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UNUSUAL CAUSES OF MYOCARDIAL ISCHEMIA
55
depression and low voltage, it would be helpful to
put the ED ultrasound probe on the chest, to look
for a pericardial effusion, as the management would
then be different, in terms of the use of heparin and
how the blood pressure should be restored. It would
be interesting to add a fl uid bolus to the usual aspi-
rin and heparin, in a patient who comes in like this,
and see how she handles that. A 31-year-old woman
would also be unusual to present with aortic dissec-
tion, but this still is a possible explanation for some-
one who presents with chest pain, hypotension, and
with EKG changes that may or may not be ischemic.
Pulmonary embolism, often a hard diagnosis to make,
can also present similarly.
DB: Clearly, not all ST elevations are an ST elevation
MI (STEMI). Even though we are in a current climate
that pushes rapid diagnosis and treatment, at the same
time, I think considering the differential diagnosis of
ST elevations is important. You mentioned several:
fi rst, pericarditis or myopericarditis, which is associ-
ated with a pericardial effusion that would distinctly
change the management, particularly with anticoagu-
lation. You also mentioned pulmonary embolism that
could also present like this, and would also change the
when she comes to the ED with a blood pressure of 88
mmHg. I don’t know what her baseline is, but given
that she has a history of hypertension, 88 mmHg is
concerning. Therefore, I must assume that not only is
this patient likely having cardiac ischemia based on her
EKG, she is also in cardiogenic shock. Given all these
things, my refl ex would be to treat her as acute myo-
cardial infarction and cardiogenic shock, and we’ll see
what happens.
DB: Going against the description of cardiogenic
shock is that the lungs are clear on examination, and
she doesn’t appear to be in respiratory distress. Should
this change your approach?
Dr Richard Harrigan: Given that our examinations
are not always perfect, especially when trying to
manage a complicated or potentially sick patient,
an appropriate early approach to this woman would
be covering your bases in terms of cardiac diseases,
which means obtaining the relevant laboratory stud-
ies, starting aspirin, holding nitrates and beta-blockers
with that blood pressure, and perhaps mixing some
heparin while the situation gets clarifi ed. Given the
diffuse EKG changes, even with the absence of PR
Figure 4.1 Unusual cause of myocardial infarction.
CHAPTER 4
56
you will need to be very careful about how you docu-
ment your decision making, and how you verbalize
your thought process with the cardiologists.
RH: In the end, unless cardiology is sitting in the
ED with the echo machine, I would bypass that step.
Using the bedside emergency ultrasound to see if you
have a signifi cant pericardial effusion without looking
at wall motion will at least limit the differential causes
of cardiogenic shock. Early cardiac catheterization is
probably a very appropriate path here. I might take
the time to run serial EKGs because, if you do see
progressive ST-segments climbing or improving with
nitrate therapy or heparin, that’s important informa-
tion that will sharpen your management.
DB: Ten years ago this case would be handled quite
differently; she would get an echocardiogram because
there are enough equivocal pieces to this case: young
age, female gender, EKG fi ndings perhaps in multiple
regions of the heart, and enough atypical historical fea-
tures to warrant getting an echocardiogram to look for
a regional wall motion abnormality. I think the envi-
ronment that we live in today makes that impossible.
We are now judged for our sensitivity for STEMI, not
our specifi city,
SG: Yet, ultimately, our job as physicians, despite con-
stant criticism from others with different agendas, is
to do what is right for the patient. You have to think
hard and fast as to whether you really believe that this
patient needs to go to the catheterization laboratory
emergently without an echocardiogram. What you
don’t want to do is put this patient through a poten-
tially life-threatening procedure that she doesn’t need.
Although I agree that taking her to the catheteriza-
tion laboratory might be the right decision here, you
need to think it through very thoroughly before you
activate the process for an emergent catheterization
setup.
DB: Looking at the laboratory evaluations, the meta-
bolic panel was normal, the complete blood count
was normal, the pregnancy test was negative, a uri-
nalysis was normal, the BNP was normal, the CK was
160, and the troponin I was 0.10, in the normal range
for this laboratory. A chest X-ray study was normal,
and she had been sent for a CT angiography (CTA)
of the chest. Given our concerns for door-to-balloon
time, I doubt we would have chosen a CTA as the
advanced test here. Would you be satisfi ed with an
management. Aortic dissection complicated by occlu-
sion of one of the vessels could also present like this.
So it’s wise for our colleagues to consider the broader
differential of ST elevations on an EKG, even though,
in patients like these, most of the time we will all be
moving faster towards early revascularization.
Dr Peter Rosen: One entity that I always forget is
ventricular aneurysm. It seems unlikely in a young
woman, but she did have a TIA sometime in the past,
and it is possible that was caused by a myocardial
infarction. An early chest X-ray study or cardiac
echocardiogram might confi rm that diagnosis.
