Age-specific mortality trends in heart failure over 25 years: a retrospective Danish nationwide cohort study.

BACKGROUND: Despite advances in heart failure care reducing mortality in clinical trials, it remains unclear whether real-life cohorts have had similar improvements in life expectancy across the age spectrum. We aimed to investigate how mortality trends changed in patients with heart failure over the past 25 years, stratified by age groups. METHODS: Using Danish nationwide registries, we identified patients with new-onset heart failure aged 18-95 years. The 5-year all-cause mortality risk and the absolute risk difference of mortality between patients with heart failure and age-matched and sex-matched heart failure-free controls were assessed using Kaplan-Meier estimates and multivariable Cox regression models. Mortality trends were analysed across five calendar periods (1996-2000, 2001-05, 2006-10, 2011-15, and 2016-20) and three age groups (<65 years, 65-79 years, and ≥80 years). FINDINGS: 194 997 patients with heart failure were included. Mortality significantly decreased from 1996-2000 (66% [95% CI 65·5-66·4]) to 2016-20 (43% [42·1-43·4]), with similar results shown in all age groups (<65 years: 35% [33·9-36·1] to 15% [14·6-16·3]; 65-79 years: 64% [63·1-64·5] to 39% [37·6-39·6]; and ≥80 years: 84% [83·1-84·3] to 73% [71·7-73·9]). Adjusted mortality rates supported these associations. The absolute risk difference declined notably in younger age groups (<65 years: 29·9% [28·8-31·0] to 12·7% [12·0-13·4] and 65-79 years: 41·1% [40·3-41·9] to 25·1% [24·4-25·8]), remaining relatively stable in those aged 80 years or older (30·6% [29·9-31·3] to 28% [27·2-28·8]). INTERPRETATION: Over 25 years, there has been a consistent decrease in mortality among patients with heart failure across age groups, albeit less prominently in patients aged 80 years or older. Further insight is needed to identify effective strategies for improving disease burden in older patients with heart failure. FUNDING: None. TRANSLATION: For the Danish translation of the abstract see Supplementary Materials section.

Long-Term Cardiovascular Risk Associated With Treatment of Attention-Deficit/Hyperactivity Disorder in Adults.

BACKGROUND: Incrementing numbers of patients treated for attention-deficit/hyperactivity disorder (ADHD) call for scrutiny concerning long-term drug-safety. OBJECTIVES: This study aims to investigate associations between long-term use of ADHD treatment and cardiovascular outcomes. METHODS: Using nationwide registers, adult patients first-time initiated on ADHD treatment between 1998 and 2020 were identified. Exposure groups were prior users, <1 defined daily dose (DDD) per day, ≥1 DDD per day determined at start of follow-up, and 1 year after patients' first claimed prescription. Outcomes were acute coronary syndromes, stroke, heart failure, and a composite of the above. RESULTS: At start of follow-up, 26,357, 31,211, and 15,696 individuals were correspondingly categorized as prior users (42% female, median age: 30 years [Q1-Q3: 23-41 years]), <1 DDD per day (47% female, median age: 31 years [Q1-Q3: 24-41 years]), and ≥1 DDD per day (47% female, median age: 33 years [Q1-Q3: 25-41 years]), respectively. Comparing ≥1 DDD per day with prior users, elevated standardized 10-year absolute risk of stroke (2.1% [95% CI: 1.8%-2.4%] vs 1.7% [95% CI: 1.5%-1.9%]), heart failure (1.2% [95% CI: 0.9%-1.4%] vs 0.7% [95% CI: 0.6%-0.8%]), and the composite outcome (3.9% [95% CI: 3.4%-4.3%] vs 3.0% [95% CI: 2.8 %-3.2%]) was found-with corresponding risk ratios of 1.2 (95% CI: 1.0-1.5), 1.7 (95% CI: 1.3-2.2), and 1.3 (95% CI: 1.1-1.5). No apparent associations were found for acute coronary syndrome (1.0% [95% CI: 0.8%-1.2%] vs 0.9% [95% CI: 0.8%-1.0%]). CONCLUSIONS: Possible associations between elevated long-term cardiovascular risk and increasing dosage of ADHD treatment use in a young patient group should warrant further investigation.

Temporal trend of first-line drug choice and treatment continuity for hypertension among citizens 75 years or over - a register-based, cohort study.

