Pediatr Cardiol DOI 10.1007/s00246-014-0902-x
ORIGINAL ARTICLE
Transesophageal Echocardiography of Intracardiac Thrombus in Congenital Heart Disease and Atrial Flutter: The Importance of Thorough Examination of the Fontan Nida Yousef • Molly Philips • Ira Shetty Vivian Wei Cui • Frank Zimmerman • David A. Roberson
•
Received: 27 November 2013 / Accepted: 25 March 2014 Ó Springer Science+Business Media New York 2014
Abstract Transesophageal echocardiography (TEE) is used in atrial flutter or fibrillation (AFF) before electric cardioversion to detect intracardiac thrombi. Previous studies have described the use of TEE to diagnose intracardiac thrombi in the left atrium and left atrial appendage, which has an incidence of 8 % among patients without congenital heart disease (CHD). In their practice the authors have noted a significant incidence of intracardiac thrombi in other structures of patients with CHD and AFF. This study aimed to determine the incidence and location of intracardiac thrombi using TEE in patients with CHD requiring electric cardioversion of AFF and to compare the use of TEE and transthoracic echo (TTE) to detect intracardiac thrombus in this population. A retrospective chart review of TEE and TTE findings for all patients with CHD who had electric cardioversion of AFF at our institution from 2005 to 2013 was conducted. The diagnosis, presence, and location of intracardiac thrombus were determined. The TEE and TTE results were compared. The study identified 27 patients with CHD who met the study entry criteria at our institution between 2005 and 2013. Seven of these patients had a single ventricle with Fontan palliation. All the patients presented with AFF and had TEE before electric cardioversion. No patients were excluded from the study. The patients ranged in age from 2 to 72 years (median, 21 years) and weighed 17–100 kg (median, 65 kg). The duration of AFF before TEE and attempted cardioversion ranged from 1 day to 3 weeks (median, 3.5 days). Intracardiac thrombus was
N. Yousef (&) M. Philips I. Shetty V. W. Cui F. Zimmerman D. A. Roberson Advocate Children’s Hospital Heart Institute, 4440 West 95th Street, Oak Lawn, IL 60453, USA e-mail: [email protected]; [email protected]
present in 18 % (5/27) of the patients and in 57 % (4/7) of the Fontan patients with AFF. No embolic events were reported acutely or during a 6-month follow-up period. Among patients with CHD who present with AFF, a particularly high incidence of intracardiac thrombi is present in the Fontan patients that may be difficult to detect by TTE. Thorough TEE examination of the Fontan and related structures is indicated before electric cardioversion of AFF. The incidence of intracardiac thrombus in CHD patients is more than double that reported in non-CHD patients. Keywords Atrial flutter Atrial fibrillation Congenital heart disease Fontan Intracardiac thrombus
Introduction Atrial flutter is the most common arrhythmia in patients with repaired or palliated congenital heart disease (CHD) [13]. It is most commonly seen as a postoperative complication of the Fontan procedure for single-ventricle atrial septal defect (ASD) repairs, the Mustard procedure for dextro-transposition of the great arteries (D-TGA), and tetralogy of Fallot (TOF) [22]. Atrial fibrillation also is seen in older patients with repaired or palliated CHD. Atrial flutter or atrial fibrillation (AFF) has deleterious effects on cardiac output and promotes the formation of intracardiac thrombus, with an increased risk for thromboembolic events [14, 21]. Patients with CHD are less likely to tolerate hemodynamic changes related to prolonged tachyarrhythmia [4]. Electric cardioversion, the treatment of choice for terminating AFF in patients with CHD, has a high success rate [30]. Transesophageal echocardiography (TEE) is routinely performed for adult patients undergoing electric cardioversion
123
Pediatr Cardiol
for AFF. The use of TEE allows visualization of left atrial appendage details and thrombi not easily detectable by transthoracic echocardiography (TTE) [6, 16, 23]. Thromboembolism most often occurs after the return of synchronous atrial contraction and has been attributed to left atrial thrombus present at the time of cardioversion. Embolic events also have been reported after cardioversion in patients who had no thrombi shown on TEE before cardioversion. The incidence of intraatrial thrombus in adult patients with AFF and no underlying CHD ranges between 1 and 8 % depending on the duration of the arrhythmia, the history of embolic events, and the history of atrial fibrillation [9]. In the general population, TEE is thought to be superior to TTE in identifying cardioembolic sources in patients with transient ischemic attacks and stroke [6, 16, 23]. In CHD, TEE helps to determine abnormal flow patterns and shunts and to provide a detailed anatomic assessment, especially when TTE views are limited or image quality is poor. In addition, three-dimensional (3D) echocardiography has been increasingly used to rule out thrombi in the Fontan conduit and may further enhance the ability to diagnose intracardiac thrombi in patients with CHD [24]. This study aimed to determine the incidence and location of intracardiac thrombi by TEE in patients with CHD requiring electric cardioversion of AFF and to compare the use of TEE and TTE in detecting intracardiac thrombi in this population.
Materials and Methods All patients with CHD presenting to our institution with AFF and stable hemodynamics are admitted to the intensive care unit. We start heparin electively if the patient is not receiving warfarin or presents with a subtherapeutic international normalized ratio (INR). Our target INR before cardioversion is 2–3. After intubation and sedation, TEE is performed, followed by electric cardioversion if no thrombus is detected. We also use 3D TEE to visualize details of cardiac anatomy and cardiac repair. After restoration of normal sinus rhythm, we start antiarrhythmic medications. For those with thrombus detected by TEE, warfarin is started, with a target INR of 2–3 for 3–4 weeks, after which the patients have a follow-up TEE and electric cardioversion. These patients also are started on long-term anticoagulation and antiplatelet agents to avoid future thromboembolic events [25, 28]. We performed a retrospective review of the TEE and TTE findings and medical records for the last 27 consecutive patients with CHD who presented at our institution between 2005 and 2013 and required electric cardioversion of AFF. The diagnosis, presence, and location of
123
intracardiac thrombi were determined. The TEE and TTE results were compared (Table 1). Spontaneous echo contrast (smoke) was defined as a swirling pattern of increased echogenicity caused by ultrasonic backscatter from red blood cell aggregates [10]. Sludge was defined as very dense spontaneous echo contrast [1] (Fig. 1). The findings were summarized in tables and analyzed using descriptive statistics including means and medians.
Results We identified 27 CHD patients presenting with AFF who had undergone TEE and electric cardioversion. Five of these patients had TEE repeated in 3–4 weeks for assessment of the previously identified intracardiac thrombus before cardioversion. Of the 27 patients, 24 had atrial flutter and 3 had atrial fibrillation. This included all of the last 27 patients presenting to our institution between 2005 and 2013 who had CHD with AFF and had undergone electric cardioversion. No patients were excluded. The patients ranged in age from 2 to 72 years (median, 21 years) and weighed 17–100 kg (median, 65 kg). The duration of AFF before TEE and attempted cardioversion ranged from 1 day to 3 weeks (median, 3.5 days). The duration of AFF was defined as the time from the onset of symptoms attributable to AFF to the time of TEE. Intracardiac thrombus was present in 18 % (5/27) of all the patients and in 57 % (4/7) of the Fontan patients with AFF (Table 1). The initial diagnosis for the four Fontan patients with intracardiac thrombi was tricuspid atresia for three patients and double-inlet left ventricle (DILV) for one patient. The thrombus was in the atriopulmonary Fontan of one patient (Fig. 2a) and in the lateral tunnel Fontan of one patient. Two patients had a thrombus in the right atrial remnant, which was connected to the pulmonary venous atrium in an extracardiac Fontan in the one patient and to the lateral tunnel Fontan in the other patient (Fig. 2b, c). None of the four Fontan-related thrombi were seen on TTE. A patient with congenital mitral valve regurgitation had a thrombus in the left atrial appendage, which was also seen on TTE (Fig. 2d). The patients with Fontan who had intracardiac thrombi showed at least one previous episode of AFF, sluggish flow within the Fontan, and moderately to severely depressed ventricular systolic function on TEE at the time of presentation with AFF. The patient who had intracardiac thrombus within the atriopulmonary Fontan showed significant dilation of the atrium. None of these patients had a history of intracardiac thrombosis. One patient had experienced stroke associated with atrial fibrillation 1 year
Mustard Rastelli
Two-patch repair
L-TGA
AVC
Atrial flutter
Atrial flutter
Atrial flutter
Atrial fibrillation
Atrial flutter
Atrial flutter
Atrial flutter
Atrial flutter
Atrial flutter
Atrial fibrillation
Atrial flutter
Atrial flutter
Atrial flutter
Atrial flutter
Atrial flutter
Atrial flutter
Atrial fibrillation
Atrial flutter
Atrial flutter
Type of arrhythmia
27
1
1
1
2
1
1
2
1
2
2
2
3
1
1
1
1
1
1
2
No. of patients
1 Day
4 Days
3 Weeks
1 Week
1 Week
1 Week
1 Week
4 Days
2 Days
1 Day
2 Days 3 Days
3 Days
2 Days
1 Day
1 Day
1 Day
1 Day
3 Weeks
1 Week
2 Weeks
3 Days
1 Day
1 Day
7 Days
5 Days
Average duration of AFF
2
21
17
63, 72
9
35
16, 17
10
26, 16
39, 55
16, 18
22, 17, 24
5
36
21
39
39
17
22, 24
Respective ages (years)
17
83
91
88, 90
42
100
46, 80
29
81, 54
81, 65
55, 60
55, 42, 45
17
55
65
65
71
58
73, 80
Respective weights (kg)
5/27
1
1
1
1
1
ICT seen on TEE
LAA
Fontan
RA remnant
RA remnant
Fontan
ICT location
1/5
Yes
No
No
No
No
Seen on TTE
AFF atrial flutter or fibrillation, ICT intracardiac thrombus, TEE transesophageal echocardiogram, TTE transthoracic echocardiogram, RA right atrium, DILV double-inlet left ventricle, MVR mitral valve regurgitation, LAA left atrial appendage, TOF teratology of Fallot, D-TGA dextro-transposition of the great arteries, L-TGA levo-transposition of the great arteries, AVC atrioventricular canal, DORV double-outlet right ventricle, ASD atrial septal defect, PA/VSD pulmonary atresia with ventricular septal defect, TAPVC total anomalous pulmonary venous connection
Total
Repair of total veins
Arterial switch
D-TGA
Rastelli
Mustard
D-TGA
TAPVC
Valvuloplasty
Ebstein’s anomaly
Truncus arteriosus
Transannular patch
TOF
Rastelli
Valvuloplasty and ring
Congenital MVR
PA/VSD
Extracardiac Fontan
DILV
Surgical closure
Lateral tunnel Fontan
DILV
ASD
Extracardiac Fontan
Tricuspid atresia
Ross procedure
Lateral tunnel Fontan
Tricuspid atersia
Arterial switch, VSD patch
Lateral tunnel Fontan
Tricuspid atresia
DORV
Atriopulmonary Fontan
Tricuspid atresia
Aortic valve stenosis
Repair/palliation
Diagnosis
Table 1 Clinical characteristics and echocardiography findings in the patient study population (n = 27)
Pediatr Cardiol
123
Pediatr Cardiol
Fig. 1 a Live three-dimensional (3D) transesophageal echocardiography (TEE) Fontan with spontaneous echo contrast (smoke). b Live 3D TEE Fontan with dense spontaneous echo contrast (sludge). c Live 3D TEE Fontan with intracardiac thrombus
before this reported episode. All the Fontan patients had significant improvement of cardiac function and flow dynamics after restoration of sinus rhythm. Notably, all the patients with Fontan and intracardiac thrombosis were receiving aspirin and warfarin. Three of the patients had a subtherapeutic INR (1.5–1.7) at presentation, and one patient had an INR of 4 at the time of presentation. No embolic events were reported acutely or during 6 months
123
of follow-up evaluation (Table 2). All the patients with intracardiac thrombosis had evaluation for hypercoagulability, with normal laboratory results. Warfarin was adjusted in the aforementioned patients to achieve a target INR of 2–3, and digoxin was started to control the ventricular rate. Follow-up TEE at 3–4 weeks showed complete resolution of thrombus in three patients and stable organized thrombus in two patients. Four of these patients subsequently had successful electric cardioversion and converted to a normal sinus rhythm at the first attempt. One patient had spontaneous conversion to sinus rhythm. The warfarin, aspirin, and antiarrhythmic medications of these patients were continued. One Fontan patient, with intracardiac thrombus and an initial diagnosis of tricuspid atresia and D-TGA, who had undergone an atriopulmonary Fontan with a valved pulmonary artery conduit, presented with recurrent atrial flutter and a severely dilated right atrium due to conduit valve stenosis and severe insufficiency. He had subsequent revision of his Fontan that comprised a takedown of the right atrium to the pulmonary artery conduit, closure of the main pulmonary artery, fenestration, a bidirectional Glenn shunt, an extracardiac Fontan conduit, bilateral Maze cryoablation, and placement of a pacemaker. The second patient, with the diagnosis of DILV and lateral tunnel Fontan, underwent radiofrequency ablation of atrial flutter but continued to have atrial arrhythmia. She eventually had placement of a transvenous atrial pacemaker for sinus node dysfunction and was maintained on betapace (sotalol) with adequate control of her arrhythmias. The third patient had trisuspid atresia, extracardiac Fontan, ablation of atrial flutter, and a recurrence of atrial flutter, and was maintained on dronedarone (Multaq) and digoxin. The fourth patient, with tricuspid atresia and lateral tunnel Fontan, had recurrent episodes of atrial fibrillation and strokes. She was receiving aspirin and warfarin with an INR of 4 and presented with atrial fibrillation and thrombus in the right atrium. This patient was maintained on digoxin, diltiazem, and warfarin. She spontaneously converted to sinus rhythm with no need for cardioversion. One patient had severe congenital mitral valve regurgitation resulting from in utero exposure to maternal antiSSA. She required mitral valve repair followed by mechanical mitral valve replacement and a left atrial Maze procedure at the age of 2 years. This patient continued to have recurrent atrial fibrillation and flutter that required electric cardioversion. She eventually had radiofrequency catheter ablation of AFF at the age of 6 years. At the time of presentation for cardioversion, her INR was 1.8. Spontaneous echo contrast smoke and sludge were common TEE findings in our patients. Of the 27 patients, 15 had smoke and 7 had sludge formation in different intracardiac locations (Fig. 3a, c). All the Fontan patients
Pediatr Cardiol
Fig. 2 a Two-dimensional (2D) transesophageal echocardiography (TEE) thrombus in the right atrium in atriopulmonary Fontan. b Twodimensional TEE thrombus in the right atrium in extracarcardiac
Fontan. c Biplane 2D TEE thrombus in the right atrium remnant in lateral tunnel Fontan. d Two-dimensional TEE thrombus in the left atrial appendage in congenital mitral valve regurgitation
Table 2 Clinical characteristics of patients with Fontan Diagnosis
Type of Fontan
Ventricular function at time of TEE and AFF
Fenestration or shunts
Previous episode of AFF
ICT
Aspirin
Warfarin (INR)
Hypercoagulable testing
Previous thrombembolic events
TA
Atriopulmonary Fontan
Decreased
No
Yes
Yes
Yes
Yes (1.5)
Normal
No
TA
Atriopulmonary Fontan
Decreased
No
Yes
No
Yes
Yes (1.7)
Not performed
No
TA
Lateral tunnel
Decreased
No
No
No
Yes
No
Not performed
No
TA
Lateral tunnel
Decreased
Fenestration with rightto-left shunt
Yes
Yes
Yes
Yes (4.0)
Normal
2 Strokes
TA
Extracardiac
Decreased
No
Yes
Yes
Yes
No
Normal
No
DILV
Lateral tunnel
Decreased
No
Yes
Yes
Yes
Yes (1.5)
Normal
No
DILV
Extracardiac
Decreased
No
Yes
No
Yes
Yes (1.6)
Not performed
No
AFF atrial flutter or fibrillation, TEE transesophageal echocardiogram, ICT intracardiac thrombus, INR international normalized ratio, TA tricuspid atresia, DILV double-inlet left ventricle
had smoke in their Fontan communication, and six of seven patients had dense spontaneous echo contrast (sludge), within either the Fontan or the right atrium remnant (Table 3). For 14 patients, 3D TEE was performed. Live 3D images and full-volume acquisitions were obtained, with subsequent analysis. Both 2D and 3D TEE were able to identify spontaneous echo contrast, sludge, and intracardiac thrombi when present. The use of 3D TEE facilitated the evaluation
of the Fontan conduit and left atrial appendage details. In addition, live 3D TEE images provided more details of the thrombus location and dimensions.
