Journal of Electrocardiology Vol. 30 No.

4 1997

Heart C o n d u c t i o n Disturbances and

Cardiovascular Collapse After
D i s o p y r a m i d e and L o w - D o s e M e t o p r o l o l
in a P a t i e n t With H y p e r t r o p h i c
Obstructive C a r d i o m y o p a t h y

A. P e r n a t , M D , B. P o h a r , M D , D s c , a n d M . H o r v a t , M D , D S c , F A C C

Abstract: Disopyramide as an antiarrhythinic can be prescribed to patients

with atrial fibrillation and, owing to its negative inotropic effect, to patients with
hypertrophic obstructive cardiomyopathy. It is known that in patients with cardiac conduction disturbances and heart failure, dis()pyramide can adversely
affect heart rhythm and conduction and induce cardiovascular collapse. A
patient with hypertrophic obstructive cardiomyopathy and paroxysms of atrial
fibrillation is described who was treated with disopyramide and alsu, during
the 5 days before admission, with metoprolol. In spite of normal cardiac conduction and function before disopyramide, this treatment was followed by
hypotension, bradycardia, and cardiac conduction disturbances. Our case
shows the potential for disopyramidc, especially when combined with metoprolol, to induce grave adverse effects even in patients with normal cardiac
conduction and ventricular function. Key words: disopyramide, metoprolol,
heart conduction disturbances, hypotension.

Disopyramide is a type Ia antiarrhythmic agent

according to the Vaughan-Williams classification (1),
which is most often used for the treatment of ventricular tachycardias and atrial fibrillation and flutter (2). It has also been s h o w n to decrease outflow
obstruction in patients with hypertrophic obstructive cardiomyopathy by virtue of its negative inotropic effect (3), and recently it has been reported to
improve diastolic function of the left ventricle in
such patients (4). Its antiarrhythmic properties

m a k e it even m o r e useful, since ventricular and

atrial arrhythmias often a c c o m p a n y hypertrophic
obstructive cardiomyopathy. The most c o m m o n side
effects of disopyramide include obstipation, dry
mouth, blurred vision, and urine retention, resulting from its anticholinergic action (5). In patients
with impaired left ventricular function, disopyramide, because of its negative inotropic action, can
precipitate worsening of heart failure, cardiogenic
shock, or electromechanical dissociation (6). A m o n g
p r o a r r h y t h m i c effects of disopyramide, prolongation
of the QT interval with associated ventricular tachycardia (7,8) and atrioventricular conduction block in
patients with preexistent bifascicular block h a v e
been described (9,10).
Beta-adreuergic blockers have b e e n a m a i n s t a y of
the t r e a t m e n t of hypertrophic obstructive cardiomy-

From the Center for Intensive Internal Medicine, University Medical

Center Ljubljana, Zaloska 7, I000 Ljubljana, Slovenia.
Reprint requests: Andrej Pernst, MD, Center for Intensive
Internal Medicine, University Medical Center Ljubljana, Zaloska
7, 1000 Ljubljana, Slovenia.
1997 Churchill Livingstone Inc.

341

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Journal of Electrocardiology Vol. 30 No. 4 October 1997

opathy. They tend to decrease outflow obstruction

owing to their negative inotropic action and slowing of the heart rate. However, in comparison with
disopyramide, they do not p r e v e n t atrial fibrillation
nor do they improve diastolic function of the left
ventricle. Like disopyramide, beta-adrenergic blockers can provoke worsening of heart failure due to a
negative inotropic effect. In patients with atrioventricular conduction block, they can provoke progression of the block due to a negative chronotropic effect.
We describe a patient with hypertrophic obstructive cardiomyopathy with no preexistent heart
conduction disturbances or heart failure, in w h o m
heart conduction block and cardiovascular collapse
evolved during disopyramide and low-dose ]iletoprolol treatment.

Case Report
A 54-year-old m a n was admitted because of slow
pulse rate, dizziness, and paresthesias in his upper
and lower limbs, which had started 3 hours previously. He had a 15-year history of hypertrophic
obstructive c a r d i o m y o p a t h y and a 5-year history of
paroxysmal atrial fibrillation. He had been treated
with a m i o d a r o n e and propranolol, but paroxysms
of atrial fibrillation recurred. Both drugs were
replaced by disopyramide 150 mg orally three
times daily, 45 days before admission, and metoprolol 25 mg orally twice a day was started in the
last 5 days before admission.
At the time of admission, the patient was distressed, his skin was pale and cold, his pulse rate
was 32 beats/min, and his blood pressure was
115/70 mmHg. His jugular venous pressure was

Fig. 1. The ECG on admission, after 45 days of disopyramide 150 mg three times daily
and 5 days of metoprolol 25
mg twice daily. The 12-lead
ECG strip shows sinus bradycardia 32 beats/rain, firstdegree atrioventricular block
with a very long PR interval
(1,480 ms), and marked prolongation of the QRS complex
(160 ms) and QT interval (800
ms). There is no atrioventricular dissociation, as seen on the
Vl lead strip at the bottom of
the figure.

clinically estimated to be about lO cmH20. The

lung fields were clear to percussion and auscultation. The heart sounds were normal, except for a
systolic ejection m u r m u r at the left sternal border
in the 4th intercostal space. The liver edge was palpable 2 cm below the right costal margin. The
extremities were w i t h o u t edema. Blood electrolyte
and hemoglobin levels were normal, and the creatinine level was 128 ~tmol/L.
The electrocardiogram (ECG) showed bradycardia (32 beats/min), broad QRS complexes (160 ms),
a very long PR interval (1,480 ms), and a prolonged
QT interval (800 ms) (Fig. 1). Right after admission,
the heart rate decreased to 26 beats/min, blood
pressure fell to 8060 mmHg, and the patient
started to lose consciousness. Atropine (2 mg) intravenously had no effect. A dobutamine infusion (10
~lg/kg/min) increased heart rate to 55 beats/min
and shortened the PR interval to 266 ms (Fig. 2).
The blood pressure increased to 105/70 mmHg.
Increased p u l m o n a r y artery pressure (56126 mmHg)
and p u l m o n a r y artery wedge pressure (26 mmHg)
were measured with a Swan-Ganz catheter at the
c o m m e n c e m e n t of dobutamine infusion. These
pressures decreased after discontinuation of the
infusion. We were able to discontinue dobutamine
infusion after 8 hours. In the following days, progressive i m p r o v e m e n t of atrioventricular conduction, narrowing of the QRS complexes, and shortening of the QT interval were noted. Disopyramide
and metoprolol were discontinued right after
admission and neither of these drugs was reintroduced later. On the fourth day, treatment with
sotalol, 80 mg orally twice daily was started. After
initiation of the sotalol treatment, neither severe
bradycardia, hypotension, nor intraventricular conduction disturbances recurred (Fig. 3).

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Fig. 2. The ECG during dobutamine infusion. Heart rate
increased to 55 beats/min, and
the PR interval shortened to
266 ms, the QRS complex to
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We have described a patient w i t h h y p e r t r o p h i c

obstructive c a r d i o m y o p a t h y in w h o m h e a r t c o n d u c t i o n disturbances and cardiovascular collapse
developed during treatment with disopyramide
and after addition of l o w - d o s e m e t o p r o l o l .
B o t h a t r i o v e n t r i c u l a r and i n t r a v e n t r i c u l a r cond u c t i o n disturbances w e r e present in o u r patient at
the time of admission. The m a r k e d l y p r o l o n g e d PR
interval with P w a v e s localized shortly after the
QRS c o m p l e x could be interpreted as an a t r i o v e n tricular j u n c t i o n a l r h y t h m with diffuse i n t r a v e n tricular block. H o w e v e r , the shape and the axis of
the P w a v e s r e m a i n e d the same, and gradual shortening of the PR interval was evident in s u b s e q u e n t
ECGs during n o r m a l i z a t i o n of the c o n d u c t i o n disturbances. Therefore, it seems that sinus b r a d y c a r dia with an e x t r e m e l y p r o l o n g e d PR interval (Firstdegree atrioventricular block) was present. In
addition to atrioventricular c o n d u c t i o n block, diffuse i n t r a v e n t r i c u l a r block and a p r o l o n g e d QT
interval w e r e present.
In electrophysiologic studies, d i s o p y r a m i d e has
b e e n f o u n d to h a v e a dual effect on the atrioventricular node; direct and vagolytic (11). Since the
direct effect p r e d o m i n a t e s , a t r i o v e n t r i c u l a r conduction is delayed (12). In the ventricular c o n d u c -

