Temporal Trends in Patient Characteristics and Outcomes of Transcatheter Aortic Valve Implantation and Surgical Aortic Valve Replacement: A Nationwide Study.

With increased use of transcatheter aortic valve implantation (TAVI) in treatment of aortic stenosis, it is important to evaluate real life data trends in outcomes. This nationwide register-based study aimed to present an outlook on temporal trends in characteristics and outcomes, including mortality. First-time consecutive Danish patients who underwent TAVI from 2010 to 2019 were included in this study. The chi-square and Kruskal-Wallis tests were performed to assess the differences in the characteristics over time and Cochrane-Armitage trend tests were used to examine changes in complications and mortality. Between 2010 and 2019, 4,847 patients (54.6% men, median age 82 [quartile 1 to quartile 3: 77 to 85] years) underwent first-time TAVI. A statistically significant decrease over time was observed for preprocedural hypertension, ischemic heart disease, and heart failure, whereas preexisting chronic obstructive lung disease and preprocedural pacemaker remained stable. We observed a significant decrease in 30- and 90-day postoperative preprocedural pacemaker implantation from 2011 to 2017, with 15.1% and 15.9% in 2011 and 8.6% and 8.9% in 2017, respectively. The incidence of for 30- and 90-day heart failure significantly decreased from 19.3% and 20.3% to 8.5% and 9.1%, respectively. We observed significant changes for 30-day atrial fibrillation, whereas the changes over time for 90-day atrial fibrillation and 30- and 90-day stroke/transient ischemic attack remained insignificant. The all-cause mortality within 30- and 90 days significantly decreased over time from 6.7% and 9.2% in 2011 to 1.5% and 2.7% in 2019 and 2016, respectively. In conclusion, this national study provides general insight on the trends of complications and mortality of TAVI, demonstrating significant reductions over time.

Risk and benefit of dual antiplatelet treatment among non-revascularized myocardial infarction patients in different age groups.

BACKGROUND: Dual anti-platelet treatment with clopidogrel and aspirin is indicated for most patients after myocardial infarction. We examined the risk/benefit relationship of dual anti-platelet treatment according to age in a nationwide cohort of 30,532 myocardial infarction patients without revascularization. METHODS: Patients admitted with first-time myocardial infarction in 2002-2010, not undergoing revascularization, were identified from nationwide Danish registers. Dual anti-platelet treatment use was assessed by claimed prescriptions. Stratified into age groups, risk of bleeding, all-cause mortality and a combined endpoint of cardiovascular death, recurrent myocardial infarction and ischaemic stroke was analysed by Cox proportional-hazard models and tested in a propensity-score matched population. RESULTS: A total of 21,302 users and 9230 non-users of dual anti-platelet treatment were included (mean age 67.02 (±13.8) years and 64.7% males). Use of dual anti-platelet treatment decreased with age: 80% (<60 years), 76% (60-69 years), 66% (70-79 years) and 52% (>79 years). We found a reduced risk of cardiovascular death, recurrent myocardial infarction and ischaemic stroke in users <60 years (Hazard ratio (HR) =0.69; 95% confidence interval (CI) 0.59-0.80), 60-69 years (HR=0.64; 95% CI 0.56-0.73), 70-79 years (HR=0.80; 95% CI 0.72-0.89) and >79 years (HR=0.92; 95% CI 0.84-1.01, NS). Risk of bleeding increased with dual anti-platelet treatment use in patients aged <60 years (HR=1.63; 95% CI 1.17-2.26), 60-69 years (HR=1.22; 95% CI 0.97-1.59, NS), 70-79 years (HR=1.42; 95% CI 1.17-1.72) and >79 years (HR=1.46; 95% CI 1.22-1.74). Similar tendencies in all four age groups were found in the propensity-matched population. CONCLUSION: Dual anti-platelet treatment use was less likely among elderly patients although similar effects regarding both risk and benefit were found in all age groups. Increased focus on initiating dual anti-platelet treatment in elderly, non-invasively treated myocardial infarction patients is warranted.

Substantial differences in initiation of oral anticoagulant therapy and clinical outcome among non-valvular atrial fibrillation patients treated in inpatient and outpatient settings.