Discussion Atrial flutter is uncommon in normal hearts and occurs with a significantly lower frequency in the general
123
Pediatr Cardiol Fig. 3 a Biplane twodimensional (2D) transesophageal echocardiography (TEE) Fontan with spontaneous echo contrast. b Biplane 2D TEE with color Fontan with spontaneous echo contrast. c Two-dimensional TEE dense spontaneous echo contrast (sludge)
population than atrial fibrillation. A higher incidence of atrial flutter was reported among adult patients hospitalized with neurologic events, depressed left ventricle (LV) function, left atrial enlargement, chronic obstructive lung disease, previous atrial fibrillation, and rheumatic mitral valve disease [17]. Among patients with CHD, however, a higher incidence of atrial flutter has been reported [15]. One study reported that 16 % of the patients who underwent the Fontan operation had atrial flutter after the operation [12]. Atrial fibrillation also can be seen in older patients with repaired or palliated CHD. At our institution, we use TEE before cardioversion for patients with CHD. The use of TEE helps us to determine abnormal flow patterns, thrombosis, and shunts, and provides a detailed anatomic assessment, especially in the case of limited TTE views or poor image quality. In addition, we have been using 3D TEE increasingly to identify thrombi in patients with CHD who weigh more than 20 kg.
123
In our experience, the visualization of thrombus size, shape, and location is enhanced using 3D TEE. In patients with lateral tunnel and extracardiac Fontan, we obtain a midesophagus, long-axis, live 3D image view, which provides visualization of the entire Fontan length as well as views from the superior and inferior Fontan orifices. Because of its large size, the atriopulmonary Fontan requires full-volume 3D imaging because it has the largest sample volume. Visualization of the left atrial appendage with biplane 3D echocardiography and live 3D echocardiography from the upper esophagus basal short-axis view is most effective. We have noticed a high incidence of intracardiac thrombi formation in these patients, and more commonly in patients with Fontan palliation. Most of the intracardiac thrombi were not seen by TTE. We also found a high incidence of abnormal intracardiac flow patterns, including spontaneous echo contrast and sludge formation in this
Pediatr Cardiol Table 3 Summary of abnormal intracardiac flow patterns seen by transesophageal echocardiogram (TEE) during the time of atrial flutter or fibrillation (AFF) Diagnosis
Repair/palliation
Smokea
Sludgeb
ICT
TA
Atriopulmonary Fontan
Fontan
Fontan
Fontan
TA
Atriopulmonary Fontan
Fontan
Fontan
TA
Lateral tunnel Fontan
Fontan
Fontan
TA
Lateral tunnel Fontan
Fontan
Fontan
RA remnant
TA
Extracardiac Fontan
RA, LA
DILV
Lateral tunnel Fontan
Fontan
Fonatn
Fontan
DILV Congenital MVR
Extracardiac Fontan Valvuloplasty and ring
Fontan RA
Fontan
Ebstein’s anomaly
Valvuloplasty
RA
Ebstein’s anomaly
Valvuloplasty
RA
D-TGA
Mustard
PVB
D-TGA
Arterial switch
RA
Aortic valve stenosis
Ross
RA, RV, LA, LV
PA/VSD
Rastelli
LA, LV
Truncus arteriosus
Rastelli
RA, RV, LA, LV
Total
15
RA remnant
LAA
RA 7
5
TA tricuspid atresia, ICT intracardiac thrombus, TA tricuspid atresia, RA right atrium, LA left atrium, DILV double-inlet left ventricle, MVR mitral valve regurgitation, LAA left atrial appendage, D-TGA dextro-transposition of the great arteries, PVB, pulmonary venous baffle, RV right ventricle, LV left ventricle, PA/VSD pulmonary atresia with ventricular septal defect a
Smoke = spontaneous echo contrast
b
Sludge = very dense spontaneous echo contrast
group of patients compared with what is reported in nonCHD patients. Spontaneous echo contrast (SEC) and dense spontaneous echo contrast (sludge) are frequently seen when patients have low blood flow velocity, dilated left atrium, dyskinetic LV, or atrial fibrillation [3, 11, 19, 27, 31, 32]. These abnormal flow patterns form in a hypercoagulable environment and may predispose patients to thromboembolic events. It is hard to detect SEC and sludge by TTE. Currently, no studies have described the incidence of SEC or the risk of early electric cardioversion in these patients in the presence of CHD. In our study, the patients who had smoke and sludge formation but no thrombus were successfully cardioverted after adequate anticoagulation. Their anticoagulation also was continued after cardioversion. No thromboembolic events were reported immediately or during 6 months of follow-up evaluation. A previous study by Horenstein et al. [18] questioned the need for routine TEE before electric cardioversion of AFF in patients with CHD. Their study included a total of 35 patients who presented with 110 episodes of AFF. Fontan palliation was performed for 18 of these patients, and TTE was performed for all the patients. However, TEE was performed only if TTE showed suspicion for
intracardiac thrombus. No thromboembolic events were reported immediately or during follow-up evaluation. The study suggested that TTE can be used for thrombus screening before cardioversion in these patients. Patients who had Fontan palliation are at increased risk for intracardiac thrombus formation due to venous stasis, low flow velocity, prosthetic material, depressed ventricular function, and an imbalance of coagulation proteins related to hepatic dysfunction and enteric losses of proteins. [7, 20, 26]. Most of these factors are related to the inherent nature of the Fontan circulation. Between 17 and 44 % of patients with Fontan experience the development of intracardiac thrombus [8, 29]. Intracardiac thrombus formation is sometimes asymptomatic and may escape detection unless periodical evaluation of the Fontan is performed. The incidence of thrombus formation after different types of Fontan operation has been reported in a number of studies. Coon et al. [5] reported a total of 592 patients who had TTE. Among these patients, 8 % had intracardiac thrombus. Arrhythmia was common at the time of thrombus detection. Stroke was diagnosed in 15 % of these patients, 50 % of whom had AFF. No significant difference in freedom from thrombus was found up to 10 years after Fontan operation between patients based on the type of
123
Pediatr Cardiol
Fontan operation or the presence of fenestration. In the same study, thrombi were most commonly detected in the systemic venous atrium and the pulmonary venous atrium. Balling et al. [2] evaluated the occurrence of intracardiac thrombi in 52 patients with different types of Fontan operation. None of the patients had acute clinical signs of a thromboembolic event, and 33 % had intracardiac thrombus, all in the right atrium. Whereas TTE failed to identify the thrombus in 16 patients, all were identified using TEE. The authors concluded that underlying cardiac disease, age at the time of the Fontan operation, type of Fontan, sex, arrhythmia, and hemodynamic findings were not predisposing factors for intracardiac thrombus formation. Because TEE is not performed routinely for asymptomatic patients with CHD, it is difficult to determine the real incidence of intracardiac thrombosis in this population. The hypercoagulable environment after cardiac repair or palliation likely predisposes these patients to intracardiac thrombosis and possible systemic or pulmonary embolization, depending on the anatomy and the presence of shunts. In addition, some embolic events can be subclinical.
Study Limitations This study was limited by the small number of patients and the retrospective design. A larger multicenter study is warranted to determine the incidence of intracardiac thrombosis in repaired or palliated CHD, to identify the risk factors for thrombosis and embolization, and to clarify the benefit of antithrombotic medications in this group of patients.
