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.

Rate of Heart Failure Following Atrial Fibrillation According to Presence of Family History of Dilated Cardiomyopathy or Heart Failure: A Nationwide Study.

Background It is poorly understood why some patients with atrial fibrillation develop heart failure (HF) and others do not. We examined the rate of developing HF in patients with atrial fibrillation with and without first-degree family members with HF or dilated cardiomyopathy (DCM). Methods and Results Using Danish nationwide registries, patients born after 1942 diagnosed with atrial fibrillation in the period 2005 to 2015 were identified and followed for up to 5 years. Patients with pre-existing HF, DCM, and/or ischemic heart disease diagnoses were excluded. Exposure was defined as a first-degree relative with HF or DCM. The rate of developing the composite end point of HF or death, and the components, was estimated with multivariable Cox proportional hazard regression models. We included 10 605 patients. A total of 17% had a family member with DCM/HF. Having a family member with HF/DCM was associated with an increased 5-year risk of the composite of HF/death (cumulative incidence, 9.2% [95% CI, 7.8-10.7] versus 5.6% [95% CI, 5.0-6.1]; adjusted hazard ratio [HR] 1.36 [95% CI, 1.13-1.64]). (HF 8.4% [95% CI, 7.0-9.8] versus 4.5% [95% CI, 4.1-5.0]); (adjusted HR, 1.49 [95% CI, 1.22-1.82]). However, familial HF/DCM was not significantly associated with an increased 5-year risk and rate of death (0.8% [95% CI, 0.4-1.2] versus 1.1% [95% CI, 0.8-1.3]); (adjusted HR, 0.80 [95% CI, 0.46-1.39]). Conclusions In patients with incident atrial fibrillation without prior ischemic heart disease or HF diagnoses, 1 of 6 had a first-degree relative with HF, and having such a family history of HF/DCM was associated with an 87% increase in 5-year incidence of HF compared with those without.

Catheter ablation and mortality, stroke and heart failure readmission with atrial fibrillation.

BACKGROUND: Recent randomised clinical trials have suggested prognostic benefits of catheter ablation in highly selected patients with atrial fibrillation (AF) and heart failure (HF). OBJECTIVES: This study sought to identify the treatment effect associated with catheter ablation in a broad population of patients with AF and HF. METHODS: Through nationwide administrative registers in Denmark, we estimated the 2-year average treatment effect (ATE) of catheter ablation for AF on a composite endpoint of HF readmission, stroke and all-cause mortality at 1-year and 5-year landmark analyses. The primary cohort was patients with AF before HF, and the second cohort of patients with HF before AF. RESULTS: A total of 13 756 patients were included with 9904 patients in the primary cohort, and 3852 in the secondary. An ATE (95% CI) reduction of the composite endpoint of 7.0% (4.5% to 9.5%) was observed in the primary cohort and 11.8% (6.0% to 17.6%) in the secondary in the 1-year landmark analysis with a reduction in all-cause mortality of 5.8% (3.7%-7.8%) and 6.3% (0.9%-11.7%), respectively. At the 5-year landmark, catheter ablation was associated with reductions in the composite endpoint and all-cause mortality in the primary (4.7% (2.3% to 7.2%), and 3.6% (1.0% to 6.3%), respectively), but not in the secondary cohort. CONCLUSIONS: Ablation was associated with decreased risk of HF readmission, stroke and all-cause mortality in patients with AF and HF. The effect is most substantial in patients with AF before HF and with catheter ablation after 1 year from the diagnosis of both conditions.

Risk of gastrointestinal bleeding associated with oral anticoagulation and non-steroidal anti-inflammatory drugs in patients with atrial fibrillation: a nationwide study.

