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Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Novo Nordisk Introduction Both atrial fibrillation (AF) and obesity have reached epidemic proportions. Obesity is an established risk factor in acute myocardial infarction (AMI), de novo AF, and AF recurrence after ablation. AF increase the risk of stroke, heart failure (HF), and death. The link between body mass index (BMI) and incident stroke, HF, AMI, or death in an AF ablation population is unknown. Purpose To examine incident stroke, HF, AMI, or death by BMI. Method Using Danish nationwide registries, all Danish patients above 18 years who underwent first-time AF ablation from January1st 2010 to December31st 2018 were identified and included at the date of ablation. Underweight patients (BMI < 18.5) were excluded. Exposure of interest was BMI and patients were stratified as normal-weight (BMI 18.5-24.9), overweight (BMI 25.0 – 29.9), obese (30.0 – 34.9), and morbidly obese (BMI ≥ 35.0). The primary endpoint was combined of either first-reached incident stroke, HF, AMI, or death. The 5-year cumulative incidence of the primary endpoint stratified by BMI, was estimated using the Aalen-Johansen estimator. The relative rates were examined using normal-weight as reference in both univariate- and multivariate-Cox models adjusted for prior HF, hypertension, age, diabetes, prior stroke, prior atherosclerotic vascular disease, and sex. Results The study cohort consisted of 7,701 patients. Median age [IQR] decreased from 64 [57, 70] to 60 [53, 66] in normal-weight and morbidly obese respectively. The prevalence of HF, ischemic heart disease, diabetes, and hypertension increased by BMI while prior stroke remained stable. Use of oral anticoagulants remained stable at around 98%. In total 1,285 patients reached the primary endpoint. By decreasing order, the most frequent endpoints were HF (564, 44%), AMI (431, 34%), stroke (199, 15%), and death (91, 7%). The cumulative incidence of the primary endpoint increased incrementally from 15%, 16%, 19%, and 21% from normal-weight to morbidly obese respectively (Figure 1). In the univariate analysis, the Hazard ratio (HR, [95% confidence interval]) increased incrementally from 1.03 [0.90 to 1.18], 1.28 [1.10 to 1.49], 1.43 [1.17 to 1.74] in overweight to morbidly obese respectively (Figure 2). In the multivariate analysis no significant differences were found. The HRs were 0.94 [0.82 to 1.08], 1.05 [0.89 to 1.23], 1.01 [0.82 to 1.24] in the overweight to morbidly obese respectively (Figure 2). Conclusion When identifying obese and morbidly obese AF ablation patients in clinical practice, the risk of either stroke, HF, AMI, or death is higher compared to normal-weight AF ablation patients, but only due to the underlying comorbidities.

Funding Acknowledgements Type of funding sources: None. Background Hypertrophic cardiomyopathy (HCM) is a common genetic cardiovascular disorder; however, detection rates remain low. While most patients are only mildly symptomatic, some develop serious complications such as heart failure (HF), atrial fibrillation (AF), and sudden cardiac death (SCD). Given the possibility of severe outcome, a large focus is put on early detection and prevention of possible HCM related complications. Syncope has long been one of these factors associated with increased risk of SCD, however little concrete data on the impact and consequences of prior syncope in a large HCM population exist. Objectives To determine the risk of ventricular tachycardia (VT), cardiac arrest (CA) and death in patients with HCM and prior history of syncope compared to HCM patients without syncope. Methods All patients aged ≥16 years diagnosed with HCM from 2005 - 2018 were identified in the Danish National Registers and included at first time diagnosis. All admissions or prior presentation of syncope were registered and analyzed for the outcome of a combined endpoint comprising occurrence of VT, CA or death. The association between HCM, syncope and the combined endpoint were investigated using multivariable cox proportional-hazard analysis adjusted for gender, age, and comorbidities. Cumulative incidence of the combined endpoint was calculated using the Aalen-Johansen estimator. Results In this study 3,856 HCM patients were included (median age 68 years [IQR 56-78]) with near equal gender distribution (males 53%, females 47%). Overall 361 (9%) of patients had a registered contact for syncope prior to HCM diagnosis. A total of 1356 patients (35%) reached the combined endpoint. Of those patients with prior syncope 163 patients (45%) reached the endpoint, compared to 1193 patients (34%) who had no registered syncope prior to HCM diagnosis. Univariate analysis showed a significantly increased risk (HR 1.5 (CI 1.3-1.8) p = Conclusion Although there was a significant increased rate of HCM patients with prior syncope reaching the combined endpoint of ventricular tachycardia, cardiac arrest and death, multivariate analysis showed this association to be mainly driven by comorbidity and age. In this cohort males with prior syncope were at a significantly higher risk of reaching the combined endpoint. More research will be needed to explore this disparity.

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 Percutaneous left atrial appendage occlusion (LAAO) is increasingly used for stroke prevention in high-risk patients with atrial fibrillation and contraindication for oral anticoagulation. However, studies evaluating comorbidities and mortality remain scarce. Objectives The aim of this study was to evaluate changes in patient characteristic over time and 1-year risk of death. Methods Using Danish nationwide registers, we included all patients undergoing first-time LAAO between 2013 and 2021. To evaluate changes in patient characteristics, the study population was stratified according to calendar year of LAAO procedure: 2013–2015, 2016–2018, and 2019–2021. Baseline patient characteristics were defined from 10 years prior to date of LAAO procedure. Antithrombotic therapy was defined as claimed prescriptions within 180 days prior to LAAO procedure. Patients were then followed until either emigration, death, one year of full follow-up, or end of study period. Baseline frailty risk was estimated with The Hospital Frailty Risk Score, a validated frailty risk assessment tool based on ICD-10 codes. The 1-year unadjusted risk of death was estimated with the Aalen-Johansen method. Results In total, 1,306 patients underwent LAAO. The number of LAAO increased from 201 procedures in 2013–2015 to 586 in 2019–2021. During follow-up, the age of the patients remained stable (2013–2015: median age: 70 years; 2016–2018: median age 69 years; 2019–2021: median age 69 years). Fewer patients had a history of ischemic stroke (2013–2015: 44.3% vs 2019–2021: 27.6%), hemorrhagic stroke (2013–2015: 32.8% vs 2019–2021: 21.0%), and previous bleeding (2013–2015: 71.1% vs 2019–2021: 59.2%). Median CHA2DS2-VASs score decreased over time (2013–2015: 4 vs 2019–2021: 3) and same trend was found in median HAS-BLED score (2013–2015: 3 vs 2019–2021: 2). In addition, fewer patients were categorized as high frailty risk (2013–2015: 16.9% vs 2019–2021: 8.9%). However, there was an increase in patients with a history of cancer (2013–2015: 11.9% vs 2019–2021: 18.9%). The use of antiplatelet therapy prior to LAAO decreased while the use of oral anticoagulation increased (2013–2015: 50.2% vs 2019–2021: 68.9%) due to a marked increase in non-vitamin K antagonist oral anticoagulants and a decrease in vitamin K antagonists (Figure 1). In total, 88 (7.22%) patients died within one year of LAAO procedure. The 1-year all-cause mortality risk in each period were similar (2013–2015: 7.0%; 2016–2018: 7.1%; 2019–2021: 6.9%). [Figure 2] Conclusion In the years 2013–2021, the annual number of LAAO procedures increased. The age of patients remained stable. Comorbidity burden decreased and fewer patients were at high frailty risk, but the 1-year mortality risks were similar. Our real-life data suggest that profiles of patients undergoing LAAO has changed considerably over time. Funding Acknowledgement Type of funding sources: None.

