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Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): The DCM-VT study was partially supported by an investigator-initiated grant (IIS-310) from Biosense Webster (a Johnson & Johnson company). The DANISH study was supported by unrestricted grants from Medtronic, St. Jude Medical, TrygFonden, and the Danish Heart Foundation. Background Endstage heart failure, ventricular tachycardia (VT) and sudden cardiac death (SCD) are sequels of non-ischaemic cardiomyopathies (NICM). Implantable cardioverter defibrillators (ICDs) can terminate VT and prevent SCD but mortality benefit has been limited in recent trials suggesting that VT may also be associated with non-sudden cardiovascular death (NSCVD). Purpose To assess the effect of VT on all-cause mortality and NSCVD in NICM patients with ICDs. Methods Two multicenter cohorts of NICM patients were merged for analysis: (1) patients randomized to ICD in the DANISH trial, which included patients with NICM, LVEF ≤35% and no prior VT and (2) the DCM-VT study cohort, which included consecutive NICM patients with any LVEF referred for ablation of sustained VT. Predictors for the primary composite outcome of all-cause death and heart transplant (death/HTx) and for the secondary outcome of NSCVD were assessed. In addition, propensity score matching was performed using the parameters age, gender, LVEF and eGFR. Finally, survival following VT occurrence was compared between DANISH and DCM-VT patients. Results A total of 828 patients (556 DANISH, 272 DCM-VT) were followed for a median of 3.9 years (2.1 – 5.8). DANISH patients had a median LVEF of 25% (20 – 30) and DCM-VT patients 35% (27 – 43). A total of 148 patients (DANISH 16.4%, DCM-VT 21.0%) experienced death/HTx and NSCVD occurred in 78 patients (7.7%, 12.9%, respectively). In multivariable analysis history of VT at inclusion was a significant predictor of the primary outcome with an adjusted hazard ratio (HRa) of 3.81 (95% CI 2.33 - 6.24) as were age [HRa 1.02 per year (1.01 - 1.04)], LVEF [HRa 0.96 per 1% increase (0.94 - 0.98)] and reduced eGFR [HRa 1.71 (1.15 – 2.53 )]. History of VT predicted NSCVD with an HRa of 7.54 (3.97 - 14.33). After matching, history of VT still predicted death/HTx [HR 4.12 (2.48 - 6.82)] and NSCVD [HR 6.92 (3.30 - 14.52)]. Risk of death/HTx, as well as NSCVD, for DANISH patients was similar to DCM-VT patients after they experienced their first VT event [HRa 0.90 (0.48 - 1.69) and HRa 1.07 (0.56 - 2.06) resp.]. Conclusions VT occurrence appears to be an important predictor of non-sudden CV death as well as all-cause death in NICM patients independent of other markers of heart failure severity. VT may be a marker of progressive disease and remodelling that could be incorporated into risk-stratification to help predict deterioration and need for HTx.

Background Current risk prediction models in ischemic heart disease (IHD) use a small set of well-known risk factors, have limited predictive capabilities, and are largely the same as they were twenty years ago. We developed and externally validated PMHnet-alpha, a neural-network based survival model for risk-stratification in ischemic heart disease that leverages the multitude of clinical features available in modern electronical health records. Methods We included 39,746 IHD patients from the regional Heart Registry that had been subjected to a coronary angiography between 2006 and 2017 with confirmed coronary artery disease. Clinical data was extracted from the Danish National Patient Registry, and electronic health records. 595 different features, consisting of diagnosis codes, procedure codes, biochemical test results, and clinical measurements were used as model inputs. Prior to model development, patients were randomly divided into a training set (n=34,746) and a tesing set (n=5,000). The testing set was not used for model development. Model performance was evaluated at six months, one years, three-, and five years of follow-up using time-dependent ROC curve analysis and Harrels' C-index. Lastly, we also assessed the calibration of the model. We benchmarked the performance of PMHnet-alpha against the GRACE Risk Score 2.0, which is widely considered to the best-performing model in current clinical use. We explored the importance of individual features using SHAP values on the trained models. Findings PMHnet-alpha had very high model discrimination on the testing data with time-dependent AUCs of 0.88 (95% CI 0.86–0.90) at six months, 0.88 (95% CI 0.86–0.90) at one year, 0.84 (95% CI 0.82–0.86) at three years, and 0.82 (95% CI 0.80–0.84) at five years. The discrimination of the benchmark model GRACE2.0 on the same data was considerably lower, 0.77 (95% CI 0.73–0.80) at six months, 0.77 (95% CI 0.74–0.80) at one year, and 0.73 (95% CI 0.70–0.75) at three years. PMHnet-alpha is undergoing external validation in other nordic countries. We identified that on-average, age, coronary pathology and smoking status were the most impactful features. Interpretation Here we present a significant improvement of the state of the art in cardiac risk prediction. PMHnet-alpha supports better and optimized use of available healthcare data, signified by the vast improvement compared to GRACE2.0. This also signifies an important paradigm shift in which data-driven strategies are necessary to transform the increasing amount of data generated in the modern healthcare system into evidence-based clinical decision making. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Novo Nordisk Foundation, NordForsk

Background Oral fluoroquinolones are commonly prescribed antibiotics. Observational studies have shown an association between fluoroquinolone-use and subsequent risk of aortic aneurysm (AA) and aortic dissection (AD) due to a potential collagen degrading effect of fluoroquinolones. Purpose To investigate if fluoroquinolone-use was associated with increased rates of AA or AD in patients without known aortic disease. Secondly, to investigate if fluoroquinolone-use was associated with increased all-cause mortality and aortic interventions in high-risk patients with known aortic disease. Methods We used a nested case-control study design in which individuals aged 30–100 years from 2003 to 2018 were included from Danish nationwide registers. Exclusion criteria were bicuspid aortic valve, coarctation of the aorta, and connective tissue disease. A main cohort and a secondary high-risk cohort were defined. The main cohort comprised patients without history of AA/AD in which two case definitions were used: 1) A broad case definition of first-time AA/AD. 2) A severe case definition of ruptured AA/AD. The high-risk cohort comprised patients surviving index AA/AD admission in which cases were defined as all-cause mortality and aortic interventions. Cases were matched on age, sex, and year of inclusion in a 1:30 ratio with controls. For the main cohort, a potential dose-response effect was investigated using groups of cumulative defined daily doses (cDDD) of fluoroquinolones. Hazard ratios (HR) with 95% confidence intervals (CI) for fluoroquinolone-use compared with amoxicillin as an active comparator were obtained from time-dependent Cox regression models using multiple exposure windows. Results The main cohort comprised 4.81 million individuals with 43,280 cases. Short-term 30-day, intermediate-term 90-day, and long-term 1-year fluoroquinolone use were all not associated with AA/AD (30-day HR 1.18 [95% CI: 0.84 to 1.66]; 90-day HR 1.12 [95% CI 0.96 to 1.30]; 1-year HR 1.00 [95% CI 0.93 to 1.07]). Using a severe case definition of ruptured AA/AD yielded comparable results. For the dose-response analysis, increasing cDDD did not confer increased rates of AA/AD (1–5 cDDD: Reference group; 6–10 cDDD: HR 1.03 [95% CI: 0.87 to 1.23]; >10 cDDD: HR 1.00 [95% CI 0.83 to 1.29]) (Figure 1). The secondary high-risk cohort included 20,195 patients surviving index admission with 9,183 cases of all-cause mortality and 1,768 cases of aortic interventions. The 30-day HR for all-cause mortality was 1.21 (95% CI 0.92 to 1.60) and the 60-day HR 1.06 (95% CI 0.89 to 1.26). No association with aortic interventions was found either (Figure 2). Conclusion Fluroquinolone-use was not associated with AA/AD. Furthermore, fluoroquinolone-use was not associated with all-cause mortality or aortic interventions in potentially susceptible patients with known aortic disease. These findings do not support an increased risk of AA/AD with fluoroquinolone-use. Funding Acknowledgement Type of funding sources: None.

Background All patients with type A aortic dissections, regardless of age, are recommended urgent aortic surgery. However, studies exploring long term outcomes in survivors are sparse, and especially, the significance of age on long-term outcomes remain unclear. Purpose We described and compared incidences across age groups of post-discharge readmission, repeated aortic surgery, and death in patients who survived surgery and hospitalization for type A aortic dissection. Methods Using data from Danish nationwide registries, we identified patients hospitalized with Stanford type A aortic dissections from 2006–2018. Survivors of hospitalization and surgery on the ascending aorta and/or aortic arch comprised the study population (Figure 1). Using cumulative incidence plots taking death into account as a competing risk and Cox regression analysis, we described long-term outcomes (rehospitalizations, repeated aortic surgery, and death) and compared different age groups. The diagnosis of type A aortic dissection in the registries used, was validated from 191 clinical records to have a positive predictive value of 94.8%. Results Of 606 initial survivors of surgery and hospitalization with type A aortic dissection, 236 (38.9%) were 69 years old (group III). Figure 2 shows cumulative incidences of outcomes according to age. During the first year, 62.5% were re-hospitalized (median number of days hospitalized was 2 days (IQR 1–8 days) and 1.4% underwent repeated aortic surgery with no significant differences across age groups (P=0.68 and P=0.39, respectively). Further, 5.9% died (group I: 3.0%, group II: 8.3%, group III: 7.4%, P=0.04). After 10 years of follow up, 8.0% had undergone repeated aortic surgery (group I: 11.5%, group II: 8.5%, group III: 1.6%, P=0.04) and 10.2% (group I), 17.0% (group II), and 22.2% (group III) had died (P=0.01). In adjusted analyses, no age differences were found in one-year outcomes, while age >69 years (group III) compared with age Conclusion Among survivors of type A aortic dissections, rehospitalizations the first year after discharge were common among all age groups, but survival was high. Repeated aortic surgery was rare, and significantly more common among younger than older patients. Evaluations of quality of life in survivors of type A aortic dissections are needed. Funding Acknowledgement Type of funding sources: None.

