Risk factors associated with clinically relevant pericardial effusion after primary cardiac implantable electronic device implantation.

INTRODUCTION: Pericardial effusion, a known complication to implantation of cardiac implantable electronic devices (CIED), may cause life-threatening cardiac tamponade. Limited knowledge is available about risk factors for clinically relevant procedural pericardial effusion. The aim is to identify the patient- and procedure-related risk factors associated with clinically relevant procedural pericardial effusion. METHOD: A nationwide observational cohort study based on data on 55 121 patients from the Danish Pacemaker Register between 2000 and 2018. We defined a clinically relevant procedural pericardial effusion related to the implantation if it occurred within 90 days after the primary CIED-procedure. Prespecified risk factors were analysed by multivariable logistic regression models to estimate the association with pericardial effusion. RESULTS: There were 115 (0.21%) patients diagnosed with clinically relevant procedural pericardial effusion, with a median age of 75 years and 38.3% were females. Of these, 80.9% lead to a subsequent pericardiocentesis procedure. In adjusted logistic regression analysis, an increased risk of clinically relevant pericardial effusion was associated with female sex (OR:1.49 [95%CI: 1.03-2.16]), heart failure (OR:1.54 [95%CI: 1.06-2.23]), previous cardiac surgery (OR:1.63 [95%CI: 1.05-2.55]), CRT-device (OR:2.05 [95%CI: 1.23-3.41]), tertiary-centres (OR:1.8 [95%CI: 1.18-2.73]), increased procedural volume per year (>1000) (OR:1.85 [95%CI: 1.03-3.30]), indication of device-implantation (atrioventricular block) (OR:2.37 [95CI: 1.45-3.87]), and increasing number of leads implanted (two leads (OR:2.39 [95%CI: 1.43-4.00]), three leads (OR:4.77 [95%CI: 2.50-9.10])). CONCLUSION: Clinically relevant procedural pericardial effusion is a rare complication after CIED-implantation in Denmark. This study reveals important patient- and procedure-related risk factors associated with clinically relevant procedural pericardial effusion.

Lifetime risk of comorbidity in patients with simple congenital heart disease: a Danish nationwide study.

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.

Type 2 diabetes mellitus and higher rate of complete atrioventricular block: a Danish Nationwide Registry.

AIMS: The present study aimed to determine the association between Type 2 diabetes mellitus (T2DM) and third-degree (complete) atrioventricular block. METHODS AND RESULTS: This nationwide nested case-control study included patients older than 18 years, diagnosed with third-degree atrioventricular block between 1 July 1995 and 31 December 2018. Data on medication, comorbidity, and outcomes were collected from Danish registries. Five controls, from the risk set of each case of third-degree atrioventricular block, were matched on age and sex to fit a Cox regression model with time-dependent exposure and time-dependent covariates. Subgroup analysis was conducted with Cox regression models for each subgroup. We located 25 995 cases with third-degree atrioventricular block that were matched with 130 004 controls. The mean age was 76 years and 62% were male. Cases had more T2DM (21% vs. 11%), hypertension (69% vs. 50%), atrial fibrillation (25% vs. 10%), heart failure (20% vs. 6.3%), and myocardial infarction (19% vs. 9.2%), compared with the control group. In Cox regression analysis, adjusting for comorbidities and atrioventricular nodal blocking agents, T2DM was significantly associated with third-degree atrioventricular block (hazard ratio: 1.63, 95% confidence interval: 1.57-1.69). The association remained in several subgroup analyses of diseases also suspected to be associated with third-degree atrioventricular block. There was a significant interaction with comorbidities of interest including hypertension, atrial fibrillation, heart failure, and myocardial infarction. CONCLUSION: In this nationwide study, T2DM was associated with a higher rate of third-degree atrioventricular block compared with matched controls. The association remained independent of atrioventricular nodal blocking agents and other comorbidities known to be associated with third-degree atrioventricular block.