Background The last four decades witnessed substantial improvements in treatment of congenital heart disease (CHD) leading to most children surviving into adulthood. Currently, the number of adults with CHD surpasses that of children. The shift in the CHD population's age composition necessitates focusing on long-term problems. A significant, but not well-investigated, issue is the risk of out-of-hospital cardiac arrest (OHCA) in adults with CHD. Purpose To investigate overall and temporal changes in the rate of OHCA associated with CHD compared with the general population. Method We conducted a nested case-control study matching all adult patients with OHCA of presumed cardiac cause between 2001 and 2015 with up to five controls from the entire Danish population on age, sex, date of OHCA and cardiac comorbidities status (at least one among ischemic heart disease, heart failure and presence of implantable cardioverter-defibrillator). Patients with CHD were identified using in- and out-patient hospital diagnoses any time prior to OHCA and divided into two mutually exclusive subgroups, either non-severe or severe CHD. The subclassification of CHD is based on a hierarchical approach previously used, where at least one severe CHD diagnosis is required to be classified as severe. We used Cox regression models to compute hazard ratios (HRs) and 95% confidence intervals (CI) of OHCA. We stratified on CHD status (non-severe, severe or control), sex and OHCA year group (2001–2008 vs 2009–2015). Results We included 35,005 OHCA cases and 175,025 controls: the median age was 72 years, 66.9% were male and 34.6% had cardiac comorbidities. In total, among cases, we identified 103 patients with non-severe CHD and 51 with severe CHD, while, among controls, 247 with non-severe CHD and 69 with severe CHD. Both non-severe and severe CHD were overall associated with higher rates of OHCA compared with the general population: HR 2.11 (95% CI, 1.68–2.66) and HR 3.93 (95% CI, 2.71–5.69), respectively (Figure A). We found similar results when we stratified the analyses according to the presence of cardiac comorbidities at date of OHCA (Figure B) and sex. When stratified by OHCA year group, we observed stable rates of OHCA associated with non-severe CHD: from HR 2.03 (95% CI, 1.36–3.03) in the period 2001–2008 to HR 2.15 (95% CI, 1.62–2.86) in the period 2009–2015. Conversely, we observed a trend towards decreasing rates of OHCA associated with severe CHD: from HR 5.04 (95% CI, 2.79–9.11) in the period 2001–2008 to HR 3.10 (95% CI, 1.80–5.19) in the period 2009–2015 Conclusions Non-severe and severe CHD were both associated with higher rates of OHCA compared with the general population. While we observed decreasing rates of OHCA over calendar year for severe CHD, they remained stable for non-severe CHD. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Gentofte University Hospital, Hellerup, Denmark

Introduction Risk of cardiovascular events following myocardial infarction (MI) is high, and secondary preventive treatment is largely focused on reducing future cardiovascular risk. As gradual implementation of guideline-based treatments successfully leads to improved survival, long-term non-cardiovascular morbidity is likely of rising importance following MI. Purpose To determine the long-term risk of non-cardiovascular morbidity in a contemporary MI population with the aim of informing the need for and scope of prolonged surveillance. Methods We included all patients with a first-time MI in Denmark from 2001–2018 matched on age, sex, and date of discharge with up to 4 general population controls. We used the Aalen-Johansen estimator to estimate 1-year and 5-year risk of non-cardiovascular morbidity with death as a competing risk. Non-cardiovascular morbidity was defined as an in-patient hospital admission for any primary cause excluding cardiovascular diagnoses (International classification of diseases, 10th revision codes: I00–99). We also calculated 2-year and 6-year risks of non-cardiovascular morbidity in a stable population of post-MI patients and matched controls, i.e., participants alive with no hospital admissions for 1 full year following study entry. Finally, we estimated 1-year and 5-year risks of cause-specific non-cardiovascular morbidity. Results A total of 124,072 patients with MI who survived to hospital discharge were matched with 496,277 general population controls. Median age was 68 years and 35.5% were female. The 1-year and 5-year risk of non-cardiovascular morbidity was elevated for patients with MI compared to controls: 38.6% (95% confidence interval: 38.3–38.9) vs 15.3% (15.2–15.4) and 64.8% (64.6–65.1) vs 45.8% (45.7–45.9), respectively (Figure 1). Regarding cause-specific morbidity, risks of respiratory disease, gastrointestinal disease, and infectious disease particularly were high (Figure 2). For example, 1-year risk of infection was 4.5% for patients with MI and 1.8% for controls and 5-year risk of respiratory disease was 16.3% for patients with MI and 9.7% for controls. Furthermore, in the stable population (patients with MI, n=50,144; controls, n=159,467, median age 64 years, 33.0% female), risk of non-cardiovascular morbidity remained elevated at 2 years (17.2% [16.8–17.5] vs 11.3% [11.1–11.5]) and 6 years (49.2% [48.7–49.7] vs 39.8% [39.6–40.1]) post MI (Figure 1). Conclusions Risk of non-cardiovascular morbidity was high in patients following myocardial infarction, particularly for respiratory disease, gastrointestinal disease, and infectious disease. The risk remained elevated during long-term follow up. The study highlights the importance of additional focus on non-CV morbidity to further improve outcomes. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Danish Heart Foundation

Background Antiplatelet therapy has been shown to reduce adverse cardiovascular (CV) events in patients with PAD, but despite the well-established medication benefit, large-scale epidemiological data evaluating antiplatelet agent of choice with low bleeding risk and high antithrombotic effect is sparse. Purpose We explored Danish healthcare registers to examine guideline-recommended antiplatelet therapy and associated risk of adverse CV outcomes in patients with PAD. Methods All patients with a first-time diagnosis of PAD between January 1, 1997 and December 31, 2016 were identified. Patients alive six months after diagnosis were divided into four treatment groups: aspirin, clopidogrel, dual therapy (DAPT), and no antiplatelet therapy. Logistic regression models were used to estimate 1-year risk of myocardial infarction (MI), stroke, CV death, all-cause mortality, and gastrointestinal (GI) bleeding. Results We identified a total of 85,771 PAD patients [median age 70.6 (IQR 63–77 years), 52% male]. The results suggest that compared to no antiplatelet therapy, use of clopidogrel alone significantly decreased 1-year risk of incident MI, stroke, CV death and all-cause mortality with odds ratios 0.56 (CI 0.46–0.68), 0.69 (CI 0.59–0.81), 0.72 (CI 0.56–0.94), and 0.79 (CI 0.65–0.97) respectively. Likewise, aspirin monotherapy was associated with only a marginal reduction in 1-year risk of stroke by 11% and all-cause mortality by 7%. Odds ratios for GI bleeding were estimated to be 1.18 (CI 1.04–1.34), 1.34 (CI 0.94–1.91), and 1.54 (CI 1.05–2.26) for aspirin, clopidogrel, and DAPT groups, respectively. Conclusion In this nationwide study, clopidogrel is associated with significantly reduced risk of MI, stroke, CV death and all-cause mortality with low risk of bleeding and appears to support clopidogrel as antiplatelet agent of choice for CV risk reduction in patients with PAD. Funding Acknowledgement Type of funding sources: None.

Introduction Guidelines recommend antiarrhythmic drugs (AAD) before ablation for atrial fibrillation (AF). However, recently published randomized clinical trials have demonstrated that ablation is more effective in maintaining sinus rhythm compared to AAD as first line therapy. Therefore, data pertaining the impact of early ablation on AF recurrence in large, unselected cohorts is highly warranted. Purpose To examine clinically relevant AF recurrence after ablation by time from AF diagnosis to ablation. Method Using Danish nationwide registries, all Danish patients above 18 years who underwent first-time AF ablation from January1st 2010 to December31st 2018 were identified and included at the date of ablation. The patients were categorized by time from diagnosis with AF to ablation. Recurrent AF was defined using a composite endpoint comprising claimed prescriptions of AAD, hospital admissions due to AF, re-ablation, or electrical cardioversions. The cumulative incidence of recurrent AF by time from diagnosis to ablation at 1-year follow-up after a blanking period of 90 days, was estimated using the Aalen-Johansen estimator, taking death as a competing risk into account. The relative rates of recurrent AF by time from diagnosis to ablation were examined using Cox models adjusted for sex, age, procedure-year, heart failure, ischemic heart disease, chronic obstructive pulmonary disease, chronic kidney disease, hypertension, and diabetes. Results The study cohort consisted of 8,098 patients. Median age [IQR] increased from 60 [52 to 66] in the early ablation group (AF ablation within 1 year after diagnosis) to 64 [57 to 70] in the late ablation group (ablation at least 3 years after diagnosis). The number of patients with a CHA2DS2-VASc score of 2 or more increased from 44% in the early ablation group to 51% in the late ablation group. Use of amiodarone remained stable, while use of Class IC anti-arrhythmic medication increased by time from diagnosis to ablation. Figure 1 shows the 1-year cumulative incidence of recurrent AF, hazard ratios (HR), and 95% confidence intervals (95% CI) stratified by time from diagnosis to ablation in years and depict that the risk of recurrent AF increased incrementally and significantly by time from diagnosis to ablation compared to the early ablation group. Figure 2 shows the 1-year cumulative incidence of recurrent AF, hazard ratios (HR), and 95% confidence intervals (CI 95%) stratified by time from diagnosis to ablation in months and depict that very early ablation (within 6 months) is associated with less recurrent AF. Conclusion In this large nationwide study examining recurrent AF post ablation, recurrence rates of AF increased incrementally according to time from AF diagnosis to AF ablation. Early ablation could potentially provide substantial benefits and improve outcomes after ablation, indicating ablation as first-line therapy might be more ideal. Funding Acknowledgement Type of funding sources: None.

