods Danish nationwide registries were used to identify patients with first-time MI by CS status between 2005 and 2015, aged 18–63 years, working before hospitalization and discharged alive. Multiple logistic regression models were used to compare groups. Results We identified 19 799 patients with MI of whom 653 had CS (3%). The median age was similar for patients with and without CS (53 years, interquartile range 47–58). One-year outcomes in patients with and without CS were as follows: 52% vs. 83% returned to work, 41% vs. 16% did not and 6% vs. 1% died. The adjusted odds ratio (OR) of returning to work was 0.53 [95% confidence limit (CI): 0.42–0.66]. In patients with CS, males and patients surviving OHCA were more likely to return to work (OR: 1.83, 95% CI: 1.15–2.92 and 1.55, 95% CI: 1.00–2.40, respectively), whereas prolonged hospitalization (OR: 0.38, 95% CI: 0.22–0.65) and anoxic brain damage (OR: 0.36, 95% CI: 0.18–0.72) were associated with lower likelihood of returning to work. Conclusion In patients with MI discharged alive, approximately 80% of those without CS returned to work at 1-year follow-up in contrast to 50% of those with CS. Among patients with CS, male sex and OHCA survivors were markers positively related to return to work, whereas prolonged hospitalization and anoxic brain damage were negatively related markers.

Aims Patients with type 1 diabetes have a high risk of cardiovascular disease. Yet, the importance of routine assessment of myocardial function in patients with type 1 diabetes is not known. Thus, we examined the prognostic importance of NT-proBNP and E/e′, an echocardiographic measure of diastolic function, in type 1 diabetes patients with preserved left ventricular ejection fraction (LVEF) and without known heart disease. Methods and results Type 1 diabetes patients without known heart disease and LVEF ≥45% enrolled in the Thousand and 1 study were included and followed through nationwide registries. The risk of major cardiovascular events (MACE) and death associated with levels of NT-proBNP and E/e′ was examined. Of 960 patients, median follow-up of 6.3 years (Q1–Q3: 5.7–7.0), 121 (12%) experienced MACE and 51 (5%) died. Increased levels of both NT-proBNP and E/e′ were associated with worse outcomes (adjusted hazard ratios for MACE = 1.56 (1.23–1.98) and 4.29 (2.25–8.16) per Loge increase for NT-proBNP and E/e′, respectively). NT-proBNP and E/e′ combined significantly improved the discrimination power of the Steno T1D risk engine (MACE, C-index: 0.813 (0.779–0.847) vs 0.779 (0.742–0.816); P = 0.0001; All-cause mortality, C-index 0.855 (0.806–0.903) vs 0.828 (0.776–0.880); P = 0.03). Conclusion In patients with type 1 diabetes, preserved ejection fraction, and no known heart disease, NT-proBNP and E/e′ were associated with increased risk of MACE and all-cause mortality. The risks associated with NT-proBNP and E/e′ combined identified patients at remarkably high risk.

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 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.

Objectives: The ability to remain in employment addresses an important consequence of stroke beyond the usual clinical parameters. However, data on the association between time to intravenous thrombolysis and workforce attachment in patients with acute ischemic stroke are sparse. Materials and methods: In this nationwide cohort study, stroke patients of working age (18-60 years) treated with thrombolysis (2011-2016) who were part of the workforce prior to admission and alive at discharge were identified using the Danish Stroke Registry. The association between time to thrombolysis and workforce attachment one year later was examined with multivariable logistic regression. Results: The study population comprised 1,329 patients (median age 51 years [25th-75th percentile 45-56], 67.3% men). The median National Institutes of Health Stroke Scale score at presentation was 4 (25th-75th percentile 2-8), and the median time from symptom-onset to initiation of thrombolysis was 140min (25th-75th percentile 104-196min). The proportion of patients who were part of the workforce at one-year follow-up was 64.6%, 64.3%, 64.9%, and 60.0% in patients receiving thrombolysis within 90min, between 91-180min, between 181-270min, and after 270min, respectively. In adjusted analysis, time to thrombolysis between 91-180min, 181-270min, and >270min was not significantly associated with workforce attachment compared with thrombolysis received ≤90min of symptom-onset (ORs 0.89 [95%CI 0.60-1.31], 0.93 [0.66-1.31], and 0.80 [0.43-1.52], respectively). Conclusions: In patients of working age admitted with stroke and treated with thrombolysis, two out of three were part of the workforce one year after discharge. There was no graded relationship between time to thrombolysis and the likelihood of workforce attachment.

