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Aims: Atrial fibrillation (AF) is a common arrhythmia associated with reduced quality of life that can lead to serious complications such as stroke and heart failure. Ablation is a safe and effective treatment for AF but is not offered equally to all patients. The aim of this study is to identify demographic groups more or less likely to undergo AF ablation., Methods and Results: All patients with newly diagnosed AF between 2010 and 2018 were identified in the Danish nationwide registries. The association between gender, age, level of education and attachment to the job market, and the likelihood of receiving AF ablation was investigated using multivariable Cox proportional hazard analysis. Cumulative incidence was calculated using the Aalen-Johansen estimator. A total of 176 248 patients were included. Men were more likely to receive ablation than women (7% vs. 3%). Patients aged 25-44 and 45-64 were most likely to receive ablation, while only 0.7% of patients aged 80 or above received ablation. The rate of ablation significantly decreased with decreasing level of education. Full-time employed patients were most likely to receive ablation, followed by self-employed, unemployed, on sick leave, undergoing education, and early retired patients. Retired patients were the least likely to receive ablation (3%)., Conclusion: This study found that women, older patients, patients with lower levels of education, and patients on social benefits are less likely to receive AF ablation. These findings suggest that there are significant social and economic disparities in AF ablation treatment in Denmark., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Following implantation of an implantable cardioverter defibrillator (ICD), patients are temporarily restricted from private motor vehicle driving and permanently prohibited from professional driving. We aimed to investigate the impact of driving restrictions following ICD implantation and in case of ICD shock on employment, daily living activities, driving concerns and driving behavior., Methods and Results: Data were retrieved from a nationwide survey on driving restrictions in Danish ICD patients, distributed in 2017 to all patients ≥18 years implanted with a first-time ICD from 2013-2016 (n=3913). Responses were linked with data from nationwide registers. The response rate was 71% (final analyzable population n=2741, 83% male, median age 67 years, 316 had experienced an ICD shock, and 911 patients reported receipt of driving restrictions of minimum 1 month). Among active professional drivers (n=175), 33% had lost their job as a direct consequence of the driving restrictions. Of those working prior to ICD implantation (n=465), 47% reported being limited in maintaining employment due to private driving restrictions. Among those restricted from driving minimum 1 month, 26% reported the restrictions overall had substantially impeded their daily living. Factors associated with substantial impediment were age <65 years (OR 1.84 [95% CI 1.35-2.52]), higher income (OR 1.47 [95% CI 1.05-2.05]) and driving ≥7 hours/week pre-implantation (OR 1.66 [95% CI 1.23-2.24]). Being nervous about driving or altering driving habits was reported by 3-7%., Conclusion: Both professional and private driving restrictions affect the ability to maintain employment and have a negative impact on ICD recipients' daily living activities., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Catheter ablation (CA) is a well-established treatment option for atrial fibrillation (AF), where sedation and analgesia are pivotal for patient comfort and lesion formation. The impact of anaesthesia type on AF recurrence rates remains uncertain. This study aimed to examine AF recurrence rates depending on conscious sedation (CS) vs. general anaesthesia (GA) during CA., Methods and Results: Utilizing nationwide data from the Danish healthcare registries, we conducted this cohort study involving adults (≥18 years) undergoing first-time CA for AF between 2010 and 2018. Patients were categorized by anaesthesia type (CS or GA), with the primary endpoint being AF recurrence, defined by a composite endpoint of either antiarrhythmic drug (AAD) prescriptions, AF-related hospital admissions, electrical cardioversions, or AF re-ablation. The impact of anaesthesia type was evaluated using multivariable Cox proportional hazards analysis. The study cohort comprised 7957 (6421 CS and 1536 GA) patients. Persistent AF, hypertension, and heart failure, as well as use of AAD, were more prevalent in the GA group. Cumulative incidences of recurrent AF were higher in the CS group at 1 (46% vs. 37%) and at 5 (68% vs. 63%) years. Multivariate analysis revealed CS as significantly associated with increased risk of AF recurrence at 5-year follow-up [hazard ratio 1.26 (95% confidence interval 1.15-1.38)], consistent across paroxysmal and persistent AF subtypes., Conclusion: This nationwide cohort study suggests a higher risk of AF recurrence with CS during CA compared to GA. These results advocate for considering GA as the preferred anaesthesia type for improved CA outcomes., Competing Interests: Conflict of interest: L.D.R.-V., J.T., C.R.Z., C.M., R.H., A.J., R.H.W., G.G.: none. M.H.R.: Speaker honoraria from Boston Scientific and CardioFocus. J.H.: Speaker fees and consultant honoraria from Boston Scientific and Biosense Webster. M.L.H.: Received research grants from Biosense Webster and Medtronic., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: The treatment of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) can be challenging since AF aggravates symptoms and increases the risk of stroke. Which factors contribute to the development of AF and stroke in HCM remains unknown. The aim of this study was to determine the incidence of AF and stroke in HCM patients and identify the risk factors., Methods and Results: Using Danish national registries, all HCM patients from 2005 to 2018 were included. The association between HCM, incident AF, and stroke was investigated using multivariable Cox proportional hazards analysis. Cumulative incidences were calculated using the Aalen-Johansen estimator. Among the 3367 patients without prevalent AF, 24% reached the endpoint of incident AF with death as a competing risk. Median follow-up time was 4 years. Atrial fibrillation incidence was equal between sexes and increased for patients with ischaemic heart disease [IHD; hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.08-1.63], hypertension (HT) (HR 1.36, 95% CI 1.14-1.67), and obstructive HCM (HR 1.27, 95% CI 1.05-1.52). Seven per cent developed stroke, with no difference detected stratifying for the presence of AF. Sub-analysis revealed that when AF was treated with oral anticoagulants (OACs), stroke was less likely (HR 0.4, 95% CI 0.18-0.86, P = 0.02). However, 34% of patients were not receiving adequate anticoagulation following AF diagnosis., Conclusion: Obstructive HCM, HT, and IHD were associated with increased risk of AF. Prevalent AF alone was not predictive of stroke; however, AF patients treated with OAC were significantly less likely to develop stroke, suggesting that this development is driven by the protective effect of OAC. Despite this, 34% of patients did not receive OAC., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aim: There are a paucity of studies investigating workforce affiliation in connection with first-time implantable cardioverter defibrillator (ICD)-implantation. This study explored workforce affiliation and risk markers associated with not returning to work in patients with ICDs., Methods: Using the nationwide Danish registers, patients with a first-time ICD-implantation between 2007 and 2017 and of working age (30-65 years) were identified. Descriptive statistic and logistic regression models were used to describe workforce affiliation and to estimate risk markers associated with not returning to work, respectively. All analyses were stratified by indication for implantation (primary and secondary prevention)., Results: Of the 4659 ICD-patients of working age, 3300 patients (71%) were members of the workforce (employed, on sick leave or unemployed) (primary: 1428 (43%); secondary:1872 (57%)). At baseline, 842 primary and 1477 secondary prevention ICD-patients were employed. Of those employed at baseline, 81% primary and 75% secondary prevention ICD-patients returned to work within 1 year, whereof more than 80% remained employed the following year. Among patients receiving sick leave benefits at baseline, 25% were employed after 1 year. Risk markers of not returning to work were 'younger age' in primary prevention ICD-patients, while 'female sex', left ventricular ejection fraction 'LVEF ≤40', 'lower income', and '≥3 comorbidities' were risk markers in secondary prevention ICD-patients. Lower educational level was a risk marker in both patient groups., Conclusion: High return-to-work proportions following ICD-implantation, with a subsequent high level of employment maintenance were found. Several significant risk markers of not returning to work were identified including 'lower educational level' that posed a risk in both patient groups., Trial Registration Number: Capital Region of Denmark, P-2019-051., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: Coronary computed tomography angiography (CCTA) can guide downstream preventive treatment and improve patient prognosis, but its use in relation to education level remains unexplored., Methods: This nationwide register-based cohort study assessed all residents in Denmark between 2008 and 2018 without coronary artery disease (CAD) and 50-80 years of age (n = 1 469 724). Residents were divided according to four levels of education: low, lower-mid, higher-mid, and high. Outcomes were CCTA, functional testing, invasive coronary angiography (ICA), revascularization, and major adverse cardiovascular and cerebrovascular events (MACCE)., Results: Individuals with the lowest education level underwent CCTA (absolute risk [AR] 3.95% individuals aged ≥50-59, AR 3.62% individuals aged ≥60-69, and AR 2.19% individuals aged ≥70-80) less often than individuals of lower-mid (AR 4.16%, AR 3.90%, and AR 2.41%), higher-mid (AR 4.38%, AR 4.30%, and AR 2.45%) and highest education level (AR 3.98%, AR 4.37%, and AR 2.30%). Similar differences were observed for functional testing. Conversely, use of ICA, and risks of revascularization and MACCE were more common among individuals of lowest education level. Among patients examined with CCTA (n = 50 234), patients of lowest education level less often underwent functional testing and more likely initiated preventive medication, underwent ICA, revascularization, and experienced MACCE., Conclusion: Despite tax-financed healthcare in Denmark, individuals of lowest education level were less likely to undergo CCTA and functional testing than persons of higher education level. Invasive coronary angiography utilization, revascularization, and MACCE risks were higher for individuals of lowest education level. Among CCTA-examined patients, patients of lowest education level were more likely to initiate preventive medication and had the highest risks of revascularization and MACCE when compared to higher education level groups. These findings suggest that the preventive potential of CCTA