Fontan Anticoagulation

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

VOL. 68, NO. 12, 2016

ª 2016 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

ISSN 0735-1097/$36.00

PUBLISHED BY ELSEVIER

http://dx.doi.org/10.1016/j.jacc.2016.06.050

EDITORIAL COMMENT

Fontan Anticoagulation A Never-Ending Debate?* Gunter Balling, MD, DRMED

T

hrombus formation is a significant cause of

et al. (2) found the absence of aspirin or warfarin

morbidity and mortality after Fontan opera-

therapy to be a powerful independent predictor of

tions. Intracardiac thrombus formation can

mortality from thromboembolism.

lead to chronic pulmonary embolism (e.g., from sys-

Despite the lack of large, prospective studies with

tem veins or subpulmonary ventricle) or stroke (e.g.,

long-term follow-up showing the efficacy of prophy-

from pulmonary veins or the systemic ventricle).

lactic therapy, most retrospective studies concluded

Those “right-sided” embolisms may result in a venti-

with a clear recommendation of lifelong routine

lation/perfusion mismatch or an elevation of pulmo-

anticoagulation or antiplatelet therapy in Fontan pa-

nary

tients (3,4).

vascular

resistance,

both

of

which

may

seriously hamper the cavopulmonary circulation. Pre-

Adults who had been treated by a Fontan operation

venting thromboembolism after the Fontan procedure

early in life had significantly reduced platelet

and the role of a proper prophylaxis remains an

numbers

ongoing discussion. The published reports are fraught

increased prothrombotic endothelial dysfunction,

but

increased

basal

platelet

activity,

with controversies about prophylactic antiplatelet

and evidence of systemic inflammation. A significant

and/or anticoagulation therapy, with some retrospec-

proportion of aspirin-treated adults showed aspirin

tive reviews supporting antiplatelet therapy, others

resistance, which might partially explain the inef-

suggesting that anticoagulants are more effective,

fectiveness of aspirin in preventing thromboembolic

and still others discouraging routine anticoagulation.

complications (5).

Marrone et al. (1) performed a systematic review

On the other hand, for warfarin therapy, the small

and meta-analysis involving 1,075 patients after

therapeutic window remains problematic. To avoid a

Fontan operations, with 220 (20.4%) in the anti-

subtherapeutic international normalized ratio or

platelet group and 855 (79.5%) in the anticoagulation

bleeding with warfarin, there are effective and safe

group. Mean follow-up ranged from 2 to 144 months,

methods for self-monitoring anticoagulation that

and the overall rate of thromboembolism was 5.2%.

are especially helpful in children when combined

The meta-analysis demonstrated the safety and effi-

with comprehensive educational support for the

cacy of a therapeutic strategy based on antiplatelet

parents (6).

therapy. The study verified that for patients with an extracardiac Fontan, antiplatelet therapy is associated with a rate of early or late thromboembolic events

and

bleeding

similar

to

that

for

SEE PAGE 1312

The retrospective study by Egbe et al. (7) in this

anti-

issue of the Journal is an important contribution to

coagulation therapy alone or for a combination with

this issue. From a large cohort of patients who had

anticoagulation and antiplatelet drugs. Yet, Khairy

undergone a Fontan procedure in a single institution, the investigators selected a subpopulation of 278 patients with a history of atrial arrhythmias over a

*Editorials published in the Journal of the American College of Cardiology

period of 2 decades. One-half of the patients showed

reflect the views of the authors and do not necessarily represent the

nonspecific symptoms. At the time of diagnosis,

views of JACC or the American College of Cardiology. From the Department of Pediatric Cardiology and Congenital Heart Diseases, German Heart Center, Technical University Munich, Munich,

actual ongoing atrial arrhythmias were present in 64%. Thrombus was detected on echocardiography

Germany. Dr. Balling has reported that he has no relationships relevant to

and computed tomography or cardiac magnetic

the contents of this paper to disclose.

resonance scans in 29% of adult patients after a

Balling

JACC VOL. 68, NO. 12, 2016 SEPTEMBER 20, 2016:1320–2

Anticoagulation After Fontan

Fontan operation and history of atrial arrhythmia.

surgery. Nevertheless, encouraging favorable data on

Right-sided embolism was detected in two-thirds and

the use of NOACs in adults with congenital heart

left-sided embolism in one-third of the events.

