Should Every Patient With Atrial Fibrillation and a CHA2DS2-VASc Score of 1 Be Anticoagulated? A Systematic Review of 37,030 Patients

Patients with atrial fibrillation (AF) are at risk of thromboembolic events. The CHA2DS2-VASc (congestive heart failure, hypertension, age 65-74, diabetes, female sex and vascular disease, which all count for 1 point, and previous transient ischemic stroke/stroke or age ≥ 75 years, which count for two points) score stratifies this risk and consequently indicates whether anticoagulation is required but leaves room for debate regarding patients with a CHA2DS2-VASc score of 1, irrespective of sex. A score of 1, irrespective of sex, is derived from varying risk factors and may represent different risks. We systematically searched PubMed from inception to July 31, 2017, for studies describing thromboembolic risk per risk factor of the CHA2DS2-VASc score in patients with AF not treated with an anticoagulant. Two independent reviewers selected, appraised, and extracted the data to determine the thromboembolic risk per risk factor. Per study, risk factors were ranked for highest through lowest risk. Five studies were included, comprising 37,030 subjects with a CHA2DS2-VASc score of 1. Numerically, the highest event rates were seen in patients without comorbidities, but aged 65-74 years, while event rates in patients with vascular disease tended to be the lowest. Age 65-74 years is associated with the highest risk, hazard ratios ranging from 1.9 (95% confidence interval, 1.7-2.1) to 3.9 (95% confidence interval, 2.3-6.6), while comorbid cardiovascular conditions are associated with lower, but still considerably increased, risks. The thromboembolic risk differed between the risk factors of the CHA2DS2-VASc score in patients with AF, with age 65-74 years associated with the highest and most consistent risk. However, all show a significantly and clinically relevant increased thromboembolic risk. Besides the differences between risk factors of the CHA2DS2-VASc score, differences within risk factors may also alter stroke risk

Effect of Spironolactone on Atrial Fibrillation in Patients with Heart Failure with Preserved Ejection Fraction: Post-Hoc Analysis of the Randomized, Placebo-Controlled TOPCAT Trial

Background: Mineralocorticoid receptor antagonists (MRAs) reduce the risk of atrial fibrillation (AF) in patients with heart failure (HF) and a reduced ejection fraction. The efficacy of MRAs for AF prevention in patients with HF and a preserved ejection fraction (HFpEF) is unclear. Objectives: We performed a secondary analysis of a randomized placebo-controlled trial to determine the efficacy of spironolactone in reducing new-onset AF and recurrence of AF in 2733 patients with symptomatic HFpEF. Methods: Patients with and without prevalent AF at baseline were included, and those with permanent AF were excluded. Patients were randomized 1:1 to spironolactone or placebo. The risk of new-onset AF or the recurrence of AF was quantified using hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). Results: At baseline, 2228 (64.7%) patients had no history of AF (spironolactone, n = 1111; placebo, n = 1117), whereas 505 (18.4%) patients had prevalent AF (spironolactone, n = 260; placebo, n = 245). During a median follow-up of 3.1 years (interquartile range [IQR] 2.0–4.9), the incidence of new-onset AF was similar in both treatment arms: spironolactone 5.2% (n = 58) versus placebo 4.4% (n = 49); p = 0.41. The risk of new-onset AF was similar in both treatment arms: HR 1.19; 95% CI 0.81–1.74; p = 0.38. AF recurrence was also similar in both treatment arms during a median follow-up of 3.3 years (IQR 1.9–4.7): spironolactone 11.5% (n = 30) versus placebo 11.8% (n = 29); p = 1.00. The risk of recurrence of AF did not differ per treatment arm: HR 0.94; 95% CI 0.57–1.58; p = 0.83. Conclusion: Spironolactone does not reduce the risk of new-onset AF or AF recurrence in patients with HFpEF. This is in contrast to results in cohorts of patients with HF and a reduced ejection fraction. Clinical trial registration: ClinicalTrials.gov identifier no. NCT00094302 (TOPCAT)

MicroRNAs in Atrial Fibrillation: from Expression Signatures to Functional Implications

Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with pronounced morbidity and mortality. Its prevalence, expected to further increase for the forthcoming years, and associated frequent hospitalizations turn AF into a major health problem. Structural and electrical atrial remodelling underlie the substrate for AF, but the exact mechanisms driving this remodelling remain incompletely understood. Recent studies have shown that microRNAs (miRNA), short non-coding RNAs that regulate gene expression, may be involved in the pathophysiology of AF. MiRNAs have been implicated in AF-induced ion channel remodelling and fibrosis. MiRNAs could therefore provide insight into AF pathophysiology or become novel targets for therapy with miRNA mimics or anti-miRNAs. Moreover, circulating miRNAs have been suggested as a new class of diagnostic and prognostic biomarkers of AF. However, the origin and function of miRNAs in tissue and plasma frequently remain unknown and studies investigating the role of miRNAs in AF vary in design and focus and even present contradicting results. Here, we provide a systematic review of the available clinical and functional studies investigating the tissue and plasma miRNAs in AF and will thereafter discuss the potential of miRNAs as biomarkers or novel therapeutic targets in A

