- Email: [email protected]
Assessing Intracardiac Thrombus Before Atrial Fibrillation Ablation
JACC: CLINICAL ELECTROPHYSIOLOGY
VOL. 2, NO. 3, 2016
ª 2016 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER
ISSN 2405-500X/$36.00 http://dx.doi.org/10.1016/j.jacep.2016.02.016
EDITORIAL COMMENT
Assessing Intracardiac Thrombus Before Atrial Fibrillation Ablation Challenges Faced After Testing* David T. Huang, MD, Waseem Sajjad, MD
A
s the treatment of symptoms related to atrial
fibrillation. The management of anticoagulation ther-
fibrillation has advanced, the management of
apy before and at the time of the ablation procedure
associated thromboembolic risks has pro-
has progressed from withholding to continuing these
gressed as well through the newly developed oral an-
oral agents as the experience in centers performing
ticoagulants. The 2014 American Heart Association/
ablation has resulted in improved safety profiles (7).
American College of Cardiology/Heart Rhythm Soci-
In this issue of JACC: Clinical Electrophysiology,
ety and the 2012 European Society of Cardiology
Frenkel et al. (8) present data that further shed light
guidelines on thromboprophylaxis for atrial fibrilla-
on the adequacy of this strategy. Atrial thrombus was
tion grant a class IIa and class Ib recommendation,
detected in 2.9% of 183 patients receiving a “non–
respectively, for using 1 of the new anticoagulants
vitamin K antagonist oral anticoagulant” (new oral
instead of warfarin for at least 3 weeks before cardio-
anticoagulant [NOAC]) and in 4.4% of 205 patients
version (1,2). This recommendation is based on sub-
receiving warfarin after at least 4 weeks of contin-
group analyses from RE-LY (Randomized Evaluation
uous use. There was no statistical difference between
of Long-Term Anticoagulation Therapy) (dabigatran),
the 2 therapies. Not surprisingly, the incidence of
ROCKET-AF (Rivaroxaban Once-Daily Oral Direct Fac-
reported thrombus was higher in patients with a high
tor Xa Inhibition Compared With Vitamin K Antago-
CHA 2DS2-VASc (Congestive Heart Failure, Hyperten-
nism for Prevention of Stroke and Embolism Trial in
sion, Age ($75 years), Diabetes, Stroke/Transient
Atrial Fibrillation) (rivaroxaban), and ARISTOTLE
Ischemic Attack, Vascular Disease, Age (65–74 years),
(Apixaban for Reduction in Stroke and Other Throm-
Sex (Female) score) score. Heart failure and persistent
boembolic Events in Atrial Fibrillation) (apixaban),
atrial fibrillation were predictors of thrombus detec-
suggesting that electrical cardioversion in patients
tion. The other finding of intrigue was a nonsignifi-
treated with these agents has a low thromboembolic
cant trend in the absence of any thrombus with the
risk that is comparable to warfarin (3–6). None of
use of apixaban, but the study was underpowered to
these trials had detection of left atrial appendage
evaluate potential differences among NOACs.
thrombus
on
transesophageal
echocardiography
(TEE) as an endpoint. These strategies have been adapted to patients undergoing ablation for atrial
SEE PAGE 295
This study uncovers several relevant questions. Is it possible that by not performing routine TEE before cardioversion in patients treated with either warfarin or a NOAC, we are missing some of these thrombi in
*Editorials published in JACC: Clinical Electrophysiology reflect the views
the presence of adequate anticoagulation in the per-
of the authors and do not necessarily represent the views of JACC:
iconversion period? Is 3 to 4 weeks of recommended
Clinical Electrophysiology or the American College of Cardiology. From the Division of Cardiology, University of Rochester Medical Center, Rochester, New York. Dr. Huang has received fellowship support from Medtronic, Boston Scientific, and St. Jude; and research support from
anticoagulation long enough for all patients with atrial fibrillation regardless of their CHA 2 DS2-VASc? Subclinical events not readily detectable by routine
Boston Scientific, Medtronic, and St. Jude. Dr. Sajjad has reported that he
examinations should not be overlooked, as learned
has no relationships relevant to the contents of this paper to disclose.
