Epilepsy and the risk of adverse cardiovascular events: A nationwide cohort study.

BACKGROUND AND PURPOSE: Epilepsy is associated with higher morbidity and mortality compared to people without epilepsy. We performed a retrospective cross-sectional and longitudinal cohort study to evaluate cardiovascular comorbidity and incident vascular events in people with epilepsy (PWE). METHODS: Data were extracted from the French Hospital National Database. PWE (n = 682,349) who were hospitalized between January 2014 and December 2022 were matched on age, sex, and year of hospitalization with 682,349 patients without epilepsy. Follow-up was conducted from the date of first hospitalization with epilepsy until the date of each outcome or date of last news in the absence of the outcome. Primary outcome was the incidence of all-cause death, cardiovascular death, myocardial infarction, hospitalization for heart failure, ischaemic stroke (IS), new onset atrial fibrillation, sustained ventricular tachycardia or fibrillation (VT/VF), and cardiac arrest. RESULTS: A diagnosis of epilepsy was associated with higher numbers of cardiovascular risk factors and adverse cardiovascular events compared to controls. People with epilepsy had a higher incidence of all-cause death (incidence rate ratio [IRR] = 2.69, 95% confidence interval [CI] = 2.67-2.72), cardiovascular death (IRR = 2.16, 95% CI = 2.11-2.20), heart failure (IRR = 1.26, 95% CI = 1.25-1.28), IS (IRR = 2.08, 95% CI = 2.04-2.13), VT/VF (IRR = 1.10, 95% CI = 1.04-1.16), and cardiac arrest (IRR = 2.12, 95% CI = 2.04-2.20). When accounting for all-cause death as a competing risk, subdistribution hazard ratios for ischaemic stroke of 1.59 (95% CI = 1.55-1.63) and for cardiac arrest of 1.73 (95% CI = 1.58-1.89) demonstrated higher risk in PWE. CONCLUSIONS: The prevalence and incident rates of cardiovascular outcomes were significantly higher in PWE. Targeting cardiovascular health could help reduce excess morbidity and mortality in PWE.

Effects of the ABC pathway on clinical outcomes in a secondary prevention population of Chinese patients with atrial fibrillation: A report from the Optimal Thromboprophylaxis in Elderly Chinese Patients with Atrial Fibrillation (ChiOTEAF) registry.

Background: The atrial fibrillation better care (ABC) pathway is a simple, comprehensive framework that facilitates provision of integrated care for atrial fibrillation (AF) patients. Objective: We evaluated management of AF patients in a secondary prevention cohort using the ABC pathway and examined the impact of ABC adherence on clinical outcomes. Methods: The Chinese Patients with Atrial Fibrillation registry is a prospective registry conducted in 44 sites across China between October 2014 and December 2018. The primary outcome was the composite of all-cause mortality/any thromboembolism (TE), all-cause death, any TE and major bleeding at 1 year. Results: Of the 6420 patients, 1588 (24.7%) had a prior stroke or transient ischemic attack and were identified as the secondary prevention cohort. After excluding 793 patients due to insufficient data, 358 (22.5%) were ABC compliant and 437 (27.5%) ABC noncompliant. ABC adherence was associated with a significantly lower risk of the composite outcome of all-cause death/TE, odds ratio (OR) 0.28 (95% confidence interval [CI]: 0.11-0.71) and all-cause death, OR 0.29 (95% CI: 0.09-0.90). Significant differences were not observed for TE, OR 0.27 (95% CI: 0.06-1.27) and major bleeding, OR 2.09 (95% CI: 0.55-7.97). Age and prior major bleeding were significant predictors of ABC noncompliance. Health-related quality of life (QOL) was higher in the ABC compliant group versus the noncompliant group (EQ score 0.83 ± 0.17 vs. 0.78 ± 0.20; p = .004). Conclusion: ABC pathway adherence in secondary prevention AF patients was associated with a significantly lower risk of the composite outcome of all-cause death/TE and all-cause death, as well as better health-related QOL.

Ventricular arrhythmias and cardiac arrest in atrial fibrillation patients with pacemakers and implantable cardioverter-defibrillators.

