Three-dimensional Transesophageal Echocardiography Demonstration of Left Atrial Appendage Echocontrast Regression after 6 Months Therapy with Dabigatran and not with Warfarin.

While warfarin therapy is efficacious in treating left atrial (LA) thrombus formation in patients with nonvalvular atrial fibrillation (AF), it does not affect red cell aggregation in vitro or LA spontaneous echo-contrast in patients. In this patient with left ventricular (LV) dysfunction secondary to AF, we observed the disappearance of dense echo-contrast in the atrial appendage after therapy with dabigatran and not with well-controlled warfarin. This allowed us to analyze accurately the appendage with three-dimensional (3D) transesophageal echocardiography (TEE) excluding thrombi and to perform electrical cardioversion to obtain a significant improvement of LV function. This case demonstrates the capability of dabigatran and not of warfarin in reducing the intense spontaneous echocontrast in atrial appendage and the ability of 3D TEE in analyzing accurately the appendage, excluding thrombi to safely perform cardioversion.

INTRODUCTION

A 63-year-old male patient was re-admitted in our hospital for persistent atrial fibrillation (AF) with left ventricular (LV) dysfunction and suspected left atrial (LA) thrombus resistant to oral anticoagulation with warfarin.

His first admission was 1 year before for AF of recent onset with high ventricular response (EHRA III-IV) complicated by ventricular arrhythmias. During the hospitalization, coronary angiography demonstrated “widespread coronary atheromasia, without hemodynamically significant lesions,” the heart rate was reduced from 150 to 90/m’ with betablocker (carvedilol) and digoxin obtaining an improvement of ejection fraction (EF) (from 38% to 45%). Electrical cardioversion was postponed after 4 weeks of warfarin anticoagulation.

Four weeks later, he was checked and because of inadequate control of prothrombin time international normalized ratio (PT-INR) (2 values below 2), he underwent a three-dimensional (3D) transesophageal echocardiography (TEE), which showed the presence of a spontaneous “echo-contrast” (SEC) with a “sludge” effect in the LA appendage (LAA) that appeared enlarged and dysfunctional. In correspondence of both LAA walls (more on the lateral wall) in the 80° projection, there was a thin wall thickening hardly to differentiate between a thrombus or pectinate muscles [Figure 1]. Therefore, cardioversion was again delayed with the indication to continue oral anticoagulation therapy with warfarin and repeat TEE after sufficient time with PT-INR in range.

Figure 1

Transesophageal echocardiography 80° section showing the presence of spontaneous echo-contrast with sludge effect in the enlarged left atrial appendage, visible also in the left atrium (arrow). Due to this echo-contrast, it is impossible to exclude the presence of thrombus in the atrial appendage. LA = Left atrium, LV = Left ventricle

For 4 months, the next TEE was postponed because of the inability to have 3 weeks of PT-INR in range. Finally, when the PT-INR was in range for 3 consecutive weeks, a second TEE showed again persistence of SEC with sludge and suspect of thrombosis in LAA.

Because of the difficult PT-INR control, warfarin was replaced with dabigatran 150 mg 2 cp/die and because of the persistent LV dysfunction, a third TEE was planned to be eventually followed by AF cardioversion.

The third 2D/3D TEE after 1 month of regularly intake of dabigatran therapy showed an important reduction of the sludge in the LAA compared to the previous ones, with the only persistence of moderate SEC [Figure 2]. With this clear view, it was possible to exclude the presence of thrombotic formations and thanks to the 3D-analysis better identify the small immobile linear formations in the LAA as pectinate muscles of the mid-distal portion [Figure 3]. Moreover, a reduced LAA function was showed (max emptying rate: 22 cm/s and poor lateral wall motion).