Background Bleeding has an important prognostic impact in patients with ST-segment elevation myocardial infarction (STEMI), yet stratification of bleeding risk to guide dual antiplatelet therapy (DAPT) is not routinely performed in clinical practice. Purpose To describe high bleeding risk (HBR) patients according to the PRECISE-DAPT (predicting bleeding complications in patients undergoing stent implantation and subsequent DAPT) score and use of P2Y12-inhibitors. Methods This single-centre observational study included consecutive patients with STEMI who were treated with percutaneous coronary intervention (PCI) from 2009–2016. Individual linkage to Danish nationwide registries was conducted to obtain information on diagnoses, claimed drugs, and vital status. Age, prior bleeding diagnosis, and blood samples before PCI (maximum 30 days before hospitalisation) were used to calculate the PRECISE-DAPT score. A score ≥25 was considered as HBR. Due to 26.7% missing on blood parameters (mainly leucocytes), the maximum and minimum values of the missing parameters and respective imputed PRECISE-DAPT scores were calculated. If both the maximum and minimum score were ≥25 or Results We identified 6179 PCI-treated patients with STEMI, of whom 5530 (89.5%) had imputed PRECISE-DAPT scores (Figure 1). A total of 1821 (32.9%) were at HBR, and these were more often female (38.3 vs. 18.2%, p-value Conclusion Every third PCI-treated all-comer with STEMI was at HBR according to the PRECISE-DAPT score. HBR patients were more often treated with potent P2Y12-inhibitors (prasugrel or ticagrelor) instead of clopidogrel. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship.

Background Sodium-glucose co-transporter-2 (SGLT2) inhibitors are a newly recommended treatment of heart failure with reduced ejection fraction (HFrEF). The consistently observed increase in haematocrit with SGLT2 inhibition is associated with a large proportion of the observed clinical benefit in different type 2 diabetes (T2D) populations. Whether the increase in haematocrit is caused by diuresis-associated haemoconcentration or is due to a direct effect on erythropoiesis is unknown. We have previously observed a decrease in ferritin alongside increases in haematocrit and haemoglobin with empagliflozin, thus indicating a direct effect on erythropoiesis. Purpose To investigate the effect of the SGLT2 inhibitor empagliflozin on erythropoiesis in patients with HFrEF. Methods The Empire HF trial was an investigator-initiated, double-blind, randomised, placebo-controlled trial conducted at two Danish university hospitals with enrolment of 190 patients from five outpatient heart failure clinics. Patients with a left ventricular ejection fraction (LVEF) of 40% or lower, with New York Heart Association (NYHA) Class I, II, or III symptoms, and on stable doses of guideline-directed HFrEF therapy were randomly assigned (1:1) to receive empagliflozin 10 mg or matching placebo once daily for 12 weeks. The present biomarker endpoints were analysed according to the intention-to-treat principle in analyses of covariance models with baseline adjustments. Results A minimum of 91 patients (96%) in each group had complete data and were included in the present analyses. Baseline characteristics were well-balanced between the allocated groups [mean age: 64 (SD 11) years; male: 85%; mean LVEF: 29 (SD 8) %; NYHA Class II: 78%; T2D: 13%; anaemia: 28%]. Serum-erythropoietin increased in the empagliflozin group compared to placebo from baseline to 12 weeks [adjusted mean difference 2.6 IU/L (95% CI 0.8–4.4; P=0.0052)]. Moreover, plasma-hepcidin decreased [adjusted ratio of change 0.68 (95% CI 0.22–1.02; P=0.067)], and mean corpuscular volume increased [adjusted ratio of change 1.01 (95% CI 1.00–1.02; P=0.0033)] compared to placebo, while no changes were observed for mean corpuscular haemoglobin concentration or plasma-iron (P>0.05). Conclusion The consistently observed increase in haematocrit with SGLT2 inhibitor treatment may not exclusively be due to diuresis-associated haemoconcentration as previously suspected. The present analyses suggest that empagliflozin increases erythropoiesis and induces changes in iron metabolism in a population of patients with HFrEF, primarily without diabetes. The observed decrease in hepcidin, and in ferritin as we have previously reported, further implies an anti-inflammatory effect, all of which may contribute to the cardioprotective properties of empagliflozin. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation;The A.P. Møller Foundation for the Advancement of Medical Science, Copenhagen, Denmark

Background The incidence of infective endocarditis (IE) is increasing in the adult population, as is the insertion of prosthetic heart valves. Patients with prosthetic heart valves are considered at high risk of IE – a complication with a high mortality. However, data on temporal changes in the incidence of IE among patients with prosthetic heart valves from unselected cohorts are sparse Purpose We aimed to examine nationwide temporal trends in the incidence of IE in patients with an implanted prosthetic heart valve in Denmark from 1999 to 2018. Methods Using Danish nationwide health-care registries we identified all patients, who underwent heart valve implantation between 1996–2018. Crude annual incidence rates per 1,000 person years (PY) of IE were computed and presented in two year intervals. Analyses were stratified by sex and age groups (80 years). Results We identified 26,604 patients with first time prosthetic valve implantation with a median age of 72.7 years at the time of implantation, 63.1% were men with a median follow-up of 6.5 years. We found 1,442 cases of first time IE. The IE incidence rate ranged from 5.4 /1,000 PY (95% CI 3.9–7.4) in calendar period 2001–2002 to 10.0/1,000 PY (95% 8.84–11.11) in calendar period 2017–2018 with an unadjusted increasing trend during the study period (ptrend Conclusion The incidence of IE following prosthetic heart valve implantation has increased slightly over the last 20 years in Denmark. Funding Acknowledgement Type of funding sources: None.

Background In addition to lifestyle intervention, guidelines recommend initiation of antidiabetic (AD) treatment within 3 months of diagnosing type 2 diabetes (T2D). Yet, patients with an initial HbA1c level between 48 and 57 mmol/mol may await effects of lifestyle intervention up to 6 months. Omitting initial AD treatment and any lifestyle-induced remission, may affect initiation of statins and renin-angiotensin system inhibitors (RASi) and, thus, cardiovascular risk. Purpose To examine whether omission of initial AD treatment is associated with an increased 5-year risk of first-time major cardiovascular event (MACE: myocardial infarction/stroke/all-cause death) compared with well-controlled patients on AD. Further, whether lower initial use of statins and RASi could explain this excess risk of MACE. Methods We used Danish registers to identify patients with a first-measured HbA1c of 48–57 mmol/mol between 2014 and 2020. We included patients aged 40–80 years without prior atherosclerotic disease that were alive the following 180 days (the index date). At date of index, we divided patients into four groups according to AD treatment and achieved HbA1c (mmol/mol): well-controlled (HbA1c ≤47) on AD; poorly controlled (HbA1c ≥48) on AD; remission (HbA1c ≤47) not on AD; poorly controlled (HbA1c ≥48) not on AD. Based on a Cox-regression model and imputations of treatment values of statins and RASi from two logistic regression models, we examined to what extent the observed standardised 5-year risk of MACE within each group could be reduced if each group had the same probability of treatment initiation with statin and RASi as well-controlled patients on AD. Results We included 14,206 patients (median age 59 [IQR 51–68] years; 52.0% men) with the following distribution according to AD group: well-controlled on AD: 22.3%; poorly controlled on AD: 14.7%; remission not on AD: 38.3%; poorly controlled not on AD: 24.6%. Patients not on AD had lower probabilities of initiation of statins and RASi compared with patients on AD (Figure 1). Compared with well-controlled on AD, the absolute 5-year risk of MACE was increased with 3.7% (95% CI 1.6–6.1) in poorly controlled on AD; 2.1% (95% CI 0.3–3.8) in remission not on AD; 3.4% (95% CI 1.6–5.3) in poorly controlled not on AD (Figure 1 and 2). If initiation of statins and RASi were the same as in the well-controlled group on AD, patients not on AD could reduce their risk of MACE with 1.0% (95% CI 0.2–1.8) in the remission group and with 2.2% (95% CI 1.2–3.2) in the poorly controlled group (Figure 2). Conclusions Patients not on initial AD treatment had an increased 5-year risk of MACE, even among those who experienced remission of T2D. Lower initial use of statin and RASi seem to explain some of the excess risk of MACE in patients not on initial AD treatment. This study emphasizes the need for greater focus on primary prevention with statins and RASi in T2D, especially among patients not on AD treatment. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Research Grant from Steno Diabetes Center Sjaelland

Background Since the introduction of transcatheter aortic valve implantation (TAVI), the management of symptomatic severe aortic stenosis has changed. Recent published European guidelines (2021) favours TAVI over surgical aortic valve replacements (SAVR) in patients with older age (≥75 years of age) or patients with high surgical risk. The study of nationwide practice patterns for AVR is important and renders the possibility to evaluate whether clinical practice differs from current guidelines. Purpose To evaluate temporal changes in use of isolated aortic valve replacement (AVR) procedures according to age in the era of TAVI in Denmark. Methods We identified all first-time aortic valve replacement procedures (TAVI or SAVR) from 2008 until the end of 2020 through administrative registries in Denmark. Patients with no prior diagnosis of aortic stenosis at time of AVR were excluded. Patients with prior AVR or valve repair were excluded. SAVR was divided according to type of prostheses: surgical bioprostheses and mechanical prostheses. To evaluate changes according to age the study cohort was divided into two age groups: Results Between 2008 and 2020, 12,313 first-time isolated AVR procedures were performed in Denmark. Volume of isolated AVR increased from 621 to 1256 procedures per year (ptrend Conclusions Volume of isolated aortic valve replacement (AVR) doubled from 2008 and 2020. The increase in isolated AVR was driven by transcatheter aortic valve implantation (TAVI). TAVI has become the predominant choice of isolated AVR in management of aortic stenosis and our results suggest that real-world practise patterns are in line with current guideline recommendations. Funding Acknowledgement Type of funding sources: None.

