BACKGROUND:Herpes Zoster (HZ) is a common disease associated with morbidity, including cardiovascular complications, particularly in older adults and immunocompromised individuals. OBJECTIVE:To explore temporal changes in the incidence of hospital contacts due to HZ and estimate the risk of stroke and myocardial infarction (MI) following a hospital contact due to HZ. METHODS:This nationwide register-based cohort study from 1994 to 2022, included all adults (≥ 18 years) living in Denmark with a hospital contact due to a first-time event of HZ registered in the national patient register as an ICD-10 code. The incidences of hospital contact due to HZ were estimated by Poisson regression and reported per 100,000 person-years (PY). Furthermore, we estimated the hazard ratio (HR) of MI or stroke up to 90 days following a hospital contact with HZ using a Cox proportional hazard model. RESULTS:We included 23,433 individuals with a hospital contact due to HZ. The incidence of HZ increased in all age groups during the period, with the highest increase in the 60-64 age group from 10 (95% CI: 8-13) to 30 (95% CI: 26-33) per 100,000 PY. The HR of a stroke or MI after a hospital contact with an HZ diagnosis was 2.65 (95% CI: 2.06-3.42, p < 0.001). CONCLUSION:We found that the incidence of hospital contacts with an HZ diagnosis increased during the past three decades. Also, the relative rate of cardiovascular events was higher after a hospital contact with an HZ diagnosis than in individuals without such an event.

Background:Despite growing initiatives to promote partially virtual care, there is still a lack of comprehensive data describing its use, patient characteristics, and medication management practices. Objective:This study aimed to examine the use of partially virtual care in the management of cardiovascular disease. Methods:We used nationwide Danish registries to identify all patients with a first-time diagnosis of atrial fibrillation (AF), heart failure (HF), pulmonary embolism (PE), or acute coronary syndrome (ACS) between 2019 and 2023. Patients were categorized as receiving partially virtual care if followed up at least once virtually or in-person care if seen solely in-person. We evaluated temporal changes in the use of partially virtual care and calculated the odds of receiving partially virtual care vs in-person care and the prevalence of initiating guideline-directed medical therapy (GDMT). For GDMT initiation, the exposure was instead the type of the patient's first follow-up visit. Multivariable logistic regression was used to estimate the odds of receiving partially virtual care, adjusted for frailty score, residence, and period of diagnosis. Separate multivariable logistic regression models were then used to estimate adjusted average differences in the prevalence of GDMT initiation between virtual and in-person follow-up among patients not already on the medication, accounting for frailty score, residence, and period of diagnosis. Results:In total, 45,919 patients with AF, 30,482 with HF, 12,451 with PE, and 12,435 with ACS were followed up. Among these, 27.3% (AF: 12,517/45,919), 51.7% (HF: 15,749/30,482), 47.5% (PE: 5918/12,451), and 37.2% (ACS: 4627/12,435) had partially virtual follow-up. The use of partially virtual follow-up increased during the COVID-19 pandemic and remained high afterward. In 2023, 17.4% (475/2731) to 35.3% (876/2481) of patients' first follow-up visits were virtual, depending on the condition. Patient-specific factors significantly associated with partially virtual care were patients residing in cities for those with AF (odds ratio [OR] 1.27, 95% CI 1.21-1.34), HF (OR 1.38, 95% CI 1.31-1.46), and PE (OR 1.14, 95% CI 1.04-1.24), but not for patients with ACS, and "high frailty" for those with AF (OR 1.63, 95% CI 1.48-1.80) and PE (OR 1.53, 95% CI 1.29-1.81). A large percentage of patients were on GDMT prior to the first follow-up visit. Differences in new initiation of GDMT were small in absolute terms across conditions, regardless of virtual or in-person follow-up; for example, for patients with HF, 2.23% initiated sodium-glucose cotransporter-2 inhibitors following a virtual visit, vs 4.47% after an in-person visit (prevalence difference -2.24%, 95% CI, -2.61 to -1.87). Conclusions:Among patients who received follow-up, a considerable proportion of patients with cardiovascular disease (from 12,517/45,919, 27.3% to 15,749/30,482, 51.7%) received partially virtual care. The odds of receiving partially virtual care varied significantly based on patient characteristics, particularly place of residence and frailty score. Finally, small absolute differences were found in the initiation of new GDMT.