BACKGROUND: Atrial fibrillation (AF) has been linked to ventricular arrhythmias (VAs) and sudden death, but few studies have specifically explored this association. OBJECTIVE: We investigated whether AF is associated with an increased risk of ventricular tachycardia (VT), ventricular fibrillation (VF) and cardiac arrests (CA) in patients with cardiac implantable electronic devices (CIEDs). METHODS: All patients with pacemakers and implantable cardioverter-defibrillators (ICDs) hospitalised between 2010 and 2020 were identified from the French National database. Patients with a prior history of VT/VF/CA were excluded. RESULTS: 701,195 patients were identified initially. After excluding 55,688 patients, 581,781 (90.1%) and 63,726 (9.9%) remained in the pacemaker and ICD groups respectively. 248,046 (42.6%) pacemaker patients had AF and 333,735 (57.4%) had no AF, whereas in the ICD group 20,965 (32.9%) had AF and 42,761 (67.1%) had no AF. The incidence of VT/VF/CA was higher in AF patients compared to non-AF patients both in pacemaker (1.47%/year vs. 0.94%/year) and ICD (5.30%/year vs. 4.21%/year) groups. After multivariable analysis, AF was independently associated with an increased risk of VT/VF/CA in pacemaker (HR 1.236 [95% CI 1.198-1.276]) and ICD (HR 1.167 [95% CI 1.111-1.226]) patients. This risk was still significant in the 1:1 propensity score-matched analysis of the pacemaker (n = 200,977 per subgroup) and ICD cohorts (n = 18,349 per subgroup), HR 1.230 [95% CI 1.187-1.274] and HR 1.134 [95% CI 1.071-1.200] respectively and in the competing risk analysis (pacemaker: HR 1.195 (95% CI 1.154-1.238], ICD: HR 1.094 [95% CI 1.034-1.157]). CONCLUSION: CIED patients with AF have a higher risk of VT/VF/CA compared to CIED patients without AF.

Clinical Phenotypes and Atrial Fibrillation Recurrences After Catheter Ablation: An Unsupervised Cluster Analysis.

Catheter ablation (CA) is a well-established treatment of atrial fibrillation (AF). Data-driven cluster analysis is able to better distinguish prognostically-relevant phenotype clusters among patients with AF. We performed a hierarchical cluster analysis in a cohort of AF patients undergoing a first CA and evaluate associations between identified clusters and recurrences of arrhythmia following ablation. The study included 209 AF patients treated with CA. A total of 3 clusters with distinct characteristics were identified. Recurrences at 1 year occurred in 27.2% in Cluster 1, 43.2% in Cluster 2 and 60.9% in Cluster 3 (P < 0.0001). Cluster classification was independently associated with arrhythmia recurrences (HR 1.58, 95% CI 1.01-2.49, P = 0.046) after adjustment for age, CHA2DS2-VASc score, left atrial volume, type of atrial fibrillation and ejection fraction. To concluded, cluster analysis identified 3 statistically-driven groups among AF patients treated with CA with different risks for arrhythmia recurrences.

Atrial Fibrillation and the Risk of Ventricular Arrhythmias and Cardiac Arrest: A Nationwide Population-Based Study.

BACKGROUND: Atrial fibrillation (AF) has been linked to an increased risk of ventricular arrhythmias (VAs) and sudden death. We investigated this association in hospitalised patients in France. METHODS: All hospitalised patients from 2013 were identified from the French National database and included if they had at least 5 years of follow-up data. RESULTS: Overall, 3,381,472 patients were identified. After excluding 35,834 with a history of VAs and cardiac arrest, 3,345,638 patients were categorised into two groups: no AF (n = 3,033,412; mean age 57.2 ± 21.4; 54.3% female) and AF (n = 312,226; 78.1 ± 10.6; 44.0% female). Over a median follow-up period of 5.4 years (interquartile range (IQR) 5.0-5.8 years), the incidence (2.23%/year vs. 0.56%/year) and risk (hazard ratio (HR) 3.657 (95% confidence interval (CI) 3.604-3.711)) of VAs and cardiac arrest were significantly higher in AF patients compared to non-AF patients. This was still significant after adjusting for confounders, with a HR of 1.167 (95% CI 1.111-1.226) and in the 1:1 propensity score-matched analysis (n = 289,332 per group), with a HR of 1.339 (95% CI 1.313-1.366). In the mediation analysis, the odds of cardiac arrest were significantly mediated by AF-associated VAs, with an OR of 1.041 (95% CI 1.040-1.042). CONCLUSION: In hospitalised French patients, AF was associated with an increased risk of VAs and sudden death.

Implications of new-onset atrial fibrillation on in-hospital and long-term prognosis of patients with acute myocardial infarction: A report from the CBD bank study.