Conclusions Patients with CHD and AFF have a particularly high incidence of intracardiac thrombi among those with Fontan, which may be difficult to detect by TTE. Thorough examination of the Fontan and related structures with TEE is indicated before electric cardioversion of AFF. The incidence of intracardiac thrombus among CHD patients is double that reported for non-CHD patients.
References 1. Ansari A, Maron BJ (1997) Spontaneous echo contrast and thromboembolism. Hosp Pract 32:109–111 2. Balling G, Vogt M, Kaemmerer H et al (2000) Intracardiac thrombus formation after the Fontan operation. J Thorac Cardiovasc Surg 119(4 Pt 1):745–752
123
3. Bernhardt P, Schmidt H, Hammerstingl C, Luderitz B, Omran H (2005) Patients with atrial fibrillation and dense spontaneous echo contrast at high risk a prospective and serial follow-up over 12 months with transesophageal echocardiography and cerebral magnetic resonance imaging. JACC 45:1807–1812 4. Brembilla-Perrot B (2000) Risk of increasing incidence of atrial flutter, the most frequent arrhythmia, after repaired congenital heart disease. Int J Cardiol 75:138–139 5. Coon PD, Rychik J, Novello RT, Ro PS, Gaynor JW, Spray TL (2001) Thrombus formation after the Fontan operation. Ann Thorac Surg 71:1990–1994 6. de Bruijn SF, Agema WR, Lammers GJ, van der Wall EE, Wolterbeek R, Holman ER, Bollen EL, Bax JJ (2006) Transesophageal echocardiography is superior to transthoracic echocardiography in management of patients of any age with transient ischemic attack or stroke. Stroke 37:2531–2534 Epub Aug 2006 7. Driscoll DJ (2007) Long-term results of the Fontan operation. Pediatr Cardiol 28:438–442 8. Earing MG, Cetta F, Driscoll DJ, Mair DD, Hodge DO, Dearani JA, Puga FJ, Danielson GK, O’Leary PW (2005) Long-term results of the Fontan operation for double-inlet left ventricle. Am J Cardiol 96:291–298 9. Elhendy A, Gentile F, Khandheria BK, Gersh BJ, Bailey KR, Montgomery SC, Seward JB, Tajik AJ (2001) Thromboembolic complications after electrical cardioversion in patients with atrial flutter. Am J Med 111:433 10. Fatkin D, Herbert E, Feneley MP (1994) Hematologic correlates of spontaneous echo contrast in patients with atrial fibrillation and implications for thromboembolic risk. Am J Cardiol 73:672–676 11. Fatkin D, Kelly RP, Feneley MP (1994) Relations between left atrial appendage blood flow velocity, spontaneous echocardiographic contrast, and thromboembolic risk in vivo. JACC 23:961–969 12. Fishberger SB, Wernovsky G, Gentles TL, Gauvreau K, Burnett J, Mayer JE Jr, Walsh EP (1997) Factors that influence the development of atrial flutter after the Fontan operation. J Thorac Cardiovasc Surg 113:80–86 13. Garson A Jr, Bink-Boelkens M, Hesslein PS, Hordof AJ, Keane JF, Neches WH, Porter CJ (1985) Atrial flutter in the young: a collaborative study of 380 cases. J Am Coll Cardiol 6:871– 878 14. Garson A Jr, Bink-Boelkens M, Hesslein PS, Hordof AJ, Keane JF, Neches WH, Porter C-BJ (1985) Atrial flutter in the young: a collaborative study of 380 cases. J Am Coll Cardiol 6:871–878. doi:10.1016/S0735-1097(85)80497-6 15. Garson AJR, Bink-Boelkens M, Hesslein PS, Hordof AJ, Keane JF, Neches WH, Porter CJ (1985) Atrial flutter in the young: a collaborative study of 380 cases. J Am Coll Cardiol 6:871–878 16. Ghali WA, Wasil BI, Brant R, Exner DV, Cornuz J (2005) Atrial flutter and the risk of thromboembolism: a systematic review and meta-analysis. Am J Med 118:101–107 17. Granada J, Uribe W, Chyou PH, Maassen K, Vierkant R, Smith PN, Hayes J, Eaker E, Vidaillet H (2000) Incidence and predictors of atrial flutter in the general population. J Am Coll Cardiol 36:2242 18. Horenstein MS, Karpawich PP, Epstein ML, Singh TP (2004) Transthoracic echocardiography for precardioversion screening during atrial flutter/fibrillation in young patients. Clin Cardiol 27:413–416 19. Ito T, Suwa M, Nakamura T, Miyazaki S, Kpbashi A et al (2001) Quantification of left atrial appendage spontaneous echo contrast in patients with chronic nonalvular atrial fibrillation. J Cardiol 37:325–333 20. Jahangiri M, Shore D, Kakkar V, Lincoln C, Shinebourne E (1997) Coagulation factor abnormalities after the Fontan
Pediatr Cardiol
21.
22.
23.
24.
25.
26.
procedure and its modifications. J Thorac Cardiovasc Surg 113:989–992 discussion 992–993 Kanter RJ, Garson A Jr (1997) Atrial arrhythmias during chronic follow-up of surgery for complex congenital heart disease. Pacing Clin Electrophysiol 20(2 Pt 2):502–511 Li Wei, Somerville J (2000) Atrial flutter in grown-up congenital heart (GUCH) patients clinical characteristics of affected population. Int J Cardiol 75:129–137 Manning WJ (1997) Role of transesophageal echocardiography in the management of thromboembolic stroke. Am J Cardiol 80:19D–28D discussion 35D–39D Mart CR (2012) Three-dimensional echocardiographic evaluation of the Fontan conduit for thrombus. Echocardiography 29:363–368. doi:10.1111/j.1540-8175.2011.01579.x Monagle P, Cochrane A, Roberts R, Manlhiot C, Weintraub R, Szechtman B, Hughes M, Andrew M, McCrindle BW, Fontan Anticoagulation Study Group (2011) A multicenter, randomized trial comparing heparin/warfarin and acetylsalicylic acid as primary thromboprophylaxis for 2 years after the Fontan procedure in children. J Am Coll Cardiol 58:645–651. doi:10.1016/j.jacc. 2011.01.061 Ohuchi H, Yasuda K, Miyazaki A, Kitano M, Sakaguchi H, Yazaki S, Tsuda E, Yamada O (2013) Haemodynamic characteristics before and after the onset of protein losing enteropathy in patients after the Fontan operation. Eur J Cardiothorac Surg 43:e49–e57. doi:10.1093/ejcts/ezs714
27. Patel SV, Flaker G (2008) Is early cardioversion for atrial fibrillation safe in patients with spontaneous echocardiographic contrast? Clin Cardiol 31:148–152 28. Potter BJ, Leong-Sit P, Fernandes SM, Feifer A, Mayer JE Jr, Triedman JK, Walsh EP, Landzberg MJ, Khairy P (2013) Effect of aspirin and warfarin therapy on thromboembolic events in patients with univentricular hearts andFontan palliation. Int J Cardiol 168:3940–3943. doi:10.1016/j.ijcard.2013.06.058 29. Shirai LK, Rosenthal DN, Reitz BA, Robbins RC, Dubin AM (1998) Arrhythmias and thromboembolic complications after the extracardiac Fontan operation. J Thorac Cardiovasc Surg 115:499–505 30. Tucker KJ, Wilson C (1993) A comparison of transoesophageal atrial pacing and direct current cardioversion for the termination of atrial flutter: a prospective, randomised clinical trial. Br Heart J 69:530–535 31. Turchetti V, Bellini MA, Ricci D, Lapi A, Donati G et al (2001) Spontaneous echo-contrast as an in vivo indicator of rheological imbalance in dilatative cardiomyopathy. Clin Hemorheol Microcirc 25:119–125 32. Zotz RJ, Muller M, Genth-Zotz S, Darius H (2001) Spontaneous echo contrast caused by platelet and leukocyte aggregates? Stroke 32:1127–1133
123
ORIGINAL ARTICLE