AIMS: Patients with atrial fibrillation (AF) are encountered and treated in different healthcare settings, which may affect the quality of care. We investigated the use of oral anticoagulant (OAC) therapy and the risk of thrombo-embolism (TE) and bleeding, according to the healthcare setting. METHODS AND RESULTS: Using national Danish registers, we categorized non-valvular AF patients (2002-11) according to the setting of their first-time AF contact: hospitalization (inpatients), ambulatory (outpatients), or emergency department (ED). Event rates and hazard ratios (HRs), calculated using Cox regression analysis, were estimated for outcomes of TE and bleeding. We included 116 051 non-valvular AF patients [mean age 71.9 years (standard deviation 14.1), 51.3% males], of whom 55.2% were inpatients, 41.9% outpatients, and 2.9% ED patients. OAC therapy 180 days after AF diagnosis among patients with a CHADS2 ≥ 2 was 42.1, 63.0, and 32.4%, respectively. Initiation of OAC therapy was only modestly influenced by CHADS2 and HAS-BLED scores, regardless of the healthcare setting. The rate of TE was 4.30 [95% confidence interval (CI) 4.21-4.40] per 100 person-years for inpatients, 2.28 (95% CI 2.22-2.36) for outpatients, and 2.30 (95% CI 2.05-2.59) for ED patients. The adjusted HR of TE, with inpatients as reference, was 0.74 (95% CI 0.71-0.77) for outpatients and 0.89 (95% CI 0.79-1.01) for ED patients. CONCLUSION: In a nationwide cohort of non-valvular AF patients, outpatients were much more likely to receive OAC therapy and had a significantly lower risk of stroke/TE compared with inpatients and ED patients. However, across all settings investigated, OAC therapy was far from optimal.

Thromboembolic risk in 16 274 atrial fibrillation patients undergoing direct current cardioversion with and without oral anticoagulant therapy.

AIMS: To study the risk of thromboembolism in a nationwide cohort of atrial fibrillation patients undergoing direct current (DC) cardioversion with or without oral anticoagulant coverage. METHODS AND RESULTS: A retrospective study of 16 274 patients in Denmark discharged from hospital after a first-time DC cardioversion for atrial fibrillation between 2000 and 2008. Use of oral anticoagulant therapy within 90 days prior and 360 days after DC cardioversion was obtained from the Danish Register of Medicinal Product Statistics. The risk of thromboembolism was estimated by calculating incidence rates and by multivariable adjusted Cox proportional-hazard models. During the initial 30 days following discharge, the thromboembolic incidence rate was 10.33 per 100 patient-years for the no prior oral anticoagulant therapy group [n = 5084 (31.2%)], as compared with 4.00 per 100 patient-years for the prior oral anticoagulant therapy group [n = 11 190 (68.8%)], [hazard ratio associated with no prior oral anticoagulant therapy was 2.25; 95% confidence interval (CI), 1.43-3.53]. Thromboembolic risk stratification by the CHADS2 and CHA2DS2-VASc scores did not change the results. Hazard ratio with no oral anticoagulant therapy was 2.21; 95% CI, 0.79-6.77 and 2.40; 95% CI, 1.46-3.95 with CHA2DS2-VASc score 0-1 and CHA2DS2-VASc score 2 or more, respectively. CONCLUSION: Direct current cardioversion for atrial fibrillation without oral anticoagulation is associated with a high risk of thromboembolism. Notably, the risk is high in the initial period after cardioversion, indicating a hazardous association between DC cardioversion without anticoagulation and thromboembolism.

Oral anticoagulation therapy after radiofrequency ablation of atrial fibrillation and the risk of thromboembolism and serious bleeding: long-term follow-up in nationwide cohort of Denmark.