Background: An increase in the incidence of atrial fibrillation (AF) during the acute phase of myocardial infarction (AMI) has been observed. But it is still unclear whether the implications of new-onset AF on in-hospital and long-term prognosis are of similar magnitude. Methods: Using data from the CBD Bank study, 3,824 consecutive AMI patients, without prior AF, were analyzed. During the index hospitalization, all patients were monitored by continuous cardiac monitoring, twice daily performed 12- or 18-lead ECGs and timely ECG checks when cardiac symptoms occurred. Follow-up visits were routinely scheduled after discharge. Primary outcomes were all-cause death and cardiovascular death occurring during hospitalization and long-term follow-up. Secondary outcome was MACEs during hospitalization. Results: During the median hospital stay of 9.0 (7.0, 11.0) days, new-onset AF was documented in 133 (3.48%) patients; 95 (71.43%) patients had AF attacks within 3 days following AMI. Independent risk factors associated with new-onset AF were older age, larger left atrial diameter, higher level of NT-proBNP, and primary PCI. New-onset AF was found to be significantly associated with in-hospital all-cause death (OR 4.33, 95%CI: 2.37-7.89, P < 0.001), cardiovascular death (OR 4.10, 95%CI: 2.18-7.73, P < 0.001), and MACEs (OR 2.51, 95%CI: 1.46-4.33, P = 0.001). A total of 112 new-onset AF and 3,338 non-AF patients were followed up for 1,090 (365, 1,694) days after discharge. There was no significant association between new-onset AF and long-term all-cause death (HR 1.21, 95%CI: 0.77-1.92, P = 0.406) or cardiovascular death (HR 1.09, 95%CI: 0.61-1.97, P = 0.764). Conclusion: New-onset AF following AMI is strongly associated with an increased risk of adverse in-hospital prognosis, but it does not affect prognosis in those who survive until hospital discharge.

Outcomes in elderly Chinese patients with atrial fibrillation and coronary artery disease. A report from the Optimal Thromboprophylaxis in Elderly Chinese Patients with Atrial Fibrillation (ChiOTEAF) registry.

Background: Atrial fibrillation (AF) and coronary artery disease (CAD) are closely related; CAD may precede or complicate the clinical course of AF. Objective: To evaluate the impact of CAD on clinical outcomes among elderly Chinese AF patients. Methods: The ChiOTEAF registry is a prospective registry conducted in 44 sites from 20 provinces in China between October 2014 and December 2018. Primary outcome was the composite of all-cause mortality/any thromboembolism (TE)/major bleeding/acute coronary syndrome (ACS). Results: The eligible cohort for this analysis included 6403 individuals (mean age 74.8 ± 10.7; 39.2% female); of these, 3058 (47.8%) had a history of CAD. On multivariate analysis, CAD was independently associated with a higher odds ratio for ACS (OR: 1.98; 95% CI: 1.12-3.52) without a significant impact on other adverse outcomes. Independent variables associated with the composite outcome among CAD patients were: (i) the use of OAC (OR: 0.55; 95% CI: 0.42-0.72), age (OR: 1.09; 95% CI: 1.08-1.11), heart failure (OR: 1.95; 95% CI: 1.51-2.50), prior ischemic stroke (OR: 1.29; 95% CI: 1.02-1.64), chronic kidney disease (OR: 1.71; 95% CI: 1.32-2.22), and chronic obstructive pulmonary disease (OR: 1.42; 95% CI: 1.06-1.89). Conclusions: AF patients with CAD were at an increased risk of developing ACS but there was no significant difference in the composite outcome, all cause death, cardiovascular death, thromboembolic events or major bleeding compared to the non-CAD group. OAC use was inversely associated with adverse events, yet their uptake was poor in the AF-CAD population.

Social determinants of health and cardiovascular outcomes in patients with heart failure.

