The Danish Atrial Fibrillation Registry: A Multidisciplinary National Pragmatic Initiative for Monitoring and Supporting Quality of Care Based on Data Retrieved from Administrative Registries.

Aim: The Danish Atrial Fibrillation (AF) Registry monitors and supports improvement of quality of care for all AF patients in Denmark. This report describes the registry's administrative and organizational structure, data sources, data flow, data analyses, annual reporting, and feedback between the registry, clinicians, and the administrative system. We also report the selection process of the quality indicators and the temporal trends in results from 2017-2021. Methods and Results: The Danish AF Registry aims for complete registration and monitoring of care for all patients diagnosed with AF in Denmark. Administrative registries provide data on contacts to general practice, contacts to private cardiology practice, hospital contacts, medication prescriptions, updated vital status information, and biochemical test results. The Danish Stroke Registry provides information on stroke events. From 2017 to 2021, the proportion with a reported echocardiography among incident AF patients increased from 39.9% (95% CI: 39.3-40.6) to 82.6% (95% CI: 82.1-83.1). The initiation of oral anticoagulant therapy among patients with incident AF and a CHA2DS2-VASc score of ≥1 in men and ≥2 in women increased from 85.3% (95% CI: 84.6-85.9) to 90.4% (95% CI: 89.9-91.0). The 1-year and 2-year persistence increased from 85.2% (95% CI: 84.5-85.9) to 88.7% (95% CI: 88.0-89.3), and from 85.4% (95% CI: 84.7-86.2) to 88.2% (95% CI: 87.5-88.8), respectively. The 1-year risk of ischemic stroke among prevalent patients with AF decreased from 0.88% (95% CI: 0.83-0.93) to 0.71% (95% CI: 0.66-0.75). Variation in clinical performance between the five administrative Danish regions was reduced. Conclusion: Continuous nationwide monitoring of quality indicators for AF originating from administrative registries is feasible and supportive of improvements of quality of care.

Atrial pacing minimization in sinus node dysfunction and risk of incident atrial fibrillation: a randomized trial.

BACKGROUND AND AIMS: High percentages of atrial pacing have been associated with an increased risk of atrial fibrillation. This study is aimed at evaluating whether atrial pacing minimization in patients with sinus node dysfunction reduces the incidence of atrial fibrillation. METHODS: In a nationwide, randomized controlled trial, 540 patients with sinus node dysfunction and an indication for first pacemaker implantation were assigned to pacing programmed to a base rate of 60 bpm and rate-adaptive pacing (DDDR-60) or pacing programmed to a base rate of 40 bpm without rate-adaptive pacing (DDD-40). Patients were followed on remote monitoring for 2 years. The primary endpoint was time to first episode of atrial fibrillation longer than 6 min. Secondary endpoints included longer episodes of atrial fibrillation, and the safety endpoint comprised a composite of syncope or presyncope. RESULTS: The median percentage of atrial pacing was 1% in patients assigned to DDD-40 and 49% in patients assigned to DDDR-60. The primary endpoint occurred in 124 patients (46%) in each treatment group (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.76-1.25, P = .83). There were no between-group differences in atrial fibrillation exceeding 6 or 24 h, persistent atrial fibrillation, or cardioversions for atrial fibrillation. The incidence of syncope or presyncope was higher in patients assigned to DDD-40 (HR 1.71, 95% CI 1.13-2.59, P = .01). CONCLUSIONS: Atrial pacing minimization in patients with sinus node dysfunction does not reduce the incidence of atrial fibrillation. Programming a base rate of 40 bpm without rate-adaptive pacing is associated with an increased risk of syncope or presyncope.

Lenient rate control versus strict rate control for atrial fibrillation: a statistical analysis plan for the Danish Atrial Fibrillation (DanAF) randomized clinical trial.