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.

Aims In atrial fibrillation (AF) patients 150 mg b.i.d. dabigatran is the standard dose, yet guidelines recommend 110 mg b.i.d. when bleeding risk is high. It is unknown to which extend these recommendations are followed in patients switching from vitamin K antagonist (VKA) to dabigatran. The aim of this study was to investigate if AF patients are switched from VKA to the appropriate dose of dabigatran. Methods and results Using nationwide registries (22 August 2011 to 31 December 2012), we identified VKA-experienced AF patients with available creatinine values who switched to dabigatran. European guidelines criteria 2012 on dabigatran dosing were examined: age ≥80 years, HAS-BLED ≥3, estimated glomerular filtration rate (eGFR) Conclusion Among VKA-experienced AF patients one in four were switched to a dabigatran dose contrary to guideline recommendations.

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.

ObjectiveHeart failure is a prothrombotic state, and it has been hypothesised that thrombosis and embolism cause non-fatal and fatal events in heart failure and reduced ejection fraction (HFrEF). We sought to determine the effect of anticoagulant therapy on clinical outcomes in patients with HFrEF who are in sinus rhythm.MethodsWe conducted an updated systematic review and meta-analysis to examine the effect of anticoagulation therapy in patients with HFrEF in sinus rhythm. Our analysis compared patients randomised to anticoagulant therapy with those randomised to antiplatelet therapy, placebo or control, and examined the endpoints of all-cause mortality, (re)hospitalisation for worsening heart failure, non-fatal myocardial infarction, non-fatal stroke of any aetiology and major haemorrhage.ResultsFive trials were identified that met the prespecified search criteria. Compared with control therapy, anticoagulant treatment did not reduce all-cause mortality (risk ratio [RR] 0.99, 95% CI 0.90 to 1.08), (re)hospitalisation for heart failure (RR 0.97, 95% CI 0.82 to 1.13) or non-fatal myocardial infarction (RR 0.92, 95% CI 0.75 to 1.13). Anticoagulation did reduce the rate of non-fatal stroke (RR 0.63, 95% CI 0.49 to 0.81, p=0.001), but this was offset by an increase in the incidence of major haemorrhage (RR 1.88, 95% CI 1.49 to 2.38, p=0.001).ConclusionsOur meta-analysis provides evidence to oppose the hypothesis that thrombosis or embolism plays an important role in the morbidity and mortality associated with HFrEF, with the exception of stroke-related morbidity.

Background: Heart failure (HF) trials initiated in the last century highlighted many differences between men and women. Of particular concern was undertreatment of women compared with men, but much has changed during the past 20 years.\ud \ud Objectives: This study sought to identify these changes, which may give a new perspective on the management of, and outcomes in, women with HF.\ud \ud Methods: The study analyzed 12,058 men and 3,357 women enrolled in 2 large HF with reduced ejection fraction (HFrEF) trials with near identical inclusion and exclusion criteria and the same principal outcomes. Outcomes were adjusted for other prognostic variables including N-terminal pro–B-type natriuretic peptide.\ud \ud Results: Women were older and more often obese than men were, had slightly higher systolic blood pressure and heart rate, and were less likely to have most comorbidities, except hypertension. Women had more symptoms and signs (e.g., pedal edema 23.4% vs 19.9%; p < 0.0001) and worse quality of life—median Kansas City Cardiomyopathy Questionnaire Clinical Summary Score 71.3 (interquartile range: 53.4 to 86.5) versus 81.3 (interquartile range: 65.1 to 92.7; p < 0.0001)—despite similar left ventricular ejection fraction and N-terminal pro–B-type natriuretic peptide. However, women had lower mortality (adjusted hazard ratio: 0.68; 95% confidence interval: 0.62 to 0.74; p < 0.001) and risk of HF hospitalization (hazard ratio: 0.80; 95% confidence interval: 0.72 to 0.89; p < 0.001). Diuretics and anticoagulants were underutilized in women. Device therapy was underused in both men and women, but more so in women (e.g., defibrillator 8.6% vs. 16.6%; p < 0.0001).\ud \ud Conclusions: Although women with HFrEF live longer than men, their additional years of life are of poorer quality, with greater self-reported psychological and physical disability. The explanation for this different sex-related experience of HFrEF is unknown as is whether physicians recognize it. Women continue to receive suboptimal treatment, compared with men, with no obvious explanation for this shortfall.

