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Case
Report -
A Case of Chest
Pain
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Dimitra
Mitsani, MD
A
58-year-old white man presented with episodic chest pain
for three days. The pain was described as substernal tightness,
lasting 15 minutes at a time, and without any radiation
or associated dyspnea, nausea, vomiting, diaphoresis, or
palpitations. The tightness would occur at rest and resolve
without any medication. The patient also noted feeling weak
for the past month and recent travel to Maine about one
month earlier.
The
patient had suffered an ischemic CVA three years ago with
residual right hemiparesis, expressive aphasia, and documented
seizure activity for which he was on treatment. His last
seizure had taken place 5 months earlier and he had been
without recurrence since his anti-seizure medication dose
was adjusted. His past medical history was also significant
for a patent foramen ovale and hypertension. He did not
have known coronary artery disease. Family history was significant
for colon cancer in his maternal grandmother. He was a retired
media consultant, 30 pack-year smoker, and occasionally
used alcohol. He was living with his mother and working
hard with his physical therapy and rehabilitation program.
His medications included warfarin, lisinopril, valproate,
and carbamazepine.
On
physical examination, he was not in acute distress but had
a depressed mood. He was afebrile, blood pressure was 150/80
mmHg, heart rate 60 beats per minute, and respiratory rate
was 12 per minute. Head and neck exam revealed a right facial
droop. Cardiac examination revealed a regularly irregular
rhythm with skipped beats but no murmurs. His lungs were
clear to auscultation bilaterally. He had severe right sided
motor paresis and sensory deficits.
An
electrocardiogram showed an intermittent, Mobitz I block
(Wenckebach pattern) and 1st degree AV block (PR interval
>400-500ms). Initial laboratory studies showed a hematocrit
of 33.6%, hemoglobin of 11.1 g/dL, sodium of 130 mEq/L,
and an INR of 2.1. Potassium, magnesium, blood urea nitrogen,
thyroid function tests, and creatinine levels were normal.
Three sets of cardiac enzymes were unremarkable. His valproate
level was therapeutic at 98 (50-100) but carbamazepine level
was slightly low at 4.4 (6-12).
HOSPITAL
COURSE
The
patient was admitted to the coronary care unit (CCU) for
close monitoring with a presumptive diagnosis of unstable
angina. The nature and etiology of his pain were in debate.
Initial differential diagnoses included acute coronary syndrome
(given symptoms as well as lack of preexisting conduction
abnormalities), Lyme disease (Lyme carditis often presents
as AV block and there was recent travel to endemic area
in Maine), medication side effects (interaction at the level
of sodium, calcium and potassium channels can produce rhythm
abnormalities and subsequent insufficient diastolic perfusion
of coronary vessels or even spasm), and pulmonary embolism
(although less likely with a therapeutic INR on admission).
He
was treated with aspirin, unfractionated heparin, nitrates,
and simvastatin. Beta-blocker therapy was held, and warfarin
was discontinued. Four serial cardiac enzymes and Lyme titers
were negative. Spiral computed tomography of the chest and
doppler ultrasound of the lower extremities were also negative.
Neurology consultation suggested substituting carbamazepine
with levatiracetam over 2 weeks.
Within
the first 24 hours, the patient had another episode of chest
pain and developed a new, Mobitz type II AV block. A dobutamine
stress-echocardiogram was done and showed no ischemic defects.
During the test, the patient experienced chest pain and
had an appropriate heart rate increase to 134 beats per
minute (85% of predicted). Metoprolol 3 mg IV improved his
symptoms, but 2 hours later, his heart rate dropped to roughly
40 beats per minute, but his blood pressure remained stable.
A repeat EKG showed complete heart block which lasted for
a period of 2 hours and then resolved. The incident was
thought to be related to the beta-blocker. A cardiac catheterization
showed normal coronary vessels and preserved left ventricular
function. The patient was then advised to consider pacemaker
placement and an electrophysiologic study.
His
hyponatremia was thought to be due to SIADH secondary to
valproate and carbamazepine. He responded to water restriction,
and sodium levels remained stable after discontinuation
of carbamazepine. Six days after the discontinuation of
the carbamazepine, the patient had no further recurrences
of Mobitz II or complete heart block. The patient remained
stable and was transferred to the general medicine service
and discharged home on hospital day 16.
GENERAL CONSIDERATIONS
The
clinical presentation of patients with conduction system
disease is indicated by the existence of three abnormal
conditions: bradycardia, inability to increase the heart
rate in response to increases in metabolic needs, and inappropriately
timed atrial and ventricular depolarization and contraction
sequences.
Sinus
node dysfunction (sick sinus syndrome) is the result
of a degenerative process involving the sinus node and the
sino-atrial area. Approximately 25% of patients with sinus
node dysfunction also have evidence of AV and bundle branch
conduction block. This dysfunction is manifested with marked
sinus bradycardia, pauses in sinus rhythm (sinus arrest),
SA block or combination of these. Similar symptoms can be
experienced by individuals without structural heart disease
under conditions of high vagal tone.
Atrioventricular
block occurs when atrial impulses fail to reach
the ventricles or when atrial impulses are conducted with
a delay.
First
degree:Prolonged
PR interval, exceeding 0.2 seconds. The components of PR
interval are intra-atrial conduction (10-50 msec), AV nodal
conduction (90-150 msec), and intra-His and His-Purkinje
conduction (22-55 msec) so conduction delay in first degree
AV block can represent prolongation in any of these times.
However, by definition, all atrial impulses reach the ventricles.