INTRODUCTION:Sex differences in treatment with Statins after Myocardial Infarction (MI) are widely recognised. This study aimed to assess differences in statin treatment initiation after MI by sex, age groups, and year of MI. METHOD:We conducted a cohort study in Denmark using registries for patients with a first-time MI between 1st January 2000 and 31st December 2024, excluding patients already treated with lipid lowering drugs up to 180 days before their MI. Descriptive statistics and multivariable Poisson regression were used to explore the effect of sex on treatment initiation. RESULTS:A total of 154,591 patients were included in the study (37% females, median age 75 years for females and 65 years for men). Overall, 54% of females versus 72% of males had initiated statin treatment within 180 days (p < .001). For females ≥40 years, significantly lower proportions were found in every year interval (p < .001 for all). Within the age groups, the relative difference between the sexes increased from 2000-2002 until 2015-2019, whereafter a decrease was found from 2015-2019 to 2020-2024, except among 60-69-year-olds for whom the decrease began earlier, starting in 2010-2014. Females had a 25% lower relative risk (RR 0.75 [0.74;0.76]) of initiating treatment. These differences remained after adjusting for age groups and year interval (RR 0.87 [0.86;0.87]) and after further adjustment for baseline characteristics (RR 0.91 [0.85;99]). CONCLUSION:A smaller proportion of females received statins than males after a MI. Disparities in treatment persisted over the years.

AIMS:To investigate the association between serial high-sensitivity cardiac troponin-T (hs-TnT) concentrations and subsequent heart failure in individuals presenting with suspected acute coronary syndrome (ACS). METHODS AND RESULTS:Utilizing Danish nationwide registries, we identified individuals without known heart failure who underwent serial hs-TnT assessment for suspected ACS between 2012 and 2019. Individuals were categorized based on the hs-TnT concentration patterns from the first to the second measurement (normal, rising, persistently elevated, or falling), the extent of hs-TnT concentration change (≤20%, >20 to 50%, or > 50%), and quartiles of peak hs-TnT levels (≤9 ng/l, 10-19 ng/l, 20-263 ng/l, and ≥ 264 ng/l). Standardized absolute and relative risks of incident hospitalization or outpatient contact for heart failure were computed using cause-specific multivariable Cox regression with average treatment effect modeling. Of 26,835 individuals, 38.8% received a discharge diagnosis of myocardial infarction, 5.1% of unstable angina, and 56.1% of suspected myocardial infarction or chest pain. Within the initial 30 days, 1122/26,835 (4.2%) persons received a heart failure diagnosis, with an additional 707/25,085 (2.8%) diagnosed between days 31-365. Subjects with two normal hs-TnT values exhibited the lowest standardized absolute risk (0-30 days: 0.3%; 31-365 days: 0.4%), while those with persistently elevated concentrations demonstrated the highest risk (0-30 days: 6.6%; 31-365 days: 4.3%). Heart failure risk also exhibited a significant, positive association with peak hs-TnT concentration. CONCLUSIONS:In individuals presenting with suspected ACS, persistent hs-TnT elevation was associated with the highest risk of subsequent heart failure. A dose-response association was observed between peak hs-TnT concentrations and incident heart failure.