Aims We examined if a congenital long QT syndrome (cLQTS) diagnosis and severity of cLQTS disease manifestation was associated with increased risk of depression, anxiety, and all-cause mortality. Methods and results All patients with known cLQTS in Denmark were identified using nationwide registries and specialized inherited cardiac disease clinics (1994–2016) and followed for up to 3 years after their cLQTS diagnosis. Risk factors for depression, anxiety, and all-cause mortality were determined using multivariable Cox proportional-hazards regression. An age- and sex-matched control population was identified (matching 1:4). Overall, 589 patients with cLQTS were identified of which 119/589 (20.2%) developed depression or anxiety during follow-up compared with 302/2356 (12.8%) from the control population (P Conclusion A severe cLQTS disease manifestation was associated with a greater risk of depression or anxiety. All-cause mortality for patients with cLQTS was low.

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.

Background In randomised clinical trials, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium–glucose cotransporter 2 (SGLT-2) inhibitors reduced cardiovascular events in patients with type 2 diabetes (T2D) at high cardiovascular risk, as compared to standard care. However, data comparing these agents in patients with T2D who are at moderate risk is sparse. Methods From Danish national registries, we included patients with T2D previously on metformin monotherapy, who started an additional glucose-lowering agent [GLP-1 RA, SGLT-2 inhibitor, dipeptidyl peptidase-4 (DPP-4) inhibitor, sulfonylurea (SU), or insulin] in the period 2010-2016. Patients with a history of cardiovascular events [heart failure (HF), myocardial infarction (MI) or stroke] were excluded. Patients were followed for up to 2 years. Cause-specific adjusted Cox regression models were used to compare the risk of hospitalisation for HF, a composite endpoint of major adverse cardiovascular events (MACE) (MI, stroke or cardiovascular death), and all-cause mortality for each add-on therapy. Patients who initiated DPP-4 inhibitors were used as reference. Results The study included 46,986 T2D patients with a median age of 61 years and of which 59% were male. The median duration of metformin monotherapy prior to study inclusion was 5.3 years. Add-on therapy was distributed as follows: 13,148 (28%) GLP-1 RAs, 2343 (5%) SGLT-2 inhibitors, 15,426 (33%) DPP-4 inhibitors, 8917 (19%) SUs, and 7152 (15%) insulin. During follow-up, 623 (1.3%, range 0.8-2.1%) patients were hospitalised for HF—hazard ratios (HR) were 1.11 (95% CI 0.89–1.39) for GLP-1 RA, 0.84 (0.52–1.36) for SGLT-2 inhibitors, 0.98 (0.77–1.26) for SU and 1.54 (1.25–1.91) for insulin. The composite MACE endpoint occurred in 1196 (2.5%, range 1.5–3.6%) patients, yielding HRs of 0.82 (0.69–0.97) for GLP-1 RAs, 0.79 (0.56–1.12) for SGLT-2 inhibitors, 1.22 (1.03–1.49) for SU and 1.23 (1.07–1.47) for insulin. 1865 (3.9%, range 1.9–9.0%) died from any cause during follow-up. HRs for all-cause mortality were 0.91 (0.78–1.05) for GLP-1 RAs, 0.79 (0.58–1.07) for SGLT-2 inhibitors, 1.13 (0.99–1.31) for SU and 2.33 (2.08–2.61) for insulin. Conclusion In a nationwide cohort of metformin-treated T2D patients and no history of cardiovascular events, the addition of either GLP-1 RA or SGLT-2 inhibitor to metformin treatment was associated with a similar risk of hospitalisation for HF and death, and a lower risk of MACE for GLP-1 RA when compared with add-on DPP-4 inhibitors. By contrast, initiation of treatment with SU and insulin were associated with a higher risk of MACE. Additionally, insulin was associated with an increased risk of all-cause mortality and hospitalisation for HF.