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tion system, p r o l o n g a t i o n of the action potential

a n d p r o l o n g a t i o n of the intraventricular c o n d u c t i o n
time h a v e b e e n observed with d i s o p y r a m i d e (13).
Therefore, all the h e a r t c o n d u c t i o n disturbances
p r e s e n t in o u r patient could be p r o v o k e d by disopyramide. However, m e t o p r o l o l h a d b e e n a d d e d to
d i s o p y r a m i d e 5 days before hospital admission. It is
possible that m e t o p r o l o l m a y h a v e h a d a role in
e x a c e r b a t i n g bradycardia and a t r i o v e n t r i c u l a r cond u c t i o n delay via its negative c h r o n o t r o p i c effect.
The role of m e t o p r o l o l is also indicated by the
a p p e a r a n c e of s y m p t o m s shortly after m e t o p r o l o l
was a d d e d to d i s o p y r a m i d e . Also, the r e s p o n s e to
d o b u t a m i n e w o u l d at least suggest this possibility.
Cases of cardiovascular collapse associated with
disopyramide
treatment
have
already
been
r e p o r t e d (14). Sinus bradycardia, a t r i o v e n t r i c u l a r
c o n d u c t i o n block, and l e n g t h e n i n g of QRS c o m plexes and the QT interval h a v e p r e c e d e d a fall in
blood pressure in all cases. H o w e v e r , all described
patients either had had reccnt m y o c a r d i a l infarction
or severe heart failure before initiation of disopyramide or had received the drug in o v e r d o s e (14,15).
In o u r patient n o signs of left v e n t r i c u l a r failure
w e r e p r e s e n t at initiation of t r e a t m e n t w i t h disopyr a m i d e (the ultrasonically estimated ejection fraction of the left ventricle was 51%, a n d the transstenotic pressure gradient was 42 m m H g ) . The

Fig. 3. The ECG on day 5,

after sotalol administration.
The atrk)ventricular and intraventricular conduction disturbances have disappeared.
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344

Journal of Electrocardiology Vol. 30 No. 4 October 1997

drugs m a y have produced sinoatrial and atrioventricular nodal toxicity w h i c h resulted in m a r k e d

sinus bradycardia and first-degree atrioventricular
block, giving rise to inadequate forward flow (cardiac output) with r a t e - d e p e n d e n t hypotension. In
addition to bradycardia and conduction disturbances, depression of left ventricular function could
also have been responsible for cardiovascular collapse. Increased p u l m o n a r y capillary wedge pressure indicates myocardial depression due to the
negative inotropic effect of the drugs. Therefore,
cardiovascular collapse m a y in part be related to
the negative inotropic effect of disopyramide. Again,
addition of metoprolol might have aggravated the
myocardial depression produced by disopyramide to
a degree that led to cardiovascular collapse.
The patient's problems did not reappear after
t r e a t m e n t with sotalol was started. However, that
does not preclude a role of metoprolol in provoking the patient's problems, since sotalol was not
associated with disopyramide, and sotalol and
metoprolol have different pharmacologic properties. On the other hand, it also indicates that not
metoprolol alone but rather the interaction
b e t w e e n disopyramide and metoprolol was the
m a i n cause of the clinical picture.
In conclusion, our case indicates a possibility of
serious side effects as a consequence of disopyramide and metoprolol interaction. Concomitant use
of disopyramide and metoprolol can induce cardiovascular collapse and grave heart conduction disturbances even in patients with normal heart function
and heart conduction. Therefore, we believe that
these two drugs should not be used in combination,
even in patients without myocardial disease.

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