Publications

Patients with AF with a high risk of stroke of non-Western origin have persistently experienced a lower chance of initiating OAC compared with patients of Danish origin during the last decades.

Abstract Background Early rhythm control (ERC) and healthy lifestyle (HLS) have been found to be related to lower dementia risk in patients with atrial fibrillation (AF), however, it has not been evaluated whether there is a synergistic effect between the two. Methods Using the Korean National Health Insurance Service database, patients who were newly diagnosed with AF between 2009 and 2016. Patients were categorized as follows: those who did not receive ERC including antiarrhythmic drug, cardioversion, AF catheter ablation within 2-year after AF diagnosis, and had 1 or more unhealthy lifestyle behaviors among current drinking, current smoking, and lack of regular exercise (group 1), those with HLS, but not receiving ERC (group 2), those receiving ERC, but with at least 1 unhealthy lifestyle behavior (group 3), and those with HLS and receiving ERC (group 4). To compare 4 groups, propensity score weighting method was used to balance the baseline characteristics of 4 groups. During follow-up, incident dementia, vascular dementia, and Alzheimer’s dementia were evaluated. Results A total of 199,947 patients were included. The mean time from AF diagnosis to implementation of ERC of groups 3 and 4 was 27±77 and 27±74 days, respectively. Among total study population, 96,907, 53,293, 29,234, and 20,513 patients were included in group 1, 2, 3, and 4, respectively. Group 4 showed the greatest risk reduction for all dementia, vascular dementia, and Alzheimer’s dementia among 4 groups (Figure). Both ERC alone and HLS alone were associated with a lower risk of vascular dementia by 20% than group 1. The combination of the two was associated with a lower risk of vascular dementia by 40% (Figure). However, the impact of ERC on the risk reduction of Alzheimer’s dementia was statistically insignificant, and maintaining HLS seemed sufficient to lower the risk of Alzheimer’s dementia (Figure). Conclusion The combination of ERC and HLS might be beneficial to prevent vascular dementia in patients with new-onset AF. To reduce the risk of Alzheimer’s dementia, maintaining HLS should be emphasized.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT03759938.

ERC and HLS were associated with a lower risk of ischemic stroke in elderly patients with new-onset AF. Concurrently implementing ERC and maintaining HLS was associated with the lowest risk of death and the composite outcome, with a modest synergistic effect on stroke prevention.

Abstract There are limited studies on the prevalence and incidence of clinically diagnosed hypertrophic myocardiopathy (HCM) and its mortality in the Chinese population, and the projected population burden of HCM over the next decades. We collected data on HCM and its mortality from the Beijing Municipal Health Commission Information Center (BMHCIC) database and estimated the prevalence and incidence based on the whole Beijing population. Calculation of population trends was performed using annual percentage change (APC) and average annual percentage change (AAPC). Finally, future HCM incidence was built by modelling projection of HCM to the next decades using Poisson regression analysis and Gray Model 1,1(GM [1,1]). The prevalence of HCM was 0.0069% (95%CI, 0.0065–0.0072%; N = 1343) in 2010, rising to 0.076% (95% CI, 0.074–0.077%; N = 16,616) in 2019, and the incidence of HCM was 6.85 per 100 000 person-year in 2010, rising to 11.76 per 100 000 person-year in 2019. Males had higher prevalence and incidence of HCM than females. The APPC for the rising incidence of HCM was 5.8% and the expected numbers will double increase in 2029 by assuming the same increase trend as the last decades. HCM had increased annual incidence of HF (APPC: 8.4, 4.4–12.6, p < 0.05), and relatively stable annual incidence of mortality (APPC: 1.2%, − 2.3% to 4.8%, p > 0.05) during the studied period. Males had lower mortality (2.70% vs. 4.20%, p < 0.001) than females. The calculated HCM prevalence was much lower compared to prior screening studies from 2004, although the predicted HCM incidence would double over the next decades. HCM was associated with a stable risk of mortality during the studied period.