is underutilized in individuals of lower education level, a proxy for socioeconomic status. Socioeconomic differences in CAD assessment, care, and outcomes are likely even larger without tax-financed healthcare., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aim: To identify the absolute risk, causes, and factors associated with rehospitalization within 1 year of discharge with a pulmonary embolism (PE)., Methods and Results: Using the Danish nationwide registries, all patients admitted with a first-time PE between 2000 and 2020 and discharged alive were included. Subsequent hospitalizations were categorized and crude cumulative incidences were used to estimate the absolute risk (AR) of any rehospitalization and specific causes of rehospitalizations. Risk factors for rehospitalization were investigated using cause specific Cox regression models.A total of 55 201 patients were identified. The median age of the study population was 70 years (inter quartile range: 59;79), and the most prevalent comorbidities were cancer (29.3%) and ischemic heart disease (12.7%). The 1-year AR of any rehospitalization after discharge with a PE was 48.6% (95% confidence interval (CI); 48.2%-48.8%). The most common cause for being rehospitalized was due to respiratory disease [1-year AR: 9.5% (95% CI: 9.3%-9.8%)], followed by cardiovascular disease [1-year AR: 6.3% (95% CI: 5.9%-6.5%)], cancer [1-year AR: 6.0% (95% CI: 5.8%-6.4%)], venous thromboembolism [1-year AR: 5.2% (95% CI: 5.0%-5.2%)], and symptom diagnoses [1-year AR: 5.2% (95% CI: 5.0%-5.4%)]. Factors that were associated with an increased risk of rehospitalization were cancer, liver disease, chronic obstructive pulmonary disease, chronic kidney disease, and immobilization., Conclusion: Patients with PE have a high risk of rehospitalization, with almost half of patients being rehospitalized within 1 year. Identification of high-risk patients may help target interventions aiming at reducing the risk of rehospitalization., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: Patients with severely reduced kidney function have been excluded from randomized controlled trials and data on the safety and efficacy of direct oral anticoagulants (DOACs) according to kidney function remain sparse. The aim was to evaluate the safety and efficacy of the DOACs across subgroups of kidney function., Methods: Using multiple Danish nationwide registers and laboratory databases, we included patients initiated on oral anticoagulants (OACs) with atrial fibrillation and available creatinine level and followed patients for 2 years to evaluate occurrence of stroke/thromboembolism (TE) and major bleeding., Results: Among 26 686 included patients, 3667 (13.7%) had an estimated glomerular filtration rate (eGFR) of 30-49 mL/min/1.73 m2 and 596 (2.2%) had an eGFR below 30 mL/min/1.73 m2. We found no evidence of differences regarding the risk of stroke/TE between the OACs (P-value interaction >0.05 for all). Apixaban was associated with a lower 2-year risk of major bleeding compared to vitamin K antagonists (VKA) [hazard ratio 0.79, 95% confidence interval (CI) 0.67-0.93], and the risk difference was significantly larger among patients with reduced kidney function (P-value interaction 0.018). Rivaroxaban was associated with a higher risk of bleeding compared to apixaban (hazard ratio 1.78, 95%CI 1.32-2.39) among patients with eGFR 30-49 mL/min/1.73 m2., Conclusions: Overall, we found no differences regarding the risk of stroke/TE, but apixaban was associated with a 21% lower relative risk of major bleeding compared to VKA. This risk reduction was even greater when comparing apixaban to VKA among patients with eGFR 15-30 mL/min/1.73 m2, and when comparing apixaban to dabigatran and rivaroxaban among patients with eGFR 30-49 mL/min/1.73 m2., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Pressure-strain loop (PSL) analysis is a novel echocardiographic tool capable of assessing myocardial work non-invasively. In this study, we aim to evaluate the prognostic value of myocardial work indices in the general population., Methods and Results: This was a prospective community-based cohort study (n = 4466). PSL analyses were performed to acquire global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency (GWE). The endpoint was a composite of heart failure or cardiovascular death (HF/CVD). Survival analysis was applied. A total of 3932 participants were included in this analysis (median age: 58 years, 43% men). Of these, 124 (3%) experienced the outcome during a median follow-up period of 3.5 years [interquartile range (IQR): 2.6-4.4 years]. Hypertension significantly modified the association between all work indices and outcome (P for interaction < 0.05), such that work indices posed a higher risk of outcome in non-hypertensive than in hypertensive participants. After adjusting for Atherosclerosis Risk in Communities (ARIC)-HF risk variables, all work indices predicted outcome in non-hypertensive participants, but only GWI, GCW, and GWE predicted outcome in hypertensive participants [GWI: hazard ratio (HR) = 1.12 (1.07-1.16), per 100 mmHg% decrease; GCW: HR = 1.12 (1.08-1.17), per 100 mmHg% decrease; GWE: HR = 1.08 (1.04-1.12), per 1% decrease]. Only GWE significantly increased C-statistics when added to ARIC-HF risk variables in hypertensive participants (C-stat 0.865 vs. 0.877, P for increment = 0.003)., Conclusion: Hypertension modifies the association between myocardial work indices and HF/CVD in the general population. All work indices are associated with outcome in normotensive participants. GWI, GCW, and GWE are independently associated with outcome in hypertension, but only GWE improves risk prediction., Competing Interests: Conflict of interest: T.B.-S.: Steering Committee member of the Amgen financed GALACTIC-HF trial; Steering Committee of the Boston Scientific financed LUX-Dx TRENDS trial; Advisory Board: Sanofi Pasteur. Advisory Board: Amgen; Speaker Honorarium: Novartis; Speaker Honorarium: Sanofi Pasteur; Research grant: GE Healthcare; Research grant: Sanofi Pasteur. O.A.S.: co-inventor of ‘Method for myocardial segment work analysis’, which was used to calculate myocardial work indices. J.H.S.: advisory board member for Medtronic and unrestricted research grants from Medtronic outside this work. The organizations had no role in any aspect of the study. The remaining authors do not have any potential conflicts of interest to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Observational studies have reported lower risks of type 2 diabetes with higher vitamin K1 intake, but these studies overlook effect modification due to known diabetes risk factors., Objective: To identify subgroups that might benefit from vitamin K1 intake, we examined associations between vitamin K1 intake and incident diabetes overall and in subpopulations at risk of diabetes., Methods: Participants from the prospective cohort, the Danish Diet, Cancer, and Health Study, with no history of diabetes were followed up for diabetes incidence. The association between intake of vitamin K1, estimated from a food frequency questionnaire completed at baseline, and incident diabetes was determined using multivariable-adjusted Cox proportional-hazards models., Results: In 54 787 Danish residents with a median (interquartile range) age of 56 (52-60) years at baseline, 6700 individuals were diagnosed with diabetes during 20.8 (17.3-21.6) years of follow-up. Vitamin K1 intake was inversely and linearly associated with incident diabetes (P < .0001). Compared to participants with the lowest vitamin K1 intake (median:57 µg/d), participants with the highest intakes (median:191 µg/d) had a 31% lower risk of diabetes (HR; 95% CI, 0.69; 0.64-0.74) after multivariable adjustments. The inverse association between vitamin K1 intake and incident diabetes was present in all subgroups (namely, men and women, ever and never smokers, low and high physical activity groups, and in participants who were normal to overweight and obese), with differences in absolute risk between subgroups., Conclusion: Higher intake of foods rich in vitamin K1 was associated with a lower risk of diabetes. If the associations observed are causal, our results indicate that more cases of diabetes would be prevented in subgroups at higher risk (men, smokers, participants with obesity, and those with low physical activity)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Aims: The risk, characteristics, and outcome of out-of-hospital cardiac arrest (OHCA) in patients with congenital heart disease (CHD) remain scarcely investigated., Methods and Results: An epidemiological registry-based study was conducted. Using time-dependent Cox regression models fitted with a nested case-control design, hazard ratios (HRs) with 95% confidence intervals of OHCA of presumed cardiac cause (2001-19) associated with simple, moderate, and severe CHD were calculated. Moreover, using multiple logistic regression, we investigated the association between pre-hospital OHCA characteristics and 30-day survival and compared 30-day survival in OHCA patients with and without CHD. Overall, 43 967 cases (105 with simple, 144 with moderate, and 53 with severe CHD) and 219 772 controls (median age 72 years, 68.2% male) were identified. Any type of CHD was found to be associated with higher rates of OHCA compared with the background population [simple CHD: HR 1.37 (1.08-1.70); moderate CHD: HR 1.64 (1.36-1.99); and severe CHD: HR 4.36 (3.01-6.30)]. Pre-hospital cardiopulmonary resuscitation and defibrillation were both associated with improved 30-day survival in patients with CHD, regardless of CHD severity. Among patients with OHCA, simple, moderate, and severe CHD had a similar likelihood of 30-day survival compared with no CHD [odds ratio 0.95 (0.53-1.69), 0.70 (0.43-1.14), and 0.68 (0.33-1.57), respectively]., Conclusion: A higher risk of OHCA was found throughout the spectrum of CHD. Patients with and without CHD showed the same 30-day survival, which relies on the pre-hospital chain of survival, namely cardiopulmonary resuscitation and defibrillation., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Influenza vaccination protects against morbidity and mortality in patients with cardiovascular disease (CVD). We aimed to describe influenza vaccine uptake in patients with CVD in a universal-access healthcare system., Methods: Using nationwide Danish registries, we included all patients with prevalent CVD, defined as heart failure (HF), atrial fibrillation (AF), ischemic heart disease (IHD), or stroke during three consecutive influenza seasons (October-December 2017-2019). The outcome was relative frequency of influenza vaccination across strata of patient characteristics., Results: There was an average of 397 346 patients with CVD yearly during 2017-2019. Vaccine uptake was 45.6% for the whole population and ranged from 55.0% in AF to 61.8% in HF among patients aged ≥65 years. Among patients aged <65 years, uptake was 32.6% in HF, 19.0% in AF, 21.1% in IHD, and 18.3% in stroke. There was a lower uptake with decreasing age: 21.6% in HF, 5.5% in AF, 7.4% in IHD, and 6.3% in stroke among males aged <45 years, as opposed to 25.5% in HF, 11.5% in AF, 13.8% in IHD, and 12.1% in stroke for males aged 45-54 years. In the further stratified analyses, uptake ranged from a low of 2.5% for males <45 