Background Attention-deficit/hyperactive-disorder (ADHD) and autism spectrum disorder (ASD) may contribute to treatment failure or a prolonged disease course in children with nocturnal enuresis (NE). We investigated the association between NE and subsequent diagnoses of ADHD or ASD. In addition, we examined whether these conditions influence NE treatment duration. Methods We conducted a nationwide register-based cohort study including all Danish residents < 18 years diagnosed with NE from January 1, 1996, to December 31, 2023. Children with NE were age- and sex-matched 1:3 to controls without NE. The primary outcome was a composite of ADHD or ASD diagnosis after NE onset. Cox proportional hazards models adjusted for age, sex, comorbidities, and concomitant medicine were used. Among children with NE, the influence of ADHD or ASD diagnosis on NE treatment duration was evaluated as a secondary outcome. Results The cohort comprised 124,558 children with NE and 373,674 controls. During follow-up, 11.3% of children with NE were diagnosed with ADHD or ASD compared with 5.6% of controls. NE was associated with an increased hazard of ADHD or ASD (adjusted HR 1.87, 95% CI 1.83–1.91), with similar estimates for ADHD and ASD individually. Children with ADHD or ASD had significantly longer NE treatment duration than their neurotypical peers, and those diagnosed during the NE course were significantly less likely to achieve dryness within one year (0% vs. 23.4%). Conclusions Children with NE have an increased risk of underlying ADHD or ASD. Children with co-occurring ADHD or ASD experienced a more prolonged course of NE treatment. These findings suggest that children with treatment-refractory NE should be clinical evaluation for underlying ADHD or ASD. Clinical Trial Number : Not applicable.

BACKGROUND:Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) improve glycemic outcomes in people with type 2 diabetes, but their generalizability to routine clinical practice remains uncertain. AIM:To evaluate the real-world effectiveness of sustained GLP-1 RA use on haemoglobin A1c (HbA1c) over 1 to 4.5 years, using dipeptidyl peptidase 4 inhibitors (DPP-4is) as an active comparator. METHODS:Using Danish nationwide registries (2012-2022), we emulated a target trial assessing the glycemic effectiveness of GLP-1 RAs. The primary outcome was the probability of improvement in defined HbA1c categories within 1 year. Longitudinal Targeted Minimum Loss-based Estimation was used to estimate the primary outcome under sustained use of GLP-1 RA and DPP 4i, controlling for baseline and time-varying confounding. RESULTS:We included 16 619 GLP-1 RA initiators and 34 196 DPP-4i initiators, each with 2.8 HbA1c measurements per patient-year. At 1 year, the probability of any HbA1c improvement was 82.7% (95% CI: 82.0% to 83.4%) under sustained GLP-1 RA versus 67.1% (95% CI: 66.5% to 67.6%) under DPP-4i, an absolute difference of 15.7% (95% CI: 14.8% to 16.5%). GLP-1 RA treatment was also associated with a lower all-cause mortality risk, with absolute reductions of 0.4% (95% CI: 0.1% to 0.7%) at 1 year and 1.1% (95% CI: 0.3% to 2.0%) at 3 years. CONCLUSION:Within the limitations of this nationwide study and the available data, sustained GLP-1 RA therapy provided superior glycemic control and was associated with a modest mortality benefit compared with DPP-4i therapy.

Timely access to specialized stroke treatment is critical for patient outcomes onset of stroke. In Region Zealand, Denmark, stroke care is centralized to a single Stroke Unit. However, it remains unclear whether distance to the Stroke Unit affects prehospital transport decisions and access to reperfusion therapy for these patients. The aim of this study was to examine whether distance to the Stroke Unit was associated with prehospital transport destination and access to reperfusion therapy among patients with suspected stroke. We conducted a retrospective cohort study of all Emergency Medical Services (EMS) dispatches for suspected stroke in Region Zealand from 2018 to 2022. The primary outcomes were transport destination (direct transport to the Stroke Unit versus local emergency department) and receipt of reperfusion treatment. Patients were categorized according to final diagnosis and transport destination: Stroke Unit or local emergency department. We examined stroke severity, time from symptom onset to EMS call, distance to Stroke Unit, and advanced treatment was administered. Descriptive characteristics were calculated for subgroups. Differences between groups were analysed using Fisher’s exact and Kruskal-Wallis tests. Among 18,289 patients with stroke-suspected dispatches, 3,989 had a confirmed stroke diagnosis. Of these, 3,225 (81