from magnetic resonance imaging and cognitive
Huang and Sajjad
JACC: CLINICAL ELECTROPHYSIOLOGY VOL. 2, NO. 3, 2016 JUNE 2016:304–6
Atrial Fibrillation and Thromboembolic Risk Assessment
testing findings in patients post–atrial fibrillation
and the primary intent likely was the safety of the
ablation (9,10).
planned procedure. It is unclear if the trans-
Conversely, this current study reported higher in-
esophageal echocardiographic findings in this report
cidences of detected thrombus and dense sponta-
were assessed by more than 1 observer per case. From
neous echocardiographic contrast in patients who are
the perspective of investigation, it would be helpful if
systemically anticoagulated than in other previous
the transesophageal echocardiographic results were
studies (11–13). Puwanant et al. (12) reported a larger
confirmed, particularly by an observer who was not
cohort of 1,058 patients who underwent TEE in
immediately confronted with the consequences of
preparation for atrial fibrillation ablation. All patients
potential thromboembolic risks from the ablation
were maintained on warfarin with a relatively strin-
procedure.
gent schedule of international normalized ratio
Findings in this report may potentially shift the
monitoring before the planned procedure. Compared
risk/benefit ratio in pre-procedural TEE in patients
to the data by Frenkel et al. (8), Puwanant et al. (12)
undergoing atrial fibrillation ablation. At present,
found significantly lower incidences of detected
routine TEE should still be considered in most pa-
intracardiac thrombus (0.6%) and dense echocardio-
tients undergoing conversion treatment for atrial
graphic contrast, “sludge” (2.1%). Although it may be
fibrillation, even with uninterrupted anticoagulation
opportune to attribute the differences in the in-
using warfarin or a NOAC. Distilled from these retro-
cidences between the 2 studies to the differences in
spective studies, patients with a CHA2DS2 -VASc of
the study population, with the patients in the Frenkel
zero with a normal left atrium size, left ventricular
et al. (8) study reporting higher composite and aver-
function, and no congestive heart failure appear to be
aged thromboembolic risk scores. Side-by-side com-
at low risk for thromboembolic findings. There is now
parison, however, shows that the Frenkel et al. (8)
a need for well-designed and properly powered pro-
study reported substantially higher rates of detected
spective trials to assess the presence and clinical
thrombus across all patients with lower risk scores of
impact of intracardiac thrombi before ablation, and
0 to 2, which is notable, especially because the lower
perhaps
cardioversion,
CHA 2 DS2-VASc used in the study by Frenkel et al. (8)
assured
anticoagulation.
is more sensitive for detecting lower-risk patients
approach
than is the CHADS 2 (Congestive Heart Failure, Hy-
thrombus despite anticoagulation therapy remains
pertension, Age, Diabetes, Stroke/Transient Ischemic
elusive. Switching to a different anticoagulant or
Attack) score used in the study by Puwanant et al. (12).
extending the duration of the same agent by several
Despite the availability of other imaging modal-
weeks continue to be the 2 main strategies. Individual
ities, TEE has remained widely accepted as the “gold
patient circumstances certainly play an important
standard” test to rule out the presence of intracardiac
role in selecting either strategy or combining the 2
thrombus in patients with atrial fibrillation (14).
strategies. RE-LATED_AF (Resolution of Left Atrial-
However, the techniques used in testing and inter-
Appendage Thrombus—Effects of Dabigatran in Pa-
pretation of results may vary. Although the finding of
tients with Atrial Fibrillation) (with dabigatran) and
spontaneous echocardiographic contrast is relatively
X-TRA (Efficacy of Once Daily Oral Rivaroxaban for
uniform, identifying thrombus in the left atrium can
Treatment of Thrombus in Left Atrial/Left Atrial
be more subjective. Although the test is well docu-
Appendage in Subjects With Nonvalvular Atrial
mented in its sensitivity, the specificity of the test is,
Fibrillation or Atrial Flutter) (with rivaroxaban) are 2
to a degree, subject to operator interpretation
upcoming trials that will address this issue.