Background: Both BNP (B-type natriuretic peptide) and NT-proBNP (N-terminal pro B-type natriuretic peptide) are widely used to aid diagnosis, assess the effect of therapy, and predict outcomes in heart failure and reduced ejection fraction. However, little is known about how these 2 peptides compare in heart failure and reduced ejection fraction, especially with contemporary assays. Both peptides were measured at screening in the PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure). Methods: Eligibility criteria in PARADIGM-HF included New York Heart Association functional class II to IV, left ventricular ejection fraction ≤40%, and elevated natriuretic peptides: BNP ≥150 pg/mL or NT-proBNP ≥600 pg/mL (for patients with HF hospitalization within 12 months, BNP ≥100 pg/mL or NT-proBNP ≥400 pg/mL). BNP and NT-proBNP were measured simultaneously at screening and only patients who fulfilled entry criteria for both natriuretic peptides were included in the present analysis. The BNP/NT-proBNP criteria were not different for patients in atrial fibrillation. Estimated glomerular filtration rate 2 was a key exclusion criterion. Results: The median baseline concentration of NT-proBNP was 2067 (Q1, Q3: 1217–4003) and BNP 318 (Q1, Q3: 207–559), and the ratio, calculated from the raw data, was ≈6.25:1. This ratio varied considerably according to rhythm (atrial fibrillation 8.03:1; no atrial fibrillation 5.75:1) and with age, renal function, and body mass index but not with left ventricular ejection fraction. Each peptide was similarly predictive of death (all-cause, cardiovascular, sudden and pump failure) and heart failure hospitalization, for example, cardiovascular death: BNP hazard ratio, 1.41 (95% CI, 1.33–1.49) per 1 SD increase, P P Conclusions: The ratio of NT-proBNP to BNP in heart failure and reduced ejection fraction appears to be greater than generally appreciated, differs between patients with and without atrial fibrillation, and increases substantially with increasing age and decreasing renal function. These findings are important for comparison of natriuretic peptide concentrations in heart failure and reduced ejection fraction.

Aims: The importance of intra-ventricular conduction delay (IVCD), the incidence of new IVCD and its relationship to outcomes in heart failure and reduced ejection fraction (HFrEF) are not well studied. We addressed these questions in the PARADIGM-HF and ATMOSPHERE trials. Methods and results: The risk of the primary composite outcome of cardiovascular death or heart failure hospitalization and all-cause mortality were estimated by use of Cox regression according to baseline QRS duration and morphology in 11 861 patients without an intracardiac device. At baseline, 1789 (15.1%) patients had left bundle branch block (LBBB), 524 (4.4%) right bundle branch block (RBBB), 454 (3.8%) non-specific IVCD, 2588 (21.8%) ‘mildly abnormal’ QRS (110–129 ms) and 6506 (54.9%) QRS