Background Diastolic dysfunction (DD) in heart failure (HF) is associated with increased myocardial cytosolic calcium, and calcium-efflux via the sodium-calcium-exchanger depends on the sodium gradient. Beta-3-adrenoceptor (β3-AR)-agonist lowers cytosolic sodium and has been shown to reverse organ congestion. Purpose To assess whether β3-AR-agonist treatment improves DD. Methods In a first-in-man randomized controlled, double-blind trial, we assigned 70 patients with HF with reduced ejection fraction (HFrEF) (NYHA II–III) and LVEF Results Baseline and follow-up echocardiographic data were available in 57 patients (59±11 years, 88% male, 49% ischemic heart disease). Baseline LVEF was 34%±8%. No significant change in DD grade was found between the groups at follow-up, p=0.72. Neither was there any clinical differences in any singular diastolic parameters within or between groups by echocardiography (E/e' placebo: 13.3±6.9 to 12.6±5.1, p=0.19 vs. mirabegron: 12.0±5.7 to 12.8±7.9, p=0.67, mean difference 1.12 [95% CI −1.68 to 4.3], p=0.37), or CCT (left atrial max volume index: between group mean difference 0.2 [95% CI −6.2 to 5.6] ml/m2, p=0.91). Conclusions In patients with HFrEF, no improvement nor worsening in DD gradings or singular diastolic parameters after β3-AR stimulation compared to placebo were identified. The findings add to previous literature questioning the role of impaired Na+-Ca2+ mediated Ca2+ export as a major culprit in DD. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Heart Centre Research Foundation, RigshospitaletThe Novo Nordic Foundation

Background Patients with cancer have higher short-term rates of cardiovascular events than the general population. However, little is known about rates of long-term cardiovascular outcomes in 5-year cancer survivors, especially in older patients. Objective We investigated the long-term rates of cardiovascular outcomes, including heart failure, atrial fibrillation, venous thromboembolism, ischemic stroke and myocardial infarction in five-year cancer survivors, overall and according to age. Methods Using Danish nationwide registries, five-year survivors of 20 of the most common cancers (diagnosed between 1994 and 2013; 15 years of age or older at the time of the diagnosis) were matched with four non-cancer controls from the background population by age and sex. Study participants with a history of any the outcomes of interest prior to index date were excluded. Rates of outcomes in the cancer and non-cancer group were compared with Cox regression models, overall and according to age (i.e., 15–39, 40–59, and >60 years). Results In total, 167,215 five-year cancer survivors were age- and sex-matched with 668,860 non-cancer controls (median age 66 years; 34.4% men, median follow-up of 6.8 years). Five-year survivors had higher associated rates of cardiovascular outcomes, irrespective of age, and the incidence rates per 1,000 person-years of cardiovascular outcomes for cancer survivors and non-cancer controls were: HF: 6.2 (95% CI: 6.1–6.4) and 5.2 (5.1–5.3), respectively; atrial fibrillation: 11.1 (10.9–11.3) and 9.3 (9.3–9.4), respectively; venous thromboembolism: 5.1 (5.0–5.2) and 2.8 (2.8–2.9), respectively; ischemic stroke: 5.8 (5.6–5.9) and 5.4 (5.4–5.5), respectively; and myocardial infarction: 3.6 (3.5–3.7) and 3.4 (3.3–3.4), respectively. The absolute rates of cardiovascular outcomes were highest in the oldest group, whereas the relative rates were more pronounced in the youngest cancer group compared with matched controls (Figure 1). Conclusions Compared with the general population, five-year cancer survivors had higher associated rates of cardiovascular outcomes across the spectrum of age. The increased rates of cardiovascular outcomes were more pronounced in the youngest group. These data underline the importance of risk assessment and prevention of cardiovascular diseases in five-year cancer survivors. Funding Acknowledgement Type of funding sources: None.

Background First-time detected atrial fibrillation (AF) during acute coronary syndrome (ACS) aggravates the prognosis and increases the risk of ischemic stroke. In this setting, AF may present as brief and transient or with recurrent episodes after discharge. However, data on the association between transient or recurrent AF and ischemic stroke in patients with ACS are sparse. Further, despite being associated with ischemic stroke, first-time detected AF patients have been reported with low oral anticoagulation (OAC) rates. Purpose To examine the associated rate of ischemic stroke and mortality in ACS survivors with transient or recurrent AF and to assess the antithrombotic practice patterns one year after ACS. Methods Using data from Danish nationwide registries, we identified all patients with first-time ACS, without known AF prior to ACS, from 2000–2017 who were alive one year after ACS discharge (index date). According to a grace period between ACS discharge and one year after ACS discharge, patients were categorized into: i) no AF; ii) first-time detected AF during ACS admission without AF recurrence (transient AF); and iii) first-time detected AF during ACS admission with a subsequent recurrent AF episode (recurrent AF). Patients who developed AF during the grace period were excluded. Patients were followed from one year post ACS discharge, and two-year rates of ischemic stroke and mortality were compared using multivariable adjusted Cox proportional hazards analysis. Further, we assessed the prescribed OAC rates in a three-month period following the index date. Results We included 116,793 patients surviving one year post ACS discharge: 111,708 (95.6%) without AF (64.9% male, median age 64 years), 2,671 (2.3%) with transient AF (58.0% male, median age 74 years), and 2,414 (2.1%) with recurrent AF (55.2% male, median age 76 years). The cumulative two-year incidence of ischemic stroke was 0.9%, 1.5%, and 2.3% for patients without AF, transient AF, and recurrent AF, respectively (Figure 1). The cumulative two-year incidence of mortality was 7.4%, 12.1%, and 20.3% for patients without AF, transient AF, and recurrent AF, respectively (Figure 1). Compared to those without AF, the adjusted two-year rates of outcomes were as follows: ischemic stroke: HR 1.15 (95% CI: 0.81–1.61) for patients with transient AF and HR 1.50 (95% CI: 1.14–1.98) for patients with recurrent AF; mortality: HR 0.98 (95% CI: 0.87–1.10) for patients with transient AF and HR 1.35 (95% CI: 1.23–1.49) for patients with recurrent AF (Figure). We identified that 20.9% for transient AF and 42.2% for recurrent AF were prescribed OAC therapy in the three-month period after one year. Conclusion In patients surviving one year after ACS with first-time detected AF, a recurrent AF episode was associated with an increased long-term rate of ischemic stroke and mortality, while transient AF yielded no statistically difference as compared with patients without AF. Funding Acknowledgement Type of funding sources: None.

Background Hemodialysis and infective endocarditis are both associated with poor patient outcome. However, despite high mortality rates for each disease entity, little attention is given to patients on hemodialysis who develop infective endocarditis. Purpose To examine patient characteristics, microbiological etiology, cardiac surgery, and outcome among patients on hemodialysis with infective endocarditis compared with patients with infective endocarditis without hemodialysis treatment. Methods With Danish nationwide registries, we identified patients with infective endocarditis between 2010–2018 and linked them to microbiological data from a nationwide microbiological registry with complete blood culture data. We included patients in the hemodialysis group if they received hemodialysis treatment within 6 months prior to their first-time infective endocarditis admission. Patients not meeting this criteria were put in the non-hemodialysis group. We used Kaplan-Meier estimates for difference in mortality and Cox regression for adjusted analysis. Results We included 4,106 patients with infective endocarditis of which 265 (6.5%) patients were also in hemodialysis treatment (66.8% men). Patients on hemodialysis were younger (median age 66 years [IQR=54.2–74.9] vs. 72.3 years [IQR=62.3–80.4]) and had a higher burden of comorbidities including hypertension (68.7 vs. 56.9%), diabetes (47.2% vs. 18.8%), and ischemic heart disease (41.1% vs. 32.2%) compared to patients without hemodialysis treatment, all p-values Conclusion Patients on hemodialysis with infective endocarditis are younger, sicker and have Staphylococcus aureus as causing agent more than twice as often as patients with infective endocarditis without hemodialysis treatment. This patient group have a higher mortality and by 5 years, 75% of patients in our hemodialysis group were dead. Funding Acknowledgement Type of funding sources: None.

Background/Introduction The general atrial fibrillation/flutter (AF) population is well explored and described, but there is sparse data on temporal changes in the incidence, AF-readmission rates, and practice patterns in patients with AF under 65 years of age from unselected cohorts. Purpose To investigate temporal changes, AF readmission rates, and practice patterns in patients under 65 years of age with first-time AF diagnosed between 2000–2018. Methods Using Danish nationwide registries, we identified patients >18 years and Results In this study 60,917 patients were included; 8,150 patients (13.4%) in 2000–2002, 11,898 (19.5%) in 2003–2006, 13,560 (22.3%) in 2007–2010, 14,167 (23.3%) in 2011–2014 and 13,142 (21.6%) in 2015–2018. No major differences were seen in patient characteristics according to calendar period. A stepwise increase, as seen in the Table, in the crude IR of AF per 100,000 PY was observed across calendar periods, except for 2015–2018 (Crude IR [95% CI]: 2000–2002: 78.7 [77.0; 80.4], 2003–2006: 86.3 [84.7; 87.8], 2007–2010: 97.9 [96.3; 99.6], 2011–2014: 102.3 [100.7; 104.0], 2015–2018: 93.6 [92.0; 95.2], while no difference in AF readmission was identified (AF-readmissions: 2000–2002: 32.7%, 2003–2006: 31.1%, 2007–2010: 32.2%, 2011–2014: 32.1% and 2015–2018: 31.7%), as seen in the Figure, right panel. In the first year following AF-diagnosis, the cumulative incidence of catheter ablation increased stepwise from 1.2% in 2000–2002 to 7.6% in 2015–2018 and electrical cardioversion from 2.0% in 2000–2002 to 8.7% in 2015–2018 (Figure, left panel). Treatment with oral anticoagulant therapy (OAC) increased from 28.5% in 2000–2002 to 47.8% in 2015–2018, while there was no change in treatment with rhythm or rate medication therapy. Conclusion From 2000–2018, we found an increase in the incidence of atrial fibrillation/flutter (AF) in patients Funding Acknowledgement Type of funding sources: None.