Background The optimal management of patients with non-ST elevation acute coronary syndromes (NSTEACS) remains a challenge. The merits of both computed tomography angiography (CTA) as a rule-out test for significant coronary artery disease and early invasive coronary angiography (ICA) are debated. Furthermore, there are limited data in older NSTEACS patients, who likely have more coronary artery calcification and are at higher risk of ACS-related complications. Methods This is a post hoc analysis of patients ≥75 years included in the Very Early Versus Standard Care Invasive Examination and Treatment of Patients with Non-ST-Segment Elevation Acute Coronary Syndrome Trial (VERDICT). The diagnostic accuracy of CTA was investigated in patients without previous coronary artery bypass grafting, renal dysfunction, or atrial fibrillation; the presence of a coronary artery stenosis ≥50% determined by ICA was used as reference. Patients were randomised to very early ICA within 12 hours of diagnosis or standard care (ICA within 48–72 hours of diagnosis) and followed for up to five years. The primary endpoint was the composite of all-cause mortality, nonfatal recurrent MI, hospital admission for refractory myocardial ischaemia or hospital admission for heart failure. Results From November 2010 to June 2016, 2147 patients were included in the VERDICT trial. Of these, 452 (21%) patients were ≥75 years of age. Most older patients had a GRACE score >140 (n=388, 88.8%). At the time of admission, older patients had lower levels of haemoglobin, estimated glomerular filtration rate, and left ventricular ejection fraction, and more often displayed elevated troponins and electrocardiogram changes indicating new ischaemia, than those Of patients ≥75 years of age, 161 (35.6%) underwent CTA before ICA. Older patients had significantly higher calcium scores than younger patients (1187±1445 vs. 499±858 Agatston units, p The primary endpoint was observed more frequently in patients ≥75 years as compared to younger patients (n=222, 49% vs. n=390, 23%, p Conclusion Among patients ≥75 years old with NSTEACS, CTA showed a high diagnostic accuracy. A very early ICA within 12 hours of diagnosis did not improve long-term composite outcome in these older patients with NSTEACS. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Rigshospitalets Research Foundation

Background The majority of patients with Hypertrophic cardiomyopathy (HCM) are mildly symptomatic or unaware of their condition, but some develop serious complications such as heart failure, atrial fibrillation (AF) as well as sudden cardiac death. Previous studies have suggested that HCM detection-rates in women are significantly lower than in men. This leads to diagnosis often being delayed to later stages of the disease in women, where symptoms are more severe. Further characterization of HCM patients to improve early detection of adverse outcomes and warning signs might improve long-term outcomes. Purpose To describe the characteristics of Danish patients diagnosed with HCM between 2005–2018 and determine trends and changes in these factors over time. Methods All patients aged 16 years or older with a diagnosis of HCM between the 1st of January 2005 and the 31st of December 2018 were identified in Danish nationwide administrative registers and included in the study. Time trends were calculated, and differences analyzed using the Cochran-Armitage trend test and linear regression. Results A total of 3856 patients were diagnosed with HCM in the study period and included in the study. The median age at diagnosis was 68 years (IQR 56 and 78 years), 53% were male, and 44% were diagnosed with obstructive HCM, while the number of patients diagnosed with HCM each year overall increased. At the time of diagnosis, 22,3% patients were previously diagnosed with ischemic heart disease, 17% with AF, 7,5% with ischemic stroke, 13,6% with heart failure. Median age and gender distribution remained stable over time, while the proportion of obstructive HCM among the newly diagnosed decreased (p = Conclusion Despite previous studies describing a gender gap in patients diagnosed with HCM, gender distribution was near equal in this cohort. The number of patients diagnosed with non-obstructive HCM is increasing and the prevalence of comorbidities such as heart failure, ischemic heart disease, and COPD decreased over time. Whether these findings are the result of improved early detection of HCM warrants further research and examination. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Herlev-Gentofte Hospital, Denmark

Background Nonsteroidal, selective mineralocorticoid receptor antagonists (MRAs) have been shown to reduce cardiovascular events among patients with diabetic nephropathy, a clinical syndrome characterized by persistent albuminuria. However, prior reports have suggested a substantial underuse of MRAs among eligible patients. In real-life, it is unknown how many have urinary excretion of albumin measured, and the cardiovascular outcomes among type 2 diabetes (T2D) patients with versus without albuminuria is relatively unknown. Purpose To identify candidates eligible for treatment with MRAs and compare the risk of cardiovascular events in real-life T2D patients with albuminuria versus without albuminuria. Methods Using the Danish nationwide registers, we identified all patients ≥18 years old with prevalent T2D at index date 1st January 2015 with an albumin-creatinine ratio (ACR) and a creatinine level measured within 365 days prior to the index date. For each patient, the last ACR and estimated glomerular filtration rate (eGFR) registered prior to the index date were used. eGFR was calculated using the CKD-EPI formula. The patients were separated into two groups consisting of patients with T2D with ACR ≥30 mg/g (albuminuria) or ACR Results A total of 158,904 patients with T2D were identified and of those 74,014 patients (47%) had urinary ACR analyzed within the last year. Of those who had ACR analyzed 29,581 (40%) patients had albuminuria. The absolute 4-year risk of the composite cardiovascular outcome in patients with albuminuria and no albuminuria was 28.6% (95% confidence interval (CI): 28.1–29.1) versus 18.7% (95% CI: 18.4–19.1), respectively. The absolute 4-year risk for the individual components were HF 7.0% (95% CI: 6.7–7.3), MI 4.4% (95% CI: 4.2–4.6), and stroke 7.6% (95% CI: 7.3–7.9) for patients with albuminuria, versus HF 4.0% (95% CI: 3.8–4.2), MI 3.2% (95% CI: 3.1–3.4), and stroke 5.5% (95% CI: 5.3–5.7) for patients with no albuminuria. Conclusion In Denmark, only 47% of patients with T2D had ACR analyzed within a year indicating lack of adherence to the national T2D guidelines. A total of 40% of those who had albuminuria analyzed were eligible for treatment with MRAs based on trial inclusion criteria, and the absolute 4-year risk of experiencing a cardiovascular event was significant. However, patients with no albuminuria still displayed a substantial risk of experiencing a composite event of HF, MI, stroke, and all-cause death. Our analyses may have implications for implementation of new MRAs in patients with T2D. Funding Acknowledgement Type of funding sources: None.