Aims The aim of this study was to describe the use of antithrombotic therapy following a bleeding event among patients with myocardial infarction (MI), and the associated risk of major adverse cardiac events (MACE). Methods and results Using Danish nationwide registries, patients hospitalized with a bleeding event within 1 year after MI were identified. Antithrombotic treatment with aspirin, clopidogrel, and/or vitamin K antagonists (VKA) was determined at the bleeding and at Day 90 and 180 post-bleed. Based on guidelines, patients were stratified into four groups: expected, reduced, discontinued, or intensified treatment. Risk of MACE (ischaemic stroke, MI, or death) within the first year was assessed by Cox proportional hazard models. A total of 3324 patients with a bleeding after MI were included. At Day 90 post-bleed, 1052 (31.7%) received expected antithrombotic treatment, 1301 (39.2%) reduced, 164 (4.9%) intensified, and 807 (24.3%) no treatment. Major adverse cardiac events occurred in 637 (19.2%) patients. With dual antiplatelet therapy as reference, adjusted hazard ratios for MACE were: aspirin 1.81 (1.06–3.09), clopidogrel 1.08 (0.64–1.82), VKA 1.08 (0.47–2.48), VKA + aspirin 1.97 (0.95–4.07), VKA + clopidogrel 0.26 (0.03–1.91), triple 1.73 (0.50–5.95), and no treatment 1.93 (1.11–3.36). Conclusion The majority of MI patients reduced or discontinued their antithrombotic therapy post-bleed. Patients in monotherapy with aspirin or no treatment post-bleed had a higher risk of MACE Further studies of optimal antithrombotic treatments after a bleed are needed.

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

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.

Aims: Employment status at time of first heart failure (HF) hospitalization may be an indicator of both self‐perceived and objective health status. In this study, we examined the association between employment status and the risk of all‐cause mortality and recurrent HF hospitalization in a nationwide cohort of patients with HF. Methods and results: We identified all patients of working age (18–60 years) with a first HF hospitalization in the period 1997–2015 in Denmark, categorized according to whether or not they were part of the workforce at time of the index admission. The primary outcome was death from any cause and the secondary outcome was readmission for HF. Cumulative incidence curves, binomial regression and Cox regression models were used to assess outcomes. Of 25 571 patients with a first hospitalization for HF, 15 428 (60%) were part of the workforce at baseline. Patients in the workforce were significantly younger (53 vs. 55 years) more likely to be male (75% vs 64%) and less likely to have diabetes (13% vs 22%) and chronic obstructive pulmonary disease (5% vs 10%) (all P < 0.0001). Not being part of the workforce was associated with a significantly higher risk of death [hazard ratio (HR) 1.59; 95% confidence interval (CI) 1.50–1.68] and rehospitalization for HF (HR 1.09; 95% CI 1.05–1.14), in analyses adjusted for age, sex, co‐morbidities, education level, calendar time, and duration of first HF hospitalization. Conclusion: Not being part of the workforce at time of first HF hospitalization was independently associated with increased mortality and recurrent HF hospitalization.

Background: To describe characteristics and outcomes in women and men with heart failure with preserved ejection fraction. Methods: Baseline characteristics (including biomarkers and quality of life) and outcomes (primary outcome: composite of first heart failure hospitalization or cardiovascular death) were compared in 4458 women and 4010 men enrolled in CHARM-Preserved (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) (EF≥45%), I-Preserve (Irbesartan in heart failure with Preserved ejection fraction), and TOPCAT-Americas (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial). Results: Women were older and more often obese and hypertensive but less likely to have coronary artery disease or atrial fibrillation. Women had more symptoms and signs of congestion and worse quality of life. Despite this, the risk of the primary outcome was lower in women (hazard ratio, 0.80 [95% CI, 0.73–0.88]), as was the risk of cardiovascular death (hazard ratio, 0.70 [95% CI, 0.62–0.80]), but there was no difference in the rate for first hospitalization for heart failure (hazard ratio, 0.92 [95% CI, 0.82–1.02]). The lower risk of cardiovascular death in women, compared with men, was in part explained by a substantially lower risk of sudden death (hazard ratio, 0.53 [0.43–0.65]; P Conclusions: There are significant differences between women and men with heart failure with preserved ejection fraction. Despite worse symptoms, more congestion, and lower quality of life, women had similar rates of hospitalization and better survival than men. Their risk of sudden death was half that of men. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00853658, NCT01035255.