Transesophageal Echocardiography of Intracardiac Thrombus in Congenital Heart Disease and Atrial Flutter: The Importance of Thorough Examination of the Fontan Nida Yousef • Molly Philips • Ira Shetty Vivian Wei Cui • Frank Zimmerman • David A. Roberson
•
Received: 27 November 2013 / Accepted: 25 March 2014 Ó Springer Science+Business Media New York 2014
Abstract Transesophageal echocardiography (TEE) is used in atrial flutter or fibrillation (AFF) before electric cardioversion to detect intracardiac thrombi. Previous studies have described the use of TEE to diagnose intracardiac thrombi in the left atrium and left atrial appendage, which has an incidence of 8 % among patients without congenital heart disease (CHD). In their practice the authors have noted a significant incidence of intracardiac thrombi in other structures of patients with CHD and AFF. This study aimed to determine the incidence and location of intracardiac thrombi using TEE in patients with CHD requiring electric cardioversion of AFF and to compare the use of TEE and transthoracic echo (TTE) to detect intracardiac thrombus in this population. A retrospective chart review of TEE and TTE findings for all patients with CHD who had electric cardioversion of AFF at our institution from 2005 to 2013 was conducted. The diagnosis, presence, and location of intracardiac thrombus were determined. The TEE and TTE results were compared. The study identified 27 patients with CHD who met the study entry criteria at our institution between 2005 and 2013. Seven of these patients had a single ventricle with Fontan palliation. All the patients presented with AFF and had TEE before electric cardioversion. No patients were excluded from the study. The patients ranged in age from 2 to 72 years (median, 21 years) and weighed 17–100 kg (median, 65 kg). The duration of AFF before TEE and attempted cardioversion ranged from 1 day to 3 weeks (median, 3.5 days). Intracardiac thrombus was
N. Yousef (&) M. Philips I. Shetty V. W. Cui F. Zimmerman D. A. Roberson Advocate Children’s Hospital Heart Institute, 4440 West 95th Street, Oak Lawn, IL 60453, USA e-mail: [email protected]; [email protected]
present in 18 % (5/27) of the patients and in 57 % (4/7) of the Fontan patients with AFF. No embolic events were reported acutely or during a 6-month follow-up period. Among patients with CHD who present with AFF, a particularly high incidence of intracardiac thrombi is present in the Fontan patients that may be difficult to detect by TTE. Thorough TEE examination of the Fontan and related structures is indicated before electric cardioversion of AFF. The incidence of intracardiac thrombus in CHD patients is more than double that reported in non-CHD patients. Keywords Atrial flutter Atrial fibrillation Congenital heart disease Fontan Intracardiac thrombus
Introduction Atrial flutter is the most common arrhythmia in patients with repaired or palliated congenital heart disease (CHD) [13]. It is most commonly seen as a postoperative complication of the Fontan procedure for single-ventricle atrial septal defect (ASD) repairs, the Mustard procedure for dextro-transposition of the great arteries (D-TGA), and tetralogy of Fallot (TOF) [22]. Atrial fibrillation also is seen in older patients with repaired or palliated CHD. Atrial flutter or atrial fibrillation (AFF) has deleterious effects on cardiac output and promotes the formation of intracardiac thrombus, with an increased risk for thromboembolic events [14, 21]. Patients with CHD are less likely to tolerate hemodynamic changes related to prolonged tachyarrhythmia [4]. Electric cardioversion, the treatment of choice for terminating AFF in patients with CHD, has a high success rate [30]. Transesophageal echocardiography (TEE) is routinely performed for adult patients undergoing electric cardioversion
123
Pediatr Cardiol
for AFF. The use of TEE allows visualization of left atrial appendage details and thrombi not easily detectable by transthoracic echocardiography (TTE) [6, 16, 23]. Thromboembolism most often occurs after the return of synchronous atrial contraction and has been attributed to left atrial thrombus present at the time of cardioversion. Embolic events also have been reported after cardioversion in patients who had no thrombi shown on TEE before cardioversion. The incidence of intraatrial thrombus in adult patients with AFF and no underlying CHD ranges between 1 and 8 % depending on the duration of the arrhythmia, the history of embolic events, and the history of atrial fibrillation [9]. In the general population, TEE is thought to be superior to TTE in identifying cardioembolic sources in patients with transient ischemic attacks and stroke [6, 16, 23]. In CHD, TEE helps to determine abnormal flow patterns and shunts and to provide a detailed anatomic assessment, especially when TTE views are limited or image quality is poor. In addition, three-dimensional (3D) echocardiography has been increasingly used to rule out thrombi in the Fontan conduit and may further enhance the ability to diagnose intracardiac thrombi in patients with CHD [24]. This study aimed to determine the incidence and location of intracardiac thrombi by TEE in patients with CHD requiring electric cardioversion of AFF and to compare the use of TEE and TTE in detecting intracardiac thrombi in this population.
Materials and Methods All patients with CHD presenting to our institution with AFF and stable hemodynamics are admitted to the intensive care unit. We start heparin electively if the patient is not receiving warfarin or presents with a subtherapeutic international normalized ratio (INR). Our target INR before cardioversion is 2–3. After intubation and sedation, TEE is performed, followed by electric cardioversion if no thrombus is detected. We also use 3D TEE to visualize details of cardiac anatomy and cardiac repair. After restoration of normal sinus rhythm, we start antiarrhythmic medications. For those with thrombus detected by TEE, warfarin is started, with a target INR of 2–3 for 3–4 weeks, after which the patients have a follow-up TEE and electric cardioversion. These patients also are started on long-term anticoagulation and antiplatelet agents to avoid future thromboembolic events [25, 28]. We performed a retrospective review of the TEE and TTE findings and medical records for the last 27 consecutive patients with CHD who presented at our institution between 2005 and 2013 and required electric cardioversion of AFF. The diagnosis, presence, and location of
123
intracardiac thrombi were determined. The TEE and TTE results were compared (Table 1). Spontaneous echo contrast (smoke) was defined as a swirling pattern of increased echogenicity caused by ultrasonic backscatter from red blood cell aggregates [10]. Sludge was defined as very dense spontaneous echo contrast [1] (Fig. 1). The findings were summarized in tables and analyzed using descriptive statistics including means and medians.