AIMS: Non-vitamin K antagonist oral anticoagulants (NOACs) are displacing vitamin K antagonists (VKAs) for stroke prophylaxis in patients with atrial fibrillation (AF). Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) could increase gastrointestinal bleeding (GIB) risks among these patients. The aim of this study was to examine the risk of GIB among Danish AF patients taking oral anticoagulants (OACs) and NSAIDs. METHODS AND RESULTS: Using nationwide administrative registries, we determined concomitant NSAID use among anticoagulant-naïve patients with AF initiating OACs between August 2011 and June 2017. We calculated short-term absolute risks differences and hazard ratios (HRs) for GIB based on multiple adjusted cause-specific Cox regressions with time-dependent NSAID treatment. Among 41 183 patients [median age 70 years (interquartile range 64-78); 55% men], 21% of patients on NOACs and 18% on VKA were co-prescribed NSAIDs. The differences in absolute risk [95% confidence interval (CI)] of GIB within 14 days of commencing concomitant NSAID therapy (vs. no concomitant NSAID therapy) were 0.10% (0.04-0.18%) for NOACs and 0.13% (0.03-0.24%) for VKA. NOACs overall were associated with less GIB than VKA [HR 0.77 (95% CI 0.69-0.85)]. Compared with OACs alone, concomitant NSAIDs doubled the GIB risk associated with NOACs overall [HR 2.01 (95% CI 1.40-2.61)] and with VKA [HR 1.95 (95% CI 1.21-2.69)]. CONCLUSION: Among this nationwide AF population taking OACs, concomitant NSAID therapy increased the short-term absolute risk of GIB. Non-vitamin K antagonist oral anticoagulants alone were associated with lower GIB risks than VKA but concomitant NSAIDs abolished this advantage. The findings align with post hoc analyses from randomized studies. Physicians should exercise appropriate caution when prescribing NSAIDs for patients with AF taking NOACs or VKA.

Incidence of atrial fibrillation in different major cancer subtypes: a Nationwide population-based 12 year follow up study.

BACKGROUND: The prevalence of both atrial fibrillation (AF) and malignancies are increasing in the elderly, but incidences of new onset AF in different cancer subtypes are not well described.The objectives of this study were therefore to determine the incidence of AF in different cancer subtypes and to examine the association of cancer and future AF. METHODS: Using national databases, the Danish general population was followed from 2000 until 2012. Every individual aged > 18 years and with no history of cancer or AF prior to study start was included. Incidence rates of new onset AF were identified and incidence rate ratios (IRRs) of AF in cancer patients were calculated in an adjusted Poisson regression model. RESULTS: A total of 4,324,545 individuals were included in the study. Cancer was diagnosed in 316,040 patients. The median age of the cancer population was 67.0 year and 51.5% were females. Incidences of AF were increased in all subtypes of cancer. For overall cancer, the incidence was 17.4 per 1000 person years (PY) vs 3.7 per 1000 PY in the general population and the difference increased with age. The covariate adjusted IRR for AF in overall cancer was 1.46 (95% confidence interval (CI) 1.44-1.48). The strength of the association declined with time from cancer diagnosis (IRR0-90days = 3.41 (3.29-3.54), (IRR-180 days-1 year = 1.57 (CI 1.50-1.64) and (IRR2-5 years = 1.12 (CI 1.09-1.15). CONCLUSIONS: In this nationwide cohort study we observed that all major cancer subtypes were associated with an increased incidence of AF. Further, cancer and AF might be independently associated.

Combining Oral Anticoagulants With Platelet Inhibitors in Patients With Atrial Fibrillation and Coronary Disease.