Background Evidence from randomized trials during the previous decades have led to several improvements in acute and secondary preventive treatments for myocardial infarction (MI). However, there is a lack of recent knowledge about the implementation of these treatments and how they affected developments in the long-term prognosis of MI. Purpose To investigate developments in long-term outcomes after first-time MI and their relation to use of guideline-recommended treatments in a contemporary total population cohort. Methods All patients with a first-time MI from 2001 to 2018 were identified through Danish nationwide registries with follow-up through October 6, 2021. The study period was divided into 3-year periods. In each period, the Aalen-Johansen method was used to estimate the absolute 1-year risk for mortality, recurrent MI, heart failure, bleeding hospitalization, and ischemic stroke. The relative frequencies of pharmaceutical treatments and use of coronary procedures were calculated. In each calendar period, the 1-year mortality and recurrent MI risk was standardized to the 2016–2018 distribution of patient characteristics, procedure use, and treatment initiation. Treatment, standardized risks, and recurrent MI risk were evaluated in patients who survived to day 28 post discharge. Results In total, 134,884 patients (median age 69 years, 36.5% female) were included and 120,473 survived to day 28 post discharge (median age 68 years, 35.2% female). From 2001–2003 to 2016–2018, the 1-year risks of mortality (23.5% to 12.1%), recurrent MI (6.8% to 3.2%), and ischemic stroke (1.8% to 1.3%) decreased. Risk of heart failure remained relatively stable, whereas the 1-year risk of bleeding hospitalization increased from 2.1% to 3.0%. This pattern remained consistent during very long durations of follow-up (Figure 1). Initiation of statins (58.0% to 86.4%) and adenosine diphosphate receptor inhibitors (42.5% to 85.6%) increased considerably. Use of coronary angiography (37.3% to 84.5%) and percutaneous coronary intervention (24.8% to 63.5%) also increased. There was an attenuated decrease in the standardized 1-year risks of mortality and recurrent MI compared to the observed reference risks: from 8.7% (reference: 11.1%) in 2001–2003 to 6.1% in 2016–2018 for mortality and from 5.6% (reference: 6.8%) in 2001–2003 to 3.1% in 2016–2018 for recurrent MI (Figure 2). Conclusions There was a substantial improvement in the long-term risk of mortality and recurrent MI for patients with first-time MI. This improved prognosis was related to an increased use of guideline recommended treatments. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Danish Heart Foundation

Background Renal endpoints like end stage renal disease (ESRD) and a 50% decline in estimated glomerular filtration rate (eGFR) have been used in recent randomized clinical trials in heart failure (HF). However, the distribution of these events in larger real-life HF cohorts is unknown Purpose We examined the risk of traditional HF endpoints like death and worsening HF and the risk of these new renal endpoints in HF with and without severe chronic kidney disease (+/−eGFR 30 ml/min/1.73 m2) at the time of diagnosis of HF. Methods From nationwide registries, we identified patients receiving a diagnosis of HF from 2014–2018. Patients were included if they had creatinine available in proximity of the diagnosis (90 days before inclusion). Outcomes comprised of: (i) all-cause mortality, (ii) HF worsening, (iii) end stage renal disease and (iv) sustained 50% eGFR decline. 4-year rates of the primary outcomes were estimated using cumulative incidence function adjusted for competing risk of death, and multivariable Cox proportional hazards models were used to examine the association of covariates with a combined endpoint of the primary outcomes. Results We included 21,959 patients with HF and known CKD status. Median age was 73.9 years, and 7% had an eGFR 0.01 for all) (figure 2). Conclusion The risks of newly introduced renal trial-endpoints in a large real-life cohort of HF patients was low compared to the risks of death or worsening HF if eGFR ≥30 ml/min/1.73 m2 at the time of diagnosis of HF. However, this pattern changed in HF patients with a eGFR Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Herlev/Gentofte Hospital

Background 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) was developed to help identify patients with out-of-hospital cardiac arrest (OHCA) who are unlikely to survive. Although survival after OHCA differs between sexes, the performance of the NULL-PLEASE score according to sex has not been tested previously. Purpose To validate the NULL-PLEASE score separately in men and women in a nationwide setting. Methods Using Danish nationwide registry data from 2001–2019, we retrospectively identified male and female OHCA survivors with return of spontaneous circulation (ROSC) or ongoing cardiopulmonary resuscitation at hospital arrival. The primary outcome was 1-day mortality. Secondary outcomes were defined as 30-day mortality and the combination of 1-year mortality or anoxic brain damage. Logistic regression with a NULL-PLEASE score of 0 as reference was used for outcome risk estimation. The predictive ability of the score was assessed using area under the receiver operating characteristics (AUCROC) curves. Results A total of 2,601 men (median age 67 years (interquartile range (IQR) 56–76 years), and 1,280 women (median age 69 years (IQR 58–79 years) were included. One-day mortality was 31% in men and 42% in women; 30-day mortality was 56% and 71% in men and women, respectively; and 63% of men and 78% of women experienced the combined outcome. For patients with a NULL-PLEASE score ≥9, absolute risks were: 1-day mortality: 82.0% (95% confidence interval [CI]: 75.6–88.4%) for men and 79.1% (95% CI: 71.3–86.8%) for women; 30-day mortality: 98.6% (95% CI: 96.6–100.0) for men and 97.1% (95% CI: 94.0–100.0%) for women; and the combined outcome: 99.3% (95% CI: 97.9–100.0%) for men and 97.1% (95% CI: 94.0–100.0%) for women. AUCROC values for 1-day mortality were 0.827 (95% CI: 0.811–0.844) for men and 0.736 (95% CI: 0.710–0.763) for women. Results were similar for 30-day mortality and for the combined outcome. ROC curves for all outcomes are shown in Figure 1 (men) and Figure 2 (women). For a NULL-PLEASE score cut-point ≥3 to predict 1-day mortality, the positive predictive value was 91.8% in men and 91.1% in women, with a sensitivity of detecting patients who die of 47.3% in men and 51.8% in women. The corresponding negative predictive value for surviving more than 1 day was 54.6% in men and 37.7% in women, and the specificity of detecting patients who survive was 93.7% in men and 85.3% in women. Conclusions In a nationwide OHCA-cohort, the NULL-PLEASE score consistently appeared to perform better in men than in women for all outcomes. Nevertheless, its predictive ability was high among both sexes. Sex-specific differences should not be overlooked in clinical decision-making in patients surviving OHCA. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Danish Heart FoundationThe Danish Foundation TrygFonden

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 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.