Results We identified 27 CHD patients presenting with AFF who had undergone TEE and electric cardioversion. Five of these patients had TEE repeated in 3–4 weeks for assessment of the previously identified intracardiac thrombus before cardioversion. Of the 27 patients, 24 had atrial flutter and 3 had atrial fibrillation. This included all of the last 27 patients presenting to our institution between 2005 and 2013 who had CHD with AFF and had undergone electric cardioversion. No patients were excluded. The patients ranged in age from 2 to 72 years (median, 21 years) and weighed 17–100 kg (median, 65 kg). The duration of AFF before TEE and attempted cardioversion ranged from 1 day to 3 weeks (median, 3.5 days). The duration of AFF was defined as the time from the onset of symptoms attributable to AFF to the time of TEE. Intracardiac thrombus was present in 18 % (5/27) of all the patients and in 57 % (4/7) of the Fontan patients with AFF (Table 1). The initial diagnosis for the four Fontan patients with intracardiac thrombi was tricuspid atresia for three patients and double-inlet left ventricle (DILV) for one patient. The thrombus was in the atriopulmonary Fontan of one patient (Fig. 2a) and in the lateral tunnel Fontan of one patient. Two patients had a thrombus in the right atrial remnant, which was connected to the pulmonary venous atrium in an extracardiac Fontan in the one patient and to the lateral tunnel Fontan in the other patient (Fig. 2b, c). None of the four Fontan-related thrombi were seen on TTE. A patient with congenital mitral valve regurgitation had a thrombus in the left atrial appendage, which was also seen on TTE (Fig. 2d). The patients with Fontan who had intracardiac thrombi showed at least one previous episode of AFF, sluggish flow within the Fontan, and moderately to severely depressed ventricular systolic function on TEE at the time of presentation with AFF. The patient who had intracardiac thrombus within the atriopulmonary Fontan showed significant dilation of the atrium. None of these patients had a history of intracardiac thrombosis. One patient had experienced stroke associated with atrial fibrillation 1 year
Mustard Rastelli
Two-patch repair
L-TGA
AVC
Atrial flutter
Atrial flutter
Atrial flutter
Atrial fibrillation
Atrial flutter
Atrial flutter
Atrial flutter
Atrial flutter
Atrial flutter
Atrial fibrillation
Atrial flutter
Atrial flutter
Atrial flutter
Atrial flutter
Atrial flutter
Atrial flutter
Atrial fibrillation
Atrial flutter
Atrial flutter
Type of arrhythmia
27
1
1
1
2
1
1
2
1
2
2
2
3
1
1
1
1
1
1
2
No. of patients
1 Day
4 Days
3 Weeks
1 Week
1 Week
1 Week
1 Week
4 Days
2 Days
1 Day
2 Days 3 Days
3 Days
2 Days
1 Day
1 Day
1 Day
1 Day
3 Weeks
1 Week
2 Weeks
3 Days
1 Day
1 Day
7 Days
5 Days
Average duration of AFF
2
21
17
63, 72
9
35
16, 17
10
26, 16
39, 55
16, 18
22, 17, 24
5
36
21
39
39
17
22, 24
Respective ages (years)
17
83
91
88, 90
42
100
46, 80
29
81, 54
81, 65
55, 60
55, 42, 45
17
55
65
65
71
58
73, 80
Respective weights (kg)
5/27
1
1
1
1
1
ICT seen on TEE
LAA
Fontan
RA remnant
RA remnant
Fontan
ICT location
1/5
Yes
No
No
No
No
Seen on TTE
AFF atrial flutter or fibrillation, ICT intracardiac thrombus, TEE transesophageal echocardiogram, TTE transthoracic echocardiogram, RA right atrium, DILV double-inlet left ventricle, MVR mitral valve regurgitation, LAA left atrial appendage, TOF teratology of Fallot, D-TGA dextro-transposition of the great arteries, L-TGA levo-transposition of the great arteries, AVC atrioventricular canal, DORV double-outlet right ventricle, ASD atrial septal defect, PA/VSD pulmonary atresia with ventricular septal defect, TAPVC total anomalous pulmonary venous connection
Total
Repair of total veins
Arterial switch
D-TGA
Rastelli
Mustard
D-TGA
TAPVC
Valvuloplasty
Ebstein’s anomaly
Truncus arteriosus
Transannular patch
TOF
Rastelli
Valvuloplasty and ring
Congenital MVR
PA/VSD
Extracardiac Fontan
DILV
Surgical closure
Lateral tunnel Fontan
DILV
ASD
Extracardiac Fontan
Tricuspid atresia
Ross procedure
Lateral tunnel Fontan
Tricuspid atersia
Arterial switch, VSD patch
Lateral tunnel Fontan
Tricuspid atresia
DORV
Atriopulmonary Fontan
Tricuspid atresia
Aortic valve stenosis
Repair/palliation
Diagnosis
Table 1 Clinical characteristics and echocardiography findings in the patient study population (n = 27)
Pediatr Cardiol
123
Pediatr Cardiol
Fig. 1 a Live three-dimensional (3D) transesophageal echocardiography (TEE) Fontan with spontaneous echo contrast (smoke). b Live 3D TEE Fontan with dense spontaneous echo contrast (sludge). c Live 3D TEE Fontan with intracardiac thrombus
before this reported episode. All the Fontan patients had significant improvement of cardiac function and flow dynamics after restoration of sinus rhythm. Notably, all the patients with Fontan and intracardiac thrombosis were receiving aspirin and warfarin. Three of the patients had a subtherapeutic INR (1.5–1.7) at presentation, and one patient had an INR of 4 at the time of presentation. No embolic events were reported acutely or during 6 months
123
of follow-up evaluation (Table 2). All the patients with intracardiac thrombosis had evaluation for hypercoagulability, with normal laboratory results. Warfarin was adjusted in the aforementioned patients to achieve a target INR of 2–3, and digoxin was started to control the ventricular rate. Follow-up TEE at 3–4 weeks showed complete resolution of thrombus in three patients and stable organized thrombus in two patients. Four of these patients subsequently had successful electric cardioversion and converted to a normal sinus rhythm at the first attempt. One patient had spontaneous conversion to sinus rhythm. The warfarin, aspirin, and antiarrhythmic medications of these patients were continued. One Fontan patient, with intracardiac thrombus and an initial diagnosis of tricuspid atresia and D-TGA, who had undergone an atriopulmonary Fontan with a valved pulmonary artery conduit, presented with recurrent atrial flutter and a severely dilated right atrium due to conduit valve stenosis and severe insufficiency. He had subsequent revision of his Fontan that comprised a takedown of the right atrium to the pulmonary artery conduit, closure of the main pulmonary artery, fenestration, a bidirectional Glenn shunt, an extracardiac Fontan conduit, bilateral Maze cryoablation, and placement of a pacemaker. The second patient, with the diagnosis of DILV and lateral tunnel Fontan, underwent radiofrequency ablation of atrial flutter but continued to have atrial arrhythmia. She eventually had placement of a transvenous atrial pacemaker for sinus node dysfunction and was maintained on betapace (sotalol) with adequate control of her arrhythmias. The third patient had trisuspid atresia, extracardiac Fontan, ablation of atrial flutter, and a recurrence of atrial flutter, and was maintained on dronedarone (Multaq) and digoxin. The fourth patient, with tricuspid atresia and lateral tunnel Fontan, had recurrent episodes of atrial fibrillation and strokes. She was receiving aspirin and warfarin with an INR of 4 and presented with atrial fibrillation and thrombus in the right atrium. This patient was maintained on digoxin, diltiazem, and warfarin. She spontaneously converted to sinus rhythm with no need for cardioversion. One patient had severe congenital mitral valve regurgitation resulting from in utero exposure to maternal antiSSA. She required mitral valve repair followed by mechanical mitral valve replacement and a left atrial Maze procedure at the age of 2 years. This patient continued to have recurrent atrial fibrillation and flutter that required electric cardioversion. She eventually had radiofrequency catheter ablation of AFF at the age of 6 years. At the time of presentation for cardioversion, her INR was 1.8. Spontaneous echo contrast smoke and sludge were common TEE findings in our patients. Of the 27 patients, 15 had smoke and 7 had sludge formation in different intracardiac locations (Fig. 3a, c). All the Fontan patients
Pediatr Cardiol
Fig. 2 a Two-dimensional (2D) transesophageal echocardiography (TEE) thrombus in the right atrium in atriopulmonary Fontan. b Twodimensional TEE thrombus in the right atrium in extracarcardiac
Fontan. c Biplane 2D TEE thrombus in the right atrium remnant in lateral tunnel Fontan. d Two-dimensional TEE thrombus in the left atrial appendage in congenital mitral valve regurgitation
Table 2 Clinical characteristics of patients with Fontan Diagnosis
Type of Fontan
Ventricular function at time of TEE and AFF
Fenestration or shunts
Previous episode of AFF
ICT
Aspirin
Warfarin (INR)
Hypercoagulable testing
Previous thrombembolic events
TA
Atriopulmonary Fontan
Decreased
No
Yes
Yes
Yes
Yes (1.5)
Normal
No
TA
Atriopulmonary Fontan
Decreased
No
Yes
No
Yes
Yes (1.7)
Not performed
No
TA
Lateral tunnel
Decreased
No
No
No
Yes
No
Not performed
No
TA
Lateral tunnel
Decreased
Fenestration with rightto-left shunt
Yes
Yes
Yes
Yes (4.0)
Normal
2 Strokes
TA
Extracardiac
Decreased
No
Yes
Yes
Yes
No
Normal
No
DILV
Lateral tunnel
Decreased
No
Yes
Yes
Yes
Yes (1.5)
Normal
No
DILV
Extracardiac
Decreased
No
Yes
No
Yes
Yes (1.6)
Not performed
No
AFF atrial flutter or fibrillation, TEE transesophageal echocardiogram, ICT intracardiac thrombus, INR international normalized ratio, TA tricuspid atresia, DILV double-inlet left ventricle
had smoke in their Fontan communication, and six of seven patients had dense spontaneous echo contrast (sludge), within either the Fontan or the right atrium remnant (Table 3). For 14 patients, 3D TEE was performed. Live 3D images and full-volume acquisitions were obtained, with subsequent analysis. Both 2D and 3D TEE were able to identify spontaneous echo contrast, sludge, and intracardiac thrombi when present. The use of 3D TEE facilitated the evaluation
of the Fontan conduit and left atrial appendage details. In addition, live 3D TEE images provided more details of the thrombus location and dimensions.