AIM: To investigate the long-term risk of thromboembolism and serious bleeding associated with oral anticoagulation (OAC) therapy beyond 3 months after radiofrequency ablation (RFA) of atrial fibrillation (AF). METHODS AND RESULTS: Linking Danish administrative registries, 4050 patients undergoing first-time RFA (2000-11) were identified. Risk of thromboembolism and serious bleeding according to OAC therapy were analysed by incidence rates (presented per 100 person-years) and Cox proportional-hazard models. The median age was 59.5 years (interquartile range, IQR: 52.8-65.2); 26.5% were females. During a median follow-up of 3.4 years (IQR: 2.0-5.6), 71 (1.8%) thromboembolism cases were identified, where incidence rates with and without OAC were 0.56 (0.40-0.78)95%CI and 0.64 (0.46-0.89)95%CI, respectively. Oral anticoagulation discontinuation remained insignificant [hazard ratio 1.42(0.86-2.35)95%CI] in multivariable analysis. Beyond 3 months after RFA 87 (2.1%) serious bleedings occurred; incidence rates with and without OAC were 0.99 (0.77-1.27)95%CI and 0.44 (0.29-0.65)95%CI, respectively. Oral anticoagulation therapy was significantly associated with serious bleeding risk [hazard ratio 2.05(1.25-3.35)95%CI]. In an age- and gender-matched cohort (1 : 4) of 15 848 non-ablated AF patients receiving rhythm-control therapy, thromboembolic rates with and without OAC were 1.34 (1.21-1.49)95%CI and 2.14 (1.98-2.30)95%CI, respectively. Adjusted incidence rate ratio was 0.53 (0.43-0.65)95%CI favouring RFA cohort. CONCLUSION: Thromboembolic risk beyond 3 months after RFA was relatively low compared with a matched non-ablated AF cohort. With cautious interpretation due to low number of events, serious bleeding risk associated with OAC seems to outweigh the benefits of thromboembolic risk reduction. Randomized studies are warranted to test our results.

Dabigatran use in Danish atrial fibrillation patients in 2011: a nationwide study.

OBJECTIVE: Dabigatran was recently approved for anticoagulation in patients with atrial fibrillation (AF); data regarding real-world use, comparative effectiveness and safety are sparse. DESIGN: Pharmacoepidemiological cohort study. METHODS/SETTINGS: From nationwide registers, we identified patients with an in-hospital or outpatient-clinic AF diagnosis who claimed a prescription of dabigatran 110 or 150 mg, or vitamin K antagonist (VKA), between 22 August and 31 December 2011. HRs of thromboembolic events (ischaemic stroke, transitory ischaemic attack and peripheral artery embolism) and bleedings were estimated using Cox regression analyses in all patients and stratified by previous VKA use. RESULTS: Overall, 1612 (3.1%) and 1114 (2.1%) patients claimed a prescription of dabigatran 110 and 150 mg, and 49640 (94.8%) of VKA. Patients treated with dabigatran 150 mg were younger with less comorbidity than those treated with dabigatran 110 mg and VKA, as were VKA naïve patients compared with previous VKA users. Recommendations set by the European Medicine Agency (EMA) for dabigatran were met in 90.3% and 55.5% of patients treated with 110 and 150 mg. Patients treated with 150 mg dabigatran, who did not fulfil the recommendations by EMA, were >80 years, patients with liver or kidney disease, patients with previous bleeding. Compared with VKA, the thromboembolic risk associated with dabigatran 110 and 150 mg was HR 3.52 (1.40 to 8.84) and 5.79 (1.81 to 18.56) in previous VKA users, and HR 0.95(0.47 to 1.91) and 1.14(0.60 to 2.16) in VKA naïve patients. Bleeding risk was increased in previous VKA users receiving dabigatran 110 mg, but not in patients with 150 mg dabigatran, nor in the VKA naïve users. CONCLUSIONS: Deviations from the recommended use of dabigatran were frequent among patients treated with 150 mg. With cautious interpretation, dabigatran use in VKA naïve patients seems safe. Increased risk of thromboembolism and bleeding with dabigatran among previous VKA users was unexpected and may reflect patient selection and 'drug switching' practices.

Temporal changes in patient characteristics and prior pharmacotherapy in patients undergoing radiofrequency ablation of atrial fibrillation: a Danish nationwide cohort study.

AIMS: Trends in patient selection and pharmacotherapy before radiofrequency ablation (RFA) of atrial fibrillation are not well studied. We examined temporal trends in RFA utilization on a nationwide scale in Denmark. METHODS AND RESULTS: Using the cross-linkage of nationwide registers, 3302 atrial fibrillation patients treated with 'first-ever' RFA between 2000 and 2009 were identified. Median age was 59 years (interquartile range 53-65) and 73.8% were males. From 2000-01 to 2008-09 the median age increased from 55 (48-61) to 61 (55-66) years (P < 0.0001). The proportion of patients with hypertension and diabetes mellitus increased from 34.8 to 50.6% (P < 0.0001) and 2.2 to 5.9% (P < 0.01), respectively. The proportion of patients with heart failure, vascular disease or previous stroke remained unchanged. The percentage of patients with CHA2DS2-VASc score ≥2 increased from 23.9 to 41.5% (P < 0.0001). The proportion of patients who did not receive any class Ic or class III antiarrhythmic drugs (AADs) within 2 years prior to 'first-ever' RFA increased from 8.7 to 22.7% (P < 0.0001). Prior use of sotalol and class Ic AADs decreased from 63 to 6.3% (P < 0.0001) and from 35 to 24% (P < 0.0001), respectively. Amiodarone and beta-blockers prior to RFA were used in 36 and 82% of all patients, respectively, without significant temporal changes. CONCLUSION: During a 10-year period, RFA was increasingly performed in older patients with higher co-morbidity, and without prior trial of antiarrhythmic therapy. These findings may provide a framework to understand the outcomes of RFA.

Obesity is a risk factor for atrial fibrillation among fertile young women: a nationwide cohort study.

AIMS: Obesity has been associated with increased risk of atrial fibrillation (AF), but whether this risk is also prevalent in younger individuals is unknown. We therefore investigated the risk of AF in relation to body mass index (BMI) among young fertile women. METHODS AND RESULTS: By cross-linkage of nationwide registers of childbirth and hospitalization, we identified 271 203 women without prior AF who gave birth in Denmark between 2004 and 2009. Body mass index (kg/m(2)) was examined as a risk factor for AF using proportional hazard models. Mean age was 30.6 years (4.7 SD) and median follow-up was 4.6 years (interquartile range 2.9-5.8). During the follow-up, 110 women were hospitalized with first-time AF; very few individuals had known risk factors for AF. Overall incidence rate of AF was 9.3 [95% confidence interval (CI): 7.7-11.2] per 100 000 person-years. According to BMI, the incidence rate of AF per 100 000 person-years was 7.4 (5.6-9.7) in normal weight (BMI: 18.5-24.9), 8.5 (5.5-13.1) in overweight (BMI: 25-29.9), 15.8 (9.3-26.7) in obese (BMI: 30-35), and 27.3 (15.5-48.1) in very obese (BMI >35) individuals. Multivariable regression analyses adjusted for age, hyperthyroidism, and previous use of beta-blockers revealed a hazard ratio of 2.04 (95% CI: 1.13-3.69) in the obese and 3.50 (1.86-6.58) in the very obese individuals compared with normal weight. CONCLUSION: Obesity is a risk factor for AF among young and essentially healthy fertile women despite the low incidence of AF. These results may have implications for prevention of AF.

Bleeding after initiation of multiple antithrombotic drugs, including triple therapy, in atrial fibrillation patients following myocardial infarction and coronary intervention: a nationwide cohort study.