to
patients
in
at-risk
patients
Furthermore,
with
the
demonstrated
with best atrial
because of the differences in the techniques used, such as imaging duration, use of echocardiographic
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
contrast, imaging frequency, multiple orthogonal
David T. Huang, Division of Cardiology, University
biplane views, and criteria such as thrombus size.
of Rochester Medical Center, 601 Elmwood Ave,
This study was a retrospective compilation of patients
Box
undergoing TEE before ablation for atrial fibrillation,
[email protected].
679,
Rochester,
New
York
14642.
E-mail:
REFERENCES 1. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. J Am Coll Cardiol
2. Camm AJ, Lip GH, Caterina RD, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation. Eur Heart J
3. Nagarakanti R, Ezekowitz MD, Oldgren J, et al. Dabigatran versus warfarin in patients with atrial fibrillation: an analysis of patients undergoing
2014;64:e1–76.
2012;33:2719–47.
cardioversion. Circulation 2011;123:131–6.
305
306
Huang and Sajjad
JACC: CLINICAL ELECTROPHYSIOLOGY VOL. 2, NO. 3, 2016 JUNE 2016:304–6
Atrial Fibrillation and Thromboembolic Risk Assessment
4. Flaker G, Lopes RD, Al-Khatib SM, et al. Efficacy and safety of apixaban in patients after cardioversion for atrial fibrillation: insights from the ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation). J Am Coll Cardiol 2014;63:1082–7. 5. Piccini JP, Stevens SR, Lokhnygina Y, et al. Outcomes after cardioversion and atrial fibrillation ablation in patients treated with rivaroxaban and warfarin in the ROCKET AF trial. J Am Coll Cardiol 2013;61:1998–2006. 6. Cappato R, Ezekowitz MD, Klein AL, et al. Rivaroxaban vs. vitamin K antagonists for cardioversion in atrial fibrillation. Eur Heart J 2014;35: 3346–55. 7. Caulkins H, Kuck KH, Cappato R, et al. 2012 HRS/EHRA/ECAS Expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up,
definitions, endpoints and research trial design. Heart Rhythm 2012;9:632–96. 8. Frenkel D, D’Amato SA, Al-Kazaz M, et al. Prevalence of left atrial thrombus detection by transesophageal echocardiography: a comparison of continuous non-vitamin K antagonist oral anticoagulant versus warfarin therapy in patients undergoing catheter ablation for atrial fibrillation. J Am Coll Cardiol EP 2016;2:295–303. 9. Herm J, Fiebach JB, Koch L, et al. Neuropsychological effects of MRI-detected brain lesions after left atrial catheter ablation for atrial fibrillation: long-term results of the MACPAF study. Circ Arrhythm Electrophysiol 2013;6:843–50. 10. Deneke T, Jais P, Scaglione M, et al. Silent cerebral events/lesions related to atrial fibrillation ablation: a clinical review. J Cardiovasc Electrophysiol 2015;26:455–63. 11. McCready JW, Nunn L, Lambiase PD, et al. Incidence of left atrial thrombus prior to atrial
fibrillation ablation: is pre-procedural trans-oesophageal echocardiography mandatory? Europace 2010;12:927–32. 12. Puwanant S, Varr BC, Shrestha K, et al. Role of the CHADS2 score in the evaluation of thromboembolic risk in patients with atrial fibrillation undergoing transesophageal echocardiography before pulmonary vein isolation. J Am Coll Cardiol 2009;54:2032–9. 13. Scherr D, Dalal D, Chilukuri K, et al. Incidence and predictors of left atrial thrombus prior to catheter ablation of atrial fibrillation. J Cardiovasc Electrophysiol 2009;20:379–84. 14. Manning WJ, Silverman DI, Gordon SP, et al. Cardioversion from atrial fibrillation without prolonged anticoagulation with use of transesophageal echocardiography to exclude the presence of atrial thrombi. N Engl J Med 1993;328:750–5.