Discussion Atrial flutter is uncommon in normal hearts and occurs with a significantly lower frequency in the general
123
Pediatr Cardiol Fig. 3 a Biplane twodimensional (2D) transesophageal echocardiography (TEE) Fontan with spontaneous echo contrast. b Biplane 2D TEE with color Fontan with spontaneous echo contrast. c Two-dimensional TEE dense spontaneous echo contrast (sludge)
population than atrial fibrillation. A higher incidence of atrial flutter was reported among adult patients hospitalized with neurologic events, depressed left ventricle (LV) function, left atrial enlargement, chronic obstructive lung disease, previous atrial fibrillation, and rheumatic mitral valve disease [17]. Among patients with CHD, however, a higher incidence of atrial flutter has been reported [15]. One study reported that 16 % of the patients who underwent the Fontan operation had atrial flutter after the operation [12]. Atrial fibrillation also can be seen in older patients with repaired or palliated CHD. At our institution, we use TEE before cardioversion for patients with CHD. The use of TEE helps us to determine abnormal flow patterns, thrombosis, and shunts, and provides a detailed anatomic assessment, especially in the case of limited TTE views or poor image quality. In addition, we have been using 3D TEE increasingly to identify thrombi in patients with CHD who weigh more than 20 kg.
123
In our experience, the visualization of thrombus size, shape, and location is enhanced using 3D TEE. In patients with lateral tunnel and extracardiac Fontan, we obtain a midesophagus, long-axis, live 3D image view, which provides visualization of the entire Fontan length as well as views from the superior and inferior Fontan orifices. Because of its large size, the atriopulmonary Fontan requires full-volume 3D imaging because it has the largest sample volume. Visualization of the left atrial appendage with biplane 3D echocardiography and live 3D echocardiography from the upper esophagus basal short-axis view is most effective. We have noticed a high incidence of intracardiac thrombi formation in these patients, and more commonly in patients with Fontan palliation. Most of the intracardiac thrombi were not seen by TTE. We also found a high incidence of abnormal intracardiac flow patterns, including spontaneous echo contrast and sludge formation in this
Pediatr Cardiol Table 3 Summary of abnormal intracardiac flow patterns seen by transesophageal echocardiogram (TEE) during the time of atrial flutter or fibrillation (AFF) Diagnosis
Repair/palliation
Smokea
Sludgeb
ICT
TA
Atriopulmonary Fontan
Fontan
Fontan
Fontan
TA
Atriopulmonary Fontan
Fontan
Fontan
TA
Lateral tunnel Fontan
Fontan
Fontan
TA
Lateral tunnel Fontan
Fontan
Fontan
RA remnant
TA
Extracardiac Fontan
RA, LA
DILV
Lateral tunnel Fontan
Fontan
Fonatn
Fontan
DILV Congenital MVR
Extracardiac Fontan Valvuloplasty and ring
Fontan RA
Fontan
Ebstein’s anomaly
Valvuloplasty
RA
Ebstein’s anomaly
Valvuloplasty
RA
D-TGA
Mustard
PVB
D-TGA
Arterial switch
RA
Aortic valve stenosis
Ross
RA, RV, LA, LV
PA/VSD
Rastelli
LA, LV
Truncus arteriosus
Rastelli
RA, RV, LA, LV
Total
15
RA remnant
LAA
RA 7
5
TA tricuspid atresia, ICT intracardiac thrombus, TA tricuspid atresia, RA right atrium, LA left atrium, DILV double-inlet left ventricle, MVR mitral valve regurgitation, LAA left atrial appendage, D-TGA dextro-transposition of the great arteries, PVB, pulmonary venous baffle, RV right ventricle, LV left ventricle, PA/VSD pulmonary atresia with ventricular septal defect a
Smoke = spontaneous echo contrast
b
Sludge = very dense spontaneous echo contrast
group of patients compared with what is reported in nonCHD patients. Spontaneous echo contrast (SEC) and dense spontaneous echo contrast (sludge) are frequently seen when patients have low blood flow velocity, dilated left atrium, dyskinetic LV, or atrial fibrillation [3, 11, 19, 27, 31, 32]. These abnormal flow patterns form in a hypercoagulable environment and may predispose patients to thromboembolic events. It is hard to detect SEC and sludge by TTE. Currently, no studies have described the incidence of SEC or the risk of early electric cardioversion in these patients in the presence of CHD. In our study, the patients who had smoke and sludge formation but no thrombus were successfully cardioverted after adequate anticoagulation. Their anticoagulation also was continued after cardioversion. No thromboembolic events were reported immediately or during 6 months of follow-up evaluation. A previous study by Horenstein et al. [18] questioned the need for routine TEE before electric cardioversion of AFF in patients with CHD. Their study included a total of 35 patients who presented with 110 episodes of AFF. Fontan palliation was performed for 18 of these patients, and TTE was performed for all the patients. However, TEE was performed only if TTE showed suspicion for
intracardiac thrombus. No thromboembolic events were reported immediately or during follow-up evaluation. The study suggested that TTE can be used for thrombus screening before cardioversion in these patients. Patients who had Fontan palliation are at increased risk for intracardiac thrombus formation due to venous stasis, low flow velocity, prosthetic material, depressed ventricular function, and an imbalance of coagulation proteins related to hepatic dysfunction and enteric losses of proteins. [7, 20, 26]. Most of these factors are related to the inherent nature of the Fontan circulation. Between 17 and 44 % of patients with Fontan experience the development of intracardiac thrombus [8, 29]. Intracardiac thrombus formation is sometimes asymptomatic and may escape detection unless periodical evaluation of the Fontan is performed. The incidence of thrombus formation after different types of Fontan operation has been reported in a number of studies. Coon et al. [5] reported a total of 592 patients who had TTE. Among these patients, 8 % had intracardiac thrombus. Arrhythmia was common at the time of thrombus detection. Stroke was diagnosed in 15 % of these patients, 50 % of whom had AFF. No significant difference in freedom from thrombus was found up to 10 years after Fontan operation between patients based on the type of
123
Pediatr Cardiol
Fontan operation or the presence of fenestration. In the same study, thrombi were most commonly detected in the systemic venous atrium and the pulmonary venous atrium. Balling et al. [2] evaluated the occurrence of intracardiac thrombi in 52 patients with different types of Fontan operation. None of the patients had acute clinical signs of a thromboembolic event, and 33 % had intracardiac thrombus, all in the right atrium. Whereas TTE failed to identify the thrombus in 16 patients, all were identified using TEE. The authors concluded that underlying cardiac disease, age at the time of the Fontan operation, type of Fontan, sex, arrhythmia, and hemodynamic findings were not predisposing factors for intracardiac thrombus formation. Because TEE is not performed routinely for asymptomatic patients with CHD, it is difficult to determine the real incidence of intracardiac thrombosis in this population. The hypercoagulable environment after cardiac repair or palliation likely predisposes these patients to intracardiac thrombosis and possible systemic or pulmonary embolization, depending on the anatomy and the presence of shunts. In addition, some embolic events can be subclinical.
Study Limitations This study was limited by the small number of patients and the retrospective design. A larger multicenter study is warranted to determine the incidence of intracardiac thrombosis in repaired or palliated CHD, to identify the risk factors for thrombosis and embolization, and to clarify the benefit of antithrombotic medications in this group of patients.