BACKGROUND: We examined the associations between family income and educational attainment with incident atrial fibrillation (AF), myocardial infarction (MI), stroke and cardiovascular (CV) death among patients with newly-diagnosed heart failure (HF). METHODS: In a nationwide Danish registry of HF patients diagnosed between 2008 and 2018, we established a cohort for each outcome. When examining AF, MI and stroke, respectively, patients with a history of these outcomes at diagnosis of HF were excluded. We used cause-specific proportional hazard models to estimate hazard ratios for tertile groups of family income and three levels of educational attainment. RESULTS: Among 27,947 AF-free patients, we found no association between income or education and incident AF. Among 27,309 MI-free patients, we found that lower income (hazard ratio 1.28 [95% CI 1.11-1.48] and 1.11 [0.96-1.28] for lower and medium vs. higher income) and education (1.23 [1.04-1.45] and 1.15 [0.97-1.36] for lower and medium vs. higher education) were associated with MI. Among 36,801 stroke-free patients, lower income was associated with stroke (1.38 [1.23-1.56] and 1.27 [1.12-1.44] for lower and medium vs. higher income) but not education. Lower income (1.56 [1.46-1.67] and 1.32 [1.23-1.42] for lower and medium vs. higher income) and education (1.20 [1.11-1.29] and 1.07 [0.99-1.15] for lower and medium vs. higher education) were associated with CV death. CONCLUSIONS: In patients with newly-diagnosed HF, lower family income was associated with higher rates of acute MI, stroke and cardiovascular death. Lower educational attainment was associated with higher rates of acute MI and cardiovascular death. There was no evidence of associations between income and education with incident AF.

In ACS, de-escalation of DAPT reduces bleeding and does not increase ischemic events vs. other DAPT strategies.

SOURCE CITATION: Shoji S, Kuno T, Fujisaki T, et al. De-escalation of dual antiplatelet therapy in patients with acute coronary syndromes. J Am Coll Cardiol. 2021;78:763-77. 34275697.

Associations of atrial fibrillation progression with clinical risk factors and clinical prognosis: A report from the Chinese Atrial Fibrillation Registry study.

BACKGROUND: An understanding of the risk factors for atrial fibrillation (AF) progression and the associated impacts on clinical prognosis are important for the future management of this common arrhythmia. We aimed to investigate the rate of progression from paroxysmal (PAF) to more sustained subtypes of AF (SAF), the associated risk factors for this progression, and its impact on adverse clinical outcomes. METHODS AND RESULTS: Using data from the Chinese trial Fibrillation Registry study, we included 8290 PAF patients. Half of them underwent initial AF ablation at enrollment. The main outcomes were ischemic stroke/systemic embolism (IS/SE), cardiovascular hospitalization, cardiovascular death, and all-cause mortality. The median follow-up duration was 1091 (704, 1634) days, and progression from PAF to SAF occurred in 881 (22.5%) nonablated patients, while 130 (3.0%) ablated patients had AF recurrence and developed SAF. The incidence rate of AF progression for the cohort was 3.87 (95% confidence interval [CI] = 3.64-4.12) per 100 patient-years, being higher in nonablated compared to ablated patients. Older age, longer AF history, heart failure, hypertension, coronary artery disease, respiratory diseases, and larger atrial diameter were associated with a higher incidence of AF progression, while antiarrhythmic drug use and AF ablation were inversely related to it. For nonablated patients, AF progression was independently associated with an increased risk of IS/SE (hazard ratio [HR] = 1.52, 95% CI = 1.15-2.01) and cardiovascular hospitalizations (HR = 1.40, 95% CI = 1.23-1.58). CONCLUSION: AF progression was common in its natural course. It was related to comorbidities and whether rhythm control strategies were used, and was associated with an increased risk of IS/SE and cardiovascular hospitalization.

The safety of discontinuation of oral anticoagulation therapy after apparently successful atrial fibrillation ablation: a report from the Chinese Atrial Fibrillation Registry study.

AIMS: We aimed to investigate the safety of discontinuing oral anticoagulation (OAC) therapy after apparently successful atrial fibrillation (AF) ablation, using data from the Chinese Atrial Fibrillation Registry study. METHODS AND RESULTS: We identified 4512 consecutive patients who underwent successful AF ablation between August 2011 and December 2017. Of them, 3149 discontinued OAC 3 months post-ablation (Off-OAC group) and 1363 continued OAC beyond this period (On-OAC group). Regular follow-up examinations were undertaken to detect AF recurrence, monitor OAC therapy, and measure clinical outcomes. Primary outcomes included thromboembolic and major bleeding (MB) events experienced beyond 3 months after ablation. Low thromboembolic and MB event rates were noted in the on-treatment analysis. The incidence rates for thromboembolism were 0.54 [95% confidence interval (CI) 0.39-0.76] and 0.86 (95% CI 0.56-1.30) per 100 patient-years, and that for MB events were 0.19 (95% CI 0.11-0.34) and 0.35 (95% CI 0.18-0.67) per 100 patient-years, for the Off-OAC and On-OAC groups over mean follow-up periods of 24.2 ± 14.7 and 23.0 ± 13.6 months, respectively. Similar results were observed in the intention-to-treat analysis. Previous history of ischaemic stroke (IS)/transient ischaemic attack (TIA)/systemic embolism (SE) [hazard ratio (HR) 3.40, 95% CI 1.92-6.02; P < 0.01] and diabetes mellitus (HR 2.06, 95% CI 1.20-3.55, P = 0.01) were independently associated with thromboembolic events, while OAC discontinuation (HR 0.71, 95% CI 0.41-1.23, P = 0.21) remained insignificant in multivariable analysis. CONCLUSIONS: This study suggests that it may be safe to discontinue OAC in post-ablation patients under diligent monitoring, in the absence of AF recurrence, history of IS/TIA/SE, and diabetes mellitus. However, further large-scale randomized trials are required to confirm this. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-OCH-13003729. URL: http://www.chictr.org.cn/showproj.aspx?proj=5831.