Background Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucacon-like-peptide-1 receptor (GLP-1R) agonists are two novel therapies in type 2 diabetes (T2D) that are recommended in patients with manifestations of cardiovascular disease or high risk of cardiovascular disease due to their cardioprotective benefits. Despite the increasing use of these drugs, there is still limited knowledge on the adherence patterns and the risk of discontinuation, according to the presence or absence of different cardiovascular conditions. Purpose To investigate the adherence and estimate the risk of discontinuation of SGLT2 inhibitors and GLP1-R agonists in patients with T2D with and without cardiovascular disease. Methods From Danish nationwide registers, we included all individuals >40 years with T2D who redeemed the first prescription of a SGLT2 inhibitor or GLP1-R agonist, between December, 2012 and December, 2018. Patients were divided into subgroups according to the presence or absence of different cardiovascular conditions (heart failure, ischemic heart disease, peripheral artery disease, atrial fibrillation), at the time of inclusion. Adherence over the course of one year after initiation of treatment was estimated by the proportion of days covered (PDC) for each subgroup, and adherence was defined as PDC 80%. The risk of discontinuation was estimated using multivariable cause-specific Cox regression models, and was defined as a break in treatment of 90 days. The Aalen-Johansen estimator was used to account for censoring and competing risks. Patients were followed until date of emigration, death or study end (December 31, 2019). Results We included 24,061 patients with T2D who initiated treatment with a SGLT2 inhibitor, and 13,899 patients with T2D who initiated treatment with a GLP1-R agonist, for the first time between December 10, 2012 and December 31, 2018. Median age at inclusion was 62 years (IQR 54–70) and 40% were female. In the analyses, 67% of the patients treated with SGLT2 inhibitors were adherent to therapy throughout the first year, whereas the same proportion of patients, 67%, were adherent to therapy with GLP-1R agonists. Mean PDC was 77% (SD 33) and 79% (31) for patients in therapy with SGLT2 inhibitors and GLP1-R agonists, respectively. No significant difference was observed related to the presence or absence of cardiovascular disease (SGLT2 inhibitor: mean PDC 77 (33) vs. 77 (33), GLP1-R agonist: 78 (32) vs. 79 (31)). Conclusions In this nationwide cohort study, we found that patients with T2D who initiated therapy with a SGLT2 inhibitor and those who initiated therapy with a GLP1-R agonist were almost equally adherent to therapy throughout the first year. Adherence in both treatment groups did not differ according to the presence or absence of cardiovascular disease. Funding Acknowledgement Type of funding sources: None.

Background Beta-blockers have in randomized clinical trials been shown to reduce the risk of life-threatening arrhythmias and sudden cardiac death (SCD) in patients with heart failure (HF), and treatment is a class 1A recommendation in current guidelines. Thus, beta-blocker treatment breaks (i.e. planned break, beta-blocker related side-effects, or poor adherence) may increase risk of life-threatening arrhythmias and SCD. Whether patients with HF and a history of beta-blocker treatment breaks before implantable cardioverter defibrillator (ICD) is associated with increased risk of device related therapy and mortality is largely unknown. Aims In patients with HF and an ICD alone or combined with cardiac resynchronization therapy (CRT-D), we examined the association between a history of a beta-blocker treatment breaks prior to device implantation and the risk of appropriate and inappropriate device related therapy (i.e., anti-tachycardia pacing [ATP] or DC shock [DC]), and all-cause mortality. Methods Using the Danish Pacemaker and ICD Registry, we identified all patients with HF receiving a first-time ICD (2000–2018). Beta-blocker treatment breaks >60 consecutive days up to 3 years prior to device implantation were identified using the National Prescription Registry. Patients were able to switch between beta-blockers and were required to be in treatment at the time of implantation. We used multivariable Cox regressions to compare the 1-year risks of device-related therapy and all-cause mortality between patients with and without a history of a beta-blocker treatment break. Results We identified 9,239 patients with HF and an ICD (82.6% male; median age 67 years). A total of 82.5% had ischemic heart disease, 33.9% atrial fibrillation, and 33.1% of ICDs were secondary prophylaxis. During one-year follow-up, 5.7% of all patients died and appropriate DC and appropriate ATP was identified for 3.9% and 6.7% of patients, respectively. Overall, 14.6% of all HF patients had one or more beta-blocker treatment break >60 days. Compared with HF patients with no history of treatment breaks, a history of treatment breaks >60 days were associated with increased risk of appropriate DC (hazard ratio (HR)=1.33; 95% confidence interval [CI], 1.02–1.73) and appropriate ATP (HR 1.30; CI, 1.06–1.59), but also inappropriate DC and ATP therapy (Figure 1). There was no difference between groups with respect to all-cause mortality (HR=0.96; CI: 0.76–1.22). Treatment breaks of >30 or >90 days were also evaluated and yielded similar results as the main analysis. Conclusion Patients with heart failure who had a history of treatment breaks with beta-blockers prior to ICD implantation was associated with a higher 1-year risk of appropriate and inappropriate shocks and anti-tachycardia pacing, but not all-cause mortality. Funding Acknowledgement Type of funding sources: None.

Background Readmissions and time spent hospitalized following transcatheter aortic valve implantation (TAVI) are important parameters of patient autonomy, particularly for frail patients with limited life-expectancy. Yet, such data remain scarce. Purpose To investigate actual time spent hospitalized the first year after TAVI. Secondly, to investigate time spent hospitalized according to frailty risk. Methods Through Danish, nationwide registries, we included all patients undergoing TAVI and alive at discharge between January 2008 and June 2020. From discharge, patients were followed until death, emigration, end of study period, or one year of follow-up, whichever came first. During follow-up, all in-patient hospital admissions were identified according to ICD-10 diagnosis codes. Length of stay was calculated, and cumulative numbers of days hospitalized was presented. Further, the proportion of patients dying within one year of follow-up was calculated. Using The Hospital Frailty Risk Score, a validated frailty risk assessment tool, patients were categorized as low, intermediate, and high frailty risk. We then evaluated the time spent hospitalized stratified by frailty risk group. Results The study population comprised 5,464 patients undergoing first-time TAVI with a median age of 81 years among whom 55.2% were males. After one year, 445 (8.1%) patients had died. In total, 2,452 (44.9%) of TAVI patients survived one year and were never admitted, whereas 3,012 (55.1%) patients were admitted at least once or died within one year of TAVI. Of these, 1,200 (21.9%) patients were admitted for more than two weeks or died within one year of TAVI (Figure 1). Regarding frailty, 3,296 (60.3%), 1,965 (36.0%), and 203 (3.7%) patients were classified as low, intermediate, and high frailty risk, respectively. In the low frailty risk group, 6.2% of patients died within one year and 50.4% survived one year without a hospital admission. By contrast, 16.7% of patients in the high frailty risk group died within one year and only 24.6% survived one year without a hospital admission. Further, 17.1% of patients in the low frailty risk group were admitted for more than two weeks or died within one year of TAVI compared with 47.3% in the high frailty risk group (Figure 2). Conclusion Readmissions in the first year after transcatheter aortic valve implantation were common and time spent hospitalized after transcatheter aortic valve implantation was significant. Our results were clearly related to frailty, which should be considered for future prevention strategies. Funding Acknowledgement Type of funding sources: None.

Background Mobitz type I 2nd degree atrioventricular (AV) block (Wenckebach) is usually considered benign. Guidelines recommend permanent cardiac pacing for patients with Mobitz type II second degree AV block (Mobitz II), but for patients with Wenckebach, permanent pacing is only indicated if the AV block causes symptoms or if the conductions delay occurs below the bundle of His. However, these guidelines are based on evidence of modest quality and a consensus amongst experts (1). Purpose This study aims to investigate if Wenckebach really is benign by comparing the risk of cardiovascular death for patients with Wenckebach to patients with normal ECGs. Methods This retrospective cohort study included 978,901 ECGs obtained from general practitioners in Denmark from 01/02/2001 to 31/10/2014. Index date was the day of the ECG recording and the patients were followed until death or end of follow up at December 2019. The association between Wenckebach and cardiovascular death was analyzed using: 1) multivariate Cox models adjusted for age and comorbidities, 2) cause-specific Cox models and 3) cumulative risk and cause-specific hazard function plots, compared to matched controls. Information about comorbidities, pacemaker, indications, and death was retrieved from Danish nationwide registries. Results From the 978,901 ECG recordings, we found 262 patients with Wenckebach, 131 patients with Mobitz II, and 229,056 patients with normal ECGs. In Wenckebach, Mobitz II, and normal ECG the median age was 76, 80, and 50 years, 76%, 63%, and 41% were male, 25%, 16%, and 3% had diabetes, 35%, 30%, and 8% had hypertension, respectively. During a mean follow-up of 11.2 years, cardiovascular death occurred in a total of 11,301 patients: 77 (29%) patients with Wenckebach, 40 (31%) patients with Mobitz II, and 11,184 (5%) patients with normal ECGs. In a matched cohort 262 Wenckebach patients were matched with 520 controls with normal ECGs. In the multivariate Cox model, Wenckebach was associated with cardiovascular death (HR: 2.14 [95% CI: 1.46–3.13], P Furthermore, the results showed that 43% of the Wenckebach patients received pacemaker with a median time to pacemaker from ECG recording being 252 days. The vast majority of the Wenckebach patients who received pacemaker had a higher degree AV block than Wenckebach as indication for the implantation. Conclusion Wenckebach on routine ECG was associated with a significant higher hazard rate of cardiovascular death compared to matched controls with normal ECGs. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Danish Heart Association