Conclusions Patients with CHD and AFF have a particularly high incidence of intracardiac thrombi among those with Fontan, which may be difficult to detect by TTE. Thorough examination of the Fontan and related structures with TEE is indicated before electric cardioversion of AFF. The incidence of intracardiac thrombus among CHD patients is double that reported for non-CHD patients.
References 1. Ansari A, Maron BJ (1997) Spontaneous echo contrast and thromboembolism. Hosp Pract 32:109–111 2. Balling G, Vogt M, Kaemmerer H et al (2000) Intracardiac thrombus formation after the Fontan operation. J Thorac Cardiovasc Surg 119(4 Pt 1):745–752
123
3. Bernhardt P, Schmidt H, Hammerstingl C, Luderitz B, Omran H (2005) Patients with atrial fibrillation and dense spontaneous echo contrast at high risk a prospective and serial follow-up over 12 months with transesophageal echocardiography and cerebral magnetic resonance imaging. JACC 45:1807–1812 4. Brembilla-Perrot B (2000) Risk of increasing incidence of atrial flutter, the most frequent arrhythmia, after repaired congenital heart disease. Int J Cardiol 75:138–139 5. Coon PD, Rychik J, Novello RT, Ro PS, Gaynor JW, Spray TL (2001) Thrombus formation after the Fontan operation. Ann Thorac Surg 71:1990–1994 6. de Bruijn SF, Agema WR, Lammers GJ, van der Wall EE, Wolterbeek R, Holman ER, Bollen EL, Bax JJ (2006) Transesophageal echocardiography is superior to transthoracic echocardiography in management of patients of any age with transient ischemic attack or stroke. Stroke 37:2531–2534 Epub Aug 2006 7. Driscoll DJ (2007) Long-term results of the Fontan operation. Pediatr Cardiol 28:438–442 8. Earing MG, Cetta F, Driscoll DJ, Mair DD, Hodge DO, Dearani JA, Puga FJ, Danielson GK, O’Leary PW (2005) Long-term results of the Fontan operation for double-inlet left ventricle. Am J Cardiol 96:291–298 9. Elhendy A, Gentile F, Khandheria BK, Gersh BJ, Bailey KR, Montgomery SC, Seward JB, Tajik AJ (2001) Thromboembolic complications after electrical cardioversion in patients with atrial flutter. Am J Med 111:433 10. Fatkin D, Herbert E, Feneley MP (1994) Hematologic correlates of spontaneous echo contrast in patients with atrial fibrillation and implications for thromboembolic risk. Am J Cardiol 73:672–676 11. Fatkin D, Kelly RP, Feneley MP (1994) Relations between left atrial appendage blood flow velocity, spontaneous echocardiographic contrast, and thromboembolic risk in vivo. JACC 23:961–969 12. Fishberger SB, Wernovsky G, Gentles TL, Gauvreau K, Burnett J, Mayer JE Jr, Walsh EP (1997) Factors that influence the development of atrial flutter after the Fontan operation. J Thorac Cardiovasc Surg 113:80–86 13. Garson A Jr, Bink-Boelkens M, Hesslein PS, Hordof AJ, Keane JF, Neches WH, Porter CJ (1985) Atrial flutter in the young: a collaborative study of 380 cases. J Am Coll Cardiol 6:871– 878 14. Garson A Jr, Bink-Boelkens M, Hesslein PS, Hordof AJ, Keane JF, Neches WH, Porter C-BJ (1985) Atrial flutter in the young: a collaborative study of 380 cases. J Am Coll Cardiol 6:871–878. doi:10.1016/S0735-1097(85)80497-6 15. Garson AJR, Bink-Boelkens M, Hesslein PS, Hordof AJ, Keane JF, Neches WH, Porter CJ (1985) Atrial flutter in the young: a collaborative study of 380 cases. J Am Coll Cardiol 6:871–878 16. Ghali WA, Wasil BI, Brant R, Exner DV, Cornuz J (2005) Atrial flutter and the risk of thromboembolism: a systematic review and meta-analysis. Am J Med 118:101–107 17. Granada J, Uribe W, Chyou PH, Maassen K, Vierkant R, Smith PN, Hayes J, Eaker E, Vidaillet H (2000) Incidence and predictors of atrial flutter in the general population. J Am Coll Cardiol 36:2242 18. Horenstein MS, Karpawich PP, Epstein ML, Singh TP (2004) Transthoracic echocardiography for precardioversion screening during atrial flutter/fibrillation in young patients. Clin Cardiol 27:413–416 19. Ito T, Suwa M, Nakamura T, Miyazaki S, Kpbashi A et al (2001) Quantification of left atrial appendage spontaneous echo contrast in patients with chronic nonalvular atrial fibrillation. J Cardiol 37:325–333 20. Jahangiri M, Shore D, Kakkar V, Lincoln C, Shinebourne E (1997) Coagulation factor abnormalities after the Fontan
Pediatr Cardiol
21.
22.
23.
24.
25.
26.
procedure and its modifications. J Thorac Cardiovasc Surg 113:989–992 discussion 992–993 Kanter RJ, Garson A Jr (1997) Atrial arrhythmias during chronic follow-up of surgery for complex congenital heart disease. Pacing Clin Electrophysiol 20(2 Pt 2):502–511 Li Wei, Somerville J (2000) Atrial flutter in grown-up congenital heart (GUCH) patients clinical characteristics of affected population. Int J Cardiol 75:129–137 Manning WJ (1997) Role of transesophageal echocardiography in the management of thromboembolic stroke. Am J Cardiol 80:19D–28D discussion 35D–39D Mart CR (2012) Three-dimensional echocardiographic evaluation of the Fontan conduit for thrombus. Echocardiography 29:363–368. doi:10.1111/j.1540-8175.2011.01579.x Monagle P, Cochrane A, Roberts R, Manlhiot C, Weintraub R, Szechtman B, Hughes M, Andrew M, McCrindle BW, Fontan Anticoagulation Study Group (2011) A multicenter, randomized trial comparing heparin/warfarin and acetylsalicylic acid as primary thromboprophylaxis for 2 years after the Fontan procedure in children. J Am Coll Cardiol 58:645–651. doi:10.1016/j.jacc. 2011.01.061 Ohuchi H, Yasuda K, Miyazaki A, Kitano M, Sakaguchi H, Yazaki S, Tsuda E, Yamada O (2013) Haemodynamic characteristics before and after the onset of protein losing enteropathy in patients after the Fontan operation. Eur J Cardiothorac Surg 43:e49–e57. doi:10.1093/ejcts/ezs714
27. Patel SV, Flaker G (2008) Is early cardioversion for atrial fibrillation safe in patients with spontaneous echocardiographic contrast? Clin Cardiol 31:148–152 28. Potter BJ, Leong-Sit P, Fernandes SM, Feifer A, Mayer JE Jr, Triedman JK, Walsh EP, Landzberg MJ, Khairy P (2013) Effect of aspirin and warfarin therapy on thromboembolic events in patients with univentricular hearts andFontan palliation. Int J Cardiol 168:3940–3943. doi:10.1016/j.ijcard.2013.06.058 29. Shirai LK, Rosenthal DN, Reitz BA, Robbins RC, Dubin AM (1998) Arrhythmias and thromboembolic complications after the extracardiac Fontan operation. J Thorac Cardiovasc Surg 115:499–505 30. Tucker KJ, Wilson C (1993) A comparison of transoesophageal atrial pacing and direct current cardioversion for the termination of atrial flutter: a prospective, randomised clinical trial. Br Heart J 69:530–535 31. Turchetti V, Bellini MA, Ricci D, Lapi A, Donati G et al (2001) Spontaneous echo-contrast as an in vivo indicator of rheological imbalance in dilatative cardiomyopathy. Clin Hemorheol Microcirc 25:119–125 32. Zotz RJ, Muller M, Genth-Zotz S, Darius H (2001) Spontaneous echo contrast caused by platelet and leukocyte aggregates? Stroke 32:1127–1133
123