Atrial Fibrillation in Older People: Concepts and Controversies.

Atrial fibrillation (AF) is the commonest cardiac rhythm abnormality and has a significant disease burden. Amongst its devastating complications is stroke, the risk of which increases with age. The stroke risk in an older person with AF is therefore tremendous, and oral-anticoagulation (OAC) therapy is central to minimizing this risk. The presence of age-associated factors such as frailty and multi-morbidities add complexity to OAC prescription decisions in older patients and often, OAC is needlessly withheld from them despite a lack of evidence to support this practice. Generally, this is driven by an over-estimation of the bleeding risk. This review article provides an overview of the concepts and controversies in managing AF in older people, with respect to the existing evidence and current practice. A literature search was conducted on Pubmed and Cochrane using keywords, and relevant articles published by the 1st of May 2019 were included. The article will shed light on common misconceptions that appear to serve as rationale for precluding OAC and focus on clinical considerations that may aid OAC prescription decisions where appropriate, to optimize AF management using an integrated, multi-disciplinary care approach. This is crucial for all patients, particularly older individuals who are most vulnerable to the deleterious consequences of this condition.

Pharmacokinetics and pharmacodynamics of oral anticoagulants used in atrial fibrillation.

INTRODUCTION: The availability of non-vitamin K antagonist oral anti-coagulants alongside vitamin K antagonists has offered a variety of options for anti-coagulation, but has also necessitated a good understanding of the pharmacological properties of each of these drugs prior to their use, to maximise the therapeutic benefit and minimise patient harm Areas covered: This review article outlines the pharmacokinetic and pharmacodynamic profiles of the currently licensed VKAs and NOACs that are most commonly used in clinical practice, with the aim of demonstrating how variations in these characteristics influence their use in clinical practice. A literature search was conducted on PubMed using keywords and relevant articles published by the 31st of December 2018 were included. Expert opinion: The effect of a drug is determined by a combination of elements which include patient characteristics and external factors, in addition to its pharmacokinetic and pharmacodynamic properties. A good understanding of these is essential. Despite the wealth of information available, particularly on VKAs, our knowledge on the pharmacology responsible for certain drug effects and inter-individual variations is still limited. Increasing efforts are being made to understand these and include focus on pharmacogenomics and drug transporter proteins.

Safety of direct oral anticoagulants in real-world clinical practice: translating the trials to everyday clinical management.

INTRODUCTION: Direct oral anticoagulants (DOACs) may be regarded as some of the most successful innovations in recent times. These drugs which were specifically developed to overcome the challenges posed by warfarin did just that and in the process, have changed the outlook towards stroke prevention with anticoagulation. The decade of experience with these drugs that has resulted in the availability of large scale data on their safety profile has aided this. Areas covered: This review examines existing real-world studies (RWS) and their interpretation to better appreciate how they either complement or contradict findings from the hallmark trials. Specific focus has been made on the safety of DOACs, on their risks of major bleeding, intra-cranial haemorrhage (ICH), gastro-intestinal (GI) bleeding and all-cause mortality compared to warfarin and each other. DOAC use in the elderly and other sub-groups are briefly discussed. Expert opinion: Results for safety outcomes according to 'real world evidence' (RWE) are in-keeping with randomised controlled trials (RCTs) and currently, all 4 DOACs have been deemed at least as effective as warfarin, while demonstrating superiority in some aspects. While real world studies act as a complementary source of knowledge, traditional RCTs remain the gold standard for determining cause-effect relationships.