Background The studies investigating the safety and efficacy of the SARS-COV2 mRNA vaccines only included a limited number of heart failure patients and no separate analyses were performed regarding the safety of the vaccines in this patient population. Purpose The aims of this study were to investigate the risk of worsening heart failure and all-cause mortality associated with the SARS-COV-2 mRNA vaccines in a nationwide cohort of patients with heart failure. Methods Using the Danish nationwide registries, two cohorts were constructed; 1) all prevalent heart failure patients in 2019 and 2) all prevalent heart failure patients in 2021 who were vaccinated with either of the two mRNA vaccines (BNT162B2 or mRNA-1273). The patients in the two cohorts were matched 1:1 using exact exposure matching on age, sex, and duration of heart failure (intervals). For patients in the 2021 cohort, the index date was defined as the date of the patients' second vaccination. Patients in the 2019 cohort were assigned the index day and month of their 1:1 match in the 2021 cohort, but used the pre-vaccination index year 2019. The primary outcomes were worsening heart failure and all-cause mortality and secondary outcomes were myocarditis and venous thromboembolism. Standardized risks were estimated based on outcome-specific Cox regression analyses, and all models were standardized to age, sex, duration of heart failure, use of SGLT2 inhibitors or Entresto, ischemic heart disease, cancer, diabetes, atrial fibrillation, and admission with heart failure Results The total study population comprised 101,786 patients, with 50,893 patients in each cohort. The median age of the study population was 74 (interquartile range (IQR); 66,81), and duration of heart failure was 4.1 (IQR: 2.0,6.7) years. The standardized risk of all-cause mortality within 90 days was 2.2% (95% CI: 2.1% to 2.4%) in the 2021 cohort and 2.6% (95% CI: 2.4% to 2.7%) in the 2019 cohort, showing a significantly lower risk difference for all-cause mortality in 2021 versus 2019 (risk difference: −0.3% (95% CI: −0.5% to −0.1%)) Figure 1)). The standardized risk of worsening heart failure within 90 days was 1.1% (95% CI: −1.0% to 1.2%) in the 2021 cohort and 1.1% (95% CI: 1.0% to 1.2%) in the 2019 cohort showing no significant difference in the risk of worsening heart failure between the two cohorts (risk difference: 0% (95% CI: −0.1% to 0.1%)). No significant differences were found for venous thromboembolism or myocarditis. Conclusion This study showed that the SARS-COV2 mRNA vaccines were not associated with an increased risk of worsening heart failure, venous thromboembolism or myocarditis, but was associated with a decreased risk of all-cause mortality. Our study may suggest that these vaccines are safe in heart failure patients. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Danish Heart FoundationLæge Sofus Carl Emil Friis og hustrus legat

Background Guideline-recommended disease-modifying pharmacological therapies for heart failure (HF) with reduced ejection fraction are underutilized, particularly among elderly patients. Purpose We examined adherence with and discontinuation of evidence-based HF pharmacotherapy, comprising of angiotensin-converting enzyme inhibitors (ACEi)/angiotensin-II receptor blockers (ARB), beta-blockers (BB) and mineralocorticoid receptor antagonists (MRA), according to age. Methods Using Danish nationwide registries, we included patients with a first HF diagnosis between 2011 and 2018. Patients were stratified into three age groups, 90 days, and the 5-year risk of discontinuation according to age groups was estimated with the Aalen-Johansen estimator. Multivariable Cox regression models were used to evaluate the treatment discontinuation rate according to age groups. Results We included a total of 29,482 patients ( Conclusion Among a nationwide cohort of HF patients, advanced age was associated with lower proportions of daily target doses, lower adherence, and a higher rate of discontinuation of ACEi/ARB and BBs. Focus on treatment adherence and optimal dosages among elderly HF patients could improve outcomes. Funding Acknowledgement Type of funding sources: None.

Background Large randomized controlled trials (RCT) have shown that COVID-19 vaccines are effective at preventing severe COVID-19. However, the RCT's are not powered to detect rare adverse events. It has been reported that the new mRNA based COVID-19 vaccines may increase the risk of thromboembolic and ischemic events. Likewise, thromboembolic and ischemic events are also known complications to infection with SARS-CoV-19. Currently, less is known about the risk-reward relationship of receiving an mRNA-based COVID-19 vaccine versus contracting COVID-19 infection with respect to thromboembolic and ischemic outcomes. Purpose To compare the risk of thromboembolic and ischemic events following COVID-19 vaccination to the risk following infection with SARS-CoV-19. Methods The study period was from March 2020 to August 2021. All individuals were >18 years old. The population was stratified into two different groups. The vaccinated group consisted of recipients of the first dose of either Moderna (mRNA-1273, n=488,220) or Pfizer-BioNTech (BNT162b2 mRNA, n=3,186,164) vaccines. Individuals who had previously tested positive for SARS-CoV-19 were excluded. The other group consisted of individuals who had tested positive for SARS-CoV-19 in the same period who had not yet received their first vaccination dose (n=233,926). The exposure period for both groups was set to 28 days following vaccination/testing positive for SARS-CoV-19 (Figure 1). Patient level data were obtained on all included individuals using nationwide registries. Primary outcomes were acute myocardial infarction (AMI), ischemic stroke, pulmonary embolism (PE), and deep venous thrombosis (DVT). Odds ratios were obtained from logistic regression models with the vaccinated group acting as reference. Multivariable models were adjusted for demographics and comorbidities. Results In the vaccinated group, mean age was 53±19 years and 50.3% were female. In the group of participants testing positive for SARS-CoV-19, mean age was 42.1±17.4 years and 50.2% were female. In total, 773 suffered a stroke, 472 suffered a PE, 500 suffered an AMI, and 484 suffered a DVT during the 28-day exposure period. We observed an increased absolute risk of all outcomes for participants testing positive for SARS-CoV-19 as compared to participants being vaccinated (stroke: 0.049% vs 0.019%, p Conclusion The risks of thromboembolic and ischemic events were substantially higher after SARS-CoV-19 infection than after vaccination in the Danish population. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Gentofte University Hospital

Background Over the last 20 years mortality has decreased for patients with heart failure (HF). However, re-hospitalization for HF is still a challenge. Further, whether the improved survival has resulted in increased rates of non HF hospitalization is unknown. Purpose This study examined the temporal trends in infection-related hospitalizations among new-onset HF patients and compared it to temporal trends in risk of worsening HF and death. Methods The study population included all Danish patients aged between 18 and 100 years old, with new-onset HF (defined according to the ICD10-code system) diagnosed between 1st January 1997 and 31st December 2017. Patients who were diagnosed with any type of cancer up to five years before their HF diagnosis were excluded to avoid cancer related infections. The outcomes of interest were infections (defined according to the ICD10-code system) and worsening of heart failure (defined as a hospital admission with HF covering at least to dates). The Aalen Johansen's estimator was used to estimate unadjusted 5-year absolute risk for all outcomes. Furthermore, a multivariate Cox analysis was made, and hazard ratios were estimated for the four time periods presented in a forest plot with the period 1997–2001 being the reference group. Adjustments for sex, age and history of comorbidities were conducted. Additionally, we stratified the infection outcome on different types of infections illustrated in 5-year cumulative incidence curves. Results The total population consisted of 147,737 patients. Over time there was a slight decrease in median age (1997–2001: 76.8 years, 2011–2017: 73.1 years) and the patients were more likely to be male (1997–2001: 53.5%, 2011–2017: 60%). Figure 1 illustrates overall absolute risk of death decreased over time 1997–2001 (62.7% [95% CI 62.2–63.2]) vs. 2011–2017 (57.9% [95% CI 41.5–42.7]). Unadjusted curves for absolute risk showed that patients with HF had a higher risk of infection over time 1997–2001 (16.4% [95% CI 16.0–16.8] vs. 2011–2017 (24.5% [95% CI 24.0–24.9]). In contrast, they have a lower risk of worsening HF 1997–2011 (26.5% [95% CI 26.1–27.0] vs. 2011–2017 (23.2% [95% CI 22.8–23.7]). Adjusted analyses provided the same result for all outcomes illustrated in figure 2. The risk of infection stratified by infection type, mark the risk of pneumonia infection as the most significant in all subintervals 1997–2001 (11.4% [95% CI 11.1–11.7]) vs. 2011–2017 (16.1% [95% CI 15.7–16.5]). The second most important was the risk of urogenital infection 1997–2001 (3.5% [95% CI 3.31–3.69]) vs. 2011–2017 (7.8% [95% CI 7.52–8.12]). Conclusion In this nationwide study, we observed that overall mortality risk and risk of hospitalization for worsening HF decreased from 1997 to 2017. In contrast, an increase in the risk of hospitalization for infection, especially pneumonia infections, increased during the same period. Future HF management programs should include strategies to prevent infections. Funding Acknowledgement Type of funding sources: None.