KEY WORDS ablation, atrial fibrillation, thrombus
VOL. 2, NO. 3, 2016
ª 2016 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER
ISSN 2405-500X/$36.00 http://dx.doi.org/10.1016/j.jacep.2016.02.016
EDITORIAL COMMENT
Assessing Intracardiac Thrombus Before Atrial Fibrillation Ablation Challenges Faced After Testing* David T. Huang, MD, Waseem Sajjad, MD
A
s the treatment of symptoms related to atrial
fibrillation. The management of anticoagulation ther-
fibrillation has advanced, the management of
apy before and at the time of the ablation procedure
associated thromboembolic risks has pro-
has progressed from withholding to continuing these
gressed as well through the newly developed oral an-
oral agents as the experience in centers performing
ticoagulants. The 2014 American Heart Association/
ablation has resulted in improved safety profiles (7).
American College of Cardiology/Heart Rhythm Soci-
In this issue of JACC: Clinical Electrophysiology,
ety and the 2012 European Society of Cardiology
Frenkel et al. (8) present data that further shed light
guidelines on thromboprophylaxis for atrial fibrilla-
on the adequacy of this strategy. Atrial thrombus was
tion grant a class IIa and class Ib recommendation,
detected in 2.9% of 183 patients receiving a “non–
respectively, for using 1 of the new anticoagulants
vitamin K antagonist oral anticoagulant” (new oral
instead of warfarin for at least 3 weeks before cardio-
anticoagulant [NOAC]) and in 4.4% of 205 patients
version (1,2). This recommendation is based on sub-
receiving warfarin after at least 4 weeks of contin-
group analyses from RE-LY (Randomized Evaluation
uous use. There was no statistical difference between
of Long-Term Anticoagulation Therapy) (dabigatran),
the 2 therapies. Not surprisingly, the incidence of
ROCKET-AF (Rivaroxaban Once-Daily Oral Direct Fac-
reported thrombus was higher in patients with a high
tor Xa Inhibition Compared With Vitamin K Antago-
CHA 2DS2-VASc (Congestive Heart Failure, Hyperten-
nism for Prevention of Stroke and Embolism Trial in
sion, Age ($75 years), Diabetes, Stroke/Transient
Atrial Fibrillation) (rivaroxaban), and ARISTOTLE
Ischemic Attack, Vascular Disease, Age (65–74 years),
(Apixaban for Reduction in Stroke and Other Throm-
Sex (Female) score) score. Heart failure and persistent
boembolic Events in Atrial Fibrillation) (apixaban),
atrial fibrillation were predictors of thrombus detec-
suggesting that electrical cardioversion in patients
tion. The other finding of intrigue was a nonsignifi-
treated with these agents has a low thromboembolic
cant trend in the absence of any thrombus with the
risk that is comparable to warfarin (3–6). None of
use of apixaban, but the study was underpowered to
these trials had detection of left atrial appendage
evaluate potential differences among NOACs.
thrombus
on
transesophageal
echocardiography
(TEE) as an endpoint. These strategies have been adapted to patients undergoing ablation for atrial
SEE PAGE 295
This study uncovers several relevant questions. Is it possible that by not performing routine TEE before cardioversion in patients treated with either warfarin or a NOAC, we are missing some of these thrombi in
*Editorials published in JACC: Clinical Electrophysiology reflect the views
the presence of adequate anticoagulation in the per-
of the authors and do not necessarily represent the views of JACC:
iconversion period? Is 3 to 4 weeks of recommended
Clinical Electrophysiology or the American College of Cardiology. From the Division of Cardiology, University of Rochester Medical Center, Rochester, New York. Dr. Huang has received fellowship support from Medtronic, Boston Scientific, and St. Jude; and research support from
anticoagulation long enough for all patients with atrial fibrillation regardless of their CHA 2 DS2-VASc? Subclinical events not readily detectable by routine
Boston Scientific, Medtronic, and St. Jude. Dr. Sajjad has reported that he
examinations should not be overlooked, as learned
has no relationships relevant to the contents of this paper to disclose.