Arterial stiffness (AS) and atrial fibrillation (AF) share commonalities in molecular and pathophysiological mechanisms and numerous studies have analyzed their reciprocal influence. The gold standard for AS diagnosis is represented by aortic pulse wave velocity, whose measurement can be affected by arrhythmias characterized by irregularities in heart rhythm, such as AF. Growing evidence show that patients with AS are at high risk of AF development. Moreover, the subset of AF patients with AS seems to be more symptomatic and rhythm control strategies are less effective in this population. Reducing AS through de-stiffening interventions may be beneficial for patients with AF and can be a new appealing target for the holistic approach of AF management. In this review, we discuss the association between AS and AF, with particular interest in shared mechanisms, clinical implications and therapeutic options.

There is renewed optimism for innovation in ICH. The standard of care for this condition now leads to improvements in mortality and long-term functional ability. Efforts to improve the patient selection and surgical techniques for operative management are ongoing.

Researchregistry: https://www.researchregistry.com/browse-the-registry#home/registrationdetails/6246bfeeeaaed6001f08dadc/.

Abstract Background Abdominal aortic aneurysmal (AAA) disease is associated with a high risk of cardiovascular events, and prophylaxis with platelet-inhibitors are recommended at diagnosis. Incident atrial fibrillation (AF) changes that indication to oral anticoagulative (OAC) therapy. However, it is unknown to what extent the recommended change of indication is reflected in the actual antithrombotic treatment in clinical practice. Purpose To evaluate the antithrombotic therapy after an incident diagnosis of atrial fibrillation in patients with established AAA. Methods In this population-based case-crossover study, using nationwide Danish registries, we identified all patients registered with a diagnosis of AAA between 1997 and 2018, and a subsequent diagnosis of AF. The case-crossover analysis was performed to compare the within-subject antithrombotic therapy in 1-year time-periods before and after AF diagnosis in the study population. A blanking period of 30 days before AF-diagnosis was applied to avoid bias from potentially delayed hospital diagnosis of AF (Figure 1.1). We excluded patients with no eligible reference window due to recent cohort entry and patients with no AF-related indication for shift to OAC (CHA2DS2-VASc score of <1 in men and <2 in women). Odds ratios (OR) with 95% confidence intervals (CIs) comparing antithrombotic therapy before and after AF diagnosis was calculated using McNemars test for matched pair's data. Subgroup analyses of patients diagnosed with AAA between 2011 and 2018 were performed to evaluate changes after introduction of current antithrombotic treatment regimens and direct oral anticoagulants. Results A total of 3052 patients were included in the case-crossover analyses. Mean age was 77.8 years and 22.3% were females. Median time from AAA to AF diagnosis was 4.6 years (IQR; 2.6–7.8). Stroke risk in the study population was high with a median CHA2DS2-VASc score of 4 (IQR: 3–5). In the case-period after AF diagnosis, 1004 prescription claims of platelet-inhibitors were registered compared with 1461 claims in the control-period before AF diagnosis, corresponding to a matched OR of 0.31 (95% CI, 0.26–0.36) (Figure 1.2). Conversely, there were 1392 prescription claims for OAC in the case-period compared with 355 in the control-period, corresponding to an OR of 15.75 (95% CI, 12.38–20.31). When restricting the study-population to patients diagnosed with AAA during 2011–2018, the OR was 0.11 (95% CI, 0.07–0.16) for a prescription claim of platelet-inhibitors and 17.7 (95% CI, 11.22–29.17) for OAC before and after AF diagnosis (Figure 1.2). Conclusion In patients with established AAA and high risk of stroke, incident AF was associated with low likelihood of treatment with platelet-inhibitor and a high likelihood of OAC-treatment compared with before AF. This association was further strengthened in patients diagnosed after 2011. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The Obel Family Foundation, DenmarkThe Augustinus Foundation, DenmarkThe sponsors played no role in the study design; data collection, analysis, or interpretation; abstract writing; or in the decision to submit the abstract. Figure 1