BACKGROUND: A key decision in the treatment of atrial fibrillation is choosing between a rhythm control strategy or a rate control strategy as the main strategy. When choosing rate control, the optimal heart rate target is uncertain. The Danish Atrial Fibrillation trial is a randomized, multicenter, two-group, superiority trial comparing strict rate control versus lenient rate control in patients with either persistent or permanent atrial fibrillation at inclusion. To prevent bias arising from selective reporting and data-driven analyses, we developed a predefined description of the statistical analysis. METHODS: The primary outcome of this trial is the physical component score of the SF-36 questionnaire. A total of 350 participants will be enrolled based on a minimal important difference of 3 points on the physical component score of the SF-36 questionnaire, a standard deviation of 10 points, a statistical power of 80% (beta of 20%), and an acceptable risk of type I error of 5%. All secondary, exploratory, and echocardiographic outcomes will be hypothesis-generating. The analyses of all outcomes will be based on the intention-to-treat principle. We will analyze continuous outcomes using linear regression adjusting for "site," type of atrial fibrillation at inclusion (persistent/ permanent), left ventricular ejection fraction (≥ 40% or < 40%), and the baseline value of the outcome (all as fixed effects). We define our threshold for statistical significance as a p-value of 0.05 and assessments of clinical significance will be based on the anticipated intervention effects defined in the sample size and power estimations. Thresholds for both statistical and clinical significance will be assessed according to the 5-step procedure proposed by Jakobsen and colleagues. DISCUSSION: This statistical analysis plan will be published prior to enrolment completion and before any data are available and is sought to increase the validity of the DANish Atrial Fibrillation trial. TRIAL REGISTRATION: Clinicaltrials.gov NCT04542785. Registered on Sept 09, 2020.

Are Prolonged Ventricular Pauses in Atrial Fibrillation a Marker of Poor Prognosis?

BACKGROUND: In patients with atrial fibrillation (AF), the long-term prognosis of long electrocardiographic pauses in the ventricular action is not well studied. METHODS: Consecutive Holter recordings in patients with AF (n = 200) between 2009 and 2011 were evaluated, focusing on pauses of at least 2.5 s. Outcomes of interest were all-cause mortality and pacemaker implantation. RESULTS: Forty-three patients (21.5%) had pauses with a mean of 3.2 s and an SD of 0.9 s. After a median follow-up of 99 months (ranging 89-111), 47% (20/43) of the patients with and 45% (70/157) without pauses were deceased. Pauses of ≥2.5 s did not constitute a risk of increased mortality: HR = 0.75 (95% CI: 0.34-1.66); p = 0.48, neither did pauses of ≥3.0 s: HR = 0.43 (95% CI: 0.06-3.20); p = 0.41. Sixteen percent of patients with pauses underwent pacemaker implantation during follow-up. Only pauses in patients referred to Holter due to syncope and/or dizzy spells were associated with an increased risk of pacemaker treatment: HR = 4.7 (95% CI: 1.4-15.9), p = 0.014, adjusted for age, sex, and rate-limiting medication. CONCLUSION: In patients with AF, prolonged electrocardiographic pauses of ≥2.5 s or ≥3.0 s are not a marker for increased mortality in this real-life clinical study.

Excessive supraventricular ectopic activity and risk of incident atrial fibrillation in a consecutive population referred to ambulatory cardiac monitoring.

BACKGROUND: Excessive supraventricular ectopic activity (ESVEA), defined as ≥720 premature atrial contractions (PAC) per day or any runs of ≥20 PACs, has been proposed as a surrogate marker for paroxysmal atrial fibrillation (PAF). OBJECTIVE: We aimed to estimate the prognostic impact of ESVEA on the future development of PAF in consecutive patients referred to ambulatory cardiac monitoring. METHODS: The cohort consists of a population with comorbidities referred to 48-hour ambulatory electrocardiogram aged 30-98 (n = 1316) between 2009 and 2011. After exclusion of known or current atrial fibrillation (AF) (n = 527) and patients with pacemakers (n = 7), 782 patients were included, with a median follow-up of 8.1 years. Events of incident AF and death were retrieved from patient records. RESULTS: Mean age was 58.6 ± 15.5 years and 56.5% were women. A total of 101 patients had ESVEA at baseline (12.9%). During follow-up, 69 (8.9%) developed incidental AF. Twenty-three patients with ESVEA developed AF (23%). Incidence rate of AF in patients with and without ESVEA was 37.1/1000 person-years and 9.1 per 1000 person-years, respectively (P < .001). ESVEA was associated with incident AF after adjustment for potential confounders in Cox regression analysis (hazard ratio [HR]: 2.39; 95% confidence interval [CI]: 1.40-4.09) and in competing risk analysis with death as competing risk (subdistribution HR: 2.35; 95% CI: 1.30-4.17). CONCLUSION: ESVEA increases the risk of incident AF substantially in a population referred to ambulatory cardiac monitoring.