AIMS: To evaluate the risk of heart failure (HF) in patients with type 2 diabetes (T2D) complicated by development of intercurrent ischaemic heart disease (IHD), end-stage renal disease (ESRD), or both, compared to patients with T2D and no IHD and ESRD.METHODS AND RESULTS: From Danish nationwide registries, we identified all patients with new-onset T2D with no history of HF between 1998 and 2015. Landmark analyses were used to estimate the 5-year absolute risk of HF at several follow-up times, and accounted for the occurrence of IHD and ESRD, identified before HF. The Aalen-Johansen estimator was used to account for censoring and the competing risk of death. A total of 285 024 patients with new-onset T2D were included. During follow-up, 19 960 developed incident HF. Among patients with T2D free of HF 5 years after T2D diagnosis, patients without IHD and ESRD had the lowest 5-year risk of HF [4.02%; 95% confidence interval (CI) 3.90-4.15), those with T2D complicated by IHD [11.51%; relative risk (RR) 2.86; 95% CI 2.72-3.02; P CONCLUSION: Patients with T2D complicated by development of intercurrent IHD, ESRD, or both, showed a significantly higher risk of HF compared to those who did not develop IHD and ESRD. An effective way to delay or prevent the development of HF in patients with T2D may be to prevent IHD and ESRD.

Introduction Despite declining incidence and mortality for acute myocardial infarction, cardiogenic shock remains a severe complication with poor in-hospital prognosis. Little is known about the temporal trends in hospitalization with acute myocardial infarction-related cardiogenic shock (AMI-CS) and the long-term prognosis. Purpose We aimed to investigate the hospitalization with first-time AMI-CS and subsequent 1-year mortality. Methods In this nationwide Danish cohort study we identified from 2005 through 2015 patients with first-time acute myocardial infarction and compared those with and without cardiogenic shock (defined by either an ICD-10 diagnosis code with cardiogenic shock and/or procedure code with inotropes or vasopressors). Patient characteristics and 1-year mortality were compared between groups using Kaplan-Meier plots and multivariable Cox regression analysis. Results We included 96,030 patients with acute myocardial infarction of whom 5.4% had cardiogenic shock. Median age was 69.7 years (IQR 59.0–80.1) and 37.5% were female among those without cardiogenic shock and 70.2 years (IQR 61.4–78.1) and 33.0% were female in those with cardiogenic shock. We observed no change in hospitalization with cardiogenic shock during the study period (5.45% in 2006 vs 5.54% for 2016, P for difference 0.6). One-year mortality was higher among those with cardiogenic shock relative those without (See Figure). Crude 1-year mortality risk associated with AMI decreased over time from 23.4% in 2006 vs 11.5% in 2016 (p for difference Cumulative 1-year mortality among patien Conclusion In a large population-based setting, this study suggests that the hospitalization for first-time AMI-CS was stable from 2005 through 2015, while mortality improved with time. However, the grave outcome related to AMI-CS remains with a 5-times higher mortality compared to AMI patients without CS. Acknowledgement/Funding Rigshospitalets Research Fund

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 Interpretation Treatment with GLP-1 receptor agonists has beneficial effects on cardiovascular, mortality, and kidney outcomes in patients with type 2 diabetes. Funding None.

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.