Background Advances in treatment of heart failure (HF) have increased survival rates. However, whether the improved life expectancy for HF patients has resulted in an increased risk of a significant comorbidity like end-stage renal disease (ESRD) is less clear. Renal dysfunction is associated with increased morbidity and mortality in HF and constitutes an important prognostic factor for HF. Further, diabetes (DM) is closely related to both HF and ESRD, but it is unknown how DM affects the risk of ESRD in patients with HF. Purpose To investigate temporal trends in ESRD in patients with HF and the subsequent risk of mortality stratified by DM. Methods Using Danish nationwide registies, we identified patients, aged 18 to 100 years, with incident HF between 2002 and 2017. The outcomes were ESRD (defined as dialysis treatment), worsening of HF (wHF, defined as rehospitalization for HF) and all-cause mortality. Three study periods were investigated 2002–2006, 2007–2011 and 2012–2017. We estimated crude 5-year incidence rates (per 1000/person-years) of the outcomes stratified by DM. Multivariate Cox regression models were performed for all outcomes stratified by DM. Further, we computed the 1-year all-cause mortality risk after diagnosis with ESRD. Results Of 124,141 patients with HF, 50,690 (41%) were women and the median age was 74.5 years [95% confidence interval (CI) 64.5–82.8]. At baseline DM was present in 20% of the patients. These patients were older, more often men and more comorbid than HF patients without DM. Over time (2002–2006 to 2012–2017) the incidence rates of ESRD (9.0 to 7.9 and 2.1 to 1.9 per 1000/person-years for DM and no-DM, respectively) and wHF (124.0 to 124.8 and 84.3 to 81.9 per 1000/person-years for DM and no-DM) remained stable, while all-cause mortality rates decreased (217.0 to 170.3 and 172.9 to 127.8 per 1000/person-years for DM and no-DM). The incidence of ESRD was lower compared with the incidence of wHF and all-cause mortality [Figure 1]. HF patients with DM had significantly higher associated rates of all three outcomes (in 2012–2017 the rates for DM vs no-DM of ESRD: 3.99 [3.27–4.86], wHF: 1.42 [1.36–1.49], all-cause mortality: 1.36 [1.31–1.41]) compared with patients without DM. We found no significant interaction between time period and DM on the rates of outcomes (p>0.05 for all) [Figure 2]. One-year all-cause mortality risk after diagnosis with ESRD was high both for HF patients with and without DM through all time periods (identical risks and 95% CI in 2012–2017: 32% [0.25–0.39]). Conclusions We did not observe a change over time in the 5-year risk of ESRD for HF patients. The incidence of ESRD remained low compared to wHF and all-cause mortality. DM was associated with increased rates of all three events, not changed over time. Conversely, all-cause mortality after diagnosis with ESRD was markedly high, irrespectively of DM. Our analyses suggest that ESRD is a less common, but fatal event in HF patients. Funding Acknowledgement Type of funding sources: None.

Background In the Danish Study to Assess the Efficacy of Implantable Cardioverter-Defibrillators [ICDs] in Patients with Non-ischaemic Systolic Heart Failure on Mortality (DANISH) trial, ICD implantation did not provide an overall survival benefit in patients with non-ischaemic systolic heart failure. A high proportion of patients in the DANISH trial received a cardiac resynchronisation therapy (CRT) device, which improves the prognosis in patients with heart failure. Therefore, it is of interest to examine whether the effect of ICD implantation in patients with non-ischaemic systolic heart failure is modified by CRT. Purpose Adding 4 years of additional follow-up to the DANISH trial, we examined the effect of ICD implantation according to status with respect to CRT implantation at baseline. Methods In the DANISH trial, 556 patients with non-ischaemic systolic heart failure were randomised to receive an ICD and 560 to receive usual clinical care (control). Patients fulfilling indications for a CRT device received a CRT-defibrillator (if randomised to ICD arm) or CRT-pacemaker (if randomised to control arm). In the ICD group, 322 patients (57.9%) received a CRT device; in the control group, 323 patients (57.7%) received a CRT device. In this extended follow-up study, patients were followed until May 18, 2020. The primary outcome was death from any cause; secondary outcomes were cardiovascular death and sudden cardiovascular death. Results During a median follow-up of 9.5 years, the ICD group did not have significantly lower all-cause mortality compared with the control group (hazard ratio [HR] 0.89 [95% CI, 0.74–1.08]). The results were independent of whether the patient received a CRT device at randomisation (patients with a CRT device: HR 0.92 [95% CI, 0.72–1.18]; patients without a CRT device: HR 0.86 [95% CI, 0.64–1.14]; P for interaction, 0.72). Similarly, ICD implantation did not reduce rates of cardiovascular death overall (HR 0.87 [95% CI, 0.70–1.09]), and this association was not modified by CRT (patients with a CRT device: HR 0.89 [95% CI, 0.66–1.19]; patients without a CRT device: HR 0.85 [95% CI, 0.60–1.20]; P for interaction, 0.86). The ICD group had significantly lower rates of sudden cardiovascular death in the overall population (HR, 0.60 [95% CI, 0.40–0.92]), and this association was not modified by CRT (patients with a CRT device: HR 0.69 [95% CI, 0.40–1.21]; patients without a CRT device: HR 0.51 [95% CI, 0.26–0.97]; P for interaction, 0.47). See Figure 1 for all results. Conclusions In this extended follow-up study of the DANISH trial, the effect of ICD implantation in patients with non-ischaemic systolic heart failure was not modified by CRT. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The DANISH trial was supported by unrestricted grants from Medtronic, St Jude Medical, Tryg Fonden, and the Danish Heart Foundation. No further funding was obtained for this follow-up study.

Background Atrial fibrillation (AF) in relation to surgery remains a clinical challenge. Major emergency abdominal surgery (e.g. ileus, perforation) is associated with postoperative complications and mortality. However, the prevalence and impact of perioperative AF in this setting is not well examined. Purpose We compared 30-days and 1-year outcomes (i.e. hospitalization of any causes, AF-related hospitalization, thromboembolic events and all-cause mortality) in patients who did and did not develop perioperative AF (POAF) in relation to their major emergency abdominal surgery. Methods We crosslinked data from Danish nationwide registries and identified all patients who underwent major emergency abdominal surgery (2000–2018) and discharged alive. Patients who developed POAF during hospitalization were matched in a 1:3 ratio on age, sex, year of surgery and category of surgery with those without POAF. Starting follow up at discharge, we examined the rates of outcomes at 30-days and 1-year post-discharge. The cumulative incidences and ratios of outcomes were assessed with the Aalen Johanson estimator together with Kaplan-Meier estimator and multivariable Cox regression analysis, respectively. Results We identified 891 patients with POAF and 64,914 patients without POAF. The matched cohort were composed of 889 patients with POAF and 2667 patients without POAF with a median age of 79 years [25th-75th percentile; 72–84 years] and 45.2% males. In general, patients with POAF had higher comorbid burden compared with patients without POAF. The cumulative incidences of a hospitalization of any cause after 30-days post-discharge were 31.2% and 22.3% in patients with and without POAF, respectively. The corresponding numbers for AF-related hospitalization were 20.8% and 1.2%, respectively. In adjusted analyses, POAF was associated with a significantly higher risk of hospitalization of any causes together with AF-related hospitalization (Figure 1 and 2). The cumulative incidences of a thromboembolic event after 30-days post-discharge were 2.2% and 0.9% in patients with and without POAF, respectively. The corresponding numbers for all-cause mortality were 9.7% and 3.2%, respectively. In adjusted analyses, POAF was associated with a significantly higher risk of a thromboembolic event together with all-cause mortality within 30-days of follow up as well as 1-year of follow up. However, the results regarding thromboembolic events did not reach statistical significance after 1-year of follow up (Figure 1 and 2). Conclusions Perioperative atrial fibrillation in relation to major emergency abdominal surgery was associated with higher 30-days and 1-year rates of hospitalizations of any causes, atrial fibrillation related hospitalization, a thromboembolic event and all-cause mortality. These findings suggest that perioperative atrial fibrillation is a strong prognostic marker of increased morbidity following major emergency abdominal surgery. Funding Acknowledgement Type of funding sources: None.

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This project has received funding from the European Union’s Horizon 2020 research and innovation programme under acronym ESCAPE-NET, registered under grant agreement No 733381, and the European Union’s COST programme under acronym PARQ, registered under grant agreement No CA19137. Background Although family history of heart failure (HF) is associated with increased risk of HF, the extent to which a family history contributes to the risk of HF needs further investigation. Purpose To determine whether a family history of unexplained HF in first-degree relatives (children or sibling) increases the rate of unexplained HF. Methods Using Danish nationwide registry data (1978-2017), we identified patients (probands) diagnosed with first unexplained HF (HF without any known comorbidities) in Denmark, and their first-degree relatives. All first-degree relatives were followed from the HF date of the proband and until an event of unexplained HF, exclusion diagnosis, death, emigration, or study end, whichever occurred first. Using the general population as a reference, we calculated adjusted standardized incidence ratios (SIR) of unexplained HF in the three groups of relatives using Poisson regression models. Results We identified 57,845 first-degree relatives to individuals previously diagnosed with unexplained HF. Having a family history was associated with a significantly increased unexplained HF rate of 2.08 (95% CI 1.82-2.38) (Figure 1). The estimate was higher among siblings (SIR 4.82 [95% CI 3.17-7.32]). Noteworthy, the rate of HF increased for all first-degree relatives when the proband was diagnosed with HF in a young age (≤50 years, SIR of 3.60 [95% CI 2.37-5.47]) and having >1 proband (SIR of 2.73 [95% CI 1.14-6.56]). The highest estimate of HF was observed if the proband was ≤40 years at diagnosis (6.12 [95% CI 3.39-11.05]) (Figure 2). Conclusion A family history of unexplained HF was associated with a two-fold increased rate of unexplained HF among first-degree relatives. If the proband age was ≤40 years, the risk was six-folded. These findings suggest that screening families of unexplained HF with onset below 50 years is indicated.

Funding Acknowledgements Type of funding sources: None. Background Procedural pericardiac effusion (PE) is considered a major complication to implantation of cardiac implantable electronic devices (CIED), including permanent pacemakers (PM), cardiac resynchronization therapy devices with defibrillators (CRT-D) or without (CRT-P), and implantable cardioverter defibrillators (ICD), as it can cause life threatening cardiac tamponade. Very little is known about risk factors for procedural PE. Aim To identify the patient- and procedure related risk factors associated with clinically relevant procedural PE. Methods & Results This is a nationwide retrospective observational cohort study based on data on 51.599 patients from the Danish Pacemaker Register. Included were all Danish patients who received their first PM, CRT or ICD from 2000 – 2018. Procedural PE was defined related to the invasive procedure if it occurred within 1 months after the invasive procedure and no cancer was diagnosed before the procedure. Pre-specified risk factors, including sex, age, year, implantation center-type and device type were analyzed by multivariable logistic regression models to estimate the association with PE. A total of 78 (0.2%) patients were diagnosed with procedural PE, with a median age of 73 years and 43% were females. In adjusted logistic regression analysis age > 70, heart failure [aOR 1.64 (1.01;2.67)], ischemic heart disease [aOR 1.84 (1.13;2.99)], direct oral anticoagulation [aOR 1.77 (1.13–2.77.)], amiodarone use [aOR 3.03 (1.75–5.22)], beta blocking agent [aOR 2.26 (1.23 –4.14)], university hospitals [aOR 2.59 (1.18 –5.67)] and PM implantation [aOR 3.38 (1.77;6.45)], were associated with PE. Conclusion Procedural PE is a rare complication after CIED implantation in Denmark. Importantly most of the risk factors for PE are modifiable. Optimizing the modifiable risk factors may reduce the risk of complication.