BACKGROUND: The optimal treatment strategy when combining antiplatelets with oral anticoagulants in patients with atrial fibrillation (AF) and myocardial infarction (MI) or undergoing percutaneous coronary intervention (PCI) is unknown. OBJECTIVES: The authors investigated the risk of bleeding, ischemic stroke, MI, and all-cause mortality associated with direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in combination with aspirin, clopidogrel, or both in patients with AF following MI and/or PCI. METHODS: Danish nationwide registries were used to identify patients with AF who were admitted with a MI and/or underwent PCI, between August 2011 and June 2017, treated with OAC in combination with antiplatelet(s). Patients were followed for 12 months or until an outcome, study end, or death. Standardized absolute risks were estimated on the basis of outcome-specific Cox regression models adjusted for potential confounders. Average treatment effects were obtained as standardized absolute risk differences (ARD) in risks at 3 and 12 months using the g-formula. RESULTS: Overall, 3,222 patients were included in the study population, of which 875 (27%) were treated with VKA+single antiplatelet therapy (SAPT), 595 (18%) were treated with DOAC+SAPT, 1,074 (33%) were treated with VKA+dual antiplatelet therapy (DAPT), and 678 (22%) were treated with DOAC+DAPT. At 3 months, there was a significant difference in the absolute risk of MI associated with DOAC+SAPT compared with VKA+SAPT (3-month ARD -1.53% (95% confidence interval: -3.08% to -0.11%), with no significant differences found regarding bleeding, ischemic stroke, and all-cause mortality. Compared with VKA+DAPT, DOAC+DAPT was associated with a significantly reduced risk of bleeding (3-month ARD -1.96%, 95% confidence interval: -3.46% to -0.88%), with no significant difference in the absolute risk of all-cause mortality, stroke, or MI. CONCLUSIONS: In a real-world population of AF patients with MI and/or after PCI, the authors found that DOAC in combination with DAPT was associated with a significantly decreased risk of bleeding and similar thromboembolic protection compared with VKA in combination with DAPT.

Coronary artery disease severity and long-term cardiovascular risk in patients with myocardial infarction: a Danish nationwide register-based cohort study.

Aim: Long-term prognostic impact of coronary artery disease (CAD) severity in stable post-myocardial infarction (MI) patients is not well known. We examined the impact of CAD severity and co-morbidity on the long-term (1 year and beyond) risk of cardiovascular events post-MI. Methods and results: From nationwide administrative and clinical registers, we identified 55 747 MI patients, during 2004-2010, who had not experienced subsequent MI, stroke, or death within 7 days post-discharge. The risk for primary composite endpoint (MI, stroke, or cardiovascular death) was estimated for the first 365 days after MI (index MI) and from day 366 to study completion (stable post-MI population), corresponding to a mean follow-up of 3.6 (2.2) years. Risk was assessed using cumulative incidence, multivariable adjusted logistic regression and Cox proportional-hazards models. The 1-year cumulative incidence for primary endpoint was 20.0% [95% confidence interval (CI), (19.6-20.3)]. Correspondingly, the 4-year cumulative incidence for primary endpoint was 21.0% (95% CI, 20.6-21.4) in patients without events on the first year. In multivariable models with no significant stenosis as reference, CAD severity was the most important risk factor for cardiovascular events the first 365 days [left main stenosis (LMS): odds ratio and 95% CI, 4.37, 3.69-5.17; 3-vessel disease (VD), 4.18, 3.66-4.77; 2-VD, 3.23, 2.81-3.72; 1-VD, 2.12,-1.85-2.43] and remained from day 366 to study completion [LMS: hazard ratio and 95% CI, 1.91, 1.64-2.22; 3-VD, 1.85,1.65-2.07; 2-VD, 1.55, 1.38-1.74; 1-VD, 1.30, 1.16-1.45]. Conclusion: Despite contemporary treatment at baseline, stable post-MI patients' 4-year outcome was similar to 1-year outcome after MI, and CAD severity remained a critical risk factor the first year and thereafter.

NSAIDs are associated with increased risk of atrial fibrillation in patients with prior myocardial infarction: a nationwide study.

AIMS: Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with increased risk of cardiovascular disease. Yet, the risk of atrial fibrillation (AF) associated with NSAIDs among patients with prior myocardial infarction (MI) has not been examined, and such data could contribute considerably to the risk-benefit assessment of NSAID use in this clinical context. METHODS AND RESULTS: Using nationwide administrative registries in Denmark, we studied patients aged ≥30 years admitted with first-time MI and without prior AF in the period of 1997-2011. Risk of AF associated with NSAID use vs. no NSAID use was analysed by multivariable time-dependent Cox proportional hazard models. Of the 86 496 patients [mean age 66 (SD 13) years; 64% men] included in this study, 44.1% filled at least one NSAID prescription after discharge from MI. During a mean follow-up of 5.3 years, 7831 (8.9%) developed AF. The confidence intervals rate (95% CI) of AF per 100 person-years with NSAID treatment was 2.2 (2.0-2.4) compared with 1.7 (1.6-1.7) without NSAIDs. In the adjusted model, the risk of AF after NSAID treatment increased [Hazard ratio (HR) 1.27 (1.14-1.40)]. An increased risk of AF was seen regardless of the type of NSAID or with short-term (0-14 days) treatment [HR 1.45 (1.24-1.69)]. When the risk of death in patients exposed [crude rate 23.3 (19.7-27.5)] vs. not exposed [crude rate 17.4 (95% CI 16.8-18.1)] to NSAIDs at the time of AF was compared, NSAID use was associated with a poorer prognosis [HR 1.35 (1.14-1.60)]. CONCLUSION: Our study suggests that the use of NSAIDs might be associated with the increased risk of AF in post-MI patients.