Rate and Rhythm Control Treatment in the Elderly and Very Elderly Patients With Atrial Fibrillation: An Observational Cohort Study of 1497 Patients

Stroke prevention and rate or rhythm control are crucial in the management of atrial fibrillation (AF). There is recent evidence for benefit of early rhythm control, yet rate control is the first choice in elderly patients. However, the efficacy and safety of rate and rhythm control in the elderly population remains largely unexplored. Therefore, we analyzed electronic health record data and investigated prescribing patterns and mortality of both strategies in elderly patients with AF. Data from patients with AF who were aged ≥75 years, used a pharmacological rate or rhythm control strategy, and visited Cardiology Centers of the Netherlands between 2007 and 2018 were extracted. Of the 1497 patients (54% female), 316 (21%) were prescribed rhythm control and 1181 (79%) rate control. Patients aged >85 years (OR: 2.28; 95% CI: 1.51-3.44, P< 0.001) and those with permanent AF (OR: 2.71; 95% CI: 1.67-4.41, P< 0.001) were more likely to receive rate control, whereas those with paroxysmal AF were less likely to receive rate control (OR: 0.42; 95% CI: 0.32-0.56, P< 0.001). After correction for relevant confounders, the mortality risk for patients using rhythm control and patients using rate control was similar (HR: 0.89; 95% CI: 0.70-1.12, P = 0.31). A more liberal approach towards prescribing a rhythm control strategy to the elderly patients with AF may be warranted and seems safe. Our data underscore the need for prospective studies to provide definite answers on efficacy and safety of rhythm control in elderly patients with AF

Migraine and cardiovascular disease: what cardiologists should know

Migraine is a chronic neurovascular disease with a complex, not fully understood pathophysiology with multiple causes. People with migraine suffer from recurrent moderate to severe headache attacks varying from 4 to 72 h. The prevalence of migraine is two to three times higher in women compared with men. Importantly, it is the most disabling disease in women <50 years of age due to a high number of years lived with disability, resulting in a very high global socioeconomic burden. Robust evidence exists on the association between migraine with aura and increased incidence of cardiovascular disease (CVD), in particular ischaemic stroke. People with migraine with aura have an increased risk of atrial fibrillation, myocardial infarction, and cardiovascular death compared with those without migraine. Ongoing studies investigate the relation between migraine and angina with non-obstructive coronary arteries and migraine patients with patent foramen ovale. Medication for the treatment of migraine can be preventative medication, such as beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, antiepileptics, antidepressants, some of the long-acting calcitonin gene-related peptide receptor antagonists, or monoclonal antibodies against calcitonin gene-related peptide or its receptor, or acute medication, such as triptans and calcitonin gene-related peptide receptor antagonists. However, these medications might raise concerns when migraine patients also have CVD due to possible (coronary) side effects. Specifically, knowledge gaps remain for the contraindication to newer treatments for migraine. All cardiologists will encounter patients with CVD and migraine. This state-of-the-art review will outline the basic pathophysiology of migraine and the associations between migraine and CVD, discuss current therapies, and propose future directions for research

Persistent atrial fibrillation: A systematic review and meta-analysis of invasive strategies

Background: Persistent atrial fibrillation (AF) is associated with higher stroke and mortality risk than paroxysmal AF (pAF). Outcomes of catheter or surgical ablation are worse in patients with persistent AF than in pAF, and the optimal invasive rhythm control strategy has not been established. Purpose: We provide a contemporary systematic overview on efficacy and safety of catheter and minimally-invasive surgical ablation for persistent AF. Methods: We systematically searched EMBASE, MEDLINE and CENTRAL from inception to July 2018 for randomized trials on surgical and catheter ablation, and included all study arms on persistent AF. Outcome was AF freedom after ≥12 months follow-up without AAD use. Random effects models were used to calculate proportions with 95%-confidence intervals. Safety consisted of adverse events during treatment and follow-up. Results: We included 6 studies on minimally-invasive surgical ablation and 56 on catheter ablation, involving 7624 patients with persistent AF. AF Freedom at 12 months was 69% (95%CI 64–74%) after surgical and 51% (95%CI 46–56%) after catheter ablation. More severe procedural adverse events occurred with surgery than with catheter ablation. Conclusions: In persistent AF patients, minimally-invasive surgical ablation is associated with more procedural complications, but higher AF freedom. As adverse events after surgical ablation appear more severe than in catheter ablation, a patient-tailored therapy choice is warranted

Prediction of atrial fibrillation recurrence after thoracoscopic surgical ablation using machine learning techniques

Thoracoscopic surgical ablation (SA) for atrial fibrillation (AF) has shown to be an effective treatment to restore sinus rhythm in patients with advanced AF. Identifying patients who will not benefit from this procedure would be valuable to improve personalized AF therapy. Machine learning (ML) techniques may assist in the improvement of clinical prediction models for patient selection. The aim of this study is to investigate how available baseline characteristics predict AF recurrence after SA using ML techniques. One-hundred-sixty clinical baseline variables were collected from 446 AF patients undergoing SA in our tertiary referral center. Multiple ML models were trained on five outcome measurements, including either all or a number of key variables selected by using the least absolute shrinkage and selection operator (LASSO). There was no difference in model performance between different ML techniques or outcome measurements. Variable selection significantly improved model performance (AUC: 0.73, 95% CI: 0.68–0.77). Subgroup analysis showed a higher model performance in younger patients ( 55 years, AUC 0.66). Recurrences of AF after SA can be predicted best when using a selection of baseline characteristics, particularly in young patients

Thoracoscopic surgical atrial fibrillation ablation in patients with an extremely enlarged left atrium

Purpose: Efficacy of pulmonary vein isolation (PVI) for atrial fibrillation (AF) decreases as left atrial (LA) volume increases. However, surgical AF ablation with unknown efficacy is being performed in patients with a giant LA (GLA). We determined efficacy of thoracoscopic AF ablation in patients with compared to without a GLA. Methods: Patients underwent thoracoscopic PVI with additional left atrial ablations lines (in persistent AF) and were prospectively followed up. GLA was defined as LA volume index (LAVI) ≥ 50 ml/m 2. Follow-up was performed with ECGs and 24-h Holters every 3 months. After a 3-month blanking period, all antiarrhythmic drugs were discontinued. The primary outcome was freedom of any atrial tachyarrhythmia ≥ 30 s during 2 years of follow-up. Results: At baseline, 68 (15.4%) patients had a GLA (LAVI: 56.7 [52.4–62.8] ml/m 2), while 374 (84.6%) had a smaller LA (LAVI: 34.8 [29.2–41.3] ml/m 2). GLA patients were older (61.9 ± 6.9 vs 59.4 ± 8.8 years, p = 0.02), more often diagnosed with persistent AF (76.5% vs 58.6%, p = 0.008). Sex was equally distributed (with approximately 25% females). GLA patients had more recurrences compared to non-GLA patients at 2-year follow-up (42.6% vs 57.2%, log rank p = 0.02). Freedom of AF was 69.0% in non-GLA paroxysmal AF patients compared to 43.8–49.3% in a combined group of GLA and/or persistent AF patients(log rank p < 0.001). Furthermore, freedom was 62.4% in non-GLA male patients, compared to 43.8–47.4 in a combined group of GLA and/or female sex(log rank p = 0.02). Conclusion: Thoracoscopic AF ablation is an effective therapy in a substantial part of GLA patients. Thoracoscopic AF ablation may serve as a last resort treatment option in these patients

Quality of life improves after thoracoscopic surgical ablation of advanced atrial fibrillation: Results of the Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery (AFACT) study

We evaluated health-related quality of life at 12 months after thoracoscopic surgical ablation in patients enrolled in the Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery study. The Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery study assessed the efficacy and safety of ganglion plexus ablation in patients with symptomatic advanced atrial fibrillation undergoing thoracoscopic surgical ablation. Patients (n = 240) underwent thoracoscopic pulmonary vein isolation with additional ablation lines in patients with persistent atrial fibrillation. Subjects were randomized to additional ganglion plexus ablation or control. Short Form 36 quality of life questionnaires were collected at baseline and at 6 and 12 months of follow-up. A total of 201 patients were eligible for quality of life analysis (age 59 ± 8 years, 72% were men, 68% had an enlarged left atrium, 57% had persistent atrial fibrillation). Patients improved in physical and mental health at 6 months (both P < .01) and 12 months (both P < .01) relative to baseline, with no difference between the ganglion plexus (n = 101) and control (n = 100) groups. Short Form 36 subscores in patients with 1 or no atrial fibrillation recurrences were similar to those in the general Dutch population after 12 months. Patients with multiple atrial fibrillation recurrences (30%) improved in mental (P < .01), but not physical health, and 6 of 8 Short Form 36 subscales remained below those of the general Dutch population. Patients with irreversible, but not with reversible procedural complications had persistently diminished quality of life scores at 12 months. Thoracoscopic surgery for advanced atrial fibrillation results in improvement in quality of life, regardless of additional ganglion plexus ablation. Quality of life in patients with no or 1 atrial fibrillation recurrence increased to the level of the general Dutch population, whereas in patients with multiple atrial fibrillation recurrences quality of life remained lower. Irreversible but not reversible procedural complications were associated with persistently lower quality of lif