BACKGROUND: Limited knowledge of antihypertensive treatment of the elderly potentially impedes effective strategies for hypertension management in this growing patient group. We aimed to investigate temporal trends for first-line drug choice for antihypertensive treatment and treatment continuity among patients ≥75 years from 2000 to 2021. METHODS: Using nationwide Danish registers, patients ≥75 years initiated for the first time on antihypertensive drugs: Angiotensin converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB), beta blockers (BB), calcium channel blockers (CCB), thiazides, or combinations, were identified. Patients with other indications than hypertension were excluded. Treatment continuity was described using claimed prescriptions the first 180 days following study entry. RESULTS: From 2000 to 2021, 170,769 patients (median age 80 years [interquartile range:77-84], 60.3% female) were included. From 2000 to 2003 to 2015-2021 the proportion of first-line drug choice increased for ACEi (8.7% to 14.9%), ARB (4.1% to 23.9%), and CCB (10.7% to 27.6%), decreased for thiazides (60.6% to 15.9%) and remained stable for BB (12.9% to 14.1%) and combinations (2.9% to 3.6%). For 157,457 patients alive after 180 days, discontinuation was highest among patients initiated on thiazides (28.3%) whereas most patients continued the same single drug regimen if they started on ACEi (55.2%), ARB (65.0%), BB (57.2%) or CCB (59.3%). CONCLUSIONS: From 2000 to 2021 thiazides have been replaced by ACEi, ARB and CCB. Thiazides had the lowest treatment continuity while ARB appeared preferred slightly over ACEi. Differences in adherence in relation to first-line drug choice may warrant scrutiny regarding recommendations for the elderly.

Familial clustering of unexplained heart failure - A Danish nationwide cohort study.

AIMS: To determine whether a family history of unexplained heart failure (HF) in first-degree relatives (children or sibling) increases the rate of unexplained HF. METHODS AND RESULTS: Using Danish nationwide registry data (1978-2017), we identified patients (probands) diagnosed with first unexplained HF (HF without any known comorbidities) in Denmark, and their first-degree relatives. All first-degree relatives were followed from the HF date of the proband and until an event of unexplained HF, exclusion diagnosis, death, emigration, or study end, whichever occurred first. Using the general population as a reference, we calculated adjusted standardized incidence ratios (SIR) of unexplained HF in the three groups of relatives using Poisson regression models. We identified 55,110 first-degree relatives to individuals previously diagnosed with unexplained HF. Having a family history was associated with a significantly increased unexplained HF rate of 2.59 (95%CI 2.29-2.93). The estimate was higher among siblings (SIR 6.67 [95%CI 4.69-9.48]). Noteworthy, the rate of HF increased for all first-degree relatives when the proband was diagnosed with HF in a young age (≤50 years, SIR of 7.23 [95%CI 5.40-9.68]) and having >1 proband (SIR of 5.28 [95%CI 2.75-10.14]). The highest estimate of HF was observed if the proband was ≤40 years at diagnosis (13.17 [95%CI 8.90-19.49]. CONCLUSION: A family history of unexplained HF was associated with a two-fold increased rate of unexplained HF among first-degree relatives. The relative rate was increased when the proband was diagnosed at a young age. These data suggest that screening families of unexplained HF with onset below 50 years is indicated.

Effects of high-dose versus standard-dose quadrivalent influenza vaccine among patients with diabetes: A post-hoc analysis of the DANFLU-1 trial.

AIM: High-dose quadrivalent influenza vaccine (QIV-HD) has been shown to be more effective than standard-dose (QIV-SD) in reducing influenza infection, but whether diabetes status affects relative vaccine effectiveness (rVE) is unknown. We aimed to assess rVE on change in glycated haemoglobin [HbA1c (∆HbA1c)], incident diabetes, total all-cause hospitalizations (first + recurrent), and a composite of all-cause mortality and hospitalization for pneumonia or influenza. METHODS: DANFLU-1 was a pragmatic, open-label trial randomizing adults (65-79 years) 1:1 to QIV-HD or QIV-SD during the 2021/22 influenza season. Cox proportional hazards regression was used to estimate rVE against incident diabetes and the composite endpoint, negative binomial regression to estimate rVE against all-cause hospitalizations, and ANCOVA when assessing rVE against ∆HbA1c. RESULTS: Of the 12 477 participants, 1162 (9.3%) had diabetes at baseline. QIV-HD, compared with QIV-SD, was associated with a reduction in the rate of all-cause hospitalizations irrespective of diabetes [overall: 647 vs. 742 events, incidence rate ratio (IRR): 0.87, 95% CI (0.76-0.99); diabetes: 93 vs. 118 events, IRR: 0.80, 95% CI (0.55-1.15); without diabetes: 554 vs. 624 events, IRR: 0.88, 95% CI (0.76-1.01), pinteraction = 0.62]. Among those with diabetes, QIV-HD was associated with a lower risk of the composite outcome [2 vs. 11 events, HR: 0.18, 95% CI (0.04-0.83)] but had no effect on ∆HbA1c; QIV-HD adjusted mean difference: ∆ + 0.2 mmol/mol, 95% CI (-0.9 to 1.2). QIV-HD did not affect the risk of incident diabetes [HR 1.18, 95% CI (0.94-1.47)]. CONCLUSIONS: In this post-hoc analysis, QIV-HD versus QIV-SD was associated with an increased rVE against the composite of all-cause death and hospitalization for pneumonia/influenza, and the all-cause hospitalization rate irrespective of diabetes status.