Unexplained Syncope and Diagnostic Yield of Tests in Syncope According to the ICD-10 Discharge Diagnosis.

BACKGROUND: The etiology of syncope according to the discharge diagnosis from hospital admissions has not been examined before. Therefore the aims of this study were to examine the diagnostic yield of tests and frequency of unexplained cases during admission and after workup after an ICD-10 diagnosis of syncope. METHODS: A retrospective chart review of 600 patients discharged with the primary ICD-10 discharge diagnosis of syncope R55.9 was performed. Causes and clinical characteristics of syncope according to the physician were noted both after initial discharge and after workup. RESULTS: During a mean follow-up period of 2.5 years (SD: ± 1.30) several diagnostic tests were used (mean number of tests per patient was 4.7 (SD: ± -2.0)) and the mean length of admission was 2.1 days (± 1.5).The final diagnosis after workup was reflex syncope in 21%, cardiac 18%, orthostatic hypotension 10%, other causes 4% and unknown/unexplained syncope in 48% with wide age differences. The diagnostic yield of tests was generally low and differed widely depending on usage during admission or usage during subsequent workup. CONCLUSIONS: The underlying etiology of syncope remains difficult to establish despite the high use of diagnostic tests and the diagnostic yield of many tests implemented in the care path is generally low.

Cardiovascular and non-cardiovascular hospital admissions associated with atrial fibrillation: a Danish nationwide, retrospective cohort study.

OBJECTIVE: To examine the excess risk of hospitalisation in patients with incident atrial fibrillation (AF). DESIGN: A nationwide, retrospective cohort study. SETTING: Denmark. PARTICIPANTS: Data on all admissions in Denmark from 1997 to 2009 were collected from nationwide registries. After exclusion of subjects previously admitted for AF, data on 4 602 264 subjects and 10 779 945 hospital admissions contributed to the study. PRIMARY AND SECONDARY OUTCOME MEASURES: Age-stratified and sex-stratified admission rates were calculated for cardiovascular and non-cardiovascular admissions. Temporal patterns of readmission, relative risk and duration of frequent types of admission were calculated. RESULTS: Of 10 779 945 hospital admissions, 729 088(6.8%) were associated with AF. Admissions for cardiovascular reasons after 1, 3 and 6 months occurred for 6.0, 14.3 and 28.4% of AF patients versus 0.2, 0.6 and 1.8 of non-AF patients. Admissions for non-cardiovascular reasons after 1, 3 and 6 months comprised 6.8, 16.1 and 33.3% of AF patients and 1.2, 3.2 and 9.7% of non-AF patients. When stratified for age, AF was associated with similar cardiovascular admission rates across all age groups, while non-cardiovascular admission rates were higher in older patients. Within each age group and for both cardiovascular and non-cardiovascular admissions, AF was associated with higher rates of admission. When adjusted for age, sex and time period, patients with AF had a relative risk of 8.6 (95% CI 8.5 to 8.6) for admissions for cardiovascular reasons and 4.0 (95% CI 4.0 to 4.0) for admission for non-cardiovascular reasons. CONCLUSIONS: This study confirms that the burden of AF is considerable and driven by both cardiovascular and non-cardiovascular admissions. These findings underscore the importance of using clinical and pharmacological means to reduce the hospital burden of AF in Western healthcare systems.