BACKGROUND: Uncertainty remains over optimal antithrombotic treatment of patients with atrial fibrillation presenting with myocardial infarction and/or undergoing percutaneous coronary intervention. We investigated the risk and time frame for bleeding following myocardial infarction/percutaneous coronary intervention in patients with atrial fibrillation according to antithrombotic treatment. METHODS AND RESULTS: Patients with atrial fibrillation and admitted with myocardial infarction or for percutaneous coronary intervention between 2000 and 2009 (11 480 subjects, mean age 75.6 years [SD ±10.3], males 60.9%) were identified by individual level linkage of nationwide registries in Denmark. Fatal or nonfatal (requiring hospitalization) bleeding was determined according to antithrombotic treatment regimen: triple therapy (TT) with vitamin K antagonist (VKA)+aspirin+clopidogrel, VKA+antiplatelet, and dual antiplatelet therapy with aspirin+clopidogrel. We calculated crude incidence rates and adjusted hazard ratios by Cox regression models. Within 1 year, 728 bleeding events were recorded (6.3%); 79 were fatal (0.7%). Within 30 days, rates were 22.6, 20.3, and 14.3 bleeding events per 100 person-years for TT, VKA+antiplatelet, and dual antiplatelet therapy, respectively. Both early (within 90 days) and delayed (90-360 days) bleeding risk with TT exposure in relation to VKA+antiplatelet was increased; hazard ratio 1.47 (1.04;2.08) and 1.36 (0.95;1.95), respectively. No significant difference in thromboembolic risk was observed for TT versus VKA+antiplatelet; hazard ratio, 1.15 (0.95;1.40). CONCLUSIONS: High risk of bleeding is immediately evident with TT after myocardial infarction/percutaneous coronary intervention in patients with atrial fibrillation. A continually elevated risk associated with TT indicates no safe therapeutic window, and TT should only be prescribed after thorough bleeding risk assessment of patients.

Vascular disease and stroke risk in atrial fibrillation: a nationwide cohort study.

BACKGROUND: Vascular disease (including myocardial infarction and peripheral artery disease) has been proposed as a less well-validated risk factor for stroke in patients with atrial fibrillation. We investigated whether vascular disease is an independent risk factor of stroke/thromboembolism in atrial fibrillation and whether adding vascular disease improves Congestive heart failure, Hypertension, Age 75 years, Diabetes, previous Stroke (CHADS(2)) risk stratification. METHODS: By using nationwide Danish registers, we identified all patients discharged with atrial fibrillation and not treated with vitamin K antagonist or heparin between 1997 and 2008. The rate of stroke/thromboembolism in patients with atrial fibrillation with and without vascular disease was determined, and the risk associated with vascular disease was estimated in Cox regression analyses. The value of adding vascular disease to the CHADS(2) score was evaluated by Net Reclassification Improvement and Integrated Discrimination Improvement. RESULTS: We included 87,202 patients with non-valvular atrial fibrillation; of these, 15,212 (17.4%) had vascular disease, 11,750 (77.2%) had myocardial infarction, 2503 (16.5%) had peripheral artery disease, and 959 (6.3%) had both. In patients with a CHADS(2) score=0, the rate of stroke/thromboembolism at 1-year follow-up was 2.31 (1.63-3.26) and 1.52 (1.34-1.73) per 100 person-years in patients with and without vascular disease, respectively. Vascular disease increased the risk of stroke/thromboembolism in both univariate (hazard ratio [HR] 1.26; confidence interval [CI], 1.18-1.35) and multivariate (HR, 1.12; CI, 1.05-1.21) analyses. The risk of stroke/thromboembolism associated with peripheral artery disease alone (HR, 1.93; CI, 1.70-2.19) was greater than the risk with myocardial infarction alone (HR, 1.12; CI, 1.04-1.21), and vascular disease significantly improved the predictive ability of the CHADS(2) score (Net Reclassification Improvement 0.032, P<.001). CONCLUSIONS: Vascular disease is an independent predictor of stroke/thromboembolism in atrial fibrillation and improves the predictive ability of the CHADS(2) score.

Lymphadenitis caused by H1N1 vaccination: case report.

A patient admitted to hospital for a supraclavicular painful mass. Ultrasonography showed soliter lymphadenopathy. He underwent H1N1 vaccination 1 week before this lymphadenopathy developed. Groosly the mass measured 1cmx0.8cmx0.8cm. It was round, yellow to brown, slightly soft. In pathologic examination, we detected edema in capsule of lymph node. The basic architecture was preserved. There was mottled appearance caused by marked proliferation of immunoblasts which were positive with CD 30. Also large, unusual immunoblasts which closely resemble mononuclear hodgkin cells were present. These unusual immunoblasts were positive with CD 30, too. For differential diagnosis, at first we should regard hodgkin lymphoma. We suggested that lymphadenitis may be a side effect of H1N1 vaccination.