Introduction Atrioventricular nodal reentry tachycardia (AVNRT), Wolf-Parkinson-White syndrome (WPW), and Ectopic atrial tachycardia (EAT) are common arrhythmias and associated with lower quality of life. The use of radiofrequency ablation (RFA) treatment has increased over time, however long-term risk of adverse outcomes after RFA in patients with AVNRT, WPW, or EAT is unknown. Purpose To examine the long-term risk of adverse outcomes and need for pacemaker after RFA in AVNRT-, WPW-, and EAT-patients. Methods Using Danish nationwide registries, patients of 18 years or older who underwent RFA for AVNRT, WPW, or EAT between January 1st 2001 and January 1st 2019 were included. Comorbidities and use of antiarrhythmic drugs were analyzed. The cumulative incidences of pacemaker implantation and a combined endpoint of death, thromboembolism (TE), ischemic heart disease (IHD), and heart failure (HF) were estimated at 5-year follow-up using the Aalen-Johansen estimator, taking death as competing risk into account. Results A total of 10.439 patients were enrolled in the study. 6187 patients were treated for AVNRT. The median age was 55 [42, 65] and 40% were male. The WPW group consisted of 2872 patients. The median age was 42 [29, 55] and 61% were male. The EAT group consisted of 1380 patients. The median age was 57 [44, 67] and 47% were male. The comorbidity burden was generelly higher in EAT patients especially regarding heart failure and hypertension. Use of antiarrhythmic drugs was higher in EAT patients compared to patients with AVNRT and WPW. Figure 1 shows the cumulative incidence of a composite endpoint of death, TE, IHD, and HF 5 years after RFA treatment and depicts that the cumulative incidence was 22.1%, 13.9% and 8.2% for EAT-, AVNRT- and WPW-patients respectively. Figure 2 shows the 5-year cumulative incidence of pacemaker implantations which was 9.0%, 4.4% and 3.1% for EAT-, AVNRT- and WPW-patients respectively. Conclusion At long-term follow-up patients with RFA for EAT have a higher risk of death, TE, IHD and HF compared to patients treated for AVNRT and WPW. EAT patients also have the highest risk of pacemaker implantation. 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 Life expectancy in patients with congenital heart disease (CHD) and patients with early acquired cardiovascular disease (CVD) has increased due to improved treatments during the last decades. As life expectancy increases, focus on long term quality of life and life satisfaction as well as determining focus areas of preventive initiatives becomes essential. Purpose To investigate whether poor life satisfaction in adolescents and young adults with CHD or significant CVD is 1) associated with physical and mental challenges and 2) inversely associated with social support and self-efficacy have a protective effect against low life satisfaction. Methods Data from a Danish nationwide cross-sectional study was used to identify all patients with either CHD or significant CVD (e.g., arrhythmia, ischemia) aged 15–24 years with at least one contact to a Danish hospital department of cardiology between 2014–2018. Life satisfaction was measured on a scale of 0–10 and dichotomized into good life satisfaction if the score was >6. Using a logistic regression model with interaction terms for sex and adjusted for age and comorbidities, we estimated the association between physical challenges (New York Heart Association classification, NYHA), mental challenges (concentration limitations or memory limitations), social support, self-efficacy, and life satisfaction. Results 1961 patients were included, 58% had CHD. Median age was 20 years and 50% were female. NYHA-class III or IV were significantly associated with poor life satisfaction (OR: 0.42 [95CI: 0.26; 0.70]) (Figure 1). Likewise, self-reported memory limitations (OR: 0.79 [95CI: 0.68; 0.91]) and concentration difficulty (OR: 0.60 [95CI: 0.51; 0.70]) were associated with poor life satisfaction (Figure 1). In contrast, reported high self-efficacy (OR: 1.67 [95CI: 1.32; 2.12]) and good social support (OR: 2.16 [95CI: 1.60; 2.93]) were both associated with high life satisfaction (Figure 1). Finally, the association between NYHA class III (OR: 0.94 [95CI: 0.34; 2.59]), memory limitations (OR: 0.79 [95CI: 0.58; 1.07]), concentration limitations (OR: 0.71 [95CI: 0.49; 1.04]), and life satisfaction was not significant among individuals with high self-efficacy but remained significant among individuals with good social support. Conclusions In adolescents and young adults with CHD or early acquired heart disease, reported physical and mental challenges were associated with reduced self-reported life satisfaction. Both reported high self-efficacy and good social support were associated with increased life satisfaction. High self-efficacy among individuals reduced the negative association between mental or physical challenges and life satisfaction. These findings highlight the need for increased focus on promoting self-efficacy and the need for good social support in adolescents and young adults with functional limitations from their CHD or CVD in order to improve their long-term life satisfaction. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Danish Heart Foundation

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.

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: Public hospital(s). Main funding source(s): Internal funding: Herlev-Gentofte Cardiovascular Research Department. Background Hypertrophic cardiomyopathy (HCM) can be associated with serious complications such as heart failure, atrial fibrillation (AF) and sudden cardiac death. The treatment of AF in HCM patients can be challenging since AF often aggravates symptoms. Previous studies have suggested that HCM patients with AF have an elevated risk of thromboembolism and stroke compared to AF patients without HCM regardless of their CHA2DS2VASc score. Purpose To determine the risk of AF and stroke in HCM patients. Methods Through the Danish National Registers all patients aged 16 or older diagnosed with HCM between the 1st of January 2005, and the 31st of December 2018 were included in the analysis. The association between HCM, AF, and stroke was investigated using multivariable Cox proportional-hazard analysis adjusted for gender, age, atrial fibrillation, ischemic heart disease, chronic obstructive pulmonary disease, chronic kidney disease and hypertension. Cumulative incidence of AF and stroke was calculated using the Aalen-Johansen estimator, taking death as a competing risk into account. Results A total of 3856 patients were included, 2060 (53,4%) were male and median age of 67,8 (IQR 56 and 77,8) years. During the study period, 384 (10%) patients were diagnosed with AF. The risk of AF was significantly lower in males (HR 0,72 (0,59–0,90), p-value = 0.003) and for patients below 60 years (HR 0,18 (0,12–0,27), p-value = 157 (4,1%) of the HCM patients developed stroke. The risk of developing stroke was significantly decreased for patients aged under 60 (HR 0,32 (0,2–0,52), p-value = Stroke risk was further analyzed in patients with known AF at time of inclusion, 656 (17%) in total. Compared to patients without AF and adjusted for age, gender and co-morbidities, there was no significant difference in stroke risk between these groups (HR 1.2 (0,81-1,76), p-value = 0.36). (Figure 2) Conclusion AF and stroke are common complications in HCM. Women are more susceptible to developing AF than men, and age over 60 at the time of diagnosis was associated with significantly higher risk of AF and stroke. HCM patients with previously known AF did not have a significantly elevated risk of stroke. More research will be needed to further explore these connections.

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.

Objectives: This study aimed to explore return to work after COVID-19 and how disease severity affects this. Study design: This is a Nationwide Danish registry–based cohort study using a retrospective follow-up design. Methods: Patients with a first-time positive SARS-CoV-2 polymerase chain reaction test between 1 January 2020 and 30 May 2020, including 18–64 years old, 30-day survivors, and available to the workforce at the time of the first positive test were included. Admission types (i.e. no admission, admission to non–intensive care unit [ICU] department and admission to ICU) and return to work was investigated using Cox regression standardised to the age, sex, comorbidity and education-level distribution of all included subjects with estimates at 3 months from positive test displayed. Results: Among the 7466 patients included in the study, 81.9% (6119/7466) and 98.4% (7344/7466) returned to work within 4 weeks and 6 months, respectively, with 1.5% (109/7466) not returning. Of the patients admitted, 72.1% (627/870) and 92.6% (805/870) returned 1 month and 6 months after admission to the hospital, with 6.6% (58/870) not returning within 6 months. Of patients admitted to the ICU, 36% (9/25) did not return within 6 months. Patients with an admission had a lower chance of return to work 3 months from positive test (relative risk [RR] 0.95, 95% confidence interval [CI] 0.94–0.96), with the lowest chance in patients admitted to an ICU department (RR 0.54, 95% CI 0.35–0.72). Female sex, older age, and comorbidity were associated with a lower chance of returning to work. Conclusion: Hospitalised patients with COVID-19 infection have a lower chance of returning to work with potential implications for postinfection follow-up and rehabilitation.

Background Congenital heart disease (CHD) is the most common major birth defect. Due to improvements in early detection and treatment during the last decades, most children survive into adulthood and currently the proportion of adults with CHD surpasses that of children. Previous studies reported an increased comorbidity prevalence in patients with simple CHD compared to a population without CHD. However, it is unclear whether these comorbidities increase the risk of death more in patients with simple CHD compared to those without. Purpose To investigate whether 40-years old individuals with simple CHD are at 1) an increased risk of developing stroke and acute myocardial infarction (AMI) and 2) whether AMI and stroke survivors with simple CHD have increased 10-year mortality compared to non-CHD matched controls. Methods Patients with simple CHD aged 40 years between 1977–2008 were identified by linking the Danish nationwide registries. Simple CHD was defined as isolated ventricular septal defect, atrial septal defect, patent ductus arteriosus or pulmonary stenosis. Patients with simple CHD were matched with 100 birthdate- and sex matched controls who did not have any CHD. We used two multiple Cox regression to compare the risk of AMI and stroke, respectively, between patients with and without simple CHD. Reported were the standardized 10-year risks for fixed comorbidity distribution according to simple CHD status. In patients who developed AMI or stroke, we used two other multiple Cox regressions to compare the risk of death between patients with and without simple CHD. Reported were the standardized 10-year risks for fixed comorbidity distribution according to simple CHD status in patients with AMI and stroke, respectively. Results We identified 2307 patients with simple CHD (54% females). The risk of developing AMI or stroke among 40-years old individuals with simple CHD was comparable to the risk in the background population – a trend of higher risk among simple CHD was seen but was not significant. The 10-year mortality after developing AMI was higher among the population with simple CHD than the matched controls (Figure 1) e.g. 10-year mortality: CHD 26.9% vs controls 20.6%. This was also the case for the 10-year mortality after developing a stroke (Figure 2) e.g. 10-year mortality 24.8% vs controls 22.6%. Conclusions Middle-aged individuals with simple CHD are not at an increased risk of developing AMI or stroke compared to the background population. However, developing stroke or AMI among individuals with simple CHD is associated with increased mortality compared to individuals without simple CHD. In the aging CHD population, the risk of atherosclerotic disease is naturally increasing. Therefore, it is of the utmost important to study long-term complications further to guide both primary and secondary prevention of cardiovascular disease in these vulnerable individuals. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Danish Heart Foundation

