Left Atrial Appendage Thrombosis During Therapy with Rivaroxaban in Elective Cardioversion for Permanent Atrial Fibrillation.

Electric external cardioversion (EEC) for permanent atrial fibrillation (AF) carries a risk of thromboembolic events (TE). The use of transesophageal echocardiography (TEE) to guide the management of atrial fibrillation may be considered a clinically effective alternative strategy to conventional therapy for patients in whom elective cardioversion is planned. Therapeutic anticoagulation with novel oral anticoagulants (NOAC) is recommended for 3 to 4 weeks before and an anticoagulation life-long therapy is recommended after EEC to reduce TE, in patients with high CHA2DS2-VASc score; however, only few data are currently available about safety of short-term anticoagulation with NOAC in the setting of EEC. Patients with increased risk of thromboembolism have not been adequately studied and the monitoring of anticoagulant effects can also have important benefits in case of drug interactions. We report a case of a 68-year old man with AF from September 2014. Moderate depression of global left ventricular systolic function was detected by echocardiographic exam. On the basis of a high thromboembolic risk, an anticoagulant therapy with rivaroxaban, at the dose of 20 mg/day, was started. TEE showed a thrombus in the left atrial appendage. This case demonstrates the utility of performing TEE prior than EEC in patients with hypokinetic cardiomyopathy other than AF in therapy with NOAC. We underline the presence of significant pharmacodynamic interference of rivaroxaban with other drugs such as oxcarbazepine.

Introduction

Electric external cardioversion (EEC) for permanent atrial fibrillation or atrial flutter (AF) carries a risk of thromboembolic events (TE). The use of transesophageal echocardiography to guide the management of atrial fibrillation may be considered a clinically effective alternative strategy to conventional therapy for patients in whom elective cardioversion is planned. Therapeutic anticoagulation with vitamin K-antagonists (VKA) or novel oral anticoagulants (NOAC) is recommended for 3 to 4 weeks before and 4 weeks after EEC to reduce TE;[1-3] however, only few data are currently available about safety of short-term anticoagulation with the NOAC (dabigatran, rivaroxaban, apixaban and edoxaban) in the setting of EEC.

Case Report

A 68-year old man was found to have permanent AF in September 2014. He was symptomatic for fatigue and dyspnea. In his medical history he had arterial hypertension, diabetes mellitus and past episodes of seizures in treatment with oxcarbazepine.

The echocardiographic exam showed: moderate depression of global left ventricular systolic function (38%), atrial enlargement and mild mitral regurgitation. The main laboratory tests (including hemochrome, coagulation, hepatic, renal and thyroid function) were normal. On the basis of a high thromboembolic risk (CHA2DS2-VASc score=4), an anticoagulant therapy with rivaroxaban, at the dose of 20 mg/day, was started.

After 6 weeks of treatment with rivaroxaban, in prevision of an EEC of AF, it was performed a TEE, which showed a thrombus in the left atrial appendage and low auricular flow rate (Figure 1 and Video 1).

Figure 1.

A) Trans-esophageal echocardiogram (TEE) showing a thrombus in the left atrial appendage and low auricular flow; B) TEE showing a low auricular flow.

EEC was not performed and the anticoagulation therapy was empirically shifted from rivaroxaban to warfarin (with a therapeutic target of international normalized ratio of 2-3). A TEE was repeated after six more weeks and demonstrated the complete resolution of the thrombus.

Discussion and Conclusions

The X-VERT[4] study enrolled adult patients, who were hemodynamically stable and had non-valvular atrial fibrillation >48 h or of unknown duration, and who were scheduled for either electrical or pharmacologic cardioversion. The trial randomized 1504 non-valvular atrial fibrillation patients undergoing elective cardioversion to rivaroxaban (20 mg once daily, 15 mg if creatinine clearance was between 30 and 49 mL/min) or dose-adjusted VKAs in a 2:1 ratio. Patients were also assigned to either an early (1-5 days) or delayed (3-8 weeks) cardioversion strategy. Among these patients, 0.51% in the rivaroxaban group experienced primary efficacy events - stroke, transient ischemic attack, peripheral embolism, myocardial infarction or cardiovascular death - compared to 1.02% in the VKA group. The percentage of primary efficacy events following early cardioversion was somewhat similar across both groups, with 0.71% of rivaroxaban patients and 1.08 percent of VKA patients experiencing events. In terms of major bleeding, results were similar across both groups with 0.6% of rivaroxaban patients and 0.8% of VKA patients experiencing bleeding events.

In another retrospective cohort study,[5] Ajay Yadlapati and coll. showed that the use of short-term dabigatran or rivaroxaban therapy for EEC of AF appears safe. No patients were found to have episodes of TE within 60 days of EEC. No patients were found to have major bleeding events.

Some studies have addressed this issue, but populations with increased risk of thromboembolism or with left ventricular dysfunction have not been adequately studied and the monitoring of anticoagulant effects can also have important benefits in case of drug interactions.

In this case we underline the presence of significant pharmacodynamic interference of rivaroxaban with other drugs such as oxcarbazepine. This drug is in fact a strong inducer of the CYP3A4 enzyme, which is important for degradation of rivaroxaban.[6] So, although the main advantage of NOAC compared to VKA is the fact that routine monitoring of the anticoagulant effects does not seem necessary, this can have important clinical benefits in case of drug interactions. The choice of rivaroxaban in this patient was probably wrong, and this drug should be used by a careful drug concentration monitoring. However, this kind of testing is not currently disposable in our center. In this case, as we demonstrated, it is very useful performing TEE prior than EEC.

However, an anticoagulation life-long therapy after EEC to reduce TE, in patients with CHA2DS2-VASc score=4, should be suggested.

Learning objective

The main learning objective is a warning to a treatment with rivaroxaban (NOA) with other drugs inducer of the CYP3A4 enzyme, which is important for degradation of rivaroxaban, in atrial fibrillation for an EEC, in patients with left heart dysfunction, in patients with high CHA2DS2-VASc score, without performing TEE.

Video

See the online video associated to this case report.

Video 1: Trans-esophageal echocardiogram showing a thrombus in the left atrial appendage and smoke in left atrial cavities.