DB: In most hospitals, access to formal echocardiog-
raphy is somewhat limited to emergency physicians,
as there are more emergency physicians who are com-
fortable performing a FAST examination, and have
growing ability to interpret a trans-thoracic echo
study. Even when formal cardiac echocardiography
is present, the ability to accurately measure cardiac
output or even left ventricle (LV) function would be
limited to just a few physicians in each facility, so ED
ultrasound may not be an option. Would you recom-
mend a formal echocardiogram as part of the triage
workup here?
SG: Part of my triage process here would entail involv-
ing cardiology early, since there are a number of things
that cardiology can do besides activating the catheter-
ization laboratory. Having cardiology involved for a
formal detailed echocardiogram may help ensure that
the patient doesn’t end up with a procedure they don’t
need, such as a catheterization.
DB: If this person does, in fact, have a STEMI, are you
concerned that if you obtain an emergent echocardio-
gram, you are going to be criticized for increasing
door-to-balloon time beyond the expected treatment
window of 90 minutes?
Dr Edward Ullman: The differential diagnosis for this
patient is large, and I think this concern depends on
how you focus in on it. If you say, “I’m worried that
this is a STEMI,” then I think you are going to be
criticized if it goes over 90 minutes. You potentially
can pursue multiple pathways by opening the labora-
tory, while at the same time telling cardiology “I’m
not 100% sure, but my thinking is that a stat echocar-
diogram will slow you down, and you are going to
have to give up the 90 minute window.” Therefore,
UNUSUAL CAUSES OF MYOCARDIAL ISCHEMIA
57
looking for wall motion, but also looking at right ven-
tricle (RV) function to give us prognostic information
as to whether this is a massive pulmonary embolus
causing the patient to be in shock, and to help guide
the need for thrombolytic therapy.
RH: Echocardiography is a poor man’s indicator of
massive or sub-massive PE. Yet this type of PE is best
identifi ed by BNP or troponin elevation, and you don’t
have those, nor do you have a low O
2
saturation,
unusual in the hypothetical setting of a PE causing
hypotension. It seems like every time I pick an avenue
to go on in this case, I am stymied by something lead-
ing me in another direction.
DB: We’ve talked a lot about the differential diagnosis
and the initial diagnostic testing. What about response
to therapy? This woman is treated initially with fl uids.
Would you be reassured if the patient became nor-
motensive after 500 cc of normal saline? Would that
reassure you that you weren’t dealing with a massive
PE or tamponade from some cause?
EU: With a PE, if she responded to 500 cc, my suspi-
cion for a massive PE would drop, particularly given an
O
2
sat of 100% and this person looking relatively well.
I would still worry about tamponade, as I don’t know
what will happen 10 minutes after the fl uid bolus. Did
she become hypotensive again? If the pressure does
drop again, then I’d be fairly concerned about tam-
ponade. The EKG doesn’t have low voltage or sinus
tachycardia, and this further lowers my concerns for
tamponade or PE.
DB: We still haven’t completely excluded pericarditis
with pericardial tamponade that resulted from hemor-
rhagic conversion of a pericardial effusion related to
the aspirin and clopidigrel used, or less likely, although
still possible, aortic dissection with rupture into the
pericardium. Therefore, I would withhold giving this
patient unfractionated heparin until I was more certain
of what was going on, given that it adds very little to
the treatment of STEMI in the absence of revascular-
ization as well. It could be added at the time of revas-
cularization in the catheter laboratory, if that turns
out to be what we are dealing with. If this really is a
massive PE, I don’t think that unfractionated heparin
would make that much of a difference and the patient
becomes a candidate for thrombolytic therapy. My
next step after the EKG in initial evaluation would be
cardiac catheterization.
Elisa D-dimer that was negative, and forgoing the
CTA in this patient?
EU: The clinical course evolved with hypotension, inter-
mittent chest pain, EKG changes, and neurologic fi nd-
ings, including weakness in the upper extremities. This
makes me wonder whether the CT angiography was
chosen for pulmonary embolism (PE) or for dissection.
RH: As it turns out, these were not new focal neuro-
logical fi ndings. Given concerns about her shortness
of breath, her age group, and her chest pain, she went
for a CTA utilizing a rule out PE protocol.
EU: Going after PE, in this case, strikes me as a little
odd. I would not have gone there fi rst, given an EKG
with infero-lateral ST-segment elevation, a normal
troponin, and hypotension. If someone was hypoten-
sive from a PE, there should be some troponin or BNP
elevation, indicating some kind of strain on the heart.
I don’t think I would have ordered a D-dimer either,
as I might not believe the result and waiting for this
result would also have consumed precious time needed
to send the patient to the catheterization laboratory.
DB: This is a very challenging presentation, as there
are some features that are atypical for just about all of
the diagnoses we have considered so far. My concern
with going to CTA for PE as the fi rst test is that you
use an opportunity to give IV contrast; when that CTA
is negative, you are still left with “is this a STEMI or
not,” and you are going to end up taking this patient
to the catheterization laboratory and subjecting her to
a second round of contrast. I would prefer instead to
proceed rapidly to cardiac catheterization, clear her
coronary anatomy with angiography, do an LV-gram
to understand what’s going on with her LV function,
and if all of that is normal, than we can move on to a
right heart catheterization looking at right-sided pres-
sures and an echocardiogram.