Background The effect of implantable cardioverter-defibrillator (ICD) therapy in patients with heart failure with reduced ejection fraction (HFrEF) and diabetes is not fully elucidated. Methods We examined the effect of ICD therapy on sudden cardiac death, cardiovascular death and all-cause mortality, according to diabetes status at baseline in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). The outcomes were analyzed by use of cumulative incidence curves and Cox regressions models. Results Of the 1676 patients randomized to an ICD or placebo, 540 (32%) had diabetes at baseline. Patients with diabetes were slightly older (61 vs 58 years) and were more often in NYHA class III (37% vs 28%). ICD therapy did not reduce the risk of sudden cardiac death in HFrEF patients with diabetes (HR = 0.85; 95% CI 0.52–1.40); even though these patients had a higher risk of sudden cardiac death compared to patients without diabetes (HR = 1.73 95% CI 1.22–2.47). By contrast, ICD therapy did reduce sudden cardiac death in HFrEF patients without diabetes (HR = 0.26; 95% CI 0.15–0.46); Pinteraction=0.002. The findings for cardiovascular and all-cause death were similar. Conclusion ICD therapy did not reduce the risk of sudden cardiac death (or, as a consequence, all-cause death) in HFrEF patients with diabetes. Conversely, an ICD reduced the risk of sudden death in patients without diabetes, irrespective of etiology. Electronic supplementary material The online version of this article (10.1007/s00392-019-01415-z) contains supplementary material, which is available to authorized users.

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.

Recent studies have suggested that transthyretin amyloidosis (ATTR) is a more common cause of heart failure (HF) than previously appreciated, and novel treatments for amyloidosis are emerging. About one-half of patients with ATTR cardiac amyloidosis have a history of carpal tunnel syndrome (CTS).This study examined the risk of amyloidosis, HF, and other adverse cardiovascular outcomes associated with CTS relative to control subjects without CTS.Using Danish nationwide registries from 1996 to 2012, 56,032 patients were identified who underwent surgical treatment for CTS, and they were compared with a sex- and age-matched cohort (ratio 1:1) from the general population to examine their risk of amyloidosis, HF, and other adverse cardiovascular outcomes. Cumulative incidence curves and Cox proportional hazard models were used to assess differences.As expected, CTS was associated with a future diagnosis of amyloidosis (hazard ratio: 12.12 [95% confidence interval: 4.37 to 33.60]). CTS was associated with a higher incidence of HF, and this held true in the adjusted analysis yielding a hazard ratio of 1.54 (95% confidence interval: 1.45 to 1.64). No significant interaction with sex was found (p = 0.5). Risk of other adverse outcomes was also associated with CTS (p 0.0001 for atrial fibrillation, atrioventricular heart block, and pacemaker implantation).Patients who undergo surgical treatment for CTS are associated with a higher risk of amyloidosis and HF relative to matched control subjects from the general population. Other cardiovascular outcomes were also increased with CTS.

Aims: Patients with non-valvular atrial fibrillation (NVAF) receiving vitamin K antagonists (VKAs) with time in therapeutic international normalized ratio (INR) range (TTR) Methods and results: Non-valvular atrial fibrillation patients receiving VKA (1 January 2010 to 31 December 2012) were identified in nationwide registries. Time in therapeutic range was calculated by the Rosendaal method by a minimum of three INR values. Time in therapeutic range of patients continuing VKA (non-switchers) were compared with patients switched from VKA to dabigatran or rivaroxaban (switchers), the only NOACs available at that time. Factors associated with switching were analysed in a multivariable logistic regression model. 7276 patients with NVAF receiving VKA were included; of these, 6437 (88.5%) patients continued VKA [57.9% male, median age 76.7 years (Q1-Q3 68.9-83.5)] and 839 (11.5%) switched to NOAC [54.0% male, median age 76.5 years (Q1-Q3 68.4-83.6)]. No significant differences in CHA2DS2-VASc and HAS-BLED scores were seen between the groups. The mean TTR for non-switchers was 64.0 [standard deviation (SD) 27.8] and 52.9 (SD 28.1) for switchers. Among non-switchers, 51% had a TTR Conclusion: A TTR below 70% was associated with switching from VKA to NOAC, yet by guidelines, most patients were still not switched.

