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.

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.

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.

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.

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.

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

AIM: Methylphenidate, a sympathomimetic drug prescribed to treat attention-deficit/hyperactivity disorder (ADHD), is associated with cardiovascular events, but few studies have explored the risk of out-of-hospital cardiac arrest (OHCA). We investigated whether methylphenidate use is associated with OHCA in the general population. METHODS AND RESULTS: Using 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 odds ratio (OR) of OHCA by comparing methylphenidate use with no use of methylphenidate.The study population consisted of 46 578 OHCA cases [median: 72 years (interquartile range: 62-81), 68.8% men] and 232 890 matched controls. Methylphenidate was used by 80 cases and 166 controls, and was associated with an increased OR of OHCA compared with non-users {OR: 1.78 [95% confidence interval (CI): 1.32-2.40]}. The OR was highest in recent starters (OR≤180 days: 2.59, 95% CI: 1.28-5.23). The OR of OHCA associated with methylphenidate use did not vary significantly by age (P-value interaction: 0.37), sex (P-value interaction: 0.94), and pre-existing cardiovascular disease (P-value interaction: 0.27). Furthermore, the ORs remained elevated when we repeated the analyses in individuals without registered hospital-based ADHD (OR: 1.85, 95% CI: 1.34-2.55), without severe psychiatric disorders (OR: 1.98, 95% CI: 1.46-2.67), without depression (OR: 1.93, 95% CI: 1.40-2.65), or in non-users of QT-prolonging drugs (OR: 1.79, 95% CI: 1.27-2.54). CONCLUSION: Methylphenidate use is associated with an increased risk of OHCA in the general population. This increased risk applies to both sexes and is independent of age and the presence of cardiovascular disease.

Sodium-glucose cotransporter-2 inhibitors compared with glucagon-like-peptide-1 receptor agonists and out-of-hospital cardiac arrest in type 2 diabetes: a nationwide nested case-control study.

AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) are antidiabetic drugs that have beneficial direct effects on the myocardium by impacting cardiac ion channels and exchangers that control cardiac electrophysiology. We investigated the relationship between SGLT-2is in comparison to glucagon-like peptide-1 receptor agonists (GLP-1as) and out-of-hospital cardiac arrest (OHCA) in individuals with type 2 diabetes. METHODS: Using data from Danish registries, we conducted a nationwide nested case-control study in a cohort of individuals with type 2 diabetes between 2013 and 2019. Cases were defined as OHCA victims from presumed cardiac causes and each case was randomly matched with five controls without OHCA based on age, sex, and index-date (OHCA date). Conditional logistic regression models were used to estimate the adjusted odds ratios (ORs) with 95% confidence interval (95% CI) of OHCA comparing SGLT-2i use with GLP-1as (reference). RESULTS: The study population consisted of 3618 OHCA cases and 18 090 matched controls. SGLT-2i was used by 91 cases and 593 controls, and was associated with reduced odds of OHCA compared with use of GLP-1a after controlling for the relevant confounders (adjusted OR 0.76 [95% CI:0.58-0.99]). The adjusted OR of OHCA associated with SGLT-2i use did not vary significantly by sex (P-value interaction: 0.461), pre-existing cardiac disease (P-value interaction: 0.762), heart failure (P-value interaction: 0.891), diabetes duration (P-value interaction: 0.101), and chronic kidney disease (P-value interaction: 0.894). CONCLUSION: Use of SGLT-2i is associated with a reduced risk of OHCA compared with use of GLP-1a in type 2 diabetes.

Long-term stress conditions and out-of-hospital cardiac arrest risk: a nested case-control study.

OBJECTIVE: Patients with stress-related disorders and anxiety are at increased risk of developing cardiovascular disease. However, the risk of out-of-hospital cardiac arrest (OHCA) is scarcely investigated. We aimed to establish whether long-term stress (post-traumatic stress disorder, adjustment disorder) or anxiety is associated with OHCA in the general population. METHODS: We conducted a nested case-control study in a nationwide cohort of individuals between 1 June 2001 and 31 December 2015 in Denmark. Cases were OHCA patients with presumed cardiac causes. Each case was matched by age, sex and date of OHCA with 10 non-OHCA controls from the general population. HRs for OHCA were derived from Cox models after controlling for common OHCA risk factors. Stratified analyses were performed according to sex, age and pre-existing cardiovascular disease. RESULTS: We included 35 195 OHCAs and 351 950 matched controls (median age 72 years; 66.8% male). Long-term stress conditions were diagnosed in 324 (0.92%) OHCA cases and 1577 (0.45%) non-OHCA controls, and were associated with higher rate of OHCA (HR 1.44, 95% CI 1.27 to 1.64). Anxiety was diagnosed in 299 (0.85%) OHCA cases and 1298 (0.37%) controls, and was associated with increased rate of OHCA (HR 1.56, 95% CI1.37 to 1.79). We found no interaction with sex, age or history of cardiovascular diseases. CONCLUSION: Patients with stress-related disorders or anxiety have an increased rate of OHCA. This association applies equally to men and women and is independent from the presence of cardiovascular disease. Awareness of the higher risks of OHCA in patients with stress-related disorders and anxiety is important when treating these patients.

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.

Needling after trabeculectomy - does augmentation by anti-metabolites provide better outcomes and is Mitomycin C better than 5-Fluoruracil? A systematic review with network meta-analyses.

PURPOSE: Favourable outcome after glaucoma surgery depends on proper control of the inflammatory response. Failing filtration bleb and consequently increased intraocular pressure is an important cause of continuous visual field deterioration after uncomplicated glaucoma surgery. The present systematic review and meta-analysis aimed to compare the effects of employing either Mitomycin C (MMC), 5-Fluoruracil (5-FU) or no anti-metabolite in needling revision of trabeculectomies. METHODS: We performed a systematic literature search in PubMed, Cochrane and EMBASE to identify randomized and non-randomized trials published between year 2000 and March 2019 comparing the efficacy of needling filtering blebs when using no anti-fibrotic agent, MMC or 5-FU in patients with glaucoma. Efficacy was defined as intraocular pressure at 12 months or latest follow-up, rate of complications, rates of success and the number of re-needling cases. Comparisons were made using network meta-analyses. RESULTS: We identified one randomized trial and five retrospective trials. Twelve months after needling revision of trabeculectomy, no significant difference was observed when comparing the effect of the use of MMC with 5-FU or without any use of anti-metabolite on intraocular pressure, complication rates, qualified success, complete success or number of re-needling cases. CONCLUSION: We found no significant difference in the efficacy of using either MMC, 5-FU or no anti-metabolite in needling revision of trabeculectomies. The number of studies meeting our inclusion criteria was limited. Considering the design of studies, only one was randomized leading to an overall low quality of evidence on the subject matter. Further research is warranted.