Sleep apnea, the risk of out-of-hospital cardiac arrest, and potential benefits of continuous positive airway pressure therapy: A nationwide study.

OBJECTIVE: Patients with sleep apnea (SA) are at increased cardiovascular risk. However, little is known about the risk of out-of-hospital cardiac arrest (OHCA) in patients with SA. Therefore, we studied the relation between SA patients who did and did not receive continuous positive airway pressure (CPAP) therapy with OHCA in the general population. METHODS: Using nationwide databases, we conducted a nested case-control study with OHCA-cases of presumed cardiac causes and age/sex/OHCA-date matched non-OHCA-controls from the general population. Conditional logistic regression models with adjustments for well-known OHCA risk factors were performed to generate odds ratio (OR) of OHCA comparing patients with SA receiving and not receiving CPAP therapy with individuals without SA. RESULTS: We identified 46,578 OHCA-cases and 232,890 matched non-OHCA-controls [mean: 71 years, 68.8% men]. Compared to subjects without SA, having SA without CPAP therapy was associated with increased odds of OHCA after controlling for relevant confounders (OR:1.20, 95%-Cl:1.06-1.36), while having SA with CPAP therapy was not associated with OHCA (OR:1.04, 95%-Cl:0.93-1.36). Regardless of CPAP therapy, age and sex did not significantly influence our findings. Our findings were confirmed in: (I) patients with neither ischemic heart disease nor heart failure (untreated SA, OR:1.24, 95%-CI:1.04-1.47; SA with CPAP, OR:1.08, 95%-CI:0.93-1.25); and (II) in patients without cardiovascular disease (untreated SA, OR:1.33, 95%-CI:1.07-1.65; SA with CPAP, OR:1.14, 95%-CI:0.94-1.39). CONCLUSION: SA not treated with CPAP was associated with OHCA, while no increased risk of OHCA was found for SA patients treated with CPAP.

Temporal Trends in the Initiation of Dialysis Among Patients With Heart Failure With or Without Diabetes: A Nationwide Study From 2002 to 2016.

BACKGROUND: The incidence and distribution of acute and chronic dialysis among patients with heart failure (HF), stratified by diabetes, remain uncertain. We hypothesized that with improved survival and rising comorbidities, the demand for dialysis would increase over time. METHODS AND RESULTS: Patients with incident HF, aged 18 to 100 years, between 2002 and 2016, were identified using Danish nationwide registers. Primary outcomes included acute and chronic dialysis initiation, HF-related hospitalization, and all-cause mortality. These outcomes were assessed in 2002 to 2006, 2007 to 2011, and 2012 to 2016, stratified by diabetes. We calculated incidence rates (IRs) per 1000 person-years and hazard ratios (HR) using multivariable Cox regression. Of 115 533 patients with HF, 2734 patients received acute dialysis and 1193 patients received chronic dialysis. The IR was 8.0 per 1000 and 3.5 per 1000 person-years for acute and chronic dialysis, respectively. Acute dialysis rates increased significantly among patients with diabetes over time, while no significant changes occurred in those without diabetes, chronic dialysis, HF-related hospitalization, or overall mortality. Diabetes was associated with significantly higher HRs of acute and chronic dialysis, respectively, compared with patients without diabetes (HR, 2.07 [95% CI, 1.80-2.39] and 2.93 [95% CI, 2.40-3.58] in 2002 to 2006; HR, 2.45 [95% CI, 2.14-2.80] and 2.86 [95% CI, 2.32-3.52] in 2007 to 2011; and 2.69 [95% CI, 2.33-3.10] and 3.30 [95% CI, 2.69-4.06] in 2012 to 2016). CONCLUSIONS: The IR of acute and chronic dialysis remained low compared with HF-related hospitalizations and mortality. Acute dialysis rates increased significantly over time, contrasting no significant trends in other outcomes. Diabetes exhibited over 2-fold increased rates of the outcomes. These findings emphasize the importance of continued monitoring and renal care in patients with HF, especially with diabetes, to optimize outcomes and prevent adverse events.