years with AF who were not vaccinated the previous season to a high of 87.0% for females ≥75 years with IHD who were vaccinated the previous season., Conclusion: Seasonal influenza vaccine uptake is suboptimal among patients with CVD, even in a universal-access healthcare system with free-of-charge vaccinations. Vaccine uptake was particularly low among young patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Cancer and heart failure (HF) share risk factors, pathophysiological mechanisms, and possibly genetics. Improved HF survival may increase the risk of cancer due to a competing risk. Whether the incidence of cancer has increased over time in patients with HF as survival has improved is unclear. Therefore, temporal trends of new onset cancer in HF patients between 1997 and 2016 were investigated., Methods and Results: Using Danish nationwide registers, 103 711 individuals alive, free of cancer, and aged 30-80 years 1 year after HF diagnosis (index date) were included between 1 January 1997 and 31 December 2016. A five-year incidence rate of cancer for each year after index date was calculated. The median age and proportion of women at the index date decreased with advancing calendar time [1997-2001: 70.3 interquartile range (Q1-Q3 62.5-75.7), 60.9% men; 2012-16: 67.6 (59.2-73.8), 67.5% men]. The five-year incidence rate of cancer was 20.9 and 20.2 per 1,000 person-years in 1997 and 2016, respectively. In a multivariable Cox regression model, the hazard rates between index years 1997 (reference) and 2016 were not significantly different [hazard ratio 1.09 (0.97-1.23)]. The five-year absolute risk of cancer did not change with advancing calendar year, going from 9.0% (1997-2001) to 9.0% (2012-16). Five-year cumulative incidence of survival for HF patients increased with advancing calendar year, going from 55.9% (1997-2001) to 74.3% (2012-2016)., Conclusion: Although cancer rates during 1997-2016 have remained stable within 1-6 years after the HF diagnosis, long-term survival following a HF diagnosis has increased significantly., Competing Interests: Conflict of interest: C.H.G. reports personal fees from lectures honorarium from Astra Zeneca unrelated to the work in question; C.T.-P. reports grants from Bayer and Novo Nordisk unrelated to the work in question; J.V.M. reports grants from Abbott, Alkem Metabolics, Eris Lifesciences, Hikma, Lupin, Sun Pharmaceuticals, Medscape/Heart.Org, ProAdWise Communications, Radcliffe Cardiology, Servier, the Corpus unrelated to the work in question; N.N.L. reports grants from Roche Diagnostics, Boehringer Ingelheim, AstraZeneca, NIHR and British Heart Foundation. Further, reports lecturer fees from Roche, Pfizer, and Novartis and consulting fees from AstraZeneca. All unrelated to the work in question; L.K. reports personal fees from speakers honorarium from Novo Nordisk, Novartis, AstraZeneca and Boehringer Ingelheim outside the submitted work; M.S. reports personal fees from lectures honorarium from Novo Nordisk, Novartis, AstraZeneca, and Boehringer Ingelheim outside the submitted work., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: In a continuously ageing population of patients with congenital heart disease (CHD), understanding the long-term risk of morbidity is crucial. The aim of this study was to compare the lifetime risks of developing comorbidities in patients with simple CHD and matched controls., Methods and Results: Using the Danish nationwide registers spanning from 1977 to 2018, simple CHD cases were defined as isolated atrial septal defect (ASD), ventricular septal defect (VSD), pulmonary stenosis, or patent ductus arteriosus in patients surviving until at least 5 years of age. There were 10 controls identified per case. Reported were absolute lifetime risks and lifetime risk differences (between patients with simple CHD and controls) of incident comorbidities stratified by groups and specific cardiovascular comorbidities. Of the included 17 157 individuals with simple CHD, the largest subgroups were ASD (37.7%) and VSD (33.9%), and 52% were females. The median follow-up time for patients with CHD was 21.2 years (interquartile range: 9.4-39.0) and for controls, 19.8 years (9.0-37.0). The lifetime risks for the investigated comorbidities were higher and appeared overall at younger ages for simple CHD compared with controls, except for neoplasms and chronic kidney disease. The lifetime risk difference among the comorbidity groups was highest for neurological disease (male: 15.2%, female: 11.3%), pulmonary disease (male: 9.1%, female: 11.7%), and among the specific comorbidities for stroke (male: 18.9%, female: 11.4%). The overall risk of stroke in patients with simple CHD was mainly driven by ASD (male: 28.9%, female: 17.5%), while the risks of myocardial infarction and heart failure were driven by VSD. The associated lifetime risks of stroke, myocardial infarction, and heart failure in both sexes were smaller in invasively treated patients compared with untreated patients with simple CHD., Conclusion: Patients with simple CHD had increased lifetime risks of all comorbidities compared with matched controls, except for neoplasms and chronic kidney disease. These findings highlight the need for increased attention towards early management of comorbidity risk factors., Competing Interests: Conflict of Interest: Christian-Torp Pedersen has received grants for studies from Bayer and Novo Nordisk unrelated to the current study. Matthew Phelps has, after the initial submission of this paper, been employed by Novo Nordisk unrelated to this study. The other authors have no potential conflicts of interest to declare in relation to the publication this article., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Valvular event timing is an integral part of echocardiographic pressure-strain loop (PSL) analyses. The impact that different event timing modalities may have on myocardial work indices is unknown., Methods and Results: A methodological study was performed on 200 subjects, including 50 healthy subjects, 50 with aortic valve sclerosis, 50 with atrial fibrillation, and 50 with reduced left ventricular ejection fraction. Valvular event timing was estimated by visual assessment, spectral Doppler, and colour tissue Doppler imaging (TDI) M-mode. These valvular event timings were added to the same PSL analyses sequentially to acquire myocardial work indices, including global work index (GWI). For the 200 participants, the median age was 72 years, 50% were men, and mean blood pressure was 143/80 mmHg. Valvular event timings differed between all three modalities and so did all myocardial work indices. Compared with visual assessment, spectral Doppler resulted in a significantly higher GWI (mean difference: 114 ± 93 mmHg%, P < 0.001), and so did TDI (mean difference: 83 ± 90 mmHg%, P < 0.001). A higher GWI by spectral Doppler than by TDI was also observed (mean difference: 30 ± 53 mmHg%, P < 0.001). In the healthy subgroup, a systematic bias was observed for spectral Doppler compared with visual assessment (mean difference: 160 ± 77 mmHg%, P < 0.001), and a similar trend was noted for TDI vs. visual assessment (mean difference: 124 ± 74 mmHg%, P < 0.001)., Conclusion: Myocardial work indices differ depending on the event timing modality used, with visual assessment yielding lower GWI values compared with Doppler-based methods. Serial PSL analyses should apply the same event timing method., Competing Interests: Conflict of interest: B.-S.: Steering Committee: Amgen financed GALACTIC-HF trial; the Boston Scientific financed LUX-Dx TRENDS trial; Advisory Board: Sanofi Pasteur; Amgen; Speaker Honorarium: Novartis; Sanofi Pasteur; GSK; research grant: GE Healthcare; Sanofi Pasteur. J.H.S.: advisory board, speaker fee, and research grant: Medtronic. P.S.: consulting fees and speaker honoraria for Biotronic. Remaining others: none., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: Overweight is associated with increased risk of atrial fibrillation (AF), but the impact of overweight and AF recurrence after ablation is less clear. Despite this, an increasing number of AF ablations are carried out in overweight patients. We investigated the impact of body mass index (BMI) on AF recurrence rates after ablation., Methods and Results: Through Danish nationwide registers, all patients undergoing first-time AF ablation between 2010 and 2018 were identified. Exposure of interest was BMI. The primary outcome was recurrent AF, defined from either any usage of antiarrhythmic medication, AF hospitalization, cardioversion, or re-ablation. A total of 9188 patients were included. Median age and interquartile range was 64 (60-75) in the normal-weight group and 60 (53-66) in the morbidly obese. There was an increase in comorbidity burden with increasing BMI, including a higher prevalence of heart failure, chronic obstructive pulmonary disease, diabetes, and hypertension. At 1- and 5-year follow ups, recurrence rates of AF increased incrementally by BMI categories. The hazard ratios and 95% confidence intervals of recurrent AF after ablation were 1.15 (1.07-1.23), 1.18 (1.09-1.28), and 1.26 (1.13-1.41) in overweight, obese, and morbidly obese, respectively, compared with normal-weight patients. Procedure duration and X-ray dose exposure also increased with increasing BMI., Conclusion: Following AF ablation, recurrence rates of AF increased incrementally with increasing BMI. Therefore, aggressive weight management pre ablation in overweight patients could potentially provide substantial benefits and improve short- and long-term outcomes after ablation., Competing Interests: Conflict of interest: JH has received consultant fees and speaker honoraria from Biosense Webster, Medtronic, and Boston Scientific, and research funding from Biosense Webster and Medtronic. R.H.W. has received consultant fees, speaker honoraria, and research funding from Biosense Webster. All remaining authors have declared no conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Outcomes after myocardial infarction (MI) improved during recent decades alongside better risk factor management and implementation of guideline-recommended treatments. However, it is unknown whether this applies to stable patients who are event-free 1 year after MI., Methods and Results: Using nationwide Danish registries, we included all patients with first-time MI during 2000-17 who survived 1 year free from bleeding and cardiovascular events (n = 82 108, median age 64 years, 68.2% male). Follow-up started 1 year after MI and continued through January 2022. Crude risks of mortality, cardiovascular events, and bleeding were estimated in consecutive 3-year periods. Standardized risks were calculated with respect to the distribution of age, sex, comorbidities, and treatments in the latter period. Guideline-recommended treatment use increased during the study period: e.g. statins (68.6-92.5%) and percutaneous coronary intervention (23.9-68.2%). The crude 5-year risks of outcomes decreased (all P-trend <0.001): Mortality, 18.6% (95% confidence interval [CI]: 17.9-19.2) to 12.5% (CI: 11.9-13.1); Recurrent MI, 7.5% (CI: 7.1-8.0) to 5.5% (CI: 5.1-6.0); Bleeding, 3.9% (CI: 3.6-4.3) to 2.7% (CI: 2.4-3.0). Crude 5-year risk of mortality in 2015-17 was as low as 2.6% for patients aged <60 years. Use of guideline-recommended treatments was