It is usually an asymptomatic and incidental finding and
can be found in healthy individuals.
Second
degree:
Mobitz Type I-WENCKEBACH: Progressive increase
in PR interval, followed by failure of AV node conduction
and nonoccurrence of a QRS complex. It usually occurs within
the AV node and does not involve the bundle branches, thus
the PR interval of the first conducted P wave of the Wenckebach
period is often prolonged and the QRS complexes are expected
to be narrow and normal appearing.
Mobitz
Type II: Abrupt failure of AV conduction not preceded
by increasing PR intervals. Here, the conduction delay can
be within the bundle of His (narrow, normal appearing QRS)
or, more commonly, distal to the bundle of His in the bundle
branches (bundle branch block pattern).
Third
degree or complete: independent atrial and ventricular
rhythms, with failure of AV conduction despite temporal
opportunity for it to occur. Atrial rate is almost always
faster than ventricular rate, QRS rhythm is an escape rhythm
and the morphology of QRS depends on its site of origin
(AV node, His, bundle branches, Purkinje). Usually occurs
with associated acute coronary syndrome (anterior). The
AV node is innervated by parasympathetic and sympathetic
nervous system and is sensitive to variations in autonomic
tone. It is supplied by the right coronary artery (90%)
or by the circumflex branch (10%). It is commonly influenced
by acute processes such as myocardial infarction (especially
of inferior wall), spasm of the right coronary artery, intoxication
with medications (digoxin, beta-blockers, calcium channel
blockers), infections (viral myocarditis, Lyme, rheumatic
fever, mononucleosis) or miscellaneous causes (sarcoidosis,
amyloidosis, cardiac mesothelioma). AV block can also be
congenital.
Degenerative
Disease: Two degenerative diseases that can be responsible
for damage to the conducting system and produce AV block
usually associated with bundle branch block are Lev’s
disease (involving calcification and sclerosis of the fibrous
cardiac skeleton, aortic and mitral valve, central fibrous
body and ventricular septum) and Lenegre’s disease
(involving the conducting system itself sparing the cardioskeleton
or the myocardium). Also, hypertension, mitral and aortic
stenosis either accelerate degeneration or promote calcification
and fibrosis of conducting system.
THE RATIONALE OF CAD WORKUP
Our
patient was initially thought to have an ACS that compromised
blood supply to the conduction system and gave rise to a
second-degree block. This was ruled out by serial cardiac
enzymes. Investigation of other potential causes such as
thyroid dysfunction and Lyme disease (trip to Maine) were
also negative. Transthoracic echocardiogram showed no area
of hypokinesis and no hemodynamic significance of the already
known interatrial shunt.
We
proceeded with a stress echocardiogram not only to evaluate
any existence of ischemia but also to assess the patient’s
chronotropic 'competence.' Of note, stress testing can be
of substantial value in assessing chronotropic response,
or competence, to increases in metabolic needs. Chronotropic
incompetence is designated when there is documented inability
to achieve a heart rate exceeding 75% of age-predicted maximum
(220-age), of 100-120/min at maximum effort, and actually
suggests sinus node dysfunction. The AV node usually responds
with enhancement of AV conduction to sympathetic drive;
so shorter PR intervals of increased AV conduction ratios
are expected in first and second degree AV block respectively.
Our patient achieved heart rate of about 85% of predicted
and was noted to show pseudo–ST elevation (with fusion
of P and T waves) but not increased AV conduction. So, no
conduction abnormality diagnosis could be established by
stress echocardiogram. Cardiac catheterization was the definitive
test to rule out CAD as the cause of his chest pain.
THE ROLE OF CARBAMAZEPINE
Carbamazepine
is a chemical derivative of tricyclic antidepressants, and
has a similar profile to that of phenytoin. It is particularly
effective in treating many forms of epilepsy as well as
cases of neuropathic pain, i.e. trigeminal neuralgia. It
acts as a sodium channel blocker and it exerts its effects
by interacting with phase I and III of the electric potential,
similar to class 1A antiarrhythmic properties. (In 1999,
degenerative changes in the AV conduction system were linked
to mutations of the SCN5A sodium channel gene). It has been
documented to show negative chronotropic and dromotropic
effects on the cardiac conduction system producing various
types of bradyarrhythmias, mainly atrioventricular block
and sinus arrest. Conduction disturbances generally disappear
after cessation of intake, and can be reproduced with provocation
tests, ie. resumption of the treatment. Dysrhythmias can
be noted while the agent maintains therapeutic levels of
plasma concentration, which suggests that this is not a
dose related side effect and there is no clear relationship
between plasma concentration and frequency of arrhythmic
event. This was illustrated in our patient who showed rhythm
disturbances at nearly sub-therapeutic levels.
It is generally recommended that if syncope or changes in
seizure-type occur in patients treated with carbamazepine,
evaluation of cardiac conduction should ensue. Studies have
shown that carbamazepine is considered safe, with only minimal
effects on the healthy conduction system of young people
(individuals of 40 years or less), in the absence of cardiac
disease. Yet, it does potentially have antiarrhythmic effect.
This is more concerning in the elderly who require careful
monitoring by EKG and plasma drug concentration.
A cause-effect relationship was established in our patient
between carbamazepine and arrhythmias since discontinuation
of regimen led to disappearance of conduction abnormalities.
Despite the fact that carbamazepine-induced cardiotoxicity
was high on the initial differential diagnosis, we were
compelled to do a comprehensive study of cardiac conduction
and rule out CAD before comfortably arriving at this conclusion.
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