Patients with cancer who have preexisting diabetes have a higher risk of cardiovascular events, and prediabetes is often overlooked. In this study of 12,649 patients with cancer identified in the Clinical Data Analysis Reporting System of Hong Kong who were receiving treatment with anthracycline drugs, prediabetes was correlated with increased deaths from cardiovascular disease and/or hospitalizations for heart failure. Patients who progressed from prediabetes to diabetes within 2 years had an increased risk of combined hospitalization for heart failure and death from cardiovascular disease. These findings indicate the importance of paying greater attention to cardiovascular risk factors, including how prediabetes is managed, in patients who have cancer and are receiving chemotherapy with anthracyclines, emphasizing the need for surveillance, follow-up strategies, and consideration of prediabetes management in cancer care.

Since the DIG study,1 which demonstrated that whilst digoxin reduced hospitalization for heart failure (HF), there was no significant overall effect on mortality, the place of digoxin in treating HF has steadily declined over recent years and has been debated.2 Selection of heart rate control therapy in patients with permanent atrial fibrillation (AF), particularly those with coexisting HF, is still an issue.3 In the recent RATE-AF trial that included patients with permanent AF and symptoms of HF, treatment with digoxin or bisoprolol did not result in a significant difference in quality of life at 6 months.4 We analysed whether the clinical outcomes differed among such patients with permanent AF and HF who are treated with either digoxin or beta-blocker in a ‘real-life’ observational study. All patients who were treated for AF in our academic institution were identified using a local database. The information for each patient was extracted from computerized data of hospitalization and consultation of our institution. We examined the clinical course of 8962 consecutive patients with AF seen over a 10-year period (2000–2010).5, 6 Among them, 1787 patients met the inclusion criteria of RATE-AF (permanent AF, age ≥60 years and New York Heart Association functional class ≥2), of whom 512 patients (29%) were treated with beta-blocker alone, 425 (24%) were treated with digoxin alone and 237 (13%) were treated with both a beta-blocker and digoxin. Adverse outcomes were investigated during follow-up and we identified the causes of death. Owing to the non-randomized nature of the study, and considering for significant differences in baseline characteristics, propensity-score matching was used to control for potential confounders of the treatment outcome relationship considering the covariates listed in Table 1. Outcomes in patients treated with beta-blocker alone or digoxin alone were compared after 1:1 propensity-score matching using the one-to-one nearest neighbour method (with a calliper of 0.1 of the standard deviation of the propensity score on the logit scale). Proportional hazard model was used for the outcome analyses and proportional hazard assumption was checked by plotting the log–log Kaplan–Meier curves and scaled Schoenfeld residuals against time plots. After propensity score matching, 270 patients treated with beta-blocker (bisoprolol 70%, carvedilol 17%, nebivolol 11%, metoprolol 2%) were matched with 270 patients treated with digoxin (dose range, 125–250 µg/day; mean dose, 194 µg/day) (Table 1). The mean follow-up period was 2.2 (±2.7) years [median 1.1 (interquartile range 0.1–3.5) years]. In total, 125 all-cause deaths (including 72 cardiovascular deaths) were recorded, corresponding to an annual death rate of 10.4%. Major clinical events (all-cause death, myocardial infarction, ischaemic stroke, or major bleeding) were recorded in 192 patients, corresponding to an annual rate of 19.1%. Risk was not statistically different in the two matched groups (beta-blocker vs. digoxin) for all-cause death [hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.67–1.35], cardiovascular death (HR 1.23, 95% CI 0.77–1.96) or major clinical events (HR 0.98, 95% CI 0.74–1.31) (Figure 1 and online supplementary Figure S1). There was no statistical interaction with year of inclusion (2005–2010 vs. 2000–2004). We found that among patients with permanent AF and symptoms of HF, there were no significant differences in the risk of all-cause death, cardiovascular mortality and major clinical events between those treated with digoxin or beta-blocker. The strengths of our