disease have just recently been published (14),

Interestingly, in the study presented by Egbe et al. (7), the cohort with a history of atrial arrhythmias was

although only a few patients with Fontan circulation were included.

being treated with 2 different regimens for preventing

The study from Egbe et al. (7) is an important

thromboembolism. The majority (65%) received an-

contribution to the stratification of risks and incidence

tiplatelet therapy (164 on aspirin, 64 on clopidogrel,

of thrombotic and embolic complications in adult

and 1 on both) and only 33% were on oral anti-

Fontan patients. We learned that the incidence is

coagulation (33 on warfarin alone; 55 on warfarin þ

especially high in the subpopulation of patients with

aspirin; and 3 were taking a nonvitamin K oral anti-

atrial arrhythmias. Of course, it would be of particular

coagulant [NOAC]). Unfortunately, one-third of pa-

interest to know the incidence in Fontan patients

tients on warfarin had subtherapeutic international

without any atrial arrhythmias, despite the fact that

normalized ratio. Nevertheless, they experienced

this might be a minority among adults with Fontan

significantly fewer thromboembolic events than the

circulation. The 2010 European Society of Cardiology

patients with antiplatelet therapy alone (11% vs. 22%;

guidelines (15) recommended the following with re-

p ¼ 0.016). Furthermore, the subset of patients with

gard to Fontan patients and anticoagulation: right

atriapulmonary connections showed the highest

atrial blood stasis and disturbed coagulation may pre-

thromboembolic risk compared with other more

dispose to thrombosis. The potential for subclinical,

modern forms of Fontan circulation.

recurrent pulmonary embolism leading to a rise in

When Fontan operations other than total cavopulmonary connection are used, as in the present

pulmonary vascular resistance has led to a recommendation by some for lifelong anticoagulation.

study (81% atriapulmonary connection), a history of

Egbe et al. (7) should be congratulated on their

clinically relevant arrhythmias and signs and symp-

retrospective study and its contributions to this dis-

toms of heart failure have been identified as strong

cussion, although the actual data did not allow a

prognostic factors of morbidity and mortality, which

general recommendation for anticoagulation therapy

is hardly surprising. In the literature, the incidence of

in all Fontan patients. However, especially in older

atrial arrhythmias and Fontan circulation is estimated

Fontan patients with atriapulmonary connections, the

around or even more than 50%. At 20-year follow-up,

prevalence of thrombotic intracardiac structures and/

overall freedom from tachycardia was estimated to be

or complications is substantial. Therefore, in my

only 46  12% (8–10). A combination of these factors

opinion, this patient group should benefit from sys-

(Fontan and arrhythmias) was strongly related to the

temic anticoagulant therapy. To drive the discussion

risk of death or transplantation and was far superior

further, the community treating any Fontan-type pa-

to any measure of cardiopulmonary exercise testing

tients should consider whether the time has come for

in assessing outcome (11). In the study from Varma

serial longitudinal transesophageal echocardiography

et al. (12), for example, the patients who received

evaluation (16), including asymptomatic patients, at

warfarin because of atrial arrhythmias had a zero

least in the adult population, in order to gain better

incidence of clinically silent pulmonary embolism.

insights into the thromboembolic risk of all Fontan

This supports expert consensus (13), where patients with a Fontan hemodynamic are considered to

patients and derive reliable, evidence-based recommendations for an antithrombotic treatment.

have a complex/severe congenital heart disease and, in the presence of atrial arrhythmias, thrombopro-

REPRINT REQUESTS AND CORRESPONDENCE: Dr.

phylaxis is reasonable, using long-term oral anti-

Gunter Balling, Department of Pediatric Cardiology

coagulation. Regarding the recommendation of more

and Congenital Heart Disease, Deutsches Herzzen-

modern anticoagulation drugs, such as NOACs, the

trum

expert group found insufficient safety and efficacy

rettstrasse 36, D 80636 Munich, Germany. E-mail:

data to recommend them in patients after Fontan

[email protected].

München

(German

Heart

Center),

Laza-

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1321

1322

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Anticoagulation After Fontan

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13. Khairy P, Van Hare GF, Balaji S, et al. PACES/

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HRS Expert Consensus Statement on the Recognition and Management of Arrhythmias in Adult Congenital Heart Disease: developed in partnership between the Pediatric and Congenital

KEY WORDS anticoagulation, atrial flutter/ fibrillation, Fontan, late complication, outcome, thromboembolism