Background Renin-angiotensin system inhibitors (RASi) are the preferred drug of choice in patients with type 2 diabetes (T2D) and albuminuria to prevent progression of chronic renal disease and cardiovascular complications. However, it is unknown whether sex-differences exist in the initiation of RASi in patients with T2D and albuminuria, and potential sex-differences in the effect of RASi on all-cause death in these patients remains untested. Purpose To examine potential sex-differences in the initiation of RASi in patients with T2D and albuminuria, and secondly whether these sex-differences are associated with mortality risk. Methods Using Danish nationwide registers, we included patients with their first albumin-creatinine ratio (ACR; index date) of ≥30 mg/g between 1 January 2014 and 20 March 2019 in patients with T2D with no prior end-stage renal disease, no acute renal failure within 90 days, and no claimed prescriptions of RASi within 15 years. We used multiple Cox regression to study the hazard ratio (HR; men vs women) of 30-day RASi initiation. In 30-day survivors, we used another multiple Cox regression to compare mortality between patients who initiated RASi and patients who did not yet initiate RASi. Reported were the sex-specific standardized 1-year risk differences for fixed comorbidity distribution according to RASi treatment. Results In 20,440 patients (44% women), 1,190 men and 682 women initiated RASi treatment within 30 days after index. The adjusted rate of RASi initiation was higher in men compared to women (HR 1.34 [1.22; 1.48]). This association was observed regardless of hypertension (no: HR 1.35 [1.20; 1.52]; yes: HR 1.34 [1.14; 1.57]) and ACR-group ((30–300] mg/g: HR 1.35 [1.22; 1.49]; ≥300 mg/g: HR 1.30 [0.98; 1.73]), although borderline significant for ACR ≥300 mg/g (p=0.071). The association declined with descending estimated glomerular filtration rate (eGFR) and was not significant for eGFR group (15–60] (eGFR (90–120]: HR 1.45 [1.28; 1.65]; (60–90]: HR 1.25 [1.06; 1.47]; (15–60]: HR 1.07 [0.77; 1.48]). 30 days after index, 49 patients (37% women) had died, and 9 patients (33% women) had emigrated. In 30-day survivors, the standardized 1-year mortality risk was 1.9% [1.4; 2.4] in men who readily initiated RASi, and 3.3% [3.0; 3.7] in men who did not (absolute reduction: 1.5% [0.9; 2.0]). In contrast, the absolute reduction was not significant in women (0.1% [−0.5; 0.8]). Standardizing according to sex, the associated 1-year mortality risk was 3.4% [3.1; 3.7] in men without RASi, and 2.8% [2.5; 3.0] in women (absolute risk difference 0.6% [0.3; 0.9]). In contrast, men with RASi were borderline significantly associated with a lower 1-year mortality risk compared to women with RASi (absolute risk difference 0.8% [0.0; 1.5], p=0.042). Conclusions In patients with T2D and albuminuria, men are more likely to initiate RASi within 30 days, and RASi appears to be associated with greater benefit on 1-year mortality risk in men. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation Figure 1Figure 2

Importance: Sodium glucose cotransporter 2 inhibitors reduce morbidity and mortality in patients with heart failure and reduced ejection fraction (HFrEF). Clinicians may find estimates of the projected long-term benefits of sodium glucose cotransporter 2 inhibitors a helpful addition to clinical trial results when communicating the benefits of this class of drug to patients. Objective: To estimate the projected long-term treatment effects of dapagliflozin in patients with HFrEF over the duration of a patient’s lifetime. Design, Setting, and Participants: Exploratory analysis was performed of Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF), a phase 3 randomized, placebo-controlled clinical trial conducted at 410 sites in 20 countries. Patients with an ejection fraction less than or equal to 40% in New York Heart Association functional classification II to IV and elevated plasma levels of N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019. Mean (SD) duration of follow-up was 17.6 (5.2) months. Interventions: Dapagliflozin, 10 mg, once daily vs placebo in addition to standard therapy. Main Outcomes and Measures: The primary composite outcome was time to first hospitalization for heart failure, urgent heart failure visit requiring intravenous therapy, or cardiovascular death. The trial results were extrapolated to estimate the projected long-term treatment effects of dapagliflozin over the duration of a patient’s lifetime for the primary outcome and the secondary outcome of death from any cause. Results: A total of 4744 patients (1109 women [23.4%]; 3635 men [76.6%]) were randomized in DAPA-HF, with a mean (SD) age of 66.3 (10.9) years. The extrapolated mean event-free survival for an individual aged 65 years from a primary composite end point event was 6.2 years for placebo and 8.3 years for dapagliflozin, representing an event-free survival time gain of 2.1 years (95% CI, 0.8-3.3 years; P = .002). When considering death from any cause, mean extrapolated life expectancy for an individual aged 65 years was 9.1 years for placebo and 10.8 years for dapagliflozin, with a gain in survival of 1.7 years (95% CI, 0.1-3.3; P = .03) with dapagliflozin. Similar results were seen when extrapolated across the age range studied. In analyses of subgroups of patients in DAPA-HF, consistent benefits were seen with dapagliflozin on both event-free and overall survival. Conclusions and Relevance: These findings indicate that dapagliflozin provides clinically meaningful gains in extrapolated event-free and overall survival. These findings may be helpful in communicating the benefits of this treatment to patients with HFrEF. Trial registration: ClinicalTrials.gov Identifier: NCT03036124.

Background Development of type 2 diabetes (T2D) is common in patients with heart failure (HF), but knowledge of future cardiovascular events is lacking. Purpose We compared risk of heart failure hospitalization (HFH) or death versus ischemic events in real-life HF patients with new-onset T2D, prevalent T2D and no T2D. Methods Using the Danish nationwide registers, we identified all patients with HF between 1998–2016. The patients were separated in two different HF cohorts based on the status of T2D. One cohort consisted of HF patients with either prevalent or absent T2D at the time of HF diagnosis. The other cohort consisted of HF patients, who developed new-onset T2D, included at time of diagnosis. The two HF cohorts were analyzed separately. Outcomes for both cohorts were analyzed as time-to-first event as either an ischemic event (i.e. composite outcome of fatal and non-fatal myocardial infarction, stroke, and peripheral artery disease), HFH, or event-free death (not related to HFH or the ischemic event). For each cohort, we estimated the five-year absolute risk of ischemic event, HFH and event-free death, along with five-year risk ratio of HFH or event-free death versus ischemic events. Effects among subgroups were investigated by stratifying both cohorts based on age, gender and comorbidities present at inclusion. Results A total of 139,264 HF patients were included between 1998 and 2016, of which 29,078 (21%) patients had prevalent T2D at baseline. A total of 11,819 (8%) developed new-onset T2D and were included in the second cohort. The median duration of time between HF diagnosis and new-onset T2D diagnosis was: 4.1 years (IQR:1.5; 5.8). The absolute five-year risk of an ischemic event in patients with new-onset T2D, prevalent T2D and no T2D was: 17.9% (95% confidence interval (CI): 17.2; 18.6), 26.1% (95% CI: 25.6; 26.7), and 18.8% (95% CI:18.6; 19.0). Corresponding estimates for HFH were: 31.5% (95% CI: 30.6; 32.3), 33.6% (95% CI: 33.0; 34.2), and 30,7% (95% CI: 30.5; 31.0). The absolute five-year risk of event-free death among patients with new-onset T2D, prevalent T2D and no T2D was: 20.9% (95% CI: 20.2; 21.7), 18.9% (95% CI:18.4; 19.3), and 18.6% (95% CI: 18.4; 18.8) (see Figure). The five-year risk ratio of experiencing HFH or event-free death versus an ischemic event was: 2.9 (95% CI: 2.8; 3.1), 2.0 (95% CI:2.0; 2.1), and 2.6 (95% CI: 2.6; 2.7) for patients with new-onset T2D, prevalent T2D and no T2D, respectively. Similar results of absolute and relative risk were present across all subgroups. Conclusion In our population of HF patients, 8% developed new-onset diabetes. Development of T2D in patients with HF increases the risk of HFH and mortality three-fold. The increased risk of new-onset T2D is higher than the importance of prevalent T2D in patients with HF. Funding Acknowledgement Type of funding source: None