associated with improved outcomes: After standardization for changes in treatments, 5-year risk of mortality in 2000-02 was 15.5% (CI: 14.9-16.2)., Conclusions: For patients who were event-free 1 year after MI, the long-term risks of mortality, cardiovascular events, and bleeding decreased significantly, along with an improved use of guideline-recommended treatments between 2000 and 2017. In the most recent period, 1 year after MI, the risk of additional events was lower than previously reported., Competing Interests: Conflict of interest: LS is employed by Novo Nordisk without relation to the current study. ACR reports aspeaker’s fee from Novartis. EF reports independent research grants from the Novo Nordisk Foundation and the Danish Heart Foundation without relation to the current study. LK reports speaker’s fees from Novo Nordisk, Novartis, Boehringer Ingelheim,AstraZeneca, and Bayer. CTP reports study grants from Bayer and Novo Nordisk without relation to the current study. MS reports lecture fees from Novo Nordisk, Astra Zeneca, Novartis, and Boehringer Ingelheim outside the current study. All author authors had no conflicts of interest to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Return to work and employment maintenance following cardiovascular disease (CVD) are important rehabilitation goals for people of working age. To identify people in particular need of vocational rehabilitation, we examined differences in return to work and subsequent detachment from employment among people with atrial fibrillation (AF), heart failure (HF), heart valve disease, and ischaemic heart disease., Methods and Results: We conducted a nationwide cohort study and included all individuals of working age (35-65 years) who were employed when diagnosed with incident CVD in 2018. We estimated sex- and age-standardized probabilities of remaining employed at 3, 6, and 12 months after diagnosis, and of detachment from employment within 6 months after having returned to work. Of 46 912 individuals diagnosed in 2018, 8187 were of working age and employed at diagnosis. The mean age was 54.7 years (SD = 6.7), and 74.0% were men. Within 1 year, 89.8% had returned to work, but within the subsequent 6 months, 23.5% of these experienced detachment from employment. At 3, 6, and 12 months after diagnosis the highest standardized probability of being employed was found among people with AF, whereas the lowest probability was found among people with HF {78.9% [95% confidence interval (CI): 77.3-80.4] vs. 62.2% [95% CI: 59.0-65.4] at 12 months}. Similarly, the highest probability of detachment was found for people with HF [30.3% (95% CI: 26.9-33.7)]., Conclusion: People with HF present the highest probability of not returning to work. There is a need for developing and documenting effects of vocational rehabilitation strategies within comprehensive cardiac rehabilitation programmes., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: A pattern of reduced basal longitudinal strain (BLS) is often observed with left ventricular (LV) hypertrophy (LVH). Whether this pattern is associated with poor outcome is unclear. We aimed to evaluate the prognostic value of regional longitudinal strain according to LV geometry., Methods and Results: We investigated participants in the 4th Copenhagen City Heart Study who had an echocardiogram with speckle tracking performed. Participants were stratified according to the presence of LVH (LV mass index ≥116 g/m2 for men and ≥96 g/m2 for women). The outcome was major adverse cardiovascular events (MACE) defined as a composite of myocardial infarction, heart failure, and/or cardiovascular death. The study population consisted of 1090 participants. Mean LVEF was 60% and 160 (15%) had LVH. During a median follow-up of 14.7 years, there were 137 events. Both BLS and midventricular strain, but not apical strain, became incrementally impaired in the spectrum from normal to hypertensives subjects without LVH, and to participants with hypertension and LVH. After multivariable adjustment, BLS and midventricular strain were independently associated with MACE in participants with LVH (BLS: HR 1.08, 95% CI 1.00-1.17, P = 0.041; midventricular strain: HR 1.10, 95% CI 1.00-1.21, P = 0.041) but not in participants without LVH (BLS: HR 0.96, 95% CI 0.90-1.01, P = 0.13; midventricular strain: HR 0.97, 95% CI 0.91-1.03, P = 0.36)., Conclusion: BLS and midventricular strain, but not apical strain, become incrementally impaired in the spectrum from normal geometry to LVH, and are independently associated with MACE in participants with LVH., Competing Interests: Conflict of interest: K.E.F.-M. was supported by a travel grant from the William Demant Foundation. F.J.O was funded by a research grant from the Danish Heart Foundation (Grant no.: 18-R125-A8534-22083). T.B.-S. was supported by grants from the Fondsbørsvekselerer Henry Hansen og Hustrus Hovedlegat and the Lundbeck Foundation. All other authors declared no conflict of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: To compare the effectiveness and safety of clopidogrel, ticagrelor, and prasugrel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI)., Methods and Results: Nationwide, registry-based study of STEMI patients treated with primary PCI (2011-17) and subsequently with aspirin and a P2Y12 inhibitor. The effectiveness outcome was major adverse cardiovascular events (MACE) defined as a composite of recurrent myocardial infarction, repeat revascularization, stroke, or cardiovascular death at 12 months. The safety outcome was bleeding requiring hospitalization at 12 months. Multivariable logistic regression with average treatment effect modeling was used to calculate absolute and relative risks for outcomes standardized to the distributions of demographic characteristics of all included subjects. We included 10 832 patients; 1 697 were treated with clopidogrel, 7 508 with ticagrelor, and 1,627 with prasugrel. Median ages were 66, 63, and 59 years (P < 0.001). Standardized relative risks of MACE were 0.75 for ticagrelor vs. clopidogrel (95% confidence interval [CI], 0.64-0.83), 0.84 for prasugrel vs. clopidogrel (95% CI, 0.73-0.94), and 1.12 for prasugrel vs. ticagrelor (95% CI, 1.00-1.24). Standardized relative risks of bleeding were 0.77 for ticagrelor vs. clopidogrel (95% CI, 0.59-0.93), 0.89 for prasugrel vs. clopidogrel (95% CI, 0.64-1.15), and 1.17 for prasugrel vs. ticagrelor (95% CI, 0.89-1.45)., Conclusion: Ticagrelor and prasugrel were associated with lower risks of MACE after STEMI than clopidogrel, and ticagrelor was associated with a marginal reduction compared with prasugrel. The risk of bleeding was lower with ticagrelor compared with clopidogrel, but did not significantly differ between ticagrelor and prasugrel., Competing Interests: Conflict of interest: D.L.B. discloses the following relationships—Advisory Board: AngioWave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, Stasys; Board of Directors: AngioWave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, TobeSoft; Chair: Inaugural Chair, American Heart Association Quality Oversight Committee; Consultant: Broadview Ventures; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), Wiley (steering committee); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither I nor Brigham and Women's Hospital receive any income from this patent.) Research Funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, 89Bio; Royalties: Elsevier (Editor, Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Takeda. M.P. discloses the following relationships—Advisory Board: AstraZeneca, Janssen-Cilag; Speaker’s Fee: AstraZeneca, Bayer, Boehringer Ingelheim, Janssen-Cilag. The remaining authors declare no conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: Using Scandinavian population-based registries, we assessed risk of stroke/systemic embolism (SE) and bleeding with non-vitamin K antagonist oral anticoagulants compared with warfarin in anticoagulation-naïve patients with atrial fibrillation (AF)., Methods and Results: This historical cohort study included 219 545 AF patients [median age 74 years; 43% women; mean CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischaemic attack, vascular disease, age 65-74 years, sex category) score 3.3] initiating apixaban, dabigatran, rivaroxaban, or warfarin in Denmark, Norway, and Sweden (1 January 2013 to 31 December 2016). The primary endpoints were stroke/SE and major bleeding. The median follow-up times were 9.7 (3.9-21.5) months for stroke/SE and 9.6 (3.8-21.3) months for bleeding. Apixaban and warfarin initiators were older and had higher CHA2DS2-VASc scores compared with dabigatran and rivaroxaban initiators. After 1:1 propensity score matching, three cohorts were created: apixaban-warfarin (n = 111 162), dabigatran-warfarin (n = 56 856), and rivaroxaban-warfarin (n = 61 198). Adjusted hazard ratios (HRs) were estimated using a Cox regression. For stroke/SE, adjusted HRs against warfarin were 0.96 [95% confidence interval (CI): 0.87-1.06] for apixaban, 0.89 (95% CI: 0.80-1.00) for dabigatran, and 1.03 (95% CI: 0.92-1.14) for rivaroxaban. For major bleeding, the HRs against warfarin were 0.73 (95% CI: 0.67-0.78) for apixaban, 0.89 (95% CI: 0.82-0.97) for dabigatran, and 1.15 (95% CI: 1.07-1.25) for rivaroxaban. The results in the dabigatran cohort did not hold in all dose-defined subgroups., Conclusion: In this large Scandinavian study among AF patients initiating oral anticoagulation, those initiating dabigatran, apixaban, and rivaroxaban had similar rates of stroke/SE to patients initiating warfarin. Rates of major bleeding were lower with apixaban and dabigatran and higher with rivaroxaban, each compared with warfarin., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Physical and mental well-being after critical illness may be objectified by the ability to work. We examined return to work among patients with myocardial infarction (MI) by cardiogenic shock (CS) status., Methods: Danish nationwide registries were used to identify patients with first-time MI by CS status between 2005 and 2015, aged 18-63 years, working before hospitalization and discharged alive. Multiple logistic regression models were used to compare groups., Results: We identified 19 799 patients with MI of whom 653 had CS (3%). The median age was similar for patients with and without CS (53 years, interquartile range 47-58). One-year outcomes in patients with and without CS were as follows: 52% vs. 83% returned to work, 41% vs. 16% did not and 6% vs. 1% died. The adjusted odds ratio (OR) of returning to work was 0.53 [95% confidence limit (CI): 0.42-0.66]. In patients with CS, males and patients surviving OHCA were more likely to return to work (OR: 1.83, 95% CI: 1.15-2.92 and 1.55, 95% CI: 1.00-2.40, respectively), whereas prolonged hospitalization (OR: 0.38, 95% CI: 0.22-0.65) and anoxic brain damage (OR: 0.36, 95% CI: 0.18-0.72) were associated with lower likelihood of returning to work., Conclusion: In patients with MI discharged alive, approximately 80% of those without CS returned to work at 1-year follow-up in contrast to 50% of those with CS. Among patients with CS, male sex and OHCA survivors were markers positively related to return to work, whereas prolonged hospitalization and anoxic brain damage were negatively related markers., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: The aim of this study was to evaluate the risk of discontinuing treatment with direct oral anticoagulants (DOACs) among patients with atrial fibrillation (AF) according to cohabitation status and gender., Methods and Results: Using the Danish national registers, we identified 32 364 patients with AF aged 40-90 years undergoing treatment with DOACs. The study period was from 2013 to 2017, and patients were followed for 2 years, or until death, outcome, or emigration. The main outcome was discontinuation of DOAC treatment for at least 30 days. The absolute 2-year risk of DOAC discontinuation was highest among men living alone [35.7%, 95% confidence interval (CI): 37.3-34.1%]. Men living alone had a 4.6% (95% CI: 6.4-2.8%) higher absolute risk of discontinuation and a 12% [hazard ratio (HR): 1.12, 95% CI: 1.04-1.20] higher relative risk of discontinuation compared with men living with a partner. Female patients living alone likewise had a higher absolute risk of DOAC discontinuation (2.6%, 95% CI: 4.4-0.09%) compared with female patients living with a partner, yet no statistically significant difference in relative risk. In an analysis evaluating gender, we found male gender to be associated with a significantly higher relative risk of DOAC discontinuation (HR: 1.33, 95% CI: 1.26-1.40) compared with female gender (P-value for interaction with cohabitant status = 0.5996)., Conclusion: In this nationwide population study, male gender and living alone were associated with a higher risk of DOAC discontinuation among patients with AF., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Left atrial enlargement predicts incident atrial fibrillation (AF). However, the prognostic value of peak atrial longitudinal strain (PALS) for predicting incident AF in participants from the general population is currently unknown. Our aim was to investigate if PALS can be used to predict AF and ischaemic stroke in the general population., Methods and Results: A total of 400 participants from the general population underwent a health examination, including two-dimensional speckle tracking echocardiography of the left atrium. The primary endpoint was incident AF at follow-up. All participants with known AF and prior stroke at baseline were excluded (n = 54). The secondary endpoint consisted of the composite of AF and ischaemic stroke. During a median follow-up of 16 years, 36 participants (9%) were diagnosed with incident AF and 30 (7%) experienced an ischaemic stroke, resulting in 66 (16%) experiencing the composite outcome. PALS was a univariable predictor of AF [per 5% decrease: hazard ratio (HR) 1.42; 95% confidence interval (CI) (1.19-1.69), P < 0.001]. However, the prognostic value of PALS was modified by age (P = 0.002 for interaction). After multivariable adjustment PALS predicted AF in participants aged <65 years [per 5% decrease: HR 1.46; 95% CI (1.06-2.02), P = 0.021]. In contrast, PALS did not predict AF in participants aged ≥65 years after multivariable adjustment [per 5% decrease: HR 1.05; 95% CI (0.81-1.35), P = 0.72]. PALS also predicted the secondary endpoint in participants aged <65 years and the association remained significant after multivariable adjustment., Conclusion: In a low-risk general population, PALS provides novel prognostic information on the long-term risk of AF and ischaemic stroke in participants aged <65 years., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: We examined associations between symptom presentation and chance of receiving an emergency dispatch and 30-day mortality among patients with acute myocardial infarction (MI)., Methods and Results: Copenhagen, Denmark has a 24-h non-emergency medical helpline and an emergency number 1-1-2 (equivalent to 9-1-1). Both services register symptoms/purpose of calls. Among patients with MI as either hospital diagnosis or cause of death within 72 h after a call, the primary symptom was categorized as chest pain, atypical symptoms (breathing problems, unclear problem, central nervous system symptoms, abdominal/back/urinary, other cardiac symptoms, and other atypical symptoms), unconsciousness, non-informative symptoms, and no recorded symptoms. We identified 4880 emergency and 3456 non-emergency calls from patients with MI. The most common symptom was chest pain (N = 5219) followed by breathing problems (N = 556). Among patients with chest pain, 95% (3337/3508) of emergency calls and 76% (1306/1711) of non-emergency calls received emergency dispatch. Mortality was 5% (163/3508) and 3% (49/1711) for emergency/non-emergency calls, respectively. For atypical symptoms 62% (554/900) and 17% (137/813) of emergency/non-emergency calls received emergency dispatch and mortality was 23% (206/900) and 15% (125/813). Among unconscious, patients 99%/100% received emergency dispatch and mortality was 71%/75% for emergency/non-emergency calls. Standardized 30-day mortality was 4.3% for chest pain and 15.6% for atypical symptoms, and associations between symptoms and emergency dispatch remained in subgroups of age and sex., Conclusion: Myocardial infarction patients presenting with atypical symptoms when calling for help have a reduced chance of receiving an emergency dispatch and increased 30-day mortality compared to MI patients with chest pain., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Aims: Due to an ageing population and increasing survival from concurrent diseases, the burden of left-sided degenerative valvular heart disease is expected to increase over time. This study aims at determining the temporal trends in incidence rates at the population level and examines whether there are socioeconomic differences., Methods and Results: A total of 133 209 patients were identified with a first-time diagnosis of aortic stenosis (AS), mitral regurgitation (MR), or aortic regurgitation (AR) in the Danish National Patient Registry in the 2000-17 period. Incidence rates (per 100 000 person-years) doubled over the period for AS (57 in 2000-02; 114 in 2015-17) and for AR (22 in 2000-02; 41 in 2015-17) and remained the same for MR (38 in both 2000-02 and 2015-17). Incidence rates increased rapidly with increasing age, most markedly for AS. Men had a higher risk of being affected [relative risk (RR) 1.69 for AS, 1.19 for MR, 1.35 for AR]. Compared to high-level education, patients with medium- and low-level education had a higher risk of being affected (RR 1.18 for AS medium level and 1.47 for AS low level; 1.03 for MR medium level and 1.14 for MR low level; 1.03 for AR medium level and 1.18 for AR low level)., Conclusions: For AS and AR, the incidence rates doubled, while the incidence rates remained at the same level for MR. The risk of being affected increased with advanced age and male gender. Patients with low-level education had a higher risk of being affected compared to patients with high-level education, especially among patients with AS., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: Patients are restricted from driving following implantable cardioverter defibrillator (ICD) implantation or shock. We sought to investigate how many patients are aware of, and adhere to, the driving restrictions, and what proportion experience an ICD shock or other cardiac symptoms while driving., Methods and Results: We performed a nationwide survey of all living Danish residents 18 years or older who received a first-time ICD between 2013 and 2016 (n = 3913) and linked their responses with nationwide registers. Of 2741 respondents (47% primary prevention, 83% male, median age 67 years), 2513 (92%) held a valid driver's license at ICD implantation, 175 (7%) of whom had a license for professional driving. Many drivers were unaware of driving restrictions: primary prevention 58%; secondary prevention 36%; post-appropriate shock 28%; professional drivers 55%. Almost all (94%) resumed non-professional driving after ICD implantation, more than one-third during the restricted period; 35% resumed professional driving. During a median follow-up of 2.3 years, 5 (0.2%) reported receiving an ICD shock while driving, one of which resulted in a traffic accident. The estimated risk of harm was 0.0002% per person-year., Conclusion: In this nationwide study, many ICD patients were unaware of driving restrictions, and more than one third resumed driving during a driving restriction period. However, the rate of reported ICD shocks while driving was very low., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Aims: Global longitudinal strain (GLS) is a strong predictor of adverse cardiovascular outcome in men. However, studies have indicated that GLS may not predict cardiovascular outcomes as effectively in women. The aim of this study was to identify echocardiographic predictors of cardiovascular morbidity and mortality in women from the general population., Methods and Results: A total of 1245 women from the general population free of heart failure (HF) and atrial fibrillation had an echocardiographic examination performed including tissue Doppler imaging. In this subset, 747 women had images eligible for strain analysis. Endpoint was a composite of acute myocardial infarction, HF, and cardiovascular death. During follow-up (median 12.5 years), 162 women (13.0%) reached the composite outcome. These women had higher left ventricular (LV) mass index (LVMI), more LV hypertrophy, lower E/A, higher E/e', larger LV dimensions, and longer deceleration time. LVMI and e' remained as significant predictors of the composite outcome [LVMI: hazard ratio (HR) 1.10, 95% confidence interval (CI) 1.03-1.17, P = 0.004, per 5 g/m2 increase] (e': HR 1.53, 95% CI 1.07-2.20, P = 0.020, per 1 cm/s decrease) after adjusting for age, hypertension, systolic blood pressure, diabetes mellitus, total cholesterol, smoking status, prevalent ischaemic heart disease, LV ejection fraction, E/e', E, E/A, interventricular septum thickness in diastole, left ventricular posterior wall in diastole, a', body surface area, and pro-brain natriuretic peptide. GLS was not an independent predictor of outcome after multivariable adjustment., Conclusion: The degree of LV hypertrophy assessed as LVMI and diastolic dysfunction evaluated by e' are associated with adverse cardiovascular outcome in women from the general population., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: Reports have suggested an increased risk of aortic and mitral regurgitation associated with oral fluoroquinolones (FQs) resulting in a safety warning published by the European Medicines Agency (EMA). However, these findings have not yet been replicated., Methods and Results: Using Danish administrative registers, we conducted a nested case-control study in a nationwide cohort of individuals between 2005 and 2018. Cases were defined as the first occurrence of aortic or mitral regurgitation. Exposure of interest was the use of oral FQs. Hazard ratios (HRs) with 95% confidence intervals (95% CI) were obtained by fitting time-dependent Cox regression models, with penicillin V as comparator, to assess the association between FQ use and incident valvular regurgitation. We identified 38 370 cases of valvular regurgitation with 1 115 100 matched controls. FQ exposure was not significantly associated with increased rates of aortic or mitral regurgitation (HR 1.02, 95% CI 0.95-1.09) compared with penicillin V users. Investigating the cumulative