P-wave indices as predictors of atrial fibrillation.

BACKGROUND: P-wave duration (PDURATION ) and P-wave area (PAREA ) have been linked to risk of atrial fibrillation (AF), but they do not improve the efficacy of Framingham AF risk score. We suggest the incorporation of both variables in one index, the P-wave area/P-wave duration (PAREA/DURATION ) index, which may be considered an expression of the average amplitude of the P wave that reflects aspects of P-wave morphology. OBJECTIVE: To assess the prognostic value of P-wave area/P-wave duration index (PAREA/DURATION index) in lead II together with other P-wave indices (PWIs) in incidence of AF in the Copenhagen Holter Study. METHODS: The study included 632 men and women, between 55 and 75 years with no apparent heart disease or AF. Baseline standard 12-lead Electrocardiography (ECGs) were analyzed manually. RESULTS: The median follow-up time was 14.7 (14.5;14.9) years. A total of 68 cases of AF and 233 cases of death were recorded. The restricted cubic spline method showed a U-shaped association between PAREA/DURATION and rate of AF. The lowest quintile of PAREA/DURATION index in lead II was associated with increased rate of AF, HR 2.80 (1.64-4.79). The addition of the new index to the Framingham model for AF improved the model in this population. The PAREA in lead II in its lowest quintile was also associated with increased rate of AF, HR 2.16 (1.25-3.75), but did not improve the Framingham model. PDURATION and P-wave terminal force (PTF) were not significantly associated with AF. CONCLUSION: A flat P wave as expressed by a small PAREA/DURATION index in lead II is associated with increased rate of incident AF beyond known AF risk factors.

Long-term clinical outcome in STEMI patients treated with primary PCI and drug-eluting or bare-metal stents: insights from a high-volume single-center registry.

OBJECTIVE: Use of drug-eluting stents (DES) in patients with ST-elevation myocardial infarction (STEMI) during routine primary percutaneous coronary intervention (pPCI) is controversial. METHODS: From January 2004 to July 2008, a total of 2,155 STEMI patients were treated with pPCI [DES or bare-metal stent (BMS)] at a single high-volume invasive center. We present 4-year outcomes in this observational registry study. RESULTS: A total of 1,725 were treated with DES and 430 with BMS. Patients treated with DES were younger and had more complex angiographic characteristics compared to BMS patients. Patients treated with DES had lower adjusted risk of target lesion revascularization (TLR) [hazard ratio (HR) = 0.68; 95% confidence interval (CI): 0.40-0.98; p = 0.04], but had a trend toward increased risk of definite stent thrombosis (HR = 1.96; 95% CI: 0.83-4.61; p = 0.12). No difference was found when evaluating all-cause mortality and non-fatal myocardial infarction. CONCLUSIONS: In this study, we set out to evaluate the independent impact of DES or BMS treatment on long-term clinical outcomes in STEMI patients treated with pPCI in a real-life setting. DES use was associated with a reduced risk of TLR, but a trend toward increased risk of stent thrombosis was found. However, this safety issue did not translate into an increased risk of death or overall non-fatal myocardial infarction for DES patients.

Field triage reduces treatment delay and improves long-term clinical outcome in patients with acute ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