Aims Stratification of patients at risk of infective endocarditis (IE) remains a cornerstone in guidance of prophylactic strategies of IE. However, little attention has been given to patients considered at moderate risk. Methods and results Using Danish nationwide registries, we assessed the risk of IE in patients with aortic and mitral valve disorders, a cardiac implantable electronic device (CIED), or hypertrophic cardiomyopathy (HCM) and compared these patient groups with (i) controls from the background population using risk-set matching and (ii) a high-risk population (prosthetic heart valve). Cumulative incidence plots and multivariable adjusted Cox proportional hazard analysis were used to compare risk of IE between risk groups. We identified 83 453 patients with aortic or mitral valve disorder, 50 828 with a CIED, and 3620 with HCM. The cumulative risk of IE after 10 years was 0.9% in valve disorder, 1.3% in CIED, and 0.5% in HCM patients. Compared with the background population, valve disorder, CIED, and HCM carried a higher associated risk of IE, hazard ratio (HR) = 8.75 [95% confidence interval (CI) 6.36–12.02], HR = 6.63 (95% CI 4.41–9.96), and HR = 6.57 (95% CI 2.33–18.56), respectively. All three study groups were associated with a lower risk of IE compared with high-risk patients, HR = 0.27 (95% CI 0.23–0.32) for valve disorder, HR = 0.28 (95% CI 0.23–0.33) for CIED, and HR = 0.13 (95% CI 0.06–0.29) for HCM. Conclusions Heart valve disorder, CIED, and patients with HCM were associated with a higher risk of IE compared with the background population but have a lower associated risk of IE compared with high-risk patients.

Background Recent studies have highlighted a high incidence of heart failure (HF) in type 2 diabetes mellitus (T2D), but it remains unclear how the development of HF affects prognosis compared to other T2D complications. Purpose To estimate the risk of death associated with the development of HF compared to ischemic heart disease (IHD), chronic kidney disease (CKD), stroke, and peripheral artery disease (PAD). Methods Incident T2D patients were identified in the period between 1998–2015, as all patients redeeming a first-time prescription of non-insulin glucose-lowering medication through Danish nationwide registers. Patients with a history of T2D complications and patients Results A total of 153,403 patients with incident T2D (median age 64 years [interquartile range (IQR):55; 72] and 54% males) were included and followed for a median of 7.4 years (IQR: 4.3; 11.5). During follow-up, 48,087 (31%) patients died. Among the patients who survived, the following number of T2D complications were present at landmark year one vs. ten: HF: 1030 (0.7%) vs. 1082 (2.2%), IHD: 3622 (2.4%) vs. 6354 (12.6%), CKD: 905 (0.6%) vs. 2084 (4.1%), stroke: 1446 (1.0%) vs. 2387 (4.7%) and PAD: 1122 (0.8%) vs. 1517 (3.0%). HF posed the most unfavorable prognosis compared to other T2D complications (see figure). The 5-year risk of death associated with HF development one, five and ten years after T2D diagnosis was: 46.9 (95% confidence interval [CI]: 43.5; 50.3), 47.6 (95% CI: 44.8; 50.3) and 41.8 (95% CI: 38.0; 45.7) respectively. The 5-year risk ratios of death associated with HF development during one, five and ten years after T2D diagnosis compared with T2D patients free of complications was: 3.2 (95% CI, 3.2; 3.3), 3.0 (95% CI 2.9; 3.1) and 2.2 (95% CI, 2.1; 2.2), respectively. Conclusion While IHD was the most common complication at each landmark year, developing HF was associated with the highest risk of death compared to the other T2D complications.

Abstract Background 5-fluorouracil (5-FU) is the third most commonly used chemotherapeutic agent in the treatment of solid malignancies across the world. The most common manifestation of cardiotoxicity associated with 5-FU is chest pain, presenting as atypical chest pain, angina on exertion or rest and acute coronary syndromes including myocardial infarction and in worse case even death. Nevertheless, a widespread appreciation of 5-FU related cardiotoxicity including myocardial infarction is poorly understood. Purpose This study aims to examine risk of myocardial infarction in patients treated with 5-FU compared to age- and sex-matched population controls. Methods and results Methods: Individuals treated with 5-FU between 2004 and 2014 in the Danish National Patient Register were identified and risk set matching was used to find background population controls matched on age and sex in a 1:5 ratio. Furthermore, two years follow-up time were added with total 13 years. Neither 5-FU patients nor controls had prior ischemic disease. Aalen-Johansen and Kaplan-Meier estimates were used to report the cumulative incidence of myocardial infarction and all-cause mortality, respectively. A multivariable Shared Frailty Cox regression analysis (adjusted for patient age, sex, hypertension, hypercholesterolemia, diabetes, chronic obstructive pulmonary disease, chronic kidney disease, heart failure and atrial fibrillation as well as selected anti-anginal medications including nitrates, beta- and calcium-blockers) was used to determine the association between 5-FU treatment and the one-year risk of myocardial infarction. Results A total of 9,012 5-FU patients and 45,060 controls formed the study population. Differences in comorbid conditions (diabetes, chronic obstructive pulmonary disease, chronic kidney disease, heart failure and atrial fibrillation) and selected anti-anginal medications (nitrates, beta- and calcium-blockers) were non-significant (all P>0.05). The one-year cumulative incidence of myocardial infarction is significantly higher for 5-FU patients at 0.8% versus 0.6% among population controls (Figure 1A), with a competing risk of death of 25.1% versus 1.2%. The risk diminishes beyond one year and becomes lower for 5-FU patients with time (Figure 1A), along with an increasing all-cause mortality (Figure 1B). The unadjusted and adjusted hazard ratio for the one-year risk of myocardial infarction were 1.38 [95% CI 1.07–1.78] and 1.54 [95% CI 1.19–1.99]. Conclusions Although the one-year risk of myocardial infarction is higher among 5-FU patients compared with population controls, the absolute risk is small and becomes insignificant beyond one year of follow-up.

Background Reflecting recent clinical trial findings, updated type 2 diabetes (T2D) guidelines recommend targeting SGLT2 inhibitors at patients at risk of heart failure (HF)-related events and GLP-1 receptor agonists at those at greater risk of atherosclerotic events. However, which cardiovascular disease phenotype in patients with T2D is more predictive of one or other type of these events is unclear. Purpose To estimate the risk of HF-related events and atherosclerotic events, according to background cardiovascular phenotype, in patients with T2D. Methods Patients with T2D and new-onset cardiovascular disease were identified using Danish health care registers (period 1995 to 2015). Patients were divided in four groups based on the primary type of cardiovascular disease: 1) HF, 2) ischemic heart disease (IHD), 3) ischemic stroke, and 4) peripheral artery disease (PAD). The absolute 5-year risks of the subsequent event, either a HF-related event or an atherosclerotic event (IHD, ischemic stroke and PAD), and the associated risk of death, were compared across the four groups. The Aalen-Johansen estimator was used to account for censoring, the competing risk of HF and atherosclerotic events, respectively, and death. Results We included 37,850 patients with T2D and new-onset cardiovascular disease. Median age was 70 years and 40% were female. Patients with HF were at higher risk of readmission for HF (18.1%; 95% confidence interval (CI): 17.2–19.0) than of an atherosclerotic event (14.2%; 13.4–15.0) (Figure). Patients with IHD were at higher risk of a new atherosclerotic event (23.5%; 22.8.-24.2) than of developing HF (9.3%; 8.9–9.8), although the risk of HF was still substantial. Conversely, patients with ischemic stroke were at low risk of HF (3.3%; 2.9–3.8) and higher risk of an atherosclerotic event (16.9%; 95% CI: 16.0–17.7). Patients with PAD had the lowest risk of HF (3.1%; 95% CI: 2.8–3.4) and the highest risk of an atherosclerotic event (35.0%; 95% CI: 33.4–36.7). Compared to a new atherosclerotic event, developing HF was associated with a higher 1-year risk of death (16.0%; 95% CI: 14.7–17.3 versus 33.0%; 95% CI: 31.8–34.2) amongst all patients. Cumulative incidence of first new event Conclusions In T2D, a patient's history of cardiovascular disease was predictive of type of subsequent cardiovascular event. While history of ischemic stroke and PAD were associated with a high risk of future atherosclerotic events, and low risk of HF, patients with IHD were at substantial risk of both types of event. Conversely, while history of HF was most predictive of future HF events, the risk of atherosclerotic events in patients with HF was also high. Our findings may help determine which type of therapy T2D patients with a particular cardiovascular disease history might benefit from – SGLT2 inhibitors, GLP-1 receptor agonists or potentially both. Acknowledgement/Funding Mariam Elmegaard Malik was funded by a research grant from Department of Cardiology, Herlev and Gentofte Hospital.