defined daily doses (cDDD) of FQs yielded similar results with no significant association between increasing FQ use and valvular regurgitation (e.g. HR 1.08, 95% CI 0.95-1.23 for cDDD >10 compared with cDDD 1-5). These results were consistent across several analyses including a cohort of patients with hypertension and using a case definition based on valvular surgical interventions., Conclusions: In a nationwide nested case-control study, FQs were not significantly associated with increased rates of valvular regurgitation. Our findings do not support a possible causal connection between FQ exposure and incident valvular regurgitation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Objective: Hypoglycemia is associated with an increased risk of cardiovascular disease including cardiac arrhythmias. We investigated the effect of hypoglycemia in the setting of acute glycemic fluctuations on cardiac rhythm and cardiac repolarization in insulin-treated patients with type 2 diabetes compared with matched controls without diabetes., Design: A non-randomized, mechanistic intervention study., Methods: Insulin-treated patients with type 2 diabetes (n = 21, age (mean ± s.d.): 62.8 ± 6.5 years, BMI: 29.0 ± 4.2 kg/m2, HbA1c: 6.8 ± 0.5% (51.0 ± 5.4 mmol/mol)) and matched controls (n = 21, age: 62.2 ± 8.3 years, BMI 29.2 ± 3.5 kg/m2, HbA1c: 5.3 ± 0.3% (34.3 ± 3.3 mmol/mol)) underwent a sequential hyperglycemic and hypoglycemic clamp with three steady-states of plasma glucose: (i) fasting plasma glucose, (ii) hyperglycemia (fasting plasma glucose +10 mmol/L) and (iii) hyperinsulinemic hypoglycemia (plasma glucose < 3.0 mmol/L). Participants underwent continuous ECG monitoring and blood samples for counterregulatory hormones and plasma potassium were obtained., Results: Both groups experienced progressively increasing heart rate corrected QT (Fridericia's formula) interval prolongations during hypoglycemia ((∆mean (95% CI): 31 ms (16, 45) and 39 ms (24, 53) in the group of patients with type 2 diabetes and controls, respectively) with similar increases from baseline at the end of the hypoglycemic phase (P = 0.43). The incidence of ventricular premature beats increased significantly in both groups during hypoglycemia (P = 0.033 and P < 0.0001, respectively). One patient with type 2 diabetes developed atrial fibrillation during recovery from hypoglycemia., Conclusions: In insulin-treated patients with type 2 diabetes and controls without diabetes, hypoglycemia causes clinically significant and similar increases in cardiac repolarization that might increase vulnerability for serious cardiac arrhythmias and sudden cardiac death.

Aims: To examine socioeconomic differences in care and outcomes in a 1-year period beginning 30 days after hospital discharge for first-time atrial fibrillation or flutter (AF) hospitalization., Methods and Results: This nationwide register-based follow-up cohort study investigated AF 30-day discharge survivors in Denmark during 2005-2014 and examined associations between patient's socioeconomic status (SES) and selected outcomes during a 1-year follow-up period beginning 30 days post-discharge after first-time hospitalization for AF. Patient SES was defined in four groups (lowest, second lowest, second highest, and highest) according to each patient's equivalized income. SES of the included 150 544 patients was: 27.7% lowest (n = 41 648), 28.1% second lowest (n = 42 321), 23.7% second highest (n = 35 656), and 20.5% highest (n = 30 919). Patients of lowest SES were older and more often women. Within 1-year follow-up, patients of lowest SES were less often rehospitalized or seen in outpatient clinics due to AF, or treated with cardioversion or ablation and were slightly more often diagnosed with stroke and heart failure (HF) and significantly more likely to die (16.1% vs. 14.9%, 11.3% and 8.1%). Hazard ratios for all-cause mortality were 0.64 (95% confidence interval 0.61-0.68) for highest vs. lowest SES, adjusted for CHA2DS2-VASc score, chronic obstructive pulmonary disease, rate- and rhythm-controlling drugs, and cohabitation status., Conclusion: In 30-day survivors of first-time hospitalization due to AF, lowest SES is associated with increased 1-year all-cause and cardiovascular mortality and fewer cardioversions, ablations, readmissions, and outpatient contacts due to AF. Our findings indicate a need for socially differentiated rehabilitation following hospital discharge for first-time AF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: The study aimed to estimate the risk of cardiac events in immune checkpoint inhibitor (ICI)-treated patients with lung cancer or malignant melanoma., Methods and Results: The study included consecutive patients with lung cancer or malignant melanoma in 2011-17 nationwide in Denmark. The main composite outcome was cardiac events (arrhythmia, peri- or myocarditis, heart failure) or cardiovascular death. Absolute risks were estimated and the association of ICI and cardiac events was analysed in multivariable Cox models. We included 25 573 patients with lung cancer. Of these, 743 were treated with programmed cell death-1 inhibitor (PD1i) and their 1-year absolute risk of cardiac events was 9.7% [95% confidence interval (CI) 6.8-12.5]. Of the 13 568 patients with malignant melanoma, 145 had PD1i and 212 had cytotoxic T-lymphocyte-associated protein-4 inhibitor (CTLA-4i) treatment. Their 1-year risks were 6.6% (1.8-11.3) and 7.5% (3.7-11.3). The hazard rates of cardiac events were higher in patients with vs. without ICI treatment. Within 6 months from 1st ICI administration, the hazard ratios were 2.14 (95% CI 1.50-3.05) in patients with lung cancer and 4.30 (1.38-13.42) and 4.93 (2.45-9.94) in patients with malignant melanoma with PD1i and CTLA-4i, respectively. After 6 months, HRs were 2.26 (1.27-4.02) for patients with lung cancer and 3.48 (1.91-6.35) for patients with malignant melanoma and CTLA-4i., Conclusions: Among patients with lung cancer and malignant melanoma, ICI treated had increased rates of cardiac events. The absolute risks were higher in these data compared with previous pharmacovigilance studies (e.g. 1.8% peri-/myocarditis 1-year risk)., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: On 13 March 2020, the Danish authorities imposed extensive nationwide lockdown measures to prevent the spread of the coronavirus disease 2019 (COVID-19) and reallocated limited healthcare resources. We investigated mortality rates, overall and according to location, in patients with established cardiovascular disease before, during, and after these lockdown measures., Methods and Results: Using Danish nationwide registries, we identified a dynamic cohort comprising all Danish citizens with cardiovascular disease (i.e. a history of ischaemic heart disease, ischaemic stroke, heart failure, atrial fibrillation, or peripheral artery disease) alive on 2 January 2019 and 2020. The cohort was followed from 2 January 2019/2020 until death or 16/15 October 2019/2020. The cohort comprised 340 392 and 347 136 patients with cardiovascular disease in 2019 and 2020, respectively. The overall, in-hospital, and out-of-hospital mortality rate in 2020 before lockdown was significantly lower compared with the same period in 2019 [adjusted incidence rate ratio (IRR) 0.91, 95% confidence interval (CI) CI 0.87-0.95; IRR 0.95, 95% CI 0.89-1.02; and IRR 0.87, 95% CI 0.83-0.93, respectively]. The overall mortality rate during and after lockdown was not significantly different compared with the same period in 2019 (IRR 0.99, 95% CI 0.97-1.02). However, the in-hospital mortality rate was lower and out-of-hospital mortality rate higher during and after lockdown compared with the same period in 2019 (in-hospital, IRR 0.92, 95% CI 0.88-0.96; out-of-hospital, IRR 1.04, 95% CI1.01-1.08). These trends were consistent irrespective of sex and age., Conclusions: Among patients with established cardiovascular disease, the in-hospital mortality rate was lower and out-of-hospital mortality rate higher during lockdown compared with the same period in the preceding year, irrespective of age and sex., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Aim: To assess the risk of stroke and thromboembolism in patients with atrial fibrillation (AF) based on risk factor combinations of the CHA2DS2-VASc score., Methods and Results: Using nationwide Danish registries, patients with AF were included from 1997 to 2015 in this retrospective observational study. A multiple logistic regression, including interactions of history of stroke with age at AF, calendar year of AF, and the CHA2DS2-VASc score risk factors (congestive heart failure, hypertension, diabetes, vascular disease, and female sex) were used to predict the personalized risks of stroke within 1 year. A total of 147 842 patients with AF were included in the study cohort (median age 76 years, range 20-100 years, 51% females). Within the first year, 6% of the cohort were diagnosed with stroke. The predicted personalized 1-year absolute risk of stroke varied widely within each CHA2DS2-VASc score. To estimate the personalized risk of stroke an online calculator was created, the Calculator of Absolute Stroke Risk (CARS), which allows calculation of all the possible combinations of the CHA2DS2-VASc score (https://hjerteforeningen.shinyapps.io/riskvisrr/)., Conclusion: Calculation of the individual risk using a risk factor-based approach as opposed to using average risk for a particular CHA2DS2-VASc score can improve risk estimates. Furthermore, CARS can assist in the communication of the stroke risk for a more evidence-based shared decision-making of whether to initiate oral anticoagulation therapy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: Patients with heart failure and low income have a high mortality risk. We examined whether lower survival among low-income patients with heart failure could be explained by different use of β -blockers, renin-angiotensin system inhibitors (RASi), and implanted devices compared with high-income patients., Methods and Results: We linked Danish national registries to identify patients with new-onset heart failure between 2005 and 2016. A total of 18 308 patients was included in the main analysis. We collected information on medical treatment and device therapy after discharge. We investigated the remaining income disparity if everybody had the same probability of treatment as the high-income patients. We used causal mediation analysis to examine to what extent treatment differences mediate the association between income and 1-year mortality in strata defined by sex and cohabitation status. If low-income patients had the same probability of initiating β-blockers and RASi treatment as high-income patients, low-income men who lived alone would increase initiation of treatment by 12.4% (CI: 10.0% to 14.9%) and as a result reduce their absolute 1-year mortality by 1.0% (CI: -1.4% to -0.5%). If low-income patients had the same probability of not having breaks in medical treatment and getting device therapy, as high-income patients, low-income patients would increase the probability of not having breaks in treatment between 1.8% and 5.8% and increase the probability of getting device therapy between 1.0% and 3.8%, across strata of sex and cohabitation status., Conclusion: Lower rates of treatment initiation appear to