Uninterrupted edoxaban vs. vitamin K antagonists for ablation of atrial fibrillation: the ELIMINATE-AF trial.

AIMS: Edoxaban is a direct factor Xa inhibitor approved for stroke prevention in atrial fibrillation (AF). Uninterrupted edoxaban therapy in patients undergoing AF ablation has not been tested. METHODS AND RESULTS: The ELIMINATE-AF trial, a multinational, multicentre, randomized, open-label, parallel-group study, was conducted to assess the safety and efficacy of once-daily edoxaban 60 mg (30 mg in patients indicated for dose reduction) vs. vitamin K antagonists (VKAs) in AF patients undergoing catheter ablation. Patients were randomized 2:1 to edoxaban vs. VKA. The primary endpoint (per-protocol population) was time to first occurrence of all-cause death, stroke, or International Society of Thrombosis and Haemostasis-defined major bleeding during the period from the end of the ablation procedure to end of treatment (90 days). Overall, 632 patients were enrolled, 614 randomized, and 553 received study drug and underwent ablation; 177 subjects underwent brain magnetic resonance imaging to assess silent cerebral infarcts. The primary endpoint (only major bleeds occurred) was observed in 0.3% (1 patient) on edoxaban and 2.0% (2 patients) on VKA [hazard ratio (95% confidence interval): 0.16 (0.02-1.73)]. In the ablation population (modified intent-to-treat population including patients with ablation), the primary endpoint was observed in 2.7% of edoxaban (N = 10) and 1.7% of VKA patients (N = 3) between start of ablation and end of treatment. There were one ischaemic and one haemorrhagic stroke, both in patients on edoxaban. Cerebral microemboli were detected in 13.8% (16) patients who received edoxaban and 9.6% (5) patients in the VKA group (nominal P = 0.62). CONCLUSION: Uninterrupted edoxaban therapy represents an alternative to uninterrupted VKA treatment in patients undergoing AF ablation

Long-term follow-up free of ventricular fibrillation recurrence after resuscitated cardiac arrest in a myotonic dystrophy type 1 patient

Cardiac involvement in myotonic dystrophy type 1 (DM1) is frequent with increased incidence of conduction disturbances and sudden cardiac death when compared with general population. We describe a 38-year-old man in whom the diagnosis of DM1 was made 8 years after occurrence of cardiac arrest owing to ventricular fibrillation and discuss management of DM1 patients at risk for sudden cardiac death

A gain-of-function mutation in the cardiac pacemaker HCN4 channel increasing cAMP sensitivity is associated with familial Inappropriate Sinus Tachycardia

Aims Inappropriate Sinus Tachycardia (IST), a syndrome characterized by abnormally fast sinus rates and multisystem symptoms, is still poorly understood. Because of the relevance of HCN4 channels to pacemaker activity, we used a candidate-gene approach and screened IST patients for the presence of disease-causing HCN4 mutations. Methods and results Forty-eight IST patients, four of whom of known familial history, were enrolled in the study. We initially identified in one of the patients with familial history the R524Q mutation in HCN4. Investigation extended to the family members showed that the mutation co-segregated with IST-related symptoms. The R524Q mutation is located in the C-linker, a region known to couple cAMP binding to channel activation. The functional relevance of the mutation was investigated in heterologous expression systems by patch-clamp experiments. We found that mutant HCN4 channels were more sensitive to cAMP than wild-type channels, in agreement with increased sensitivity to basal and stimulated adrenergic input and with a faster than normal pacemaker rate. The properties of variant channels indicate therefore that R524Q is a gain-of-function mutation. Increased channel contribution to activity was confirmed by evidence that when spontaneously beating rat newborn myocytes were transfected with R524Q mutant HCN4 channels, they exhibited a faster rate than when transfected with wild-type HCN4 channels. Conclusion This is the first report of a gain-of-function HCN4 mutation associated with IST through increased sensitivity to cAMP-dependent activation

Can we improve outcomes in AF patients by early therapy?

Atrial fibrillation affects at least 1% of the population and causes marked society-wide morbidity and mortality. Current management of atrial fibrillation including antithrombotic therapy and management of concomitant conditions in all patients, rate control therapy in most patients, and rhythm control therapy in patients with severe atrial fibrillation-related symptoms can alleviate atrial fibrillation-related symptoms but can neither effectively prevent recurrent atrial fibrillation nor suppress atrial fibrillation-related complications. Hence, there is a need for better therapy of atrial fibrillation

A Multicenter, Long-Term Study on Arrhythmias in Children with Ebstein Anomaly

To assess the prevalence, history, and treatment of arrhythmias, in particular preexcitation and Wolff–Parkinson–White (WPW) syndrome, in patients with Ebstein anomaly (EA) during childhood and adolescence, we performed a multicenter retrospective study of all consecutive live-born patients with EA, diagnosed, and followed by pediatric cardiologists between 1980 and 2005 in The Netherlands. During a follow-up after EA diagnosis of 13 years 3 months (range: 6 days to 28 years 2 months), 16 (17%) of the 93 pediatric EA patients exhibited rhythm disturbances. Nine patients showed arrhythmic events starting as of the neonatal period. Supraventricular tachycardia was noted in 11 patients. One patient died in the neonatal period due to intractable supraventricular tachycardia resulting in heart failure and one patient died at 5 weeks of age most probably due to an arrhythmic event. The 14 surviving patients all show preexcitation, albeit 4 of them intermittently, and all have a right-sided accessory pathway location. Nine patients underwent catheter ablation of an accessory pathway. Only four patients are currently on antiarrhythmic drugs. The 17% prevalence of rhythm disturbances in pediatric EA patients, most commonly supraventricular arrhythmias, is significantly lower than in adult EA patients. Life-threatening rhythm disturbances are not frequent early in life. Symptomatic patients are well treated with radiofrequency catheter ablation

Stroke risk associated with balloon based catheter ablation for atrial fibrillation: Rationale and design of the MACPAF Study

<p>Abstract</p> <p>Background</p> <p>Catheter ablation of the pulmonary veins has become accepted as a standard therapeutic approach for symptomatic paroxysmal atrial fibrillation (AF). However, there is some evidence for an ablation associated (silent) stroke risk, lowering the hope to limit the stroke risk by restoration of rhythm over rate control in AF. The purpose of the prospective randomized single-center study "Mesh Ablator versus Cryoballoon Pulmonary Vein Ablation of Symptomatic Paroxysmal Atrial Fibrillation" (MACPAF) is to compare the efficacy and safety of two balloon based pulmonary vein ablation systems in patients with symptomatic paroxysmal AF.</p> <p>Methods/Design</p> <p>Patients are randomized 1:1 for the Arctic Front^®or the HD Mesh Ablator^®catheter for left atrial catheter ablation (LACA). The predefined endpoints will be assessed by brain magnetic resonance imaging (MRI), neuro(psycho)logical tests and a subcutaneously implanted reveal recorder for AF detection. According to statistics 108 patients will be enrolled.</p> <p>Discussion</p> <p>Findings from the MACPAF trial will help to balance the benefits and risks of LACA for symptomatic paroxysmal AF. Using serial brain MRIs might help to identify patients at risk for LACA-associated cerebral thromboembolism. Potential limitations of the study are the single-center design, the existence of a variety of LACA-catheters, the missing placebo-group and the impossibility to assess the primary endpoint in a blinded fashion.</p> <p>Trial registration</p> <p>clinicaltrials.gov NCT01061931</p

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation

Abstract not availableHugh Calkins, Gerhard Hindricks, Riccardo Cappato, Young-Hoon Kim, Eduardo B. Saad … Prashanthan Sanders … et al