Background Emergency cricothyroidotomy is a rare but potentially lifesaving rescue airway procedure in patients with failed conventional airway management. Comprehensive nationwide data on patient characteristics, procedural success and clinical outcomes remain limited, particularly for patients with out-of-hospital cardiac arrest (OHCA). Methods This nationwide registry-based observational cohort study included all patients undergoing prehospital emergency cricothyroidotomy in Denmark between 2016 and 2023. Cases were identified through nationwide prehospital medical records and the Danish Helicopter Emergency Medical Services database using iterative free-text searches and manual validation. OHCA patients undergoing emergency cricothyroidotomy were identified through linkage with the Danish Cardiac Arrest Register. Results A total of 71 validated prehospital emergency cricothyroidotomy cases were identified, including 48 OHCA patients and 23 patients without OHCA. Overall procedural success was achieved in 87.3% of cases, including 83.3% in patients with OHCA and 95.7% in patients without OHCA. Aspiration (32.4%) and oropharyngeal bleeding (33.8%) were the most frequent indications. Among the 48 patients with OHCA, return of spontaneous circulation was achieved in 25.0%, 30-day survival was 4.5%, and one-year survival was 2.3%. Overall, emergency cricothyroidotomy was performed in 48 of 39,885 nationwide OHCA patients (0.12%). Conclusion Prehospital emergency cricothyroidotomy was an exceedingly rare procedure but demonstrated high procedural success in this nationwide physician-staffed Emergency Medical Services system. Survival among patients with OHCA was relatively low, reflecting the critical condition of patients requiring emergency cricothyroidotomy.

BACKGROUND:Restarting direct oral anticoagulants (DOACs) after a serious bleeding event in patients with atrial fibrillation (AF) presents a clinical dilemma, with limited evidence on the balance between stroke prevention and recurrent bleeding risk. METHODS:Using nationwide Danish registries (2012-2021), we identified AF patients (Congestive heart failure, Hypertension, Age ≥75 (doubled), Diabetes, Stroke (doubled), Vascular disease, Age 65-74, and Sex category (female) (CHA₂DS₂-VASc score ≥2)) who experienced a first serious bleeding event while on DOAC therapy. Patients were grouped by timing of DOAC restart: within 60 days ('early restarters') vs after 60 days ('late restarters'). HRs for stroke, recurrent bleeding and a composite endpoint (stroke or serious bleeding) were estimated using multivariable Cox models. A secondary analysis examined outcomes across six time-varying antithrombotic treatment regimens. RESULTS:Among 10 291 patients who survived 60 days postbleeding, 5970 restarted DOAC early and 4321 later. The early restart group had a lower rate of stroke (HR 0.89; 95% CI 0.74 to 1.08), but the interval includes both moderate benefit and no clear difference, indicating uncertainty in the stroke reduction. Recurrent bleeding was more frequent in early restarters (HR 1.21; 95% CI 1.07 to 1.36). In the time-varying analysis, DOAC monotherapy was associated with reduced stroke risk compared with no treatment (HR 0.78; 95% CI 0.68 to 0.89). However, bleeding risk was also higher during DOAC monotherapy (HR 1.26; 95% CI 1.15 to 1.38). CONCLUSIONS:Restarting DOACs early after a serious bleeding event in AF patients may reduce stroke risk but is associated with an increased risk of recurrent bleeding. DOAC monotherapy appears to offer the best stroke protection, though with elevated bleeding risk. These findings highlight the need for individualised decision-making and further trials to define optimal timing for DOAC resumption.

Background Early and reliable predictions of elevated cardiac troponin levels from electrocardiograms (ECGs) in the prehospital setting could serve as a valuable risk stratification tool, guiding triage and early intervention in patients with suspected acute coronary syndrome, and especially in patients presenting with electrocardiographic non-ST elevation (NSTE). Therefore, the primary objective of this study was to investigate whether machine learning applied to the prehospital ECG can enable early identification of patients at high risk of myocardial infarction. Methods and Results A total of 100,334 patients with a prehospital ECG and in-hospital troponin measurement available were included in this study. A random forest model was developed to predict elevated cardiac troponin T (>14 ng/L) from the prehospital ECG. Mean age was 64.72 (17.05) and 55.13% of the cohort were male. Five-fold cross-validation showed an area under the receiver operating characteristics curve of 0.88 and area under the precision-recall curve of 0.89. Positive predictive value was 0.80 and negative predictive value was 0.79. Results on the internal independent test cohort and achieved similar performance. Supplementary analyses showed that the model was able to identify NSTE patients with elevated troponin T as well as identified a gap in time to definitive treatment for NSTE patients compared to those with ST elevation (STE). Conclusion Machine learning applied to the prehospital ECG can identify patients at high risk of myocardial injury before biomarker results are available, with potential to streamline patient flow and reduce time to definitive treatment in patients with suspected acute coronary syndrome.

