Case Study

Asian Cardiovascular & Thoracic Annals

0(0) 1–4
A rare case of late-onset ! The Author(s) 2020
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DOI: 10.1177/0218492320981483
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Prabhakaran Aranganathan, Bivin Wilson ,

Anandhakumar Rangan, Arunkumar Boopathi and
Ramprakash Balasundaram

Abstract
Ticagrelor is a potent reversible P2Y12 inhibitor with proven superiority over clopidogrel. Ticagrelor increases the
tissue concentration of adenosine, thereby leading to bradyarrhythmia. This complication is reported to occur very early
after initiating the drug. A randomized controlled trial reported that ticagrelor-induced pauses have an early onset
without much clinical impact. However, our patient developed ticagrelor-induced hemodynamically significant sinus
arrest 10 months after coronary artery stenting, which improved after stopping the drug. Ticagrelor should be con-
sidered as one of the uncommon reasons for late-onset sinus pause or bradyarrhythmia.

Keywords
Bradycardia, sinus arrest, ticagrelor

Introduction
The benefits of primary coronary angioplasty are
threatened by stent thrombosis that needs to be tackled
with appropriate antiplatelet agents. Ticagrelor is a
potent reversible P2Y12 inhibitor with proven superi-
ority over clopidogrel, and is a class 1 recommenda-
tion.1 A known but rare side-effect of ticagrelor,
apart from bleeding, is bradyarrhythmia due to ventric-
ular pauses, which is reported to occur immediately
after initiation.2
Case report
A 55-year-old man on treatment for hypertension, dys-
lipidemia, and seizure disorder on carbamazepine pre-
sented with complaints of extreme tiredness and
vomiting for 2 weeks, followed by transient loss of con-
sciousness and profuse sweating. Almost 10 months
ago, he had a non-ST-elevation myocardial infarction
with two-vessel coronary artery disease, for which
stenting of the left anterior descending artery and
right coronary artery was performed. He was on stan-
dard cardiac medications including ticagrelor, aspirin,
and metoprolol 25 mg. In the emergency department,
he was drowsy and his hemodynamics were deranged
with a fluctuating heart rate, the lowest being 15–20
beats/min, and non-recordable blood pressure. The
possibility of acute coronary syndrome, hyperkalemia,
carbamazepine toxicity, or cerebrovascular accident
were considered. An initial electrocardiogram showed
sinus arrest with recurrent long pauses of >4 s (Figure
1). The blood pressure improved with administration of
dopamine and noradrenaline. Subsequent electrocar-
diograms revealed accelerated junctional rhythm and
accelerated idioventricular rhythm (Figure 2,
Figure 3). There were intermittent episodes of sinus
recovery suggesting a reversible cause. There were no
new regional wall abnormalities and an ejection frac-
tion of 60% on echocardiography. Troponin I and cre-
atine kinase MB were negative. All blood tests
including potassium levels were normal. Brain comput-
ed tomography ruled out intracerebral hemorrhage.
The patient was stabilized with a temporary
pacemaker. Coronary angiography revealed patent
Department of Cardiology, G. Kuppuswamy Naidu Memorial Hospital,
Coimbatore, India
Corresponding author:
Bivin Wilson, Department of Cardiology, G. Kuppuswamy Naidu
Memorial Hospital, Coimbatore, India.
Email: bivwilson@gmail.com
2 Asian Cardiovascular & Thoracic Annals 0(0)

Figure 1. Electrocardiogram showing a long sinus pause >4 seconds.

Figure 2. Electrocardiogram showing accelerated junctional rhythm.

Figure 3. Electrocardiogram showing accelerated idioventricular rhythm.

Aranganathan et al.
Figure 4. Angiogram left anterior oblique view showing a
patent stent in the right coronary artery.
Figure 5. Angiogram PA cranial view showing a patent stent in
left anterior descending artery.
Figure 6. Electrocardiogram showing sinus rythm after stopping ticagrelor.
3
stents with no new flow-limiting lesions (Figure 4,
Figure 5). In view of the rare possibility of carbamaz-
epine toxicity, the drug was withheld and carbamaze-
pine levels were found to be normal. The beta blocker
also was withheld. Over 2 days, although the patient
regained sinus rhythm, he continued to be pacemaker-
dependent with occasional junctional rhythm and sinus
arrests. He was scheduled for permanent pacemaker
insertion. We did not consider ticagrelor as the possible
culprit because he had tolerated the drug for almost
10 months after stenting. However, we decided to
stop ticagrelor and observe him for 2 days before per-
manent pacemaker implantation. There was a remark-
able improvement in his rhythm the next day, and he
regained sinus rhythm with a baseline heart rate of 60–
70 beats/min (Figure 6); 24-h Holter monitoring did
not reveal any significant long pauses. Hence, it was
concluded that the sinus arrest was induced by ticagre-
lor as we observed immediate and complete recovery
on stopping the drug. Ticagrelor was replaced with
clopidogrel and other standard medications were
restarted at discharge. We are planning to restart beta
blocker administration after the 1-month follow-up.
An electrophysiological study was not carried out
because a clear iatrogenic mechanism was elucidated
and complete recovery was documented on Holter
monitoring after stopping the drug.
Discussion
Adenosine diphosphate binds to P2Y12 receptors initi-
ating platelet aggregation which is inhibited by ticagre-
lor. According to the PLATO trial,3 ticagrelor can
induce bradycardia, the mechanism of which is less
well established. It inhibits adenosine uptake by eryth-
rocytes, resulting in increased adenosine tissue concen-
tration,4 leading to sinus node dysfunction and
atrioventricular block. Ticagrelor-induced bradycardia
4 Asian Cardiovascular & Thoracic Annals 0(0)
and its reversal has been reported in several case
reports.5–8 In the PLATO trial, ventricular pauses of
more than 3 s and more than 5 s were noted in 5.8%
and 2.0% of patients, respectively, in first week. After
one month, 2.1% and 0.8% of patients developed ven-
tricular pauses >3 s and >5 s, respectively.3 All other
reports have mentioned that bradyarrhythmia happens
immediately after ticagrelor initiation.6,7
In our case, we concluded that the sinus arrest was
induced by ticagrelor because we ruled out all other
reversible causes, and there was complete sinus recovery
after stopping the drug for two days. This case highlights
a very unusual side-effect of ticagrelor: late-onset sinus
arrest. Even though the PLATO trial declared that tica-
grelor can induce pauses with an early onset and without
clinical impact, our report suggests that it can occur as
late as 10 months and with significant hemodynamic
instability. Electrophysiologists should to be aware of
this entity for appropriate management of the condition
and to avoid unnecessary pacemaker implantation for a
potentially reversible cause.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
ORCID iD
Bivin Wilson https://orcid.org/0000-0002-9506-7368
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