mediate the poorer survival seen among patients with heart failure and low income, but only in males living alone., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: Pre-existing cardiovascular diseases (CVDs) have been proposed to identify patients at higher risk of adverse coronavirus disease 2019 (COVID-19) outcomes, but existing evidence is conflicting. Thus, it is unclear whether pre-existing CVDs are independently important predictors for severe COVID-19., Methods and Results: In a nationwide Danish cohort of hospital-screened COVID-19 patients aged ≥40, we investigated if pre-existing CVDs predict the 30-day risk of (i) composite outcome of severe COVID-19 and (ii) all-cause mortality. We estimated 30-day risks using a Cox regression model including age, sex, each CVD comorbidity, chronic obstructive pulmonary disease-asthma, diabetes, and chronic kidney disease. To illustrate CVD comorbidities' importance, we evaluated the predicted risks of death and severe infection, for each sex, along ages 40-85. In total, 4090 COVID-19 hospital-screened patients were observed as of 26 August 2020; 22.1% had ≥1 CVD, 23.7% had severe infection within 30 days and 12.6% died. Predicted risks of both outcomes at age 75 among men with single CVD comorbidities did not differ in clinically meaningful amounts compared with men with no comorbidities risks for the composite outcome of severe infection; women with heart failure (28.2%; 95% CI 21.1-37.0%) or atrial fibrillation (30.0%; 95% CI: 24.2-36.9%) showed modest increases compared with women with no comorbidities (24.0%; 95% CI: 21.4-26.9%)., Conclusions: The results showing only modest effects of CVDs on increased risks of poor COVID-19 outcomes are important in allowing public health authorities and clinicians to provide more tailored guidance to cardiovascular patients, who have heretofore been grouped together as high risk due to their disease status., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Prevention of adverse outcomes in individuals with high cholesterol levels may be improved by intensified lipid-lowering treatment (LLT). We studied whether treatment goals of low-density lipoprotein cholesterol (LDL-C) were reached within 1 year from baseline (defined as first LDL-C measurement) in a Danish population., Methods and Results: Danish registries were used to identify all persons in the Northern Region of Denmark who had LDL-C measured between 1997 and 2012 and who were naïve to LLT. Patients were categorized in LDL-C <5 or ≥5 mmol/L and further subdivided into low, high, and very high predicted cardiovascular (CV) risk as suggested by European guidelines for risk stratification. Initiation of LLT and lipid target levels were assessed after 1 year (3.0, 2.5, and 1.8 mmol/L, respectively). In this study, we examined the intensity of LLT and whether treatment goals were reached. More patients with LDL-C ≥5 mmol/L, regardless of the CV risk, initiated LLT compared with patients who had a very high CV risk and LDL-C <5 mmol/L. In total, 37.7% (n = 32 581) of all patients with a follow-up LDL-C, and 25.1% (n = 3229) of patients with LDL-C ≥5 mmol/L, had achieved their target levels after 1 year. Only 45.2% (n = 4545) of the LDL-C ≥5 mmol/L high-risk patients with a follow-up LDL-C had started LLT 12 months after baseline., Conclusion: Less than half of patients presenting with an LDL-C ≥5 mmol/L start LLT within 1 year, representing a missed opportunity for both primary and secondary prevention of CV disease., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: More patients survive myocardial infarction (MI) with cardiogenic shock (CS), but long-term outcome data are sparse. We aimed to examine rates of heart failure hospitalization and mortality in MI hospital survivors., Methods and Results: First-time MI patients with and without CS alive until discharge were identified using Danish nationwide registries between 2005 and 2017. One-, 5-, and 1- to 5-year rates of heart failure hospitalization and mortality were compared using landmark cumulative incidence curves and Cox regression models. We identified 85 865 MI patients of whom 2865 had CS (3%). Cardiogenic shock patients were of similar age as patients without CS (median age years: 68 vs. 67), and more were men (70% vs. 65%). Cardiogenic shock was associated with a higher 5-year rate of heart failure hospitalization compared with patients without CS [40% vs. 20%, adjusted hazard ratio (HR) 2.90 (95% confidence interval (CI) 2.67-3.12)]. The increased rate of heart failure hospitalization was evident after 1 year and in the 1- to 5-year landmark analysis among 1-year survivors. All-cause mortality was higher at 1 year among CS patients compared with patients without CS [18% vs. 8%, adjusted HR 3.23 (95% CI 2.95-3.54)]. However, beyond the first year, the mortality for CS was not markedly different compared with patients without CS [12% vs. 13%, adjusted HR 1.15 (95% CI 1.00-1.33)]., Conclusion: Among MI hospital survivors, CS was associated with a markedly higher rate of heart failure hospitalization and 1-year mortality compared with patients without CS. However, among 1-year survivors, the remaining 5-year mortality was similar for MI patients with and without CS., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: To investigate whether incident atrial fibrillation or flutter (AF) diagnosis increases the risk of psychiatric outcomes compared with the general population., Methods and Results: First-time AF patients and population controls naive to psychiatric disease or filled prescriptions for psychotropic drugs were identified in Danish nationwide registries during 2005-14. AF patients were matched 1:2 with exposure density matching. Patients and controls were compared for 1-year cumulative incidences of depression, anxiety, and stress disorders, and for filled drug prescriptions for antidepressant, anxiolytic, selected antipsychotics, and hypnotics. Lastly, we examined 1-year cumulative incidences of a composite endpoint of the above-mentioned diagnoses or drug redemptions. We included 146 377 AF patients and 292 754 matched controls, 55% men and median age 74 (25-75% 65-82) years. AF patients had significantly higher cumulative incidences of composite endpoints. Furthermore, filled prescriptions for anxiolytics and hypnotics were significantly higher for AF patients compared with healthy population controls. The cumulative incidence of the composite endpoint was significantly higher in AF patients relative to controls 11.1% vs. 8.3%. For the composite endpoint, a significantly higher risk was apparent both in unadjusted (HR: 2.76, 95% CI: 2.67-2.85) and adjusted (HR: 2.51, 95% CI: 2.43-2.60) models for AF patients vs. controls in the first 3 months after study inclusion., Conclusion: First-time AF patients were significantly more likely to have psychiatric outpatient or hospital contacts and to fill prescriptions for psychotropic drugs compared with healthy population controls. The risk was significantly elevated only during the first 3 months after AF diagnosis., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: Little is known about cardiac structure and function among atrial fibrillation (AF) subtypes; paroxysmal AF vs. persistent AF (PxAF), and across AF burden. We sought to assess differences in left atrial (LA) measures by AF subtype and burden., Methods and Results: This was a cross-sectional echocardiographic substudy of a randomized trial of AF patients scheduled for catheter ablation. Patients had an echocardiogram performed 0-90 days prior to study inclusion. We performed conventional echocardiographic measures, left ventricular (LV) and LA speckle tracking. Measures were compared between AF subtype and burden (0%, 0-99%, and 99-100%) determined by 72-h Holter monitoring. Of 212 patients, 107 had paroxysmal AF and 105 had PxAF. Those with PxAF had significantly reduced systolic function (LV ejection fraction: 48% vs. 53%; P < 0.001), larger end-systolic and end-diastolic LA volumes (LAVi and LAEDVi), reduced LA emptying fraction (LAEF: 29% vs. 36%, P < 0.001), and reduced LA strain (LAs) (LAs: 20% vs. 26%, P < 0.001). LA measures remained significantly lower in PxAF after multivariable adjustments. All LA measures and measures of systolic function were significantly impaired in patients with 99-100% AF burden, whereas all measures were similar between the other groups (LAVi: 40mL/m2 vs. 33mL/m2 vs. 34mL/m2; LAEDVi: 31mL/m2 vs. 21mL/m2 vs. 22mL/m2, LA emptying fraction: 23% vs. 35% vs. 36%, LAs: 16% vs. 25% vs. 25%, for 99-100%, 0-99%, and 0% AF, respectively, P < 0.001 for all). These differences were consistent after multivariable adjustments., Conclusion: LA mechanics differ between AF subtype and burden and these characteristics influence the clinical interpretation of these measures., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: Research regarding out-of-hospital cardiac arrest (OHCA) survival of diabetes patients is sparse and it remains unknown whether initiatives to increase OHCA survival benefit diabetes and non-diabetes patients equally. We therefore examined overall and temporal survival in diabetes and non-diabetes patients following OHCA., Methods: Adult presumed cardiac-caused OHCAs were identified from the Danish Cardiac Arrest Registry (2001-2014). Associations between diabetes and return of spontaneous circulation upon hospital arrival and 30-day survival were estimated with logistic regression adjusted for patient- and OHCA-related characteristics., Results: In total, 28,955 OHCAs were included of which 4276 (14.8%) had diabetes. Compared with non-diabetes patients, diabetes patients had more comorbidities, same prevalence of bystander-witnessed arrests (51.7% vs. 52.7%) and bystander cardiopulmonary resuscitation (43.2% vs. 42.0%), more arrests in residential locations (77.3% vs. 73.0%) and were less likely to have shockable heart rhythm (23.5% vs. 27.9%). Temporal increases in return of spontaneous circulation and 30-day survival were seen for both groups (return of spontaneous circulation: 8.8% in 2001 to 22.3% in 2014 (diabetes patients) vs. 7.8% in 2001 to 25.7% in 2014 (non-diabetes patients); and 30-day survival: 2.8% in 2001 to 9.7% in 2014 vs. 3.5% to 14.8% in 2014, respectively). In adjusted models, diabetes was associated with decreased odds of return of spontaneous circulation (odds ratio 0.74 (95% confidence interval 0.66-0.82)) and 30-day survival (odds ratio 0.56 (95% confidence interval 0.48-0.65)) (interaction with calendar year p =0.434 and p =0.243, respectively)., Conclusion: No significant difference in temporal survival was found between the two groups. However, diabetes was associated with lower odds of return of spontaneous circulation and 30-day survival.

Aims: The aim of this study was to compare nationwide incidence rate (IR) of sudden cardiac death (SCD) in persons aged 1-49 years with and without diabetes mellitus (DM)., Methods and Results: The study population consisted of all persons in Denmark aged 1-49 years in 2000-09, which equals 27.1 million person-years. All 14 294 deaths in the 10-year period were included. By using the highly descriptive Danish death certificates, 1698 cases of sudden and unexpected death were identified. Through review of autopsy reports, discharge summaries, and the Danish registries, we identified 1363 cases of SCD. The Danish Register of Medicinal Product Statistics was used to identify persons with type 1 DM and type 2 DM. Among the 14 294 decedents, there were 669 with DM, of which 118 suffered SCD (9% of all SCD), making SCD the leading cause of death among young persons with DM. Among those aged 1-35 years, the IR of SCD-DM was 21.9 per 100 000 person-years compared to 2.6 per 100 000 person-years among persons without DM [IR ratio 8.6, 95% confidence interval (CI) 5.8-28.6]. Within the age range 36-49 years, the IR among persons with DM was 119.8 per 100 000 person-years compared to 19.7 per 100 000 person-years among persons without DM (IR ratio 6.1, 95% CI 4.7-7.8)., Conclusion: We found that young persons with DM aged 1-35 years had >8-fold higher SCD IR compared to young persons without DM. Our study highlights the need for early cardiovascular risk monitoring and assessment in young persons with DM., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: The prognostic value of myocardial performance index (MPI) has not yet been assessed in patients with atrial fibrillation (AF). The aim of this study was to evaluate the prognostic value of MPI by tissue Doppler imaging (TDI) M-mode in AF patients., Methods and Results: Echocardiograms from 210 patients with AF during examination were analysed offline. Patients with known heart failure (HF) were excluded. Time intervals were measured using an M-mode line through the mitral valve leaflets to provide a colour diagram of the mitral leaflet movement so all time intervals could be measured from one cardiac cycle. MPI was calculated as the sum of isovolumic relaxation time and isovolumic contraction time divided by the ejection time [(IVRT+IVCT)/ET]. During a median follow-up of 2.4 years, 84 patients (40%) reached the combined endpoint of major adverse cardiovascular events (MACE), being all-cause mortality, HF, myocardial infarction, or stroke. Increasing MPI was significantly associated with an increased risk of MACE, and the risk increased with 20% per 0.1 increase in MPI [hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.10-1.32; P < 0.001]. Increasing MPI was also significantly associated with a lower left ventricular ejection fraction (LVEF) (P < 0.001). Nevertheless, MPI remained an independent predictor even after adjustment for age, sex, diabetes mellitus, left atrial volume, and LVEF (HR 1.12, 95% CI 1.01-1.25; P = 0.038)., Conclusion: Increasing MPI was significantly associated with increased risk of MACE and remained an independent predictor after multivariable adjustment. This demonstrates that the MPI obtained by TDI M-mode might be useful in assessing cardiac function in AF patients with ongoing arrhythmia during examination., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: To investigate whether diabetes confers higher relative rates of cardiovascular events in women compared with men using contemporary data, and whether these sex-differences depend on age., Methods and Results: All Danish residents aged 40-89 years without a history major adverse cardiovascular events, including heart failure, as of 1 January 2012 until 31 December 2016 were categorized by diabetes-status and characterized by individual-level linkage of Danish nationwide administrative registers. We used Poisson regression to calculate overall and age-dependent incidence rates, incidence rate ratios, and women-to-men ratios for myocardial infarction, heart failure, ischaemic stroke, or cardiovascular death (MACE-HF). Among 218 549 (46% women) individuals with diabetes, the absolute rate of MACE-HF was higher in men than in women (24.9 vs. 19.9 per 1000 person-years). Corresponding absolute rates in men and women without diabetes were 10.1 vs. 7.0 per 1000 person-years. Comparing individuals with and without diabetes, women had higher relative rates of MACE-HF than men [2.8 (confidence interval, CI 2.9-2.9) in women vs. 2.5 (CI 2.4-2.5) in men] with a women-to-men ratio of 1.15 (CI 1.11-1.19, P < 0.001). The relative rates of MACE-HF were highest in the youngest and decreased with advancing age for both men and women, but the relative rates were higher in women across all ages, with the highest women-to-men ratio between age 50 and 60 years., Conclusion: Although men have higher absolute rates of cardiovascular complications, the relative rates of cardiovascular complications associated with diabetes are higher in women than in men across all ages in the modern era., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Catheter ablation for atrial fibrillation (CAF) improves symptoms, but whether CAF improves outcome is less clear. The purpose of this study was to investigate whether CAF is associated with improved outcome in atrial fibrillation (AF) patients with previous direct current (DC) cardioversion., Methods and Results: We performed a nationwide cohort study including all patients who underwent their 1st direct current cardioversion for AF in the period 2003-15 (N = 25 439). End points were all-cause death, cardiovascular death, stroke/thromboembolism, and incident heart failure (HF). Catheter ablation for AF was treated as a time-varying covariate and the association with outcome was assessed using Cox regression. We also constructed a propensity-matched cohort and assessed the association between CAF and outcome. Median follow-up was 5.3 years (inter-quartile range 3.0-8.7 years). A total of 3509 patients (13.8%) underwent CAF during the study period. Following adjustment for age, gender, comorbidities, medications, educational level, household income, and CHA2DS2VASc score, CAF was associated with reduced risks of all-cause death, cardiovascular death, and incident HF [all-cause death: hazard ratio (HR) 0.69, P < 0.001; cardiovascular death: HR 0.68, P = 0.003; incident HF: HR 0.76, P = 0.011]. Catheter ablation for AF was not associated with a reduced risk of stroke/thromboembolism. These results were replicated in a propensity-matched cohort., Conclusion: In AF patients with a prior DC cardioversion, CAF was associated with a reduced risk of all-cause and cardiovascular death. This may be due to a reduced risk of HF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: We sought to determine whether socioeconomic position affects the survival of patients with heart failure treated in a national healthcare system., Methods: We linked national Danish registers, identified 145,690 patients with new-onset heart failure between 2000 and 2015, and obtained information on education and income levels. We analysed differences in survival by income quartile and educational level using multiple Cox regression, stratified by sex. We standardised one-year mortality risks according to income level by age, year of diagnosis, cohabitation status, educational level, comorbidities and medical treatment of all patients. We standardised one-year mortality risk according to educational level by age and year of diagnosis., Results: One-year mortality was inversely related to income. In women the standardised average one-year mortality risk was 28.0% in the lowest income quartile and 24.3% in the highest income quartile, a risk difference of -3.8% (95% confidence interval (CI) -4.9% to -2.6%). In men the standardised one-year mortality risk was 26.1% in the lowest income quartile and 20.2% in the highest income quartile, a risk difference of -5.8% (95% CI -6.8% to -4.9%). Similar gradients in standardised mortality were present between the highest and lowest educational levels: -6.6% (95% CI -9.6% to -3.5%) among women and -5.0% (95% CI -6.3% to -3.7%) among men., Conclusions: Income and educational level affect the survival of patients with heart failure, even in a national health system. Research is needed to investigate how socioeconomic differences affect survival.

Aims: The aim of this study was to describe the use of antithrombotic therapy following a bleeding event among patients with myocardial infarction (MI), and the associated risk of major adverse cardiac events (MACE)., Methods and Results: Using Danish nationwide registries, patients hospitalized with a bleeding event within 1 year after MI were identified. Antithrombotic treatment with aspirin, clopidogrel, and/or vitamin K antagonists (VKA) was determined at the bleeding and at Day 90 and 180 post-bleed. Based on guidelines, patients were stratified into four groups: expected, reduced, discontinued, or intensified treatment. Risk of MACE (ischaemic stroke, MI, or death) within the first year was assessed by Cox proportional hazard models. A total of 3324 patients with a bleeding after MI were included. At Day 90 post-bleed, 1052 (31.7%) received expected antithrombotic treatment, 1301 (39.2%) reduced, 164 (4.9%) intensified, and 807 (24.3%) no treatment. Major adverse cardiac events occurred in 637 (19.2%) patients. With dual antiplatelet therapy as reference, adjusted hazard ratios for MACE were: aspirin 1.81 (1.06-3.09), clopidogrel 1.08 (0.64-1.82), VKA 1.08 (0.47-2.48), VKA + aspirin 1.97 (0.95-4.07), VKA + clopidogrel 0.26 (0.03-1.91), triple 1.73 (0.50-5.95), and no treatment 1.93 (1.11-3.36)., Conclusion: The majority of MI patients reduced or discontinued their antithrombotic therapy post-bleed. Patients in monotherapy with aspirin or no treatment post-bleed had a higher risk of MACE Further studies of optimal antithrombotic treatments after a bleed are needed., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: To determine whether beta-blockers, aspirin, and statins are underutilized after first-time myocardial infarction (MI) in patients with chronic obstructive pulmonary disease (COPD) compared with patients without COPD. Further, to determine temporal trends and risk factors for non-use., Methods and Results: Using Danish nationwide registers, we performed a cross-sectional study investigating the utilization of beta-blockers, aspirin, and statins after hospitalization for first-time MI among patients with and without COPD from 1995 to 2015. Risk factors for non-use were examined in multivariable logistic regression models. During 21 years of study, 140 278 patients were included, hereof 13 496 (9.6%) with COPD. Patients with COPD were less likely to use beta-blockers (53.2% vs. 76.2%, P < 0.001), aspirin (73.9% vs. 78.8%, P < 0.001), and statins (53.5% vs. 61.9%, P < 0.001). Medication usage increased during the study period but in multivariable analyses, COPD remained a significant predictor for non-use: odds ratio (95% confidence interval) for non-use of beta-blockers 1.86 (1.76-1.97); aspirin 1.24 (1.16-1.32); statins 1.50 (1.41-1.59). Analyses stratified by ST-segment elevation myocardial infarction (STEMI) and non-STEMI showed similar undertreatment of COPD patients. Risk factors for non-use of beta-blockers in COPD included increasing age, female sex, and increasing severity of COPD (frequent exacerbations, use of multiple inhaled medications, and low lung function). Similar findings were demonstrated for aspirin and statins., Conclusion: Beta-blockers, and to a lesser extent aspirin and statins, were systematically underutilized by patients with COPD following hospitalization for MI despite an overall increase in the utilization over time. Increasing severity of COPD was a risk factor for non-use of the medications., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)