Patients with atrial fibrillation (AF) may face an elevated risk of influenza-related complications, including cardiovascular and respiratory adverse outcomes. However, limited knowledge exists regarding the excess burden of hospitalizations and mortality due to influenza activity among patients with AF at a population level. We sought to estimate the excess number of deaths and hospitalizations associated with influenza activity among individuals with AF in Denmark. Data on weekly number of deaths and hospitalizations among patients with AF in Denmark were collected from the nationwide registries. Weekly estimates of influenza circulation were based on the proportion of positive influenza samples analyzed at all hospitals in Denmark during the study period. We used a time-series linear regression model to correlate the weekly estimates of influenza circulation with the weekly number of deaths and hospitalizations to estimate the annual excess number of deaths and hospitalizations associated with influenza circulation among patients with AF in Denmark. The model also incorporated data on weekly mean temperature in Denmark and restricted cubic spline terms to account for seasonal changes and trends over time. Confidence intervals were derived using block bootstrapping. During the study period encompassing 8 influenza seasons from 2010-2018, an annual mean of 141,746 patients were living with AF. An annual mean of 25,181 samples were tested for influenza at all Danish hospitals with a mean proportion of positive samples of 7.9% (Figure 1). Based on our model, influenza activity was associated with an annual excess of 298 all-cause deaths (95% CI 126-564 deaths) and 86 cardiovascular deaths (95% CI 45-204 deaths) corresponding to 2.3% of all all-cause deaths (95% CI 1.0-4.3% deaths) and 1.8% of all cardiovascular deaths (95% CI 1.0-4.3% deaths) in patients with AF in Denmark (Figure 1). Influenza activity was also associated with an annual excess of 387 hospitalizations for pneumonia or influenza (95% CI 148-667 hospitalizations for pneumonia or influenza) corresponding to 5.5% of all hospitalizations for pneumonia or influenza (95% CI 2.3-8.8%) among patients with AF. Based on the results of our model, approximately 2.3% of all deaths and 5.5% of all hospitalizations for pneumonia or influenza may be attributed to influenza activity among patients with AF in Denmark, suggesting substantial morbidity and mortality associated with influenza in patients with AF.Figure 1.

BACKGROUND:In patients with mitral regurgitation (MR), atrial fibrillation (AF), or heart failure (HF), are common indications for mitral valve surgery (MVS). However, whether first-time admissions for AF and HF are associated with similar prognostic impact remains unclear. AIM:To evaluate the risk of mortality after MVS among patients with recent hospitalization for AF or HF. METHODS:Using Danish nationwide registries (2000-2023), we identified patients undergoing first-time MVS for MR. Based on admissions within 6 months before surgery, patients were categorized as: (1) no new AF/HF (no first-time admission for AF or HF), (2) AF group (first-time admission for AF but not HF), or (3) HF group (first-time admission for HF, irrespective of admission for AF). We examined the 1-year rate of HF admission from discharge using multivariable Cox regression. From the date of MVS, we examined the rate of mortality. RESULTS:Compared with patients with no new AF/HF, the adjusted rate of admission for HF was significantly higher in the AF group (hazard ratio [HR] 1.55; 95% CI: 1.19-2.02) and the HF group (HR 1.67; 95% CI: 1.33-2.11). When examining mortality, we observed a higher 30-day risk among patients in the HF group, and no difference between groups beyond 30 days of follow-up. CONCLUSION:In patients undergoing MVS for MR, first-time admission for AF or HF within 6 months before MVS was associated with increased risk of admission for HF after MVS. Mortality appeared higher in the HF group during the initial 30 days postsurgery.