Figure 2

Transesophageal echocardiography after 1 month of dabigatran; 80° section showing disappearance of spontaneous echo-contrast in the enlarged left atrial appendage; in correspondence of the lateral appendage wall, a thin wall thickening is visible hardly to differentiate between thrombus or pectinate muscles. LA = Left atrium, LV = Left ventricle

Figure 3

Three-dimensional transesophageal echocardiography 80° section after 1 month of dabigatran without echo-contrast in the atrial appendage; thanks to the three-dimensional analysis, it is possible to identify the small immobile linear formations in the lateral appendage wall (arrows) as pectinate muscles of the mid-distal portion. LA = Left atrium, LAA = Left atrial appendage, LUPV = Left upper pulmonary vein

Hence, electric cardioversion was performed with 100 J synchronized direct current shock, with restoration of sinus rhythm. The day after the patient was discharged with the improvement of clinical conditions and indication to continue therapy with dabigatran 150 mg.

After 4 weeks, the patient was asymptomatic also for heavy exercise (NYHA I), and the LVEF recovered almost completely to a value of 57% at biplane Simpson.

DISCUSSION

In this case, we demonstrate for the first time, (1) the capability of dabigatran and not of warfarin in reducing the intense spontaneous echocontrast in LAA following 6 months of therapy and (2) the ability of 3D TEE in analyzing accurately the LAA, after SEC disappearance, and excluding LAA thrombi to safely perform external cephalic version (ECV) in a patient with LV dysfunction secondary to AF.

The clinical importance of SEC is its association with LA thrombus, increased thromboembolic complications, and death.[1] This link is stronger for dense SEC as demonstrated by Bernhardt in 128 patients with AF and dense SEC, performing serial, prospective TEE, and cranial magnetic resonance imaging, and concluded that patients with dense SEC have a high likelihood of cerebral embolism (28 of 128, 22%) and/or death, despite oral anticoagulation.[2]

Despite effective anticoagulation (both with warfarin or direct new oral anticoagulants), the presence of LA thrombus can rarely occur. While warfarin therapy is efficacious in treating LA thrombus formation in patients with nonvalvular AF,[3] it does not affect red cell aggregation in vitro or LA SEC in patients.[4]

Ito et al. using integrated backscatter concluded that quantitative value of SEC was not changed by warfarin, whereas both studies demonstrated that patients with SEC had larger LA dimension and lower LAA velocity.[4]

Therefore, a controversial effect of warfarin is observed in reducing the risk of thromboembolism[3] in AF, without reducing LA SEC.

The explanation for this paradox is that smoke-like echoes are influenced by various hematologic factors, such as the hematocrit[5] and the fibrinogen concentration, but they are not affected by warfarin therapy.

This is also confirmed by a case report with attenuation of LA SEC during antiplatelet therapy,[6] considered to be due to the disaggregatory effect of platelets.

Concerning the thrombolytic effect of dabigatran in LAA in several clinical cases, Nagamoto et al. demonstrated the disappearance of thrombus in LAA with dabigatran 220 mg/day in three patients >80 years with paroxysmal and persistent AF without a previous story of anticoagulation therapy;[7] Morita et al. with dabigatran 300 mg/day in a 72-year-patient with permanent AF (CHA2DS2-VASc 5), after a little reduction of the thrombus with warfarin;[8] Lee et al. with dabigatran 220 mg/day in a 72-year-patient with permanent AF (CHA2DS2-VASc 3), after 1 year of inadequate use of warfarin; Vidal and Vanerio in a 59-year-patient with uncertain duration AF, after a period with warfarin at low time in therapeutic range.[9]

Our case is the first one in humans to demonstrate the disappearance of dense SEC in the LAA after therapy with dabigatran 150 mg twice daily and not with well-controlled warfarin, adding a supplementary effect previously demonstrated with antiaggregation therapy to the thrombolytic effect.

3D echo adds information to the analysis of cardiac structures and can depict more accurately LAA thrombi;[10] in our patient, the real time 3D TEE echo allowed an additional diagnostic capability in the differential diagnosis of suspected LAA thrombi. After cardioversion, longitudinal strain analysis can detect early improvement of cardiac performance.

CONCLUSION

In this patient with LV dysfunction secondary to AF, we observed the disappearance of dense SEC in the LAA after therapy with dabigatran and not with well-controlled warfarin. This allowed us to analyze accurately the LAA with 3D TEE echo excluding thrombi and to perform ECV to obtain a statistically significant improvement of LV function.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.