study are that it was based on a cohort of fair size, the population studied was representative of the majority of unselected patients with AF and we were able to take into account the severity of HF. Although not being a randomized study, our analysis included more patients and had a longer follow-up than in the RATE-AF trial,4 resulting in a 10-fold higher number of clinical events. Some secondary/exploratory outcomes differed between the two arms in RATE-AF, including several cardiovascular outcomes and adverse events that were in favour of digoxin. This was not the case in the present study and in this regard, the results of the two studies are not fully convergent. There remain significant knowledge gaps about how digitalis works and how it should be used in the modern treatment of AF. Since the DIG study,1 which demonstrated that whilst digoxin reduced HF hospitalization there was no significant overall effect on mortality, the place of digoxin in treating HF has steadily declined over recent years. In one of the very few trials in this area, the combination of carvedilol and digoxin appears generally superior to either carvedilol or digoxin alone in the management of AF in patients with HF.7 An increased mortality among digoxin-treated patients has been found in some observational studies in the last two decades.8 However, there was no adjustment to severity of HF in most of these studies. Results in other cohorts of AF patients found a neutral association of digoxin with outcomes leading to renewed questions.9 We do not intend to compare our study to a randomized clinical trial. It was based on an observational cohort design and subject to the risk of residual confounders. This has to be considered since digoxin is often used after beta-blockers have failed. The use of propensity matching may not be able to account for such inherent bias in selection of patients. We were not able to evaluate baseline and achieved heart rate in our analysis. Also, serum concentrations of digoxin are a possible determinant of adverse clinical events. Even if we were not able to adjust for serum drug concentration, unavailable in our data sources, measures of renal function (with matched adjustment) and dose of digoxin treatment were collected, which is an added value in comparison with previous studies. Finally, considering the putative mechanisms of either improved or worsened outcome with either beta-blocker or digoxin and the relatively wide CIs in our results, a trial or a propensity analysis with hard endpoint might require a quite larger sample size than that in the present study. While an increase in sudden death may be a concern with digoxin, we acknowledge that we have an insufficient sample size to prove any difference in outcome for sudden death. In conclusion, among patients with permanent AF and symptoms of HF, there was no significant difference in the risk of all-cause death, cardiovascular mortality and major clinical events between those treated with digoxin or beta-blocker when differences in patient characteristics were accounted for. Concerns regarding the use of digoxin, such as the narrow therapeutic window and drug interactions, were not issues resulting in worse clinically relevant cardiovascular outcomes with the approach used in the current study for HF patients with permanent AF. Conflict of interest: G.Y.H.L.: consultant and speaker for BMS/Pfizer, Boehringer Ingelheim and Daiichi-Sankyo. No fees are received personally. L.F.: consultant or speaker fees of small amounts for Bayer, BMS/Pfizer, Boehringer Ingelheim, Medtronic and Novartis outside of this work. All other authors have nothing to disclose. Figure S1. Cumulative incidence of all-cause death (top left panel), cardiovascular death (top right panel), stroke/thromboembolic events (middle left panel), acute coronary syndrome (middle right panel) and major clinical events (all-cause death, acute coronary syndrome, need for revascularization, ischaemic stroke/thromboembolic event or major bleeding, lower panel) in matched patients with permanent atrial fibrillation and heart failure treated with digoxin or beta-blocker during follow-up of 2.5 ± 3.0 years (median 1.2, interquartile range 0.3–4.4 years). Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

PRECISE-DAPT score appeared useful to identify AF patients undergoing PCI at further increased risk of bleeding complications and may help clinicians identifying the antithrombotic regimen intensity with the best benefit-risk ratio in an individual patient.