Lower Recurrence Rates of Atrial Fibrillation and MACE Events After Early Compared to Late Ablation: A Danish Nationwide Register Study.

BACKGROUND: Guidelines recommend prioritizing treatment with antiarrhythmic drugs before referral of patients with atrial fibrillation to ablation, delaying a potential subsequent ablation. However, delaying ablation may affect ablation outcomes. We sought to investigate the impact of duration from diagnosis to ablation on the risk of atrial fibrillation recurrence and adverse events. METHODS AND RESULTS: Using Danish nationwide registries, all patients with first-time ablation for atrial fibrillation were identified and included from 2010 to 2018. Patients were divided into 4 groups by diagnosis-to-ablation time: <1.0 year (early ablation), 1.0 to 1.9 years, 2.0 to 2.9 years, and >2.9 years (late ablation). The primary end point was atrial fibrillation recurrence after the 90-day blanking period, defined by admission for atrial fibrillation, cardioversions, use of antiarrhythmic drugs, or repeat atrial fibrillation ablations. The secondary end point was a composite end point of heart failure, ischemic stroke, or death, and each event individually. The study cohort consisted of 7705 patients. The 5-year cumulative incidence of atrial fibrillation recurrence in the 4 groups was 42.9%, 54.8%, 55.9%, and 58.4%, respectively. Hazard ratios were 1.20 (95% CI, 1.07-1.35), 1.29 (95% CI, 1.13-1.47), and 1.40 (95% CI, 1.28-1.53), respectively, with the early ablation group as reference. The hazard ratio for the combined secondary end point was 1.22 (95% CI, 1.04-1.44) in the late ablation group compared with the early ablation group. CONCLUSIONS: In patients undergoing ablation for atrial fibrillation, early ablation was associated with a significantly lower risk of atrial fibrillation recurrence. Furthermore, the associated risk of heart failure, ischemic stroke, or death was significantly lower in early-compared with late-ablation patients.

Oral anticoagulation for stroke prevention in atrial fibrillation and advanced kidney disease.

Background: The net benefit of oral anticoagulation (OAC) with vitamin K antagonists or direct oral anticoagulants in patients with advanced chronic kidney disease and atrial fibrillation remains uncertain. Objectives: We examined the use, efficacy, and safety of OAC in patients with estimated glomerular filtration rate (eGFR) of <30 mL/min/1.73 m2 (including dialysis-treated patients) and atrial fibrillation. Methods: In a retrospective cohort study, patients diagnosed with atrial fibrillation and eGFR of <30 mL/min/1.73 m2 were identified in national Danish registers between 2010 and 2022. Initiation of OAC was identified based on redemption of a relevant prescription. One-year risks of thromboembolic event, major bleeding, and death associated with OAC and no treatment were computed and standardized to the distribution of risk factors in the sample based on hazards determined in multiple Cox regression models adjusted for age and sex. Results: A total of 3208 patients were included (mean age 80 years, 52.8% males, 20.9% chronic dialysis). OAC was initiated in 1375 (42.9%) patients, of whom 48.1% were vitamin K antagonists and 51.9% were direct oral anticoagulants. One-year risks in nontreated and anticoagulated patients were 4.8% (95% CI, 3.8%-5.7%) and 3.6% (95% CI, 2.8%-4.6%; P = .028) for thromboembolic event, 7.6% (95% CI, 6.6%-8.7%) and 10.5% (95% CI, 9.3%-12.1%; P < .001) for major bleeding, and 36.3% (95% CI, 34.2%-38.3%) and 29.6% (95% CI, 27.6%-31.6%; P < .001) for death, respectively. Conclusion: In a retrospective study on patients with advanced chronic kidney disease and atrial fibrillation, OAC was associated with overall decreased 1-year risk of thromboembolic event and death offset by increased 1-year risk of major bleeding.

Use of proton pump inhibitors is associated with increased risk of out-of-hospital cardiac arrest in the general population: a nested case-control study.

AIMS: Proton pump inhibitors (PPIs) impair cardiac repolarization and prolong the QT interval and may potentially be proarrhythmic. However, risk of out-of-hospital cardiac arrest (OHCA) is scarcely investigated. We studied whether past or current PPI use is associated with OHCA in the general population. METHODS AND RESULTS: We conducted a nationwide nested case-control study with OHCA-cases of presumed cardiac causes and age/sex/OHCA-date-matched non-OHCA-controls from the general population. Exposure to PPI was categorized into three mutually exclusive groups of current-, past-, and non-use. Conditional logistic regression analyses with adjustments for risk factors of OHCA was used to calculate the odds ratio (OR) of OHCA comparing PPI use with non-users. We identified 46578 OHCA-cases and 232890 matched non-OHCA-controls (mean:71 years, 68.8% men). PPI was used by 8769 OHCA-cases and 21898 non-OHCA-controls, and current use of PPI was associated with increased odds of OHCA compared with non-users (OR:1.32 [95%-CI:1.28 -1.37]), while past use conferred no increase in the odds of OHCA (OR:1.01 [95%-CI:0.98-1.04]). This increased odds of OHCA occurred in both sexes. Finally, the ORs remained elevated when we repeated the analyses in individuals without registered ischemic heart disease (OR:1.36 [95%-CI:1.31-1.41]), without heart failure (OR:1.33 [95%-CI:1.29-1.38]), or without any cardiovascular comorbidities (OR:1.84 [95%-CI:1.70-2.00]). Also, the OR remained elevated when H2-antagonists served as the reference group (OR:1.28 [95%-CI:1.11-1.47]). CONCLUSION: PPI use is associated with an increased risk of OHCA in the general population. Considering the widespread use of PPIs, this study raises concerns and need for awareness to balance the benefit and risk of treatment.

Protocol for a randomised controlled trial comparing warfarin with no oral anticoagulation in patients with atrial fibrillation on chronic dialysis: the Danish Warfarin-Dialysis (DANWARD) trial.

INTRODUCTION: Atrial fibrillation is highly prevalent in patients on chronic dialysis. It is unclear whether anticoagulant therapy for stroke prevention is beneficial in these patients. Vitamin K-antagonists (VKA) remain the predominant anticoagulant choice. Importantly, anticoagulation remains inconsistently used and a possible benefit remains untested in randomised clinical trials comparing oral anticoagulation with no treatment in patients on chronic dialysis. The Danish Warfarin-Dialysis (DANWARD) trial aims to investigate the safety and efficacy of VKAs in patients with atrial fibrillation on chronic dialysis. The hypothesis is that VKA treatment compared with no treatment is associated with stroke risk reduction and overall benefit. METHODS AND ANALYSIS: The DANWARD trial is an investigator-initiated trial at 13 Danish dialysis centres. In an open-label randomised clinical trial study design, a total of 718 patients with atrial fibrillation on chronic dialysis will be randomised in a 1:1 ratio to receive either standard dose VKA targeting an international normalised ratio of 2.0-3.0 or no oral anticoagulation. Principal analyses will compare the risk of a primary efficacy endpoint, stroke or transient ischaemic attack and a primary safety endpoint, major bleeding, in patients allocated to VKA treatment and no treatment, respectively. The first patient was randomised in October 2019. Patients will be followed until 1 year after the inclusion of the last patient. ETHICS AND DISSEMINATION: The study protocol was approved by the Regional Research Ethics Committee (journal number H-18050839) and the Danish Medicines Agency (case number 2018101877). The trial is conducted in accordance with the Helsinki declaration and standards of Good Clinical Practice. Study results will be disseminated to participating sites, at research conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBERS: NCT03862859, EUDRA-CT 2018-000484-86 and CTIS ID 2022-502500-75-00.

Clinical Trajectories and Long-Term Outcomes of Alcoholic Versus Other Forms of Dilated Cardiomyopathy.

BACKGROUND: Alcoholic cardiomyopathy (ACM) is a form of dilated cardiomyopathy (DCM) occurring secondary to long-standing heavy alcohol use and is associated with poor outcomes, but the cause-specific risks are insufficiently understood. METHOD: Between 1997 and 2018, we identified all patients with a first diagnosis of ACM or DCM. The cumulative incidence of different causes of hospitalisation and mortality in the two groups was calculated using the Fine-Gray and Kaplan-Meier methods. RESULTS: A Total of 1,237 patients with ACM (mean age 56.3±10.1 years, 89% men) and 17,211 individuals with DCM (mean age 63.6±13.8 years, 71% men) were identified. Diabetes (10% vs 15%), hypertension (22% vs 31%), and stroke (8% vs 10%) were less common in ACM than DCM, whereas obstructive lung disease (15% vs 12%) and liver disease (17% vs 2%) were more prevalent (p<0.05). Cumulative 5-year mortality was 49% in ACM vs 33% in DCM, p<0.0001, multivariable adjusted hazards ratio 2.11 (95% confidence interval 1.97-2.26). The distribution of causes of death was similar in ACM and DCM, with the predominance of cardiovascular causes in both groups (42% in ACM vs 44% in DCM). 5-year cumulative incidence of heart failure hospitalisations (48% vs 54%) and any somatic cause (59% vs 65%) were also similar in ACM vs DCM. At 1 year, the use of beta blockers (55% vs 80%) and implantable cardioverter defibrillators (3% vs 14%) were significantly less often used in ACM vs DCM. CONCLUSIONS: Patients with ACM had similar cardiovascular risks and hospitalisation patterns as other forms of DCM, but lower use of guideline-directed cardiovascular therapies and greater mortality.

Efficacy and safety of oral anticoagulants according to kidney function among patients with atrial fibrillation.

BACKGROUND AND AIMS: Patients with severely reduced kidney function have been excluded from randomized controlled trials and data on safety and efficacy of direct oral anticoagulants (DOACs) according to kidney function remain sparse. The aim was to evaluate 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/1.73m2 and 596 (2.2%) had an eGFR below 30 mL/min/1.73m2. 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 VKA (risk 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 higher risk of bleeding compared to apixaban (risk ratio 1.78, 95%CI 1.32-2.39) among patients with eGFR 30-49 mL/min/1.73m2. 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 and rivaroxaban among patients with eGFR 15-30 mL/min/1.73m2, and when comparing apixaban to dabigatran and rivaroxaban among patients with eGFR 30-49 mL/min/1.73m2.

The relationship between coronary artery calcium and layer-specific global longitudinal strain in patients with suspected coronary artery disease.

PURPOSE: Layer-specific global longitudinal strain (GLS) may provide important insights in patients with suspected coronary artery disease (CAD). We aimed to investigate the association between layer-specific GLS and coronary artery calcium score (CACS) in patients suspected of CAD. METHODS: We performed a retrospective study of patients suspected of CAD who underwent both an echocardiogram and cardiac computed tomography (median 42 days between). Layer-specific (endocardial-, whole-layer-, and epicardial-) GLS was measured using speckle tracking echocardiography. We assessed the continuous association between layer-specific GLS and CACS by negative binomial regression, and the association with high CACS (≥400) using logistic regression. RESULTS: Of the 496 patients included (mean age 59 years, 56% male), 64 (13%) had a high CACS. Those with high CACS had reduced GLS in all layers compared to those with CACS < 400 (endocardial GLS: -20.5 vs. -22.7%, whole-layer GLS: -17.7 vs. -19.4%, epicardial GLS: -15.3 vs. -16.9%, p < .001 for all). Negative binomial regression revealed a significant continuous association showing increasing CACS with worsening GLS in all layers, which remained significant after multivariable adjustment including SCORE chart risk factors. All layers of GLS were associated with high CACS in univariable analyses, which was consistent after multivariable adjustment (endocardial GLS: OR = 1.11 (1.03-1.20); whole-layer GLS: OR = 1.14 (1.04-1.24); epicardial GLS: OR = 1.16 (1.05-1.29), per 1% absolute decrease). CONCLUSION: In this study population with patients suspected of CAD and normal systolic function, impaired layer-specific GLS was continuously associated with increasing CACS, and decreasing GLS in all layers were associated with presence of high CACS.

Association between travel distance and face-to-face consultations with general practitioners before an incident acute myocardial infarction: a nationwide register-based spatial epidemiological study.

OBJECTIVES: This study examined the association between travel distance to the general practitioner's (GP) office and no face-to-face GP consultation within 1 year before an incident acute myocardial infarction (AMI). DESIGN: A prospective cohort study using multilevel spatial logistic regression analysis of nationwide register data. SETTING: Nationwide study including contacts to GPs in Denmark prior to an incident AMI in 2005-2017. PARTICIPANTS: 121 232 adults (≥30 years) with incident AMI were included in the study. PRIMARY AND SECONDARY OUTCOMES MEASURES: The primary outcome was odds of not having a face-to-face GP consultation within 1 year before an incident AMI. RESULTS: In total, 13 108 (10.8%) of the 121 232 individuals with incident AMI had no face-to-face consultation with the GP within 1 year before the AMI. Population density modified the association between travel distance and no face-to-face GP consultation. Increased odds of no face-to-face GP consultation was observed for medium (25th-75th percentile/1123-5449 m) and long (>75th percentile/5449 m) compared with short travel distance (<25th percentile/1123 m) among individuals living in small cities (OR (95% credible intervals) of 1.19 (1.10 to 1.29) and 1.19 (1.06 to 1.33), respectively) and rural areas (1.46 (1.26 to 1.68) and 1.48 (1.29 to 1.68), respectively). No association was observed for individuals living in large cities and the capital. CONCLUSIONS: Travel distance above approximately 1 km was significantly associated with no face-to-face GP consultation before an incident AMI among individuals living in small cities and rural areas. The structure of the healthcare system should consider the importance of geographical distance between citizens and the GP in remote areas.

Coronary angiography in patients with kidney dysfunction and myocardial injury: A retrospective cohort study on management of myocardial injury in hospitalized patients with kidney disease.

BACKGROUND: Although kidney insufficiency has been shown to be associated with increased risk of myocardial injury, benefit of coronary angiography (CAG) and revascularization remains uncertain, with implications on management strategies and outcomes. We aimed to compare rates of CAG and revascularization and subsequent risk of cardiovascular and kidney outcomes in hospitalized patients with myocardial injury and kidney dysfunction. METHODS: Retrospective cohort study encompassing hospitalized patients with myocardial injury i.e. elevated troponin I or T and an eGFR ≤60 ml/min/1.73 m2 identified between 2011 and 2021 in Danish national registers. 30-day odds for CAG were computed across granular eGFR-categories based on multiple logistic regression. Standardized one-year risks of cardiovascular and kidney outcomes including mortality were determined based on hazards obtained in multiple Cox regression. RESULTS: A total of 52,798 patients with myocardial injury were identified. CAG was performed in 14.3 % (n = 7549). 30-day odds ratios for CAG were 0.64 [0.60-0.68], 0.38 [0.34-0.42], 0.18 [0.14-0.22], and 0.35 [0.30-0.40] in patients with eGFR 31-45 ml/min/1.73 m2, eGFR 15-30 ml/min/1.73 m2 for eGFR<15 ml/min/1.73 m2 and chronic dialysis, respectively (eGFR 46-60 ml/min/1.73 m2 as reference). Median follow-up was 4.1 years. One-year mortality risk differences associated with CAG and revascularization (no CAG as reference) were -7.8 [-7.0; -8.7] and -9.1 [-8.4; -9.9] for eGFR 46-60 ml/min/1.73 m2; -7.0 [-5.7;-8-3] and -8.0 [-6.6; -9.5] for eGFR 31-45 ml/min/1.73 m2; -5.4 [-3.0; -7.2] and -5.2 [-2.2; -8.3] for eGFR 15-30 ml/min/1.73 m2; -8.8 [-3.1; -13.7] and -5.4 [3.1; -13.4] for eGFR<15 ml/min/1.73 m2; and -4.9 [-0.1; -9.7] and -4.2 [1.5; -9.2] for chronic dialysis, respectively. CONCLUSION: Probability of CAG following myocardial injury declined with progressive kidney dysfunction. Overall, CAG was associated with lower mortality irrespective of kidney function and subsequent revascularization.

Fluoroquinolones do not provide added risk of out-of-hospital cardiac arrest: a nationwide study.

AIM: Conflicting results have been reported regarding the association between fluoroquinolones (FQs) and the risk of out-of-hospital cardiac arrest (OHCA). In particular, it has not become clear whether OHCA in FQ users is related to the inherent comorbidities or whether there is a direct pro-arrhythmic effect of FQs. Therefore, we studied the relation between FQs and OHCA in the general population. METHODS: Through Danish nationwide registries, we conducted a nested case-control study with OHCA cases of presumed cardiac causes and age/sex/OHCA date-matched non-OHCA controls from the general population. Conditional logistic regression models with adjustments for well-known risk factors of OHCA were employed to estimate the OR with 95% CI of OHCA comparing FQs with amoxicillin. RESULTS: The study population consisted of 46 578 OHCA cases (mean: 71 years (SD: 14.40), 68.8% men) and 232 890 matched controls. FQ was used by 276 cases and 328 controls and conferred no increase in the odds of OHCA compared with amoxicillin use after controlling for the relevant confounders (OR: 0.91 (95% CI: 0.71 to 1.16)). The OR of OHCA associated with FQ use did not vary significantly by age (OR≤65: 0.96 (95% CI: 0.53 to 1.74), OR>65: 0.88 (95% CI: 0.67 to 1.16), p value interaction=0.7818), sex (ORmen: 0.96 (95% CI: 0.70 to 1.31), ORwomen: 0.80 (95% CI: 0.53 to 1.20), p value interaction=0.9698) and pre-existing cardiovascular disease (ORabsent: 1.02 (95% CI: 0.57 to 1.82), ORpresent: 0.98 (95% CI: 0.75 to 1.28), p value interaction=0.3884), including heart failure (ORabsent: 0.93 (95% CI: 0.72 to 1.22), ORpresent: 1.11 (95% CI: 0.61 to 2.02), p value interaction=0.7083) and ischaemic heart disease (ORabsent: 0.85 (95% CI: 0.64 to 1.12), ORpresent: 1.38 (95% CI: 0.86 to 2.21), p value interaction=0.6230). CONCLUSION: Our findings do not support an association between FQ exposure and OHCA in the general population. This lack of association was consistent in men and women, in all age categories, and in the presence or absence of cardiovascular disease.