from magnetic resonance imaging and cognitive
Huang and Sajjad
JACC: CLINICAL ELECTROPHYSIOLOGY VOL. 2, NO. 3, 2016 JUNE 2016:304–6
Atrial Fibrillation and Thromboembolic Risk Assessment
testing findings in patients post–atrial fibrillation
and the primary intent likely was the safety of the
ablation (9,10).
planned procedure. It is unclear if the trans-
Conversely, this current study reported higher in-
esophageal echocardiographic findings in this report
cidences of detected thrombus and dense sponta-
were assessed by more than 1 observer per case. From
neous echocardiographic contrast in patients who are
the perspective of investigation, it would be helpful if
systemically anticoagulated than in other previous
the transesophageal echocardiographic results were
studies (11–13). Puwanant et al. (12) reported a larger
confirmed, particularly by an observer who was not
cohort of 1,058 patients who underwent TEE in
immediately confronted with the consequences of
preparation for atrial fibrillation ablation. All patients
potential thromboembolic risks from the ablation
were maintained on warfarin with a relatively strin-
procedure.
gent schedule of international normalized ratio
Findings in this report may potentially shift the
monitoring before the planned procedure. Compared
risk/benefit ratio in pre-procedural TEE in patients
to the data by Frenkel et al. (8), Puwanant et al. (12)
undergoing atrial fibrillation ablation. At present,
found significantly lower incidences of detected
routine TEE should still be considered in most pa-
intracardiac thrombus (0.6%) and dense echocardio-
tients undergoing conversion treatment for atrial
graphic contrast, “sludge” (2.1%). Although it may be
fibrillation, even with uninterrupted anticoagulation
opportune to attribute the differences in the in-
using warfarin or a NOAC. Distilled from these retro-
cidences between the 2 studies to the differences in
spective studies, patients with a CHA2DS2 -VASc of
the study population, with the patients in the Frenkel
zero with a normal left atrium size, left ventricular
et al. (8) study reporting higher composite and aver-
function, and no congestive heart failure appear to be
aged thromboembolic risk scores. Side-by-side com-
at low risk for thromboembolic findings. There is now
parison, however, shows that the Frenkel et al. (8)
a need for well-designed and properly powered pro-
study reported substantially higher rates of detected
spective trials to assess the presence and clinical
thrombus across all patients with lower risk scores of
impact of intracardiac thrombi before ablation, and
0 to 2, which is notable, especially because the lower
perhaps
cardioversion,
CHA 2 DS2-VASc used in the study by Frenkel et al. (8)
assured
anticoagulation.
is more sensitive for detecting lower-risk patients
approach
than is the CHADS 2 (Congestive Heart Failure, Hy-
thrombus despite anticoagulation therapy remains
pertension, Age, Diabetes, Stroke/Transient Ischemic
elusive. Switching to a different anticoagulant or
Attack) score used in the study by Puwanant et al. (12).
extending the duration of the same agent by several
Despite the availability of other imaging modal-
weeks continue to be the 2 main strategies. Individual
ities, TEE has remained widely accepted as the “gold
patient circumstances certainly play an important
standard” test to rule out the presence of intracardiac
role in selecting either strategy or combining the 2
thrombus in patients with atrial fibrillation (14).
strategies. RE-LATED_AF (Resolution of Left Atrial-
However, the techniques used in testing and inter-
Appendage Thrombus—Effects of Dabigatran in Pa-
pretation of results may vary. Although the finding of
tients with Atrial Fibrillation) (with dabigatran) and
spontaneous echocardiographic contrast is relatively
X-TRA (Efficacy of Once Daily Oral Rivaroxaban for
uniform, identifying thrombus in the left atrium can
Treatment of Thrombus in Left Atrial/Left Atrial
be more subjective. Although the test is well docu-
Appendage in Subjects With Nonvalvular Atrial
mented in its sensitivity, the specificity of the test is,
Fibrillation or Atrial Flutter) (with rivaroxaban) are 2
to a degree, subject to operator interpretation
upcoming trials that will address this issue.
to
patients
in
at-risk
patients
Furthermore,
with
the
demonstrated
with best atrial
because of the differences in the techniques used, such as imaging duration, use of echocardiographic
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
contrast, imaging frequency, multiple orthogonal
David T. Huang, Division of Cardiology, University
biplane views, and criteria such as thrombus size.
of Rochester Medical Center, 601 Elmwood Ave,
This study was a retrospective compilation of patients
Box
undergoing TEE before ablation for atrial fibrillation,
[email protected].