Atrial fibrillation onset before heart failure or vice versa: what is worst? A nationwide register study.

AIMS: Atrial fibrillation (AF) and heart failure (HF) often coexist. However, whether AF onset before HF or vice versa is associated with the worst outcome remains unclear. A consensus of large studies can guide future research and preventive strategies to better target high-risk patients. METHODS AND RESULTS: We included all Danish cases with the coexistence of AF and HF (2005-17) using nationwide registries. Patients were divided into three separate groups (i) AF before HF, (ii) HF before AF, or (iii) AF and HF diagnosed concurrently (±30 days). Adjusting landmark Cox analyses (index date was the time of the latter diagnosis of AF or HF) were used for evaluating the association of the three groups with a composite outcome of ischaemic stroke or death. Among a total of 49 042 patients included, 40% had AF before HF, 27% had HF before AF, and 33% had AF and HF diagnosed concurrently. The composite endpoint accrued more often in patients with HF before AF compared to the two other groups (<0.001), and this remained significant in the adjusted analyses with hazard ratios (95% confidence intervals) of 1.26 (1.22-1.30) compared to AF before HF. Finally, antihypertensive treatment, oral anticoagulants, amiodarone, statins, and AF ablation were associated with a lower hazard ratio of the composite endpoint (all < 0.001). CONCLUSIONS: In this large Danish national cohort, diagnosis of HF before AF was associated with an increased absolute risk of death compared to AF before HF and AF and HF diagnosed concurrently. Antihypertensive treatment, oral anticoagulants, amiodarone, statins, and AF ablation may improve prognosis.

Treated periodontitis and recurrent events after first-time myocardial infarction: A Danish nationwide cohort study.

AIM: To investigate the association between previous periodontal treatment and recurrent events after first-time myocardial infarction (MI). MATERIALS AND METHODS: From the Danish nationwide registries, patients with first-time MI between 2000 and 2015 were divided into three groups according to oral health care within 1 year prior to first-time MI. A multiple logistic regression model provided adjusted odds ratios (ORs) with 95% confidence intervals (CIs) to assess the 3-year risk of major adverse cardiovascular events (MACE). RESULTS: A total of 103,949 patients were included. Patients with treated periodontitis (PD) prior to first-time MI had an adjusted 3-year risk of MACE similar to patients presumed periodontally healthy (OR 0.97 [95% CI 0.92-1.03]). Patients with no prior dental visits were significantly older, had more comorbidities and showed significantly increased adjusted 3-year risks of MACE (OR 1.47 [95% CI 1.42-1.52]), cardiovascular death (OR 1.71 [95% CI 1.64-1.78]) and heart failure (OR 1.13 [95% CI 1.07-1.20]) compared with patients presumed periodontally healthy. CONCLUSIONS: Patients with treated PD 1 year prior to first-time MI had a similar risk of recurrent cardiovascular events as patients presumed periodontally healthy. No dental visit prior to first-time MI was an independent risk factor for recurrent events.

Impact of Nationwide COVID-19 Lockdowns on the Implantation Rate of Cardiac Implantable Electronic Devices.