Funding Acknowledgements Type of funding sources: None. Background To lower the risk of sudden cardiac death, patients with Brugada Syndrome (BrS) are recommended to avoid intake of drugs known to increase the risk of arrhythmias or the development of type-1 BrS ECG. However, information on adherence to these recommendations among patients with BrS is limited. Purpose To examine treatment with non-recommended drugs before and after diagnosis with BrS, risk factors of treatment with these drugs, and whether treatment was associated with a higher risk of hospitalization with ventricular arrhythmias or death. Methods All patients diagnosed with BrS in Denmark (1995-2018) with >12 months of follow-up were identified through nationwide registries using the ICD-10 diagnosis code DI472M (PPV 95.8%). Relevant BrS risk drugs were identified and grouped as drugs to "avoid" or "preferably avoid" in agreement with the likelihood of promoting arrhythmias and type-1 BrS ECG according to brugadadrugs.org(1) (accessed August 2021). Multiple logistic regression (adjusted for sex, age, year of diagnosis, and relevant comorbidities and drugs) was performed to identify factors associated with risk drug use during follow-up. Results We identified 270 patients with BrS. Median age at the time of diagnosis was 46.2 years [IQR 32.6-57.6], 70.4% were male. Before the time of diagnosis, 16 patients (5.9%) were treated with a drug to "avoid" or "preferably avoid" (n=5 and n=12, respectively). During a median follow-up of 79 months, 89 patients (33%) were treated with at least one BrS risk drug after the time of diagnosis (table). A total of 22 patients with BrS (8.1%) received ≥2 different drugs at any time during follow-up. There was no significant difference in proportions of patients receiving a risk drug the year prior to diagnosis (12.2%) compared to each of the five years following diagnosis (year 1-5, respectively: 12.2%; 9.7%; 12.3%; 13.6%; 13.5% (p>0.05 for all)). Females had an odds ratio (OR) of 2.21 [95% CI 1.21-4.03] for use of risk drugs. Also associated with a greater likelihood of risk drug use after diagnosis were having a psychiatric disease at baseline (OR=4.80 [1.72-13.41]) and any use of a risk drug within 90 days prior to diagnosis (OR=8.54 [2.13-34.31]) (figure). During follow-up, six patients were hospitalized for ventricular arrhythmias; none had redeemed a prescription of a risk drug. In total, 12 patients died, of which five (41.7%) had redeemed a prescription of one or more risk drugs within 50 days of death. Conclusions 1/3 patients with BrS received a risk drug at any time point after diagnosis. No change in proportions of patients treated with risk drugs was identified after time of diagnosis. 5/12 patients that died during follow-up had redeemed a prescription of one or more risk drugs within 50 days of death. Female sex, any psychiatric diagnosis, and use of a non-recommended drug before diagnosis with BrS were associated with a greater likelihood of risk drug use after diagnosis.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation The Danish Foundation TrygFonden Background Clinical decision-making in patients with out-of-hospital cardiac arrest (OHCA) admitted to the hospital is challenging, and multiple scoring systems have been developed to predict survival. The NULL-PLEASE score (Nonshockable rhythm, Unwitnessed arrest, Long no-flow or Long low-flow period, blood pH 7.0 mmol/L, End-stage renal disease on dialysis, Age ≥85 years, Still resuscitation, and Extracardiac cause) may be able to identify patients with OHCA who are unlikely to survive; however, this score system have not previously been tested in a nationwide setting. Purpose The aim of this study was to validate the NULL-PLEASE clinical score to identify patients with OHCA in the Danish population who are unlikely to survive. Methods We retrospectively validated the predictive ability of the NULL-PLEASE score, using Danish nationwide registry data from 2001-2015. We identified OHCA survivors who had return of spontaneous circulation (ROSC) or ongoing cardiopulmonary resuscitation at hospital arrival and all NULL-PLEASE score parameters available. The primary outcome was 1-day mortality, and the secondary outcome was 30-day mortality. Outcomes were estimated using multivariable logistic regression with a NULL-PLEASE score of zero as reference. Results A total of 868 patients with all NULL-PLEASE score parameters available was included in the analysis. Overall, 1-day mortality was 33%, and 30-day mortality was 62%. A NULL-PLEASE score >0 (assessed as a continuous variable) was associated with significantly increased 1-day mortality (odds ratio (OR): 1.62, 95% confidence interval (CI): 1.51-1.74) as well as significantly increased 30-day mortality (OR: 1.80, 95% CI: 1.66-1.96). Figures 1 and 2 show the ROC curves of NULL-PLEASE and 1-day mortality and 30-day mortality, respectively. Area under the curve (AUC) for 1-day mortality was 0.81, and AUC for 30-day mortality was 0.83. Assessed categorically, a NULL-PLEASE score ≥5 was associated with a particularly high OR for mortality: 1-day mortality (OR: 7.46, 95% CI: 5.42-10.27), and 30-day mortality (OR: 10.596, 95% CI: 7.32-15.33). Conclusions In a large nationwide OHCA-cohort, we found that a NULL-PLEASE score >0 was associated with higher 1-day mortality as well as higher 30-day mortality.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation The Danish Foundation TrygFonden Background Serum potassium levels outside the normal range are associated with increased short-term mortality in patients with acute cardiovascular disease such as acute heart failure. In survivors of out-of-hospital cardiac arrest (OHCA), the initial serum potassium concentration is often outside the normal range. However, it is unknown whether there is an association between initial serum potassium level and short-term mortality in OHCA survivors. Purpose The aim of this study was to describe potential associations between serum potassium level and 30-day survival in patients surviving OHCA. Methods We identified 1630 patients who had return of spontaneous circulation (ROSC) at hospital arrival, and a registered post-OHCA serum-potassium value, using Danish nationwide registry data from 2001-2015. Thirty-day survival was analyzed according to the following seven predefined potassium levels: 6.0 mmol/L. Thirty-day survival was estimated using a multivariable Cox regression (reference normokalemia 3.5–4.6 mmol/L). The multivariable model included age, sex, Charlson comorbidity index, witnessed status, performance of CPR and first registered heart rhythm. Results During 30-day follow-up, survival in the seven strata was 29 (55.8%), 52 (61.9%), 167 (63.3%), 543 (58.7%), 66 (35.5%), 12 (28.6%), and 18 (23.4%), respectively. Standardized average risk ratios (ARR) of 30-day survival was significantly lower for all groups with hyperkalemia compared with normokalemia: 4.7-5.5 mmol/L: (ARR: 0.86, 95% confidence interval (95% CI): 0.74–0.96); 5.5-6.0 mmol/L: (ARR: 0.76, 95% CI: 0.52–0.98); >6.0 mmol/L: (ARR: 0.64, 95% CI: 0.50–0.79). Survival did not differ significantly in patients with hypokalemia compared with normokalemia: Conclusions In OHCA survivors, hyperkalemia was associated with reduced 30-day survival compared with normokalemia. This association was independent of age, sex, Charlson comorbidity index, witnessed status, performance of CPR and first registered heart rhythm. Conversely, hypokalemia was not associated with reduced 30-day survival in this patient population.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The study was supported by The Innovation Fund Denmark [12-135225], The Research Foundation for the Capital Region of Denmark [no grant number], The Danish Heart Foundation [11-04-R83-A3363-22625], Aalborg University Talent Management Programme [no grant number], Arvid Nilssons Fond [no grant number], Skibsreder Per Henriksen, R. og Hustrus Fond [no grant number], Medtronic [no grant number], and the AFFECT-EU consortium which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 847770. Background The interest in heart rhythm monitoring and technologies to detect arrhythmia is increasing. The prevalence and prognostic significance of subclinical bradyarrhythmias is unknown. Objectives To assess the accidental diagnosis of bradyarrhythmia and its subsequent treatment and prognostic impact in persons screened for atrial fibrillation compared to unscreened persons. Methods We utilized a randomized trial of ≥70-year-olds with cardiovascular risk factors recruited outside the hospital setting to receive implantable loop recorder screening for atrial fibrillation (ILR group) vs. usual care (Control group). Time-to-event analyses were performed for bradyarrhythmia, pacemaker implantation, syncope, and sudden cardiovascular death. Results A total of 6004 participants were randomized (mean age 75 years, 47% women, 91% with hypertension, 20% with prior syncope), 4503 to Control and 1501 to ILR. The median follow-up period was 64.5 [59.3, 69.8] months. A total of 675 deaths occurred with an overall rate of 2.16 (2.00-2.33) per 100 person-years, and 67 sudden cardiovascular deaths occurred with a rate of 0.21 (0.15-0.28) for the Control group and 0.23 (0.14-0.37) for the ILR group (hazard ratio (HR) 1.11 (0.64-1.90), p=0.71)). The overall rate of incident bradyarrhythmia was 1.63 (1.49-1.79) per 100 person-years, and bradyarrhythmia was diagnosed in 172 (3.82%) and 312 (20.8%) participants in the Control and ILR group, respectively (HR 6.21 (5.15-7.48), p Overall, a pacemaker was implanted in 132 (2.93%) and 66 (4.40%) participants (HR 1.53 (1.14-2.06), p Conclusions Bradyarrhythmias are highly common in ≥70-year-olds with cardiovascular risk factors. Compared to Control, ILR monitoring led to a six-fold increase in diagnosis of bradyarrhythmia and a significant increase in pacemaker implantations, but no change in the risk of syncope or sudden death.