BACKGROUND:Hyperglycemia is common in intensive care unit (ICU) patients and associated with increased mortality. Despite several randomized clinical trials within glucose management in critical illness, the effects of insulin treatment, and its timing, in patients with moderate hyperglycemia remain uncertain. RESEARCH QUESTION:In acutely admitted ICU patients with moderate hyperglycemia, does insulin treatment improve clinical outcomes and does timing of insulin initiation matter? STUDY DESIGN AND METHODS:We performed a multicenter target trial emulation using targeted minimum loss-based estimation. We included patients from four ICUs at Karolinska University Hospitals, Solna, Huddinge, from 2010 to 2021. We assessed the effect of early insulin treatment compared with delayed or no insulin treatment on 30-day all-cause mortality in acutely admitted adult ICU patients with moderate hyperglycemia (10 - 13.9 mmol/L). RESULTS:We included 5,755 patients with moderate hyperglycemia; 3,149 (54.7%) received early insulin therapy (intervention group) and 2,606 (45.3%) received delayed or no insulin therapy (control group). The adjusted 30-day mortality was 22.1% (95% CI 21.1 - 23.1) for patients receiving insulin within 6 hours and 24.4% (95% CI 23.5 - 25.4) for patients with later or no insulin treatment, corresponding to an absolute risk reduction of 2.3% (95% CI 1.1 - 3.6). Absolute risk was reduced by 7.7%-points (CI 95% 6.5 - 8.9) when insulin was initiated within 1 hour of the first episode of moderate hyperglycemia and by 6.6%-points (CI 95% 5.4 - 7.8) with initiation within 2 hours. This effect was modified in several subgroups. INTERPRETATIONS:In this target trial emulation, early insulin treatment of moderate hyperglycemia showed reduced mortality in acutely admitted adult ICU patients - particularly when insulin was initiated within 2 hours following hyperglycemia. These findings support further investigation in timing of insulin initiation.

Background:Semaglutide is not approved for glycemic management in type 1 diabetes (T1D) due to limited evidence and safety concerns. Nevertheless, its use is increasing. We investigated glycemic and safety outcomes of semaglutide in a nationwide cohort of individuals with T1D. Methods:Using Danish registries (2018-2024), we identified individuals with T1D initiating semaglutide and matched them 1:4 using exposure density matching to unexposed control persons with T1D following them for up to two years. Glycemic trajectories were modeled using a piecewise mixed model. Cause-specific Cox models were used to estimate hospitalization rates for hypoglycemia and diabetic ketoacidosis compared with matched controls. Aalen-Johansen estimator was used to estimate adherence while accounting for death as a competing risk. Findings:We identified 879 individuals with T1D initiating semaglutide (multiple daily injections (MDI): n = 622; insulin pump: n = 257). HbA1c decreased by 5.7 mmol/mol (0.52%) (95% CI: 5.0-6.3) during the first six months and remained stable thereafter in semaglutide users while remaining unchanged in the control group. Compared with matched controls semaglutide use was not associated with an increased rate of hospitalization for hypoglycemia (HR 0.64; 95%CI: 0.35; 1.19) or diabetic ketoacidosis (HR 0.73; 95%CI; 0.34; 1.57). The cumulative probability of adherence to semaglutide at one year was 50% (95% CI: 47-54). No difference in HbA1c reduction from 0 to 6 months was observed between MDI compared to insulin pump users (P = 0.42). The median semaglutide dose redeemed during follow-up was 1.0 mg. Interpretation:In this nationwide cohort of individuals with T1D, semaglutide use was associated with no increased rate of hospitalization for hypoglycemia and no increased diabetic ketoacidosis rate, and a clinically meaningful reduction of HbA1c. Funding:This study received no funding.