AIM: The COVID-19 pandemic resulted in a significant decrease in the number of hospital admissions for severe emergent cardiovascular diseases during lockdowns worldwide. This study aimed to determine the impact of both the first and the second Danish nationwide lockdown on the implantation rate of cardiac implantable electronic devices (CIEDs). METHODS: We retrospectively analysed the number of CIED implantations performed in Denmark and stratified them into 3-week intervals. RESULTS: The total number of de novo CIED implantations decreased during the first lockdown by 15.5% and during the second by 5.1%. Comparing each 3-week interval using rate ratios, a significant decrease in the daily rates of the total number of de novo and replacement CIEDs (0.82, 95% CI [0.70, 0.96]), de novo CIEDs only (0.82, 95% CI [0.69, 0.98]), and non-acute pacemaker implantations (0.80, 95% CI [0.63, 0.99]) was observed during the first interval of the first lockdown. During the second lockdown (third interval), a significant decrease was seen in the daily rates of de novo CIEDs (0.73, 95% CI [0.55, 0.97]), and of pacemakers in total during both the second (0.78, 95% CI [0.62, 0.97]) and the third (0.60, 95% CI [0.42, 0.85]) intervals. Additionally, the daily rates of acute pacemaker implantation decreased during the second interval (0.47, 95% CI [0.27, 0.79]) and of non-acute implantation during the third interval (0.57, 95% CI [0.38, 0.84]). A significant increase was observed in the number of replacement procedures during the first interval of the second lockdown (1.70, 95% CI [1.04, 2.85]). CONCLUSIONS: Our study found only modest changes in CIED implantations in Denmark during two national lockdowns.

Aortic Root Dilatation in Hypertensive Patients with Left Ventricular Hypertrophy-Application of A New Multivariate Predictive Model. The Life Study.

BACKGROUND: Available nomograms to predict aortic root (AoR) diameter for body surface area have limitations. The purpose of this study was to evaluate the use of a new multivariate predictive model to identify AoR dilatation in hypertensive patients with left ventricular hypertrophy. METHODS: 943 of 961 patients in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiographic sub-study had the necessary baseline characteristics and echocardiographic 2D measurements of AoR size to be included. RESULTS: Predicted AoR (Sinus of Valsalva) diameter was 1.519 + (age [years] × 0.010) + (height [cm] × 0.010) - (gender [1 = M, 2 = F] × 0.247), and a measured AoR diameter exceeding the 97.5-percentile of this estimate was considered dilated. Measured AoR diameter was larger in men than in women (3.75 vs. 3.48 cm, p < 0.001) and AoR diameter predicted by the model was larger than predicted by nomogram (3.52 vs. 3.28 cm, p < 0.001). Using the multivariate model to identify patients with AoR dilatation, the prevalence was 13.7% in men and 12.3% in women (p = 0.537). There was consensus of AoR phenotype (normal/dilated) between model and nomogram in 92.8% of the patients. In multivariate logistic regression, AoR dilatation by model definition was predicted by presence of aortic regurgitation (OR 2.67, p < 0.001) and SD increase in age (OR 0.75, p = 0.023), pulse pressure (OR 0.64, p < 0.001), left ventricular mass index (OR 1.36, p = 0.08) and stroke volume (OR 1.45, p = 0.002), but not by body weight. CONCLUSIONS: Using the proposed model the prevalence of AoR dilatation was equal in men and women and the model seems to address the effects of gender, age and body size on AoR size. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT00338260.

Severe mental illness is associated with increased mortality and severe course of COVID-19.

OBJECTIVE: Psychiatric disorders have been associated with unfavourable outcome following respiratory infections. Whether this also applies to coronavirus disease 2019 (COVID-19) has been scarcely investigated. METHODS: Using the Danish administrative databases, we identified all patients with a positive real-time reverse transcription-polymerase chain reaction test for COVID-19 in Denmark up to and including 2 January 2021. Multivariable cox regression was used to calculate 30-day absolute risk and average risk ratio (ARR) for the composite end point of death from any cause and severe COVID-19 associated with psychiatric disorders, defined using both hospital diagnoses and redemption of psychotropic drugs. RESULTS: We included 144,321 patients with COVID-19. Compared with patients without psychiatric disorders, the standardized ARR of the composite outcome was significantly increased for patients with severe mental illness including schizophrenia spectrum disorders 2.43 (95% confidence interval [CI], 1.79-3.07), bipolar disorder 2.11 (95% CI, 1.25-2.97), unipolar depression 1.70 (95% CI, 1.38-2.02), and for patients who redeemed psychotropic drugs 1.70 (95% CI, 1.48-1.92). No association was found for patients with other psychiatric disorders 1.13 (95% CI, 0.86-1.38). Similar results were seen with the outcomes of death or severe COVID-19. Among the different psychiatric subgroups, patients with schizophrenia spectrum disorders had the highest 30-day absolute risk for the composite outcome 3.1% (95% CI, 2.3-3.9%), death 1.2% (95% CI, 0.4-2.0%) and severe COVID-19 2.7% (95% CI, 1.9-3.6%). CONCLUSION: Schizophrenia spectrum disorders, bipolar disorder, unipolar depression and psychotropic drug redemption are associated with unfavourable outcomes in patients with COVID-19.