RH: If you are content that it’s not an aortic dissec-
tion, you could say, “I’m going to cover my bases with
heparin,” because if this is a PE or coronary ischemia,
heparin will be useful.
SG: Given that this is a patient who is hypotense, if
she is having a PE, she may be an appropriate candi-
date for thrombolysis. We know that the sooner you
lyse this patient, the more likely you are to have some
benefi t. If I am not going to send this patient for CTA,
perhaps I should do an echocardiogram. Not only
CHAPTER 4
58
SG: The most likely etiologies at this point are either
coronary vasospasm or a Takotsubo cardiomyopathy.
There are other forms of cardiomyopathy that may
cause depressed left ventricular function, but these
myopathies are more likely to cause a global hypoki-
nesis without regional wall variation.
DB: What would be the next step in management of
this patient, as the patient leaves the catheterization
laboratory?
RH: These patients are initially managed as acute
coronary syndromes. With stable vital signs, now that
you know there is no the coronary artery disease, you
can withdraw the therapy that is given for ACS such as
clopidigrel and heparin. Occasionally, a LV thrombus
is described with apical ballooning syndrome, and in
that instance, heparin might still be useful, but this is
not the norm. If there is evidence by echocardiogram
of outfl ow obstruction, then beta-blockade would be
helpful for relaxation of the hyperkinetic segment.
Beta-blockade would have been reasonable in coro-
nary artery syndrome as well, and may have already
been started. If there is overt cardiac failure with
this diminished left ventricular function, then further
beta-blockade acutely would probably not be helpful;
instead, after load reduction, if the blood pressure tol-
erates it, would be more advantageous.
DB: This is a diagnosis that we are not likely to be able
to make accurately in the ED. The pathognomonic
features do not allow us or our colleagues to make
this diagnosis defi nitively up front. Most of these cases
will go to the catheterization laboratory for coronary
angiography, and the diagnosis will be made when the
coronaries appear normal and not obstructed, and
the apical ballooning is found on left ventriculogram.
In retrospect, since many of these cases are believed
to be preceded by a period of intense stress or cat-
echolamine excess, was there anything in the history
that in retrospect could have been a clue?
RH: When we went back and talked to her some
more, she did report more serious life stressors imme-
diately preceding the development of symptoms.
Unfortunately, this history was not elicited on presen-
tation. Although this syndrome has been classically
associated with a single antecedent event, these car-
diac catheterization fi ndings have also been described
in people where a single precipitating event cannot be
identifi ed.
DB: The hypotension evident on admission improved
with intravenous normal saline. During the admission
process, the patient intermittently experienced chest
pain. Repeat cardiac enzymes were elevated with a
peak troponin I of 3.1, and the EKG remained abnor-
mal. Unfractionated heparin was started in light of
the EKG changes and presumed acute coronary syn-
drome (ACS), and plans for emergent cardiac cath-
eterization were made. Since a second set of cardiac
markers were obtained, was it wise to hold off on
cardiac catheterization?
RH: Given that she looked better and the EKG
was static, and despite a worrisome EKG here, the
ST-segments were not classically territorial injury
changes. Although all of us may have pushed for ear-
lier catheterization, I understand somewhat how this
unfolded.
PR: When you are facing a complex problem that has
many contradictory and all life-threatening explana-
tions, you have to expect that you can’t get all of them
eliminated in a timely fashion. Our best strategy is to
select the course that will give us maximum informa-
tion, while stabilizing the patient. That choice will also
have to be dependent upon the local facility; in a ter-
tiary care center, it may be easy to mobilize the catheter
laboratory 24 hours a day, but in another institution
the catheterization team may have to come in from
home, and it might be more prudent to select a differ-
ent imaging study such as a CTA, as was done here.
Since there is no clear-cut correct answer, one must be
guided by your institution, and your consultants, to do
something. The clear wrong answer is to do nothing.
DB: An echocardiogram was obtained that showed
moderate to marked LV dilatation, a decreased ejec-
tion fraction of 20% in each chamber, and akinesis
of the apical walls and hypokinesis of the mid-apical,
infraseptal, and antero-lateral walls of the LV. There
was mild to moderate mitral regurgitation. Coronary
angiography revealed no evidence of coronary artery
disease, and confi rmed the wall motion abnormality
seen on echocardiogram. Ejection fraction was calcu-
lated to be 47%. Without being able to see the echo or
the LV gram, what is being described here is akinesis of
the apex and severe hypokinesis of the distal anterior
wall and septal wall and lateral wall. What is the dif-
ferential diagnosis at this point in this patient without
coronary artery disease?
UNUSUAL CAUSES OF MYOCARDIAL ISCHEMIA
59
mitral regurgitation. Coronary angiography revealed
no angiographic evidence of coronary artery disease
and confi rmed the wall motion abnