Progression of Device-Detected Subclinical Atrial Fibrillation and the Risk of Heart Failure

Background

Long-term continuous monitoring detects short-lasting, subclinical atrial fibrillation (SCAF) in approximately one-third of older individuals with cardiovascular conditions. The relationship between SCAF, its progression, and the development of heart failure (HF) is unclear.

Atrial fibrillation: the role of common and rare genetic variants

Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting 1–2% of the general population. A number of studies have demonstrated that AF, and in particular lone AF, has a substantial genetic component. Monogenic mutations in lone and familial AF, although rare, have been recognized for many years. Presently, mutations in 25 genes have been associated with AF. However, the complexity of monogenic AF is illustrated by the recent finding that both gain- and loss-of-function mutations in the same gene can cause AF. Genome-wide association studies (GWAS) have indicated that common single-nucleotide polymorphisms (SNPs) have a role in the development of AF. Following the first GWAS discovering the association between PITX2 and AF, several new GWAS reports have identified SNPs associated with susceptibility of AF. To date, nine SNPs have been associated with AF. The exact biological pathways involving these SNPs and the development of AF are now starting to be elucidated. Since the first GWAS, the number of papers concerning the genetic basis of AF has increased drastically and the majority of these papers are for the first time included in a review. In this review, we discuss the genetic basis of AF and the role of both common and rare genetic variants in the susceptibility of developing AF. Furthermore, all rare variants reported to be associated with AF were systematically searched for in the Exome Sequencing Project Exome Variant Server.     

Periprocedural Intracardiac Echocardiography for Left Atrial Appendage Closure: A Dual-Center Experience

ObjectivesThis dual-center study sought to demonstrate the utility and safety of intracardiac echocardiography (ICE) in providing adequate imaging guidance as an alternative to transesophageal echocardiography (TEE) during Amplatzer Cardiac Plug device implantation.BackgroundOver 90% of intracardiac thrombi in atrial fibrillation originate from the left atrial appendage (LAA). Patients with contraindications to anticoagulation are potential candidates for LAA percutaneous occlusion. TEE is typically used to guide implantation.MethodsICE-guided percutaneous LAA closure was performed in 121 patients to evaluate the following tasks typically achieved by TEE: assessment of the LAA dimension for device sizing; guidance of transseptal puncture; verification of the delivery sheath position; confirmation of location and stability of the device before and after release and continuous monitoring to detect procedural complications. In 51 consecutive patients, we compared the measurements obtained by ICE and fluoroscopy to choose the size of the device.ResultsThe device was successfully implanted in 117 patients, yielding a technical success rate of 96.7%. Procedural success was achieved in 113 cases (93.4%). Four major adverse events (3 cardiac tamponades and 1 in-hospital transient ischemic attack) occurred. There was significant correlation in the measurements for device sizing assessed by angiography and ICE (r = 0.94, p < 0.0001).ConclusionsICE imaging was able to perform the tasks typically provided by TEE during implantation of the Amplatzer Cardiac Plug device for LAA occlusion. Therefore, we provide evidence that the use of ICE offered accurate measurements of LAA dimension in order to select the correct device sizes.     

Diagnosis and Management of Atrial Fibrillation: An Overview

Atrial fibrillation (AF) has been defined as the new cardiovascular “epidemic”. Its prevalence is rising in developed countries, and the associated social and economic costs are high. In the last few years, there has been an increasing interest in understanding the mechanisms of AF and its management. New pharmacotherapies together with novel techniques for surgical and catheter treatment of AF have been developed, allowing the maintenance of sinus rhythm and the alleviation of symptoms in a large number of patients with AF. However, there are still some challenges that need to be addressed. This article gives an overview of the current state of the art on novel techniques for diagnosis and management of AF.     

Comparison of the effect of edoxaban,a direct factor Xa inhibitor,with a direct thrombin inhibitor,melagatran, and heparin on intracerebral hemorrhage induced by collagenase in rats

Introduction

Intracerebral hemorrhage (ICH) is a major clinical concern with anticoagulation therapy. The effect of a new oral direct FXa inhibitor, edoxaban, was determined in a rat model of ICH and compared with a direct thrombin inhibitor, melagatran, and heparin.

Methods

To induce ICH, 0.1 U collagenase type VII was injected into the striatum of male Wistar rats under anesthesia with thiopental or halothane. Immediately after ICH induction, edoxaban, melagatran, or heparin were infused intravenously. Five hours after ICH induction, the brain was removed and ICH size was measured. To estimate the margin of safety, antithrombotic effects were evaluated in a rat venous thrombosis model.

Results

Edoxaban at 6 mg/kg/h significantly increased ICH volume (1.8-fold) and prolonged prothrombin time (PT) 2.8-fold compared to the vehicle group. No deaths were observed with edoxaban. Melagatran at 1 mg/kg/h increased ICH volume at 1 mg/kg/h (2.8-fold) with 6.1-fold PT prolongation. At 3 mg/kg/h, all rats died due to severe ICH (3.9-fold). Heparin at both 100 and 500 U/kg/h significantly increased ICH. At 500 U/kg/h, 5 out of 8 rats died. The doses required for 50% inhibition of thrombosis of edoxaban, melagatran, and heparin were 0.045 mg/kg/h, 0.14 mg/kg/h, and 55 U/kg/h, respectively. The safety margins between antithrombotic and ICH exacerbation effects of these anticoagulants were 133, 7.1, and 1.8, respectively.

Conclusion

The safety margin of edoxaban was wider than that of melagatran or heparin. These results suggest that edoxaban may be preferable from the perspective of ICH exacerbation risk.     

Improvement of anticoagulant treatment using a dynamic decision support algorithm: A Danish Cohort study

Introduction

Warfarin is the most widely prescribed vitamin K antagonist and in the United States and Europe more than 10 million people are currently in long-term oral anticoagulant treatment. This study aims to retrospectively validate a dynamic statistical model providing dosage suggestions to patients in warfarin treatment.

Materials and methods

The model was validated on a cohort of 553 patients with a mean TTR of 83%. Patients in the cohort were self-monitoring and managed by a highly specialised anticoagulation clinic. The predictive model essentially consists of three parts handling INR history, warfarin dosage and biological noise, which allows for prediction of future INR values and optimal warfarin dose to stay on INR target. Further, the model is based on parameters initially being set to population values and gradually individualised during monitoring of patients.

Primary outcome

Time in therapeutic range was used as surrogate quality measure of the treatment, and model-suggested dosage of warfarin was used to assess the accuracy of the model performance.

Results

The accuracy of the model predictions measured as median absolute error was 0.53 mg/day (interquartile range from 0.25 to 1.0). The model performance was evaluated by the difference between observed and predicted warfarin intake in the preceding week of an INR measurement. In more than 70% of the cases where INR measurements were outside the therapeutic range, the model suggested a more reasonable dose than the observed intake.

Conclusion

Applying the proposed dosing algorithm can potentially further increase the time in INR target range beyond 83%.     

Increased thrombin generation in splanchnic vein thrombosis is related to the presence of liver cirrhosis and not to the thrombotic event

Introduction

In recent years there have been increasing evidence associating liver disease with hypercoagulability, rather than bleeding. The aim of the study was to evaluate the haemostatic potential in patients with liver disease.

Patients and methods

We measured thrombin generation in the presence and absence of thrombomodulin in patients with portal vein thrombosis (PVT, n = 47), Budd-Chiari syndrome (BCS, n = 15) and cirrhosis (n = 24) and compared the results to those obtained from healthy controls (n = 21). Fifteen patients with PVT and 10 patients with BCS were treated with warfarin and were compared to an equal number of patients with atrial fibrillation matched for prothrombin time-international normalized ratio. We assessed resistance to thrombomodulin by using ratios [marker measured in the presence/absence of thrombomodulin].

Results

There were no differences in thrombin generation between patients on warfarin treatment and their controls. Cirrhotic patients generated more thrombin in the presence of thrombomodulin and exhibited thrombomodulin resistance compared to controls [p = 0.006 for endogenous thrombin potential (ETP) and p < 0.001 for peak thrombin and both ratios ETP and peak] and patients with non-cirrhotic PVT (p = 0.001, p = 0.006, p < 0.001, p < 0.001 for ETP, peak, ratio ETP, ratio peak, respectively). The patients with cirrhotic PVT exhibited higher ETP (p = 0.044) and peak (p = 0.02) in the presence of thrombomodulin than controls, as well as thrombomodulin resistance (ETP and peak ratios: p = 0.001).

Conclusions

Hypercoagulability and thrombomodulin resistance in patients with cirrhosis were independent of the presence of splanchnic vein thrombosis. The hypercoagulability in patients with cirrhotic PVT could have implications for considering longer or more intensive treatment with anticoagulants in this group.