SuPAR is associated with death and adverse cardiovascular outcomes in patients with suspected coronary artery disease.

BACKGROUND: The inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is associated with presence and severity of coronary artery disease (CAD) and incident death and myocardial infarction (MI). We sought to validate this finding in a further cohort of patients with suspected CAD. METHODS: Plasma suPAR was available in 1635 patients (73% with CAD) undergoing coronary angiography at a single regional Danish hospital between 2003 and 2005. Patients were followed for adverse cardiovascular outcomes of death, cardiac death and MI over a median follow-up of 4.2 years. RESULTS: In multivariate Cox models, adjusted for established cardiovascular risk factors, the biomarkers C-reactive protein, troponin-T and N-terminal-pro brain natriuretic peptide and the number of stenotic vessels, suPAR was independently associated with the combined endpoint of death/MI, hazard ratio (HR) 1.88; cardiovascular death, HR 2.01; and non-fatal MI, HR 1.53; (all p ≤ .037) per doubling of suPAR concentration. A plasma cutoff for suPAR ≥ 3.5 ng/mL was also significantly associated with death/MI, HR 1.51; p = .005. The C-statistic for the multivariate model predicting death/MI improved from 0.712 to 0.730 (p for difference .008) after inclusion of suPAR. However, suPAR was not associated with presence or extent of CAD (p > .05). CONCLUSION: These results validate previous findings that demonstrate suPAR to be an independent predictor of death/MI in patients with suspected or known CAD, however suPAR was not associated with presence or extent of CAD in our cohort. Probably because suPAR reflects end organ damage rather than the degree of atherosclerosis. BRIEF SUMMARY: We demonstrate that the inflammatory biomarker soluble urokinase plasminogen activator receptor is an independent predictor of death/myocardial infarction in patients with suspected or known coronary artery disease, but is not associated with the presence or severity of coronary artery disease.

Diabetes and risk of peripheral artery disease in patients undergoing first-time coronary angiography between 2000 and 2012 - a nationwide study.

BACKGROUND: The risk of peripheral artery disease (PAD) in patients with diabetes mellitus (DM) and coronary artery disease (CAD) is an important and inadequately addressed issue. Our aim is to examine the impact of DM on risk of PAD in patients with different degrees of CAD characterized by coronary angiography (CAG). METHODS: Using nationwide registers we identified all patients aged ≥18 years, undergoing first time CAG between 2000 and 2012. Patients were categorized into DM/Non-DM group, and further classified into categories according to the degree of CAD i.e., no-vessel disease, single-vessel disease, double-vessel disease, triple-vessel disease, and diffuse disease. Risk of PAD was estimated by 5-year cumulative-incidence and adjusted multivariable Cox-regression models. RESULTS: We identified 116,491 patients undergoing first-time CAG. Among these, a total of 23.969 (20.58%) had DM. Cumulative-incidence of PAD among DM patients vs. non-DM were 8.8% vs. 4.9% for no-vessel disease, 8.2% vs. 4.8% for single-vessel disease, 10.2% vs. 6.0% for double-vessel disease, 13.0% vs. 8.4% for triple-vessel disease, and 6.8% vs. 6.1% for diffuse disease, respectively. For all patients with DM, the cox-regression analysis yielded significantly higher hazards of PAD compared with non-DM patients with HR 1.70 (no-vessel disease), 1.96 (single-vessel disease), 2.35 (double-vessel disease), 2.87 (triple-vessel disease), and 1.46 (diffuse disease), respectively (interaction-p 0.042). CONCLUSION: DM appears to be associated with increased risk of PAD in patients with and without established CAD, with increasing risk in more extensive CAD. This observation indicates awareness on PAD risk in patients with DM, especially among patients with advanced CAD.