Survival has improved substantially for patients with Hodgkin lymphoma (HL), but long-term quality of life (QoL) remains incompletely understood. This was a Danish, nationwide, cross-sectional study of QoL among persons with a diagnosis of HL matched 1:10 to general population comparators. Questionnaires included the HeartQoL, the European Organization for Research and Treatment of Cancer Quality of Life Core-30 (QLQ-C30), the Short Form-36 (SF-36), and the EuroQoL Health Questionnaire (EQ-5D). Mean differences (MD) were estimated using linear regression adjusted for sex and age, and stratified by time since diagnosis (0-5, > 5-10, and > 10 years). Overall, 1777 patients with HL (42% of 4156 invited) and 6166 matched comparators (14% of 41 558 invited) responded, and median age was similar (HL: 59, comparators: 61). Most had classical HL (92%). HL groups had consistently and significantly lower QoL than their respective comparators, with 0-5, > 5-10, and > 10 years post-diagnosis MDs of -0.27, -0.28, and -0.24 for the HeartQoL, -7.4, -7.6, and -5.6 points for the QLQ-C30 summary score, -4.5, -4.9, and -4.2 points for the SF-36 physical component summary, and -0.05, -0.05, and -0.04 for the EQ-5D index. The relative difference between the HL group and comparators decreased from baseline to > 10 years post-diagnosis, but differences remained clinically important. The most pronounced symptoms were fatigue and dyspnea. To summarize, persons with HL experience reductions in QoL compared with the general population, even > 10 years post-diagnosis. The observed differences were clinically relevant within several domains and emphasize the need for a multidisciplinary approach to survivorship care.

ABSTRACT Background Anemia is common in patients with atrial fibrillation (AF). Prior studies have associated anemia—based on a single pre‐procedural hemoglobin measurement—with AF recurrence after catheter ablation. However, it remains unclear whether chronic anemia confers a different risk compared with transient anemia. This study evaluated the association between transient and chronic anemia and AF recurrence following first‐time catheter ablation. Methods In this nationwide cohort study, we included 15 017 patients from the Danish National Ablation Database undergoing first‐time AF ablation between 2010 and 2024 with available hemoglobin measurements within 12 months prior to the procedure. Patients were categorized as having no anemia, transient anemia, or chronic anemia based on repeated hemoglobin measurements. The primary outcome was AF recurrence within 1 year after a 90‐day blanking period, defined as a composite of AF‐related hospitalization, cardioversion, antiarrhythmic drug use, or repeat ablation. Associations were assessed using multivariable Cox proportional hazards models. Results A total of 877 patients (5.8%) had chronic anemia and 1592 (10.6%) had transient anemia. During follow‐up, 3445 patients (23.6%) experienced AF recurrence. The 1‐year cumulative incidence of recurrence was highest in patients with chronic anemia (32.5%), followed by transient anemia (24.2%) and no anemia (23.0%). Compared with non‐anemic patients, chronic anemia was independently associated with an increased risk of AF recurrence (adjusted hazard ratio [HR]: 1.36; 95% confidence interval [CI]: 1.18–1.56), whereas transient anemia was not (HR: 0.98; 95% CI: 0.87–1.10). Conclusion Chronic—but not transient—anemia prior to first‐time catheter ablation was independently associated with a higher risk of AF recurrence.

Background Supraventricular tachycardia (SVT) is a common type of arrythmia leading to patient distress and substantial health care utilization. Although the mechanistic underpinnings of SVT are well elucidated, the etiologies remain unknown. Objectives This study aimed to determine to what extent SVT may be heritable using a classical biometrical twin study design. Methods Monozygotic and same-sex dizygotic twin pairs born in Denmark, in which one or both members were diagnosed with SVT between 1977 and 2024, were identified through the Danish Twin Registry and the Danish National Patient Registry. The risk in the co-twin following the index-twin’s diagnosis was estimated by using Cox proportional hazards models. Heritability of SVT was assessed by using probandwise concordance rates and biometrical models. Results Of 32,324 twin pairs (12,006 monozygotic and 20,318 dizygotic pairs), at least one SVT diagnosis was identified in 663 twin pairs. After an SVT diagnosis in the index-twin, the risk of SVT was significantly higher in monozygotic co-twins compared with dizygotic co-twins (HR: 3.61; 95% CI: 1.35-9.63; P = 0.01), which remained significant after adjusting for age and sex (HR: 3.3; 95% CI: 1.24-8.89; P = 0.01). The probandwise concordance rate was significantly higher in monozygotic twins compared with dizygotic twins (9% vs 3%; P < 0.001). Biometrical models indicated that 35% of SVT risk could be attributed to genetics and 65% to unique environmental components. Conclusions Based on a large nationwide population of monozygotic and same-sex dizygotic twins, this is the first study to quantify the genetic and environmental contributions to SVT.