Background Early identification of individuals at risk of out-of-hospital cardiac arrest (OHCA) remains difficult. Little is known about symptoms presented when contacting a medical helpline prior to OHCA. Aim To examine the registered prodromal symptoms when patients phoned to seek medical help prior to OHCA. Methods OHCA patients (≥18 years) were identified from the Danish Cardiac Arrest Registry (2014–2018) and linked with calls to the non-emergency (1813-Medical Helpline) and Emergency Medical Services 1–1-2 (112). We examined (1) symptoms registered within 30 days before OHCA, categorized into eight groups and stratified by time-period and call-type; (2) hospital diagnoses and medical prescriptions according to symptom groups within 180 days before these calls. Results Among 974 OHCA patients who called in total within 30 days before OHCA, 816 OHCA patients (males 57%, median age 76 years [Q1-Q3: 65–84]) had a registered symptom and some of them called more than once (1,145 calls by 816 patients). Overall, the most reported group of symptoms was “Other” (29%), containing a diverse group of prodromal symptoms registered by the caregiver that did not fit into the other categories (Figure), followed by breathing problems (15%). When stratified by time-period (Figure) the most common symptom group remained “Other”. This was followed by symptoms related to the Central Nervous System (CNS)/Unconsciousness (17%) for the time-period within 0–7 days before OHCA, and by breathing problems (19%) and trauma/exposure (17%) for the time-period within 8–30 days before OHCA (Figure). When stratified by call-type, most patients (60.8%) called the 1813-Medical Helpline, where “Other” (35%) and abdominal/back/urinary (14%) symptom groups were the most common. While breathing problems (24%) and CNS/Unconsciousness (21%) were highly reported among calls to 112. Within 180-days before contact with the medical helpline, independently of the symptom group presented, respiratory-related hospital diagnoses and antibiotic medications were common. Conclusions Patients with OHCA who called emergency and non-emergency medical helpline 30 days before OHCA had diverse prodromal symptoms; the largest category were “Other” symptoms, followed by breathing-related symptoms. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union's Horizon 2020 under the ESCAPE-NET program;Helsefonden Figure 1. Classification of the prodromal symptoms among patients that called for medical assistance. Stratified by the time-period within 0–7 days and 8–30 days before OHCA. The number of calls within 0–7 days before OHCA = 471 (399 patients), and the number of calls within 8–30 days before OHCA = 674 (500 patients).

ObjectiveIt remains unknown whether patient socioeconomic factors affect interventions and survival after out-of-hospital cardiac arrest (OHCA), and whether a socioeconomic effect on bystander interventions affects survival. Therefore, this study examined patient socioeconomic disparities in prehospital factors and survival.MethodsFrom the Danish Cardiac Arrest Registry, patients with OHCA ≥30 years were identified, 2001–2014, and divided into quartiles of household income (highest, high, low, lowest). Associations between income and bystander cardiopulmonary resuscitation (CPR) and 30-day survival with bystander CPR as mediator were analysed by logistic regression and mediation analysis in private witnessed, public witnessed, private unwitnessed and public unwitnessed arrests, adjusted for confounders.ResultsWe included 21 480 patients. Highest income patients were younger, had higher education and were less comorbid relative to lowest income patients. They had higher odds for bystander CPR with the biggest difference in private unwitnessed arrests (OR 1.74, 95% CI 1.47 to 2.05). For 30-day survival, the biggest differences were in public witnessed arrests with 26.0% (95% CI 22.4% to 29.7%) higher survival in highest income compared with lowest income patients. Had bystander CPR been the same for lowest income as for highest income patients, then survival would be 25.3% (95% CI 21.5% to 29.0%) higher in highest income compared with lowest income patients, resulting in elimination of 0.79% (95% CI 0.08% to 1.50%) of the income disparity in survival. Similar trends but smaller were observed in low and high-income patients, the other three subgroups and with education instead of income. From 2002 to 2014, increases were observed in both CPR and survival in all income groups.ConclusionOverall, lower socioeconomic status was associated with poorer prehospital factors and survival after OHCA that was not explained by patient or cardiac arrest-related factors.

Background Influenza infection is associated with an increased risk of acute myocardial infarction (AMI) and stroke. It is currently unknown whether influenza vaccination may reduce mortality in patients with hypertension. Purpose To determine whether influenza vaccination is associated with lower risks of death in hypertensive patients without significant cardiovascular or other chronic disease. Methods Using nationwide registers, we identified all patients with hypertension in Denmark during 9 consecutive influenza seasons in the period 2007–2016 who were treated with at least 2 different classes of antihypertensive medication (beta-blockers, diuretics, calcium antagonists or renin-angiotensin system inhibitors). Patients who were not 18–100 years old or had ischemic heart disease, heart failure, chronic obstructive lung disease, cancer or cerebrovascular disease were excluded. Prior to each influenza season we assessed the exposure to influenza vaccination. End-points were death from all causes, from AMI or stroke, or cardiovascular death. For each season, patients were followed from December 1 until April 1 the next year, spanning the period of high influenza activity in Denmark. Results A total of 608,452 Patients were followed for a median of 5 seasons (interquartile-range: 2–8 seasons), with total follow-up time of 975,902 person-years. The vaccine coverage during study seasons ranged from 26% to 36%. During follow-up, 21,571 patients died of all-causes (3.5%), 12,270 patients died of cardiovascular causes (2.0%) and 3,846 patients died of AMI/stroke (0.6%). Vaccination was associated with older age, Diabetes Mellitus, atrial fibrillation, lower educational level, lower income and higher medication use. In unadjusted analysis considering all seasons, vaccination was significantly associated with increased risk of all-cause death, cardiovascular death and death from AMI/stroke. However, following adjustment for season, age, sex, comorbidities, medications, income, education, and more, vaccination was significantly associated with reduced risks of all-cause death, cardiovascular death and death from AMI/stroke (Figure). PY, person-years. Conclusion In a nationwide study spanning 9 consecutive influenza seasons including more than 600,000 hypertensive patients without significant cardiovascular disease identified through medication use, influenza vaccination was significantly associated with a reduced risk of death from all-causes, cardiovascular causes and AMI/stroke. Influenza vaccination may improve patient outcome in hypertension. Acknowledgement/Funding Daniel Modin was supported by the Herlev & Gentofte University Hospital Internal Research Fund and by the Novo Nordisk Foundation.

Aims To study the long-term prognostic information obtained from an exercise test following an acute myocardial infarction. Methods Between 1979 and 1983, 1773 consecutive patients were admitted to Glostrup County Hospital with an acute myocardial infarction. Of 1430 patients who were alive after 3 weeks, 718 performed an exercise test. Survival data were available after 15 years for all patients. Results Participation in an exercise test was associated with a risk reduction of death of 56% (95% confidence interval, 49–65%) when adjusting for known differences between the groups. Among patients who performed the test, most indicators of ischaemia were without prognostic information. Exercise tolerance, expressed in metabolic equivalents, was the best predictor of future mortality (relative risk 0·86 for an increase of one metabolic equivalent (0·80–0·92)). Only ST-segment depression of 2mm or more could identify a population with an increased risk of death (relative risk 1·45 (1·08–1·95)). Conclusion Patients who perform an exercise test after acute myocardial infarction are a low risk population compared to those who do not perform it. The detection of ischaemia during the test is of marginal prognostic value. Exercise capacity is the most powerful predictor of death that can be obtained from the test.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Innovation Fund Denmark Background and aims Stroke is a leading cause of mortality and disability, and atrial fibrillation (AF) is an important and potentially modifiable risk factor for stroke. AF screening can substantially increase the amount of patients diagnosed and treated, but randomized trials have yet to demonstrate a significant decrease in strokes following screening. N-terminal prohormone of brain natriuretic peptide (proBNP) is an established biomarker for AF and could potentially be used to select patients for screening. We a used randomized trial of AF screening vs usual care to investigated the usefulness of proBNP as a tool to select patients for screening to prevent outcomes. Methods The LOOP Study randomized AF-naïve individuals aged >70 years with additional stroke risk factors in a 1:3 ratio to either continuous AF screening using implantable loop recorder (ILR) with initiation of anticoagulation upon detection of AF, or usual care. In this post-hoc analysis, study participants with a baseline measurement of proBNP were included, and the effect of screening vs usual care was compared in groups according to proBNP tertiles. Results Of 6004 participants randomized, 5819 (97%) had proBNP measured. The tertiles of proBNP were at A total of 1014 participants (17.4%) were diagnosed with AF (ILR 32.1% vs Control 12.5%), and 310 (5.3%) endured a stroke or systemic arterial embolism (SAE) (ILR 4.5% vs Control 5.6%). In the lower two tertiles of proBNP, 13% were diagnosed with AF (ILR 26.6% vs Control 8.3%), and 4.6% endured a stroke or SAE (ILR 4.6% vs Control 4.6%), whereas in the highest tertile of proBNP, 25.9% were diagnosed with AF (ILR 42.9% vs 20.3%), and 6.73% endured a stroke or SAE (ILR 4.4% vs Control 7.5%). In the lower two tertiles of proBNP, there was no protective effect from AF screening as compared with usual care (hazard ratio (HR) 1.00 (95% CI 0.71-1.41), p=0.999), whereas in the highest tertile of proBNP there was a significant effect of screening (HR 0.59 (95% CI 0.37-0.93), p=0.021) (Figure 2). More details including proBNP cutoffs, and the impact on stroke subtypes, disability and mortality will be presented at the Congress. Conclusions In a population at increased risk of stroke, proBNP pose a useful biomarker to select individuals for AF screening to prevent stroke. In persons with increased proBNP, the effect of screening could be significant, whereas there is no signal towards effects from screening in people with normal proBNP levels.