Background: Infective endocarditis (IE) may cause debilitating physical and mental changes that can interfere with activities of daily living. Admission to a nursing home and need for domiciliary care following hospitalization for IE represent such relevant outcomes, yet no such data have been reported.Methods: Using Danish nationwide registries, we identified all patients discharged alive after a first-time IE hospitalization in the period 1996 to 2014. These were matched by age, sex, calendar year, and relevant comorbidities with the background population in a 1:1 ratio. The 1-year rate of nursing home admission and initiation of domiciliary care, respectively, were assessed by multivariable Cox regression analyses.Results: In total, 4,493 IE patients were matched with 4,493 control subjects from the background population (median age: 66.8 years; interquartile range: 54.1, 76.7; 67.8% men). The 1-year incidence of nursing home admission was significantly higher among IE patients compared with the matched population (3.4% vs. 1.0%; hazard ratio: 7.95; 95% confidence interval: 4.00–15.77). Furthermore, IE patients had an increased use of domiciliary care compared with the matched population (6.6% vs. 2.1%; hazard ratio: 4.39; 95% confidence interval: 2.74–7.05). Factors associated with an increased risk of nursing home admission and domiciliary care among IE patients included older age, living alone, longer length of hospital stay, cardiovascular comorbidities, and stroke during admission.Conclusions: Patients who survived IE had an 8× higher incidence of nursing home admission and a 4× higher incidence of initiation of domiciliary care than their counterparts from the matched population.HighlightsWe found that patients who survive IE have an 8× higher incidence of nursing home admission and a 4× higher incidence of initiation of domiciliary care than their counterparts from the matched population.We show that IE is associated with debilitating physical and mental changes that are necessary to consider assessing the severity of IE and the follow-up on patients surviving IE.We believe that this paper contributes important research findings emphasizing the importance of the follow-up on patients surviving IE.

Background NT-proBNP (N-terminal pro-B-type natriuretic peptide) is useful in diagnosis and prognostication in heart failure (HF). We examined the relationship between NT-proBNP and outcomes in patients with HF and preserved ejection fraction, with and without atrial fibrillation (AF). Methods and Results Among 3835 HF with preserved ejection fraction patients enrolled in the I-Preserve (Irbesartan in Heart Failure With Preserved Systolic Function trial) or TOPCAT trial (Treatment of Preserved Cardiac Function in Heart Failure With an Aldosterone Antagonist), 719 (19%) patients had AF on their baseline ECG. Median (Q1–Q3) levels of NT-proBNP were 1286 pg/mL (778–2072) in those with AF and 288 pg/mL (122–704) in those without ( P Conclusions Event rates in HF with preserved ejection fraction patients without AF and with NT-proBNP Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifiers: NCT00094302 and NCT00095238.

This study examined the relationship between income inequality and heart failure outcomes.The income inequality hypothesis postulates that population health is influenced by income distribution within a society, with greater inequality associated with worse outcomes.This study analyzed heart failure outcomes in 2 large trials conducted in 54 countries. Countries were divided by tertiles of Gini coefficients (where 0% represented absolute income equality and 100% represented absolute income inequality), and heart failure outcomes were adjusted for standard prognostic variables, country per capita income, education index, hospital bed density, and health worker density.Of the 15,126 patients studied, 5,320 patients lived in Gini coefficient tertile 1 countries (coefficient: 33%), 6,124 patients lived in tertile 2 countries (33% to 41%), and 3,772 patients lived in tertile 3 countries (41%). Patients in tertile 3 were younger than tertile 1 patients, were more often women, and had less comorbidity and several indicators of less severe heart failure, yet the tertile 3-to-1 hazard ratios (HRs) for the primary composite outcome of cardiovascular death or heart failure hospitalization were 1.57 (95% confidence interval [CI]: 1.38 to 1.79) and 1.48 for all-cause death (95% CI: 1.29 to 1.71) after adjustment for recognized prognostic variables. After additional adjustments were made for per capita income, education index, hospital bed density, and health worker density, these HRs were 1.46 (95% CI: 1.25 to 1.70) and 1.30 (95% CI: 1.10 to 1.53), respectively.Greater income inequality was associated with worse heart failure outcomes, with an impact similar to those of major comorbidities. Better understanding of the societal and personal bases of these findings may suggest approaches to improve heart failure outcomes.