Effectiveness of high-dose versus standard-dose quadrivalent influenza vaccine against recurrent hospitalizations and mortality in relation to influenza circulation: A post-hoc analysis of the DANFLU-1 randomized clinical trial.

OBJECTIVES: To evaluate the relative effectiveness of high-dose quadrivalent influenza vaccine (QIV-HD) versus standard-dose quadrivalent influenza vaccine (QIV-SD) against recurrent hospitalizations and its potential variation in relation to influenza circulation. METHODS: We did a post-hoc analysis of a pragmatic, open-label, randomized trial of QIV-HD versus QIV-SD performed during the 2021-2022 influenza season among adults aged 65-79 years. Participants were enrolled in October 2021-November, 2021 and followed for outcomes from 14 days postvaccination until 31 May, 2022. We investigated the following outcomes: Hospitalizations for pneumonia or influenza, respiratory hospitalizations, cardio-respiratory hospitalizations, cardiovascular hospitalizations, all-cause hospitalizations, and all-cause death. Outcomes were analysed as recurrent events. Cumulative numbers of events were assessed weekly. Cumulative relative effectiveness estimates were calculated and descriptively compared with influenza circulation. The trial is registered at Clinicaltrials.gov: NCT05048589. RESULTS: Among 12,477 randomly assigned participants, receiving QIV-HD was associated with lower incidence rates of hospitalizations for pneumonia or influenza (10 vs. 33 events, incidence rate ratio [IRR] 0.30 [95% CI, 0.14-0.64]; p 0.002) and all-cause hospitalizations (647 vs. 742 events, IRR 0.87 [95% CI, 0.76-0.99]; p 0.032) compared with QIV-SD. Trends favouring QIV-HD were consistently observed over time including in the period before active influenza transmission; i.e. while the first week with a ≥10% influenza test positivity rate was calendar week 10, 2022, the first statistically significant reduction in hospitalizations for pneumonia or influenza was already observed by calendar week 3, 2022 (5 vs. 15 events, IRR 0.33 [95% CI, 0.11-0.94]; p 0.037). DISCUSSION: In a post-hoc analysis, QIV-HD was associated with lower incidence rates of hospitalizations for pneumonia or influenza and all-cause hospitalizations compared with QIV-SD, with trends evident independent of influenza circulation levels. Our exploratory results correspond to a number needed to treat of 65 (95% CI 35-840) persons vaccinated with QIV-HD compared with QIV-SD to prevent one additional all-cause hospitalization per season. Further research is needed to confirm these hypothesis-generating findings.

Cannabis for chronic pain: cardiovascular safety in a nationwide Danish study.

BACKGROUND AND AIMS: A rising number of countries allow physicians to treat chronic pain with medical cannabis. However, recreational cannabis use has been linked with cardiovascular side effects, necessitating investigations concerning the safety of prescribed medical cannabis. METHODS: Using nationwide Danish registers, patients with chronic pain initiating first-time treatment with medical cannabis during 2018-21 were identified and matched 1:5 to corresponding control patients on age, sex, chronic pain diagnosis, and concomitant use of other pain medication. The absolute risks of first-time arrhythmia (atrial fibrillation/flutter, conduction disorders, paroxysmal tachycardias, and ventricular arrhythmias) and acute coronary syndrome were reported comparing medical cannabis use with no use. RESULTS: Among 1.88 million patients with chronic pain (46% musculoskeletal, 11% cancer, 13% neurological, and 30% unspecified pain), 5391 patients claimed a prescription of medical cannabis [63.2% women, median age: 59 (inter-quartile range 48-70) years] and were compared with 26 941 control patients of equal sex- and age composition. Arrhythmia was observed in 42 and 107 individuals, respectively, within 180 days. Medical cannabis use was associated with an elevated risk of new-onset arrhythmia {180-day absolute risk: 0.8% [95% confidence interval (CI) 0.6%-1.1%]} compared with no use [180-day absolute risk: 0.4% (95% CI 0.3%-0.5%)]: a risk ratio of 2.07 (95% CI 1.34-2.80) and a 1-year risk ratio of 1.36 (95% CI 1.00-1.73). No significant association was found for acute coronary syndrome [180-day risk ratio: 1.20 (95% CI 0.35-2.04)]. CONCLUSIONS: In patients with chronic pain, the use of prescribed medical cannabis was associated with an elevated risk of new-onset arrhythmia compared with no use-most pronounced in the 180 days following the initiation of treatment.