OBJECTIVES: We evaluated the independent impact of field triage on treatment delay and long-term clinical outcome in a large contemporary, consecutive population of ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (pPCI). BACKGROUND: Reduction of treatment delay is crucial for patients with STEMI. METHODS: From January 2005 to July 2008, 1,437 STEMI patients were treated with pPCI at a single high-volume invasive center. We present the 1-year outcome in this observational registry study. RESULTS: A total of 616 patients were admitted by field triage and 821 by emergency departments. Baseline and angiographic variables were similar in the 2 populations. Patients admitted by field triage had a significantly shorter median door-to-balloon time compared with patients admitted by emergency department triage (83 min, interquartile range 67 to 100 min vs. 103 min, interquartile range 80 to 135 min; p<0.001). Door-to-balloon times of less than the recommended 90 min were achieved in 61% of field triage patients, but only in 36% of nonfield-triage patients (p<0.001). After adjustment for relevant baseline variables, patients admitted by field triage had a reduced risk of reaching the combined end point of all-cause mortality or nonfatal myocardial infarction (hazard ratio: 0.67; 95% confidence interval: 0.46 to 0.97; p=0.035). CONCLUSIONS: This study shows that field triage of STEMI patients to pPCI significantly reduces treatment delay and improves outcome. These results emphasize the value of field triage as an important tool in the quest to improve clinical outcomes in STEMI patients undergoing pPCI.

Long-term prognosis in an ST-segment elevation myocardial infarction population treated with routine primary percutaneous coronary intervention: from clinical trial to real-life experience.

BACKGROUND: We sought to describe the long-term prognosis after routine primary percutaneous coronary intervention (pPCI) in a contemporary consecutive population of patients with presumed ST-segment elevation myocardial infarction, compare it with similar results from the landmark DANAMI-2 trial, and to identify a possible impact of time of presentation and referral pattern. METHODS AND RESULTS: Long-term prognosis in 1019 presumed ST-segment elevation myocardial infarction patients, treated according to modern routine pPCI during the year 2004, was analyzed and compared with similar data from the DANAMI-2 trial. Furthermore, we analyzed the impact of patient presentation to the angioplasty center during "off hours" (4 pm to 8 am plus weekends and holidays) and the impact of being referred from noninvasive hospitals. At 3 years, 20.4% in the routinely treated population versus 19.6% in the DANAMI-2 trial reached the combined end point of death, reinfarction, or stroke (P=0.68), whereas the all-cause mortality was 13.0% and 13.7%, respectively (P=0.65). Patients admitted during off hours had the same risk of reaching the combined end point of death, reinfarction, or stroke compared with patients admitted during office hours (hazards ratio, 1.04; 95% CI, 0.8 to 1.5; P=0.81). Door-to-balloon times of less than 90 minutes were achieved in 60% among patients admitted directly to an invasive center but only in 40% among transferred patients (P<0.001). Despite this difference, no difference in unadjusted or adjusted long-term prognosis was found between the 2 groups. CONCLUSIONS: This study shows that ST-segment elevation myocardial infarction patients treated with contemporary routine pPCI achieve a similar long-term prognosis as patients in the landmark randomized pPCI trial (DANAMI-2). Furthermore, the long-term prognosis was the same regardless of whether the pPCI was performed during off hours or office hours. Thus, pPCI including transportation of patients from noninvasive centers can be applied successfully in a real-life population.

Early changes in serum IL-6 and VEGF levels predict clinical outcome following first-line therapy in aggressive non-Hodgkin's lymphoma.

Inflammatory cytokines play important roles in the pathogenesis of lymphomas and may reflect underlying biological processes including tumour-host interactions with prognostic information that is not afforded by conventional clinical parameters. Several lines of evidence suggest that serum levels of interleukin (IL)-6 and vascular endothelial growth factor (VEGF) are independent indicators of long-term outcome in non-Hodgkin's lymphoma (NHL), but the clinical impact of early serial monitoring of these cytokines has not been reported. Serum samples from 64 newly diagnosed patients with aggressive NHL were obtained before the first cycle of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and then weekly until the second cycle was given. Serum IL-6 and VEGF were measured by commercial enzyme-linked immunosorbent assays (ELISA). Pre-treatment serum IL-6 and VEGF levels were significantly correlated to response rate and overall survival. A significant decrease of IL-6 and VEGF levels was observed in the first weeks after CHOP therapy in patients achieving a complete remission after treatment. Multivariate analysis indicated that early changes of IL-6 and VEGF serum levels within the first 3 weeks after initiation of chemotherapy were independent predictors of clinical response even when corrected for the influence of clinical prognostic factors. Only changes in serum IL-6 level had borderline significance for the prediction of overall survival. The data indicate that serial measurements of serum IL-6 and VEGF may be early prognostic indicators and support the hypothesis of a clinical impact by early recognition of poor-risk patients and candidates for new treatment options.