Researchers have often considered the impact that online dating has had on gay communities; with some arguing that changes in social behavior may impact the spread of HIV. However, these conclusions are based on the premise that the Internet has fundamentally changed the way gay and bisexual men connect with their communities. Addressing this issue, we searched the PubMed and Web of Science databases for studies examining Internet use and interpersonal connectedness among gay and bisexual men to determine whether those who used the Internet to find sexual partners exhibited different patterns of community connectedness. Though sporadic, findings suggest that Internet use may be associated with lower gay identity, community attachment, and social embeddedness. However, recent reports have suggested that online sex seeking might be associated with greater, not less, interpersonal connectedness. We conclude that additional longitudinal analyses and consistent measurement of gay men's social behavior are needed to draw more definite conclusions.

Introduction Survival after acute myocardial infarction (AMI) is associated with receiving adequate and often time-dependent treatment as well as sociodemographic characteristics of the patient. Access to adequate AMI treatment might depend on where you live as distance to the nearest hospital differs substantially across the country. Moreover, where you live is to some degree influenced by your socioeconomic position and economical resources. The interplay between the geographical and social inequalities in survival after an AMI is not clearly understood and it remains unclear whether geographical patterns in survival can be explained by sociodemographic factors. This study aimed to examine whether the geographical patterns in survival after incident AMI can be explained by individual- and neighborhood-level sociodemographic characteristics. Methods The study population consisted of patients (≥ 30 years) with an incident AMI between 1 January 2005 and 31 December 2014 registered in the National Patient Register or the Danish Register of Causes of Death. The population was followed for a maximum of 365 days or until emigration, study end or death, whichever came first. The year 2005 was used as run-in period to ensure adequate results estimates across calendar years. Hence, the study period was 1 January 2006 to 31 December 2014. Poisson regression of incidence rates of all-cause mortality with a geographical component as a random effect was performed in R by use of the Bayesian Integrated Nested Laplace Approximations (INLA) method. The analysis included the individual-level variables age, sex, ethnicity, calendar year, cohabitation status, disposable household income, and educational level and the neighborhood-level variables population density, socioeconomic position, and ethnical composition of the neighborhood. Results The study population consisted of 95,274 patients with incident AMI contributing with 62,8210 person-years at-risk between 2006 and 2014. During the study period 28,194 deaths occurred within 365 days. Crude mortality rates varied substantially across the country as well as across neighborhood and individual-level characteristics, e.g., 53.2/100 person-years died within 365 days after an AMI in neighborhoods with low socioeconomic position, whereas this number was 36.7/100 person-years in high socioeconomic position neighborhoods. Results from the model only including calendar year and the geographically structured random effect component showed clear geographical patterns in survival after an AMI with especially the northern part of Jutland being a high-risk area. After additionally including sociodemographic characteristics of the population and neighborhood in the model the variation in survival after an AMI decreased across the country, but high-risk areas were still observed. Results on fixed effects from the adjusted model showed that persons with low educational level, low-income level and persons living in neighborhoods with low socioeconomic position had an increased incidence rate ratio (IRR) of dying within 365 days after AMI compared to the most educated and affluent population groups [IRRs (95% confidence intervals) of 1.29 (1.23–1.36), 1.26 (1.20–1.32) and 1.11 (1.05–1.17), respectively]. Furthermore, risk of dying within 365 days after an AMI decreased throughout the study period. Results from sensitivity analyses showed that the geographical patterns were more pronounced in out-of-hospital than in-hospital deaths. Conclusions Evident geographical and social inequalities in survival after an incident AMI exist in Denmark. Sociodemographic characteristics at the individual- and neighborhood-level explained part of the geographical variation in survival after an AMI; however, marked geographical patterns in survival after AMI persisted. Further studies are needed to explain the remaining geographical inequalities in survival after an AMI, especially with focus on out-of-hospital deaths.

Arctic char, Salvelinus alpinus L., and Atlantic salmon, Salmo salar L., were fed a commercial diet with or without supplementation of 1.5% Na+-lactate. Dietary Na+-lactate enhanced growth of Arctic char, while that of salmon was unaffected. Dietary 14C-lactate was retained for significantly longer in the stomach of Arctic char than that of Atlantic salmon. Changes in intestinal cholytaurin hydrolase activity, a bacterially produced enzyme, may indicate that dietary lactate affects the intestinal microbiota of Arctic char but not that of Atlantic salmon. Analysis of bile acids of char showed that dietary Na+-Iactate influenced neither intestinal nor gallbladder bile acid composition. Although Arctic char possesses the classical entero-hepatic circulation pathway, no extra loss of bile acids from the fish was observed. It is concluded that the retention time of diet in the stomach of char is significantly longer than that of salmon. This may increase the antibacterial action of lactate in the former, favouring the colonization of lactic-acid-tolerant bacteria in the intestinal tract, some of which produce the enzyme cholytaurin hydrolase.

A time-dependent, nonplanar, two-dimensional magnetohydrodynamic computer model is used to simulate a series, separately examined, of solar flare-generated shock waves and their subsequent disturbances in interplanetary space between the sun and the earth's magnetosphere. The 'canonical' or ansatz series of shock waves include initial velocities near the sun over the range 500 to 3500 km/s. The ambient solar wind, through which they propagate, is taken to be a steady state homogeneous plasma (that is, independent of heliolongitude) with a representative set of plasma and magnetic field parameters. Complete sets of solar wind plasma and magnetic field parameters are presented and discussed. Particular attention is addressed to the MHD model's ability to address fundamental operational questions vis-a-vis the long-range forecasting of geomagnetic disturbances. These questions are: (1) will a disturbance (such as the present canonical series of solar flare shock waves) produce a magnetospheric and ionospheric disturbance, and, if so, (2) when will it start, (3) how severe will it be, and (4) how long will it last? The model's output is used to compute various solar wind indices of current interest as a demonstration of the model's potential for providing 'answers' to these questions.

Some recent solar observations show that a bipolar magnetic flux in an active region tends to disappear in situ, in less than one solar rotation, without evidence of spreading. This feature is difficult to explain if it is assumed that magnetic buoyancy is the dominant force in controlling dynamics of a magnetic flux tube, since the assumption implies no other force to submerge the tube. These observations may be explained by assuming that a convective motion is the major cause for the formation of a Ω -shaped geometry of the magnetic flux tube, but that the flux tube thus arisen is submerged by the counteracting Lorentz force as the convective motion decays. A two-dimensional MHD simulation method is used to demonstrate this possibility.

A recently developed nonplanar, time-dependent magnetohydrodynamic (MHD) model (Wuet al., 1983) was used to study the interplanetary disturbances produced by a compound event in the heliosphere. That is, a steady-state interplanetary medium is first disturbed by a simulated equatorially-fluctuating current sheet. After a few days (100 hr), the disturbed interplanetary medium is again perturbed by a solar-flare-generated shock wave. Attention is directed toward the differences that are caused by the presence of the equatorially-fluctuating (warped) current sheet.