BACKGROUND:Community first responder (CFR) systems have been implemented to reduce time to cardiopulmonary resuscitation (CPR) and defibrillation after out-of-hospital cardiac arrest (OHCA). In the Capital Region of Denmark, CFR system activation relies on manual activation by emergency medical service (EMS) call takers, which may lead to underutilization of the system. OBJECTIVES:The aim of this study was to examine the proportion of OHCAs in which the CFR system was activated and to identify characteristics of OHCAs associated with system activation. METHODS:This register-based study in the Capital Region of Denmark included all OHCAs from September 2017 to December 2023. Excluded were OHCAs with exclusion criteria for CFR system activation (OHCAs caused by suicide, trauma, or OHCAs in nursing homes) and OHCAs not recognized by call takers. Binomial regression models were used to calculate relative risks for system activation in relation to patient age and sex, EMS response time, time of day, and OHCA location. Age, EMS response time, and time of day were modeled categorically. Differences in system activation between call takers were analyzed, excluding low-volume call takers, and interaction tests were performed to identify potential effect modifiers. RESULTS:Call takers activated the CFR system in 2,486 (57.5%) of 4,320 OHCAs eligible for CFR system activation. The following characteristics were associated with higher likelihood of CFR system activation: patient age 51 to 80 years; OHCAs in private homes (risk ratio [RR]: 1.53; 95% CI: 1.41-1.66), longer EMS response time (RR: 1.27; 95% CI: 1.13-1.44), and OHCAs occurring in nighttime in private homes (RR: 1.10; 95% CI: 1.03-1.19). Female patients aged 0 to 20 years, 66 to 80 years, and >80 years received less CFR system activation compared with male patients in the same age groups (RR: 0.25 [95% CI: 0.02-0.95]; RR: 0.88 [95% CI: 0.81-0.96]; and RR: 0.77 [95% CI: 0.68-0.86], respectively). Finally, considerable variability was observed in CFR system activation among call takers (Q1-Q3: 48.0%-68.0%). CONCLUSIONS:The CFR system was activated in <60% of eligible OHCAs. CFR system activation was higher among certain patient groups, and excessive variability in CFR system activation among call takers was identified. These findings are important for improving CFR systems.

Background The HeartRunner trial was an investigator-initiated, randomized clinical controlled trial (RCT) examining whether community first responders (CFRs) activated through a smartphone application can improve survival after out-of-hospital cardiac arrest (OHCA). Objectives The study compared standard care alone versus standard care with the addition of dispatched CFRs for patients with OHCA. Methods The trial was conducted in the Capital Region of Denmark, with a catchment area of approximately 1.9 million inhabitants. By May 2019, 15,401 citizens had registered to serve as CFRs (837/100,000 inhabitants) and roughly 6,200 automated external defibrillators (344/100,000 inhabitants) were publicly accessible in the study area (2.4 defibrillators per km2).The primary outcome was 30-day survival. Secondary outcomes included bystander defibrillation, bystander cardiopulmonary resuscitation, return of spontaneous circulation before hospital arrival, favorable neurological outcome at hospital discharge, and 1-year survival. As safety outcomes, the trial examined the potential physical or psychological risk involved for the activated CFR. The trial was expected to randomize 4,188 cases of suspected OHCAs over a period of 7 years and was terminated February 28, 2026, when inclusion was completed. The full study protocol is available at www.clinicaltrials.gov (identifier: NCT03835403).