Download Syncope secondary to second-degree atrioventricular block with

Syncope secondary to second-degree atrioventricular block
with donepezil use
Aneley Hundae, MD, Aasim Afzal, MD, Manish D. Assar, MD, and Jeffrey M. Schussler, MD
Donepezil, an acetylcholinesterase inhibitor, is approved for the treatment
of mild to moderate dementia secondary to Alzheimer’s disease. Although
most prescribers are aware of the common gastrointestinal side effects of
donepezil, cardiovascular side effects are rarely observed. Cardiovascular
side effects of donepezil have almost always been observed in patients
with a history of conduction defects or sick sinus syndrome. We report a
case of a woman with early onset Alzheimer’s disease and no history of
cardiac disease who developed second-degree heart block after a few
weeks of therapy with donepezil. Withdrawal of donepezil led to resolution
of the atrioventricular block.
D
onepezil, along with galantamine and rivastigmine, has
been commonly prescribed for treatment of Alzheimer’s
disease. Although cardiovascular adverse events have
been reported, they are rarely experienced. This case
highlights atrioventricular block as a potential adverse effect
of donepezil.
CASE PRESENTATION
A 50-year-old woman who had developed early onset
Alzheimer’s dementia at the age of 45 was brought to the hospital
after she experienced a witnessed syncopal event. According to
her husband, she lost consciousness for about a minute with no
signs of seizure activity. Her husband reported that she had been
“slow” for a few days. She was not on any prescription medication other than donepezil, which was started a few days prior
to presentation. Her family indicated that she had been taking
donepezil regularly and did not take more than the prescribed
dosage. The family history was significant for Alzheimer’s disease.
On physical exam, there were signs of advanced dementia. Thyroid function, syphilis serology, and vitamin B12 were normal or
negative. The electrocardiogram (ECG) obtained by paramedics
showed second-degree atrioventricular block (AVB) (Figure 1)
with a heart rate of 30 beats per minute. No previous ECG was
available for comparison. An echocardiogram showed a normal
left ventricular ejection fraction and no structural abnormalities.
The patient was admitted to the hospital and donepezil was
stopped. Her heart rate gradually rose, and no new syncopal
events occurred. A later ECG showed sinus rhythm, with only
a first-degree AVB (Figure 2). The patient remained asymptomProc (Bayl Univ Med Cent) 2014;27(4):325–326
atic during the rest of her hospital stay and was subsequently
discharged. At 1-month follow-up, her ECG showed no AVB.
DISCUSSION
Cholinesterase inhibitors are a class of drugs that include
donepezil, rivastigmine, and galantamine. They inhibit acetylcholinesterase enzyme in the central nervous system and increase acetylcholine, which is deficient in Alzheimer’s disease
(1). Donepezil is highly selective for the central nervous system
and is widely used in Alzheimer’s disease. Common side effects include nausea, diarrhea, malaise, and dizziness. In theory,
the cholinergic effect of donepezil can cause sinus bradycardia
and AVB. Donepezil, being a cholinesterase inhibitor, leads to
increased levels of acetylcholine, which stimulates glycinergic
and GABAergic inhibitory receptors by vagal neurotransmission, which in turn act to slow the heart rate (2). Theoretically,
donepezil and other acetylcholinesterase inhibitors can aggravate
preexisting nodal disease and lead to AVB (2). Heart rhythm
disturbances, however, are rare (3). In a study of 1762 patients
with Alzheimer’s disease on donepezil, Dunn et al reported
nausea, diarrhea, malaise, dizziness, and insomnia as common
side effects, with no reported cardiac rhythm disturbances (4).
Bordier et al reviewed 16 patients with Alzheimer’s disease
who presented with syncope. AVB was present in 2 of the 16
cases (5). Suleyman et al (3) reported complete AVB and ventricular arrhythmia associated with donepezil use.
Rowland et al have suggested guidelines for managing cardiovascular risks prior to and during treatment with acetylcholinesterase inhibitors. A heart rate check is recommended
at baseline, and if the rate is <50 beats per minute, the cause of
bradycardia needs to be investigated before starting the medication. Monthly follow-up is recommended after drug initiation
or dosage change, and 6-month follow-up is recommended
during the drug maintenance phase (2).
From the Department of Internal Medicine (Hundae), Division of Cardiology (Afzal,
Schussler), Baylor University Medical Center at Dallas; and the Department of
Internal Medicine, Texas A&M College of Medicine (Schussler).
Corresponding author: Jeffrey M. Schussler, MD, Division of Cardiology,
Department of Internal Medicine, 621 N. Hall Street, Suite 400, Dallas, TX 75226
(e-mail: [email protected]).
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Figure 1. Electrocardiogram at the time of syncope showing second-degree atrioventricular block.
Figure 2. Electrocardiogram before discharge; second-degree atrioventricular block had changed to first-degree atrioventricular block.
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Baylor University Medical Center Proceedings
Volume 27, Number 4