679,
Rochester,
New
York
14642.
E-mail:
REFERENCES 1. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. J Am Coll Cardiol
2. Camm AJ, Lip GH, Caterina RD, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation. Eur Heart J
3. Nagarakanti R, Ezekowitz MD, Oldgren J, et al. Dabigatran versus warfarin in patients with atrial fibrillation: an analysis of patients undergoing
2014;64:e1–76.
2012;33:2719–47.
cardioversion. Circulation 2011;123:131–6.
305
306
Huang and Sajjad
JACC: CLINICAL ELECTROPHYSIOLOGY VOL. 2, NO. 3, 2016 JUNE 2016:304–6
Atrial Fibrillation and Thromboembolic Risk Assessment
4. Flaker G, Lopes RD, Al-Khatib SM, et al. Efficacy and safety of apixaban in patients after cardioversion for atrial fibrillation: insights from the ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation). J Am Coll Cardiol 2014;63:1082–7. 5. Piccini JP, Stevens SR, Lokhnygina Y, et al. Outcomes after cardioversion and atrial fibrillation ablation in patients treated with rivaroxaban and warfarin in the ROCKET AF trial. J Am Coll Cardiol 2013;61:1998–2006. 6. Cappato R, Ezekowitz MD, Klein AL, et al. Rivaroxaban vs. vitamin K antagonists for cardioversion in atrial fibrillation. Eur Heart J 2014;35: 3346–55. 7. Caulkins H, Kuck KH, Cappato R, et al. 2012 HRS/EHRA/ECAS Expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up,
definitions, endpoints and research trial design. Heart Rhythm 2012;9:632–96. 8. Frenkel D, D’Amato SA, Al-Kazaz M, et al. Prevalence of left atrial thrombus detection by transesophageal echocardiography: a comparison of continuous non-vitamin K antagonist oral anticoagulant versus warfarin therapy in patients undergoing catheter ablation for atrial fibrillation. J Am Coll Cardiol EP 2016;2:295–303. 9. Herm J, Fiebach JB, Koch L, et al. Neuropsychological effects of MRI-detected brain lesions after left atrial catheter ablation for atrial fibrillation: long-term results of the MACPAF study. Circ Arrhythm Electrophysiol 2013;6:843–50. 10. Deneke T, Jais P, Scaglione M, et al. Silent cerebral events/lesions related to atrial fibrillation ablation: a clinical review. J Cardiovasc Electrophysiol 2015;26:455–63. 11. McCready JW, Nunn L, Lambiase PD, et al. Incidence of left atrial thrombus prior to atrial
fibrillation ablation: is pre-procedural trans-oesophageal echocardiography mandatory? Europace 2010;12:927–32. 12. Puwanant S, Varr BC, Shrestha K, et al. Role of the CHADS2 score in the evaluation of thromboembolic risk in patients with atrial fibrillation undergoing transesophageal echocardiography before pulmonary vein isolation. J Am Coll Cardiol 2009;54:2032–9. 13. Scherr D, Dalal D, Chilukuri K, et al. Incidence and predictors of left atrial thrombus prior to catheter ablation of atrial fibrillation. J Cardiovasc Electrophysiol 2009;20:379–84. 14. Manning WJ, Silverman DI, Gordon SP, et al. Cardioversion from atrial fibrillation without prolonged anticoagulation with use of transesophageal echocardiography to exclude the presence of atrial thrombi. N Engl J Med 1993;328:750–5.
KEY WORDS ablation, atrial fibrillation, thrombus