Complete resolution of left atrial appendage thrombosis with oral dabigatran etexilate in a patient with Myotonic Dystrophy type 1 and atrial fibrillation

Abstract

Myotonic Dystrophy type 1 (DM1) is the most common muscular dystrophy in adult life characterized by muscle dysfunction and cardiac conduction abnormalities. Atrial fibrillation frequently occurs in DM1 patients. It’s related to the discontinuous and inhomogeneous propagation of sinus impulses and to the prolongation of atrial conduction time, caused by progressive fibrosis and fatty replacement of the myocardium. AF predisposes to a hyper-coagulable state and to an increased risk of thromboembolism. We report the first case of complete resolution of left atrial appendage thrombosis with oral dabigatran etexilate in a myotonic dystrophy type I patient with atrial fibrillation scheduled for transesophageal echocardiogram-guided direct current cardioversion.

Introduction

Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adult life with an incidence of 1:8000 births and a worldwide prevalence ranging from 2.1 to 14.3/100.000 inhabitants. Cardiac involvement is noticed in about 80% of cases, and it often precedes the skeletal muscle one (1). Paroxysmal atrial arrhythmias (atrial fibrillation, atrial flutter, atrial tachycardia) frequently occur in DM1 patients with a prevalence up to 25% (2) and seem to increase mortality in this population (3). Modern pacemakers (PMs) and implantable cardiac defibrillators (ICDs) include detailed algorithms and functions to facilitate the diagnosis and management of frequent paroxysmal atrial tachy-arrhythmias often undetected during conventional clinical follow-up (4-11). Atrial fibrillation (AF) predisposes to a hypercoagulable state and an increased risk of thromboembolism (TE) (12, 13). The incidence of left atrial appendage thrombosis before direct current cardioversion (DCC) has been widely studied in AF population, ranging from 6 to 18% (14, 15). Non-Vitamin K Antagonist oral anticoagulants (NOAC) are increasingly used for the prevention and treatment of thrombi formation owing to the inherent limitations of Vitamin K antagonist oral anticoagulants (VKAs) (16). We report the first case of a left atrial appendage thrombosis effectively treated by dabigatran etexilate, a direct inhibitor of thrombin, in a DM1 patient with AF scheduled for transesophageal echocardiogram (TEE)-guided direct current cardioversion (DCC).

Case report

A 45-year-old DM1 woman with arterial hypertension, previously implanted with a dual chambers pacemaker for advanced atrioventricular block, came to our observation for PM check and cardiologic therapy optimization before cataract surgery. She was taking perindopril (4 mg/die) and magnesium pidolate (2.25 g/die). She referred a recent onset of palpitations and dyspnea. Standard (12-lead electrocardiogram) ECG confirmed the diagnosis of atrial fibrillation with a mean ventricular rate of 160 bpm (Fig. 1). PM interrogation showed atrial high rate electrograms (AHRE) faster than 220 bpm, that lasted longer than 5 minutes with irregularity and incoherence of RR intervals (Fig. 2) and arose five days before the cardiologic evaluation. Transthoracic echocardiogram showed a slightly reduced left ventricular systolic function (Simpson’s biplane ejection fraction: 48%) and a mild left atrial enlargement (left atrial volume index: 29 mL/m²). Considering the patients’ symptoms and the need to restore sinus rhythm before surgical procedure, a TEE-guided DCC was performed, which showed the presence of a thrombus in left atrial appendage (Fig. 3). The patient started a beta-blocker therapy for rate control (bisoprolol 2.5 mg/die) and oral anticoagulant therapy (warfarin 5 mg/die) to dissolve the thrombus and prevent the risk of systemic thrombo-embolic events. However, at one-month follow-up, due to a non-optimal response to warfarin therapy, evaluated by the International Normalized Ratio (INR) of the prothrombin time, a switch form VKA to NOAC therapy with dabigatran was performed at a dosage of 150 mg/bid. Eight weeks after, TEE revealed the complete resolution of the left atrial appendage thrombus (Fig. 4), allowing us to perform a safe and successful direct current cardioversion, that restored the sinus rhythm at 65 bpm. The therapy with dabigatran was prolonged for 4 weeks after cardioversion due to the high risk of thromboembolic events (CHA2DS2-Vasc Score: 2). At the date, twelve months after DCC procedure, no bleeding events or side-effects are reported.

Figure 1.

Atrial fibrillation detected by standard 12-lead electrocardiogram.

Figure 2.

Atrial high rates electrograms detected by pacemaker diagnostics.

Figure 3.

Transesophageal echocardiographic evaluation. See the presence of a thrombus in left atrial appendage.

Figure 4.

Transesophageal echocardiography evaluation eight weeks after treatment with dabigatran etexilate.

Discussion

Cardiac involvement in DM1 patients occurs as a degenerative process with progressive fibrosis and fatty replacement not only limited to the specialized conduction system, but also extended to initially unaffected areas of the atrial myocardium (17). This anatomo-pathological substrate, causing the discontinuous and inhomogeneous propagation of sinus impulses and the prolongation of atrial conduction time, may facilitate the onset and perpetuation of atrial arrhythmias in these patients (18-24), as usually happens in other clinical conditions (25-30). AF is one of the most common supraventricular arrhythmias observed in DM1 population, characterized by chaotic and uncoordinated atrial activity which predisposes to a hypercoagulable state and an increased risk of TE (12, 13). DCC quickly and effectively converts AF to sinus rhythm; however, it carries an inherent risk of stroke, which is substantially reduced by the administration of anticoagulation therapy. An early initiation of such therapy is important in all patients scheduled for cardioversion. Patients who have been in AF for periods longer than 48 h should start oral anticoagulation therapy at least 3 weeks before cardioversion and will continue it for at least 4 weeks afterwards (31). However, the difficulties in achieving an optimal anticoagulation with conventional warfarin therapy, likely related to several factors such as the slow onset of action, variable pharmacologic effects, numerous food and drug interactions and periodic closely target INR monitoring (32) make it difficult the therapeutic management in clinical practice and reduce the real-life patients’ compliance. All these challenges have prompted an extensive research and developed NOAC, now available for stroke prevention in AF patients and used in various clinical settings (33-38). Dabigatran etexilate, a direct inhibitor of thrombin, emerged as the first new generation oral anticoagulants potentially able to replace warfarin in preventing arterial TE in patients with AF (39-41). A post-hoc analysis of the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study in patients who underwent cardioversion with or without TEE guidance, showed that dabigatran treatment has a low and comparable frequency of adverse events compared to warfarin (42). These results were confirmed by a long term propensity score matched study in real world setting (43). The potential thrombolytic effect of dabigatran has been previously described (43, 44) as it is able to create a easier and faster anticoagulation milieu while inhibiting thrombin binding to fibrin and fibrin degradation products. In contrast warfarin anticoagulation, in its loading phase, could also exert a transient thrombogenic action (45).

Conclusions

The present case is the first report of a complete left atrial appendage thrombosis resolution obtained by oral dabigatran etexilate in a DM1 patient with AF, scheduled for TEE guided direct electrical cardioversion. The use of NOAC therapy should be particularly useful in this population of patients, for their variable cognitive impairment and consequent poor compliance with periodic INR monitoring.