Atrial fibrillation and anticoagulation in patients with breast cancer.

Objectives. To examine the long-term risk of thromboembolism and bleeding in patients with atrial fibrillation comparing patients with and without recent breast cancer in subgroups with or without anticoagulation therapy, respectively. Design. Using nationwide registries, patients with breast cancer from 1998-2015 and subsequent atrial fibrillation within 3 years were stratified on anticoagulation and matched 1:3 on age, sex and comorbidities with atrial fibrillation patients without breast cancer. Risks of thromboembolism and bleeding were estimated by Aalen-Johansen and multivariable cox regression models. Results. Atrial fibrillation patients with and without anticoagulation were matched, respectively (201 and 525 with breast cancer matched with 603 and 1,575 without breast cancer). In patients with CHA2DS2-VASc-score >1 and anticoagulation the three years risks of thromboembolism were 4.2% (95% confidence interval (CI) 1.1-7.3) and 3.2% (CI 1.5-4.9) in patients with and without breast cancer. The risks of bleeding were 5.3% (CI 1.7-8.9) and 5.1% (CI 3.0-7.1), respectively. Breast cancer was associated with a similar risk of thromboembolism in patients with and without anticoagulation, respectively (Hazard ratio (HR) 1.10, CI 0.63-1.92 and HR 1.11, CI 0.82-1.50) and a similar risk of bleeding in patients with and without anticoagulation, respectively (HR 1.01, CI 0.56-1.84 and HR 0.85, CI 0.57-1.27) compared with the matched controls. Conclusions. Breast cancer was not associated with altered risk of thromboembolism or bleeding in patients with atrial fibrillation irrespective of treatment with anticoagulation. Our analyses suggest that atrial fibrillation diagnosed in patients with breast cancer should be considered as primary atrial fibrillation.

Prognostic Importance of Diastolic Dysfunction in Relation to Post Procedural Aortic Insufficiency in Patients Undergoing Transcatheter Aortic Valve Replacement.

OBJECTIVES: We sought to examine whether baseline diastolic dysfunction (DD) is associated with increased mortality in patients who develop aortic insufficiency (AI) after transcatheter aortic valve replacement (TAVR). BACKGROUND: Significant post-TAVR AI is associated with increased mortality, likely secondary to adverse hemodynamics secondary to volume overload and decreased LV compliance from chronic pressure overload. However, the effect of baseline DD on outcomes of patients with post-TAVR AI has not been studied. METHODS: A total of 195 patients undergoing TAVR were included in the study. Patients with moderate-to-severe mitral stenosis, prior mitral valve replacement or atrial fibrillation were excluded. DD was classified at baseline by a 2-step approach as recommended by the American Society of Echocardiography while AI was evaluated 30 days post-TAVR. Follow up data up to 2 years post-TAVR was used in survival analysis. RESULTS: Patients with severe baseline DD who developed ≥mild post-TAVR AI had increased mortality compared to all other patients (HR = 3.89, CI: 1.76-8.6, P = 0.001), which remained significant after adjusting for post-TAVR AI, pre-TAVR AI, baseline mitral regurgitation, ejection fraction, pulmonary artery pressure, creatinine clearance and history of stroke. CONCLUSIONS: Even mild post-TAVR AI may have a negative impact on outcomes of patients with underlying severe DD. © 2016 Wiley Periodicals, Inc.

Stroke in patients with aortic stenosis: the Simvastatin and Ezetimibe in Aortic Stenosis study.

BACKGROUND AND PURPOSE: There are limited data on risk stratification of stroke in aortic stenosis. This study examined predictors of stroke in aortic stenosis, the prognostic implications of stroke, and how aortic valve replacement (AVR) with or without concomitant coronary artery bypass grafting influenced the predicted outcomes. METHODS: Patients with mild-to-moderate aortic stenosis enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Diabetes mellitus, known atherosclerotic disease, and oral anticoagulation were exclusion criteria. Ischemic stroke was the primary end point, and poststroke survival a secondary outcome. Cox models treating AVR as a time-varying covariate were adjusted for atrial fibrillation and congestive heart failure, hypertension, age≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years and female sex (CHA2DS2-VASc) scores. RESULTS: One thousand five hundred nine patients were followed for 4.3±0.8 years (6529 patient-years). Rates of stroke were 5.6 versus 21.8 per 1000 patient-years pre- and post-AVR; 429 (28%) underwent AVR and 139 (9%) died. Atrial fibrillation (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.1-6.6), CHA2DS2-VASc score (HR 1.4 per unit; 95% CI, 1.1-1.8), diastolic blood pressure (HR, 1.4 per 10 mm Hg; 95% CI, 1.1-1.8), and AVR with concomitant coronary artery bypass grafting (HR, 3.2; 95% CI, 1.4-7.2, all P≤0.026) were independently associated with stroke. Incident stroke predicted death (HR, 8.1; 95% CI, 4.7-14.0; P<0.001). CONCLUSIONS: In patients with aortic stenosis not prescribed oral anticoagulation, atrial fibrillation, AVR with concomitant coronary artery bypass grafting, and CHA2DS2-VASc score were the major predictors of stroke. Incident stroke was strongly associated with mortality. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00092677.

Statin treatment, new-onset diabetes, and other adverse effects: a systematic review.

Statin treatment prevents cardiovascular diseases probably beyond their lipid-lowering effect. Increasing evidence suggests that statins might increase the risk of new-onset diabetes; however, diabetes is known to increase the risk of cardiovascular diseases. The majority of the literature suggests an increased risk of new-onset diabetes in patients treated with statins in a number of different settings and that the risk appears greatest among the more potent statins. Furthermore, a dose-response curve has been shown between statin treatment and the development of diabetes. Possible mechanisms include muscle insulin resistance, lower expression of GLUT-4 in adipocytes impairing glucose tolerance and suppression of glucose-induced elevation of intracellular Ca(2+) level. However, other side effects have been reported such as increased risk of myotoxicity, increased liver enzymes, cataracts, mood disorders, dementias, hemorrhagic stroke and peripheral neuropathy, which should maybe be added to the increased risk of new-onset diabetes, when considering the risk- benefit ratio of statin treatment.

Regression of electrocardiographic left ventricular hypertrophy or strain is associated with lower incidence of cardiovascular morbidity and mortality in hypertensive patients independent of blood pressure reduction - A LIFE review.

Cornell product criteria, Sokolow-Lyon voltage criteria and electrocardiographic (ECG) strain (secondary ST-T abnormalities) are markers for left ventricular hypertrophy (LVH) and adverse prognosis in population studies. However, the relationship of regression of ECG LVH and strain during antihypertensive therapy to cardiovascular (CV) risk was unclear before the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study. We reviewed findings on ECG LVH regression and strain over time in 9193 hypertensive patients with ECG LVH at baseline enrolled in the LIFE study. The composite endpoint of CV death, nonfatal MI, or stroke occurred in 1096 patients during 4.8±0.9years follow-up. In Cox multivariable models adjusting for randomized treatment, known risk factors including in-treatment blood pressure, and for severity ECG LVH by Cornell product and Sokolow-Lyon voltage, baseline ECG strain was associated with a 33% higher risk of the LIFE composite endpoint (HR. 1.33, 95% CI [1.11-1.59]). Development of new ECG strain between baseline and year-1 was associated with a 2-fold increased risk of the composite endpoint (HR. 2.05, 95% CI [1.51-2.78]), whereas the risk associated with regression or persistence of ECG strain was attenuated and no longer statistically significant (both p>0.05). After controlling for treatment with losartan or atenolol, for baseline Framingham risk score, Cornell product, and Sokolow-Lyon voltage, and for baseline and in-treatment systolic and diastolic blood pressure, 1 standard deviation (SD) lower in-treatment Cornell product was associated with a 14.5% decrease in the composite endpoint (HR. 0.86, 95% CI [0.82-0.90]). In a parallel analysis, 1 SD lower in-treatment Sokolow-Lyon voltage was associated with a 16.6% decrease in the composite endpoint (HR. 0.83, 95% CI [0.78-0.88]). The LIFE study shows that evaluation of both baseline and in-study ECG LVH defined by Cornell product criteria, Sokolow-Lyon voltage criteria or ECG strain improves prediction of CV events and that regression of ECG LVH during antihypertensive treatment is associated with better outcome, independent of blood pressure reduction.

Association between long-term statin use and cataract surgery: a nationwide study on 505 105 cataract surgery patients.

AIMS: To assess the association between statin use and cataract surgery according to different statin treatment durations in patients with different cardiovascular risk profiles. METHODS AND RESULTS: We performed a nested case-control study using Danish registries, covering the period from 1 January 1996 to 31 December 2020. We defined cases as surgically treated cataract patients, matched in a 1:1 ratio by sex and age with controls not undergoing cataract surgery. The exposure of interest was statin use in different durations (1, 5 and 10 years) compared with never use of statins. Conditional logistic regression provided adjusted HRs and corresponding 95% CIs in subgroups defined by established atherosclerotic cardiovascular disease, diabetes, hypertension and individuals without these comorbidities. We identified 505 150 cataract surgery cases and found no increased HR of cataract surgery with statin treatment at any duration in any of the subgroups with established atherosclerotic cardiovascular disease, diabetes or hypertension. CONCLUSION: Our findings do not support a possible association between long-term statin use and cataract in patients with established atherosclerotic cardiovascular disease, diabetes or hypertension. Although we found an association between statin use and cataract in individuals without these comorbidities, increasing durations of statin use did not yield higher cataract surgery rates.

Ongoing Opioid Treatment and Symptoms of Myocardial Infarction in Calls to the Emergency Medical Services.

Background: Ongoing opioid treatment can potentially modify symptoms of myocardial infarction (MI) and cause a lack of recognition and treatment delay. Objectives: The purpose of this study was to examine MI symptoms and the time to hospitalization for patients in ongoing opioid treatment compared to patients without ongoing opioid treatment. Methods: We evaluated calls to the Copenhagen Emergency Medical Services in Denmark from 2014 to 2018. Calls were included when followed by hospitalization and a diagnosis of MI. Symptoms of MI and the time from call to hospitalization in patients in ongoing opioid treatment initiated prior to the onset of MI were compared to a control group of MI patients without opioid treatment. Results: In total, 6,633 calls were included; 552 calls from patients in opioid treatment and 6,081 calls from controls. Patients in opioid treatment were older and had more comorbidities than controls. Chest pain was less prevalent in MI patients in opioid treatment compared to controls (adjOR: 0.70; 95% CI: 0.57-0.85). The median time from the call to hospitalization was longer in patients in opioid treatment than in controls (50 vs 47 minutes; P = 0.006). Conclusions: In calls to the Emergency Medical Services, opioid treatment initiated prior to the onset of MI was associated with less frequent chest pain in MI. Therefore, awareness of ongoing opioid treatment may improve telephone triage of patients with MI, as symptom presentation in opioid-treated patients may differ and potentially challenge and delay the emergency response.

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.

The effect of discontinuing beta-blockers after different treatment durations following acute myocardial infarction in optimally treated, stable patients without heart failure: a Danish, nationwide cohort study.

AIMS: We studied the effect of discontinuing beta-blockers following myocardial infarction in comparison to continuous beta-blocker use in optimally treated, stable patients without heart failure. METHODS AND RESULTS: Using nationwide registers, we identified first-time myocardial infarction patients treated with beta-blockers following percutaneous coronary intervention or coronary angiography. The analysis was based on landmarks selected as 1, 2, 3, 4, and 5 years after the first redeemed beta-blocker prescription date. The outcomes included all-cause death, cardiovascular death, recurrent myocardial infarction, and a composite outcome of cardiovascular events and procedures. We used logistic regression and reported standardized absolute 5-year risks and risk differences at each landmark year. Among 21 220 first-time myocardial infarction patients, beta-blocker discontinuation was not associated with an increased risk of all-cause death, cardiovascular death, or recurrent myocardial infarction compared with patients continuing beta-blockers (landmark year 5; absolute risk difference [95% confidence interval]), correspondingly; -4.19% [-8.95%; 0.57%], -1.18% [-4.11%; 1.75%], and -0.37% [-4.56%; 3.82%]). Further, beta-blocker discontinuation within 2 years after myocardial infarction was associated with an increased risk of the composite outcome (landmark year 2; absolute risk [95% confidence interval] 19.87% [17.29%; 22.46%]) compared with continued beta-blocker use (landmark year 2; absolute risk [95% confidence interval] 17.10% [16.34%; 17.87%]), which yielded an absolute risk difference [95% confidence interval] at -2.8% [-5.4%; -0.1%], however, there was no risk difference associated with discontinuation hereafter. CONCLUSION: Discontinuation of beta-blockers 1 year or later after a myocardial infarction without heart failure was not associated with increased serious adverse events.

Effect of lipid lowering on new-onset atrial fibrillation in patients with asymptomatic aortic stenosis: the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study.

BACKGROUND: Lipid-lowering drugs, particularly statins, have anti-inflammatory and antioxidant properties that may prevent atrial fibrillation (AF). This effect has not been investigated on new-onset AF in asymptomatic patients with aortic stenosis (AS). METHODS: Asymptomatic patients with mild-to-moderate AS (n = 1,421) were randomized (1:1) to double-blind simvastatin 40 mg and ezetimibe 10 mg combination or placebo and followed up for a mean of 4.3 years. The primary end point was the time to new-onset AF adjudicated by 12-lead electrocardiogram at a core laboratory reading center. Secondary outcomes were the correlates of new-onset AF with nonfatal nonhemorrhagic stroke and a combined end point of AS-related events. RESULTS: During the course of the study, new-onset AF was detected in 85 (6%) patients (14.2/1,000 person-years of follow-up). At baseline, patients who developed AF were, compared with those remaining in sinus rhythm, older and had a higher left ventricular mass index a smaller aortic valve area index. Treatment with simvastatin and ezetimibe was not associated with less new-onset AF (odds ratio 0.89 [95% CI 0.57-1.97], P = .717). In contrast, age (hazard ratio [HR] 1.07 [95% CI 1.05-1.10], P < .001) and left ventricular mass index (HR 1.01 [95% CI 1.01-1.02], P < .001) were independent predictors of new-onset AF. The occurrence of new-onset AF was independently associated with 2-fold higher risk of AS-related outcomes (HR 1.65 [95% CI 1.02-2.66], P = .04) and 4-fold higher risk of nonfatal nonhemorrhagic stroke (HR 4.04 [95% CI 1.18-13.82], P = .03). CONCLUSIONS: Simvastatin and ezetimibe were not associated with less new-onset AF. Older age and greater left ventricular mass index were independent predictors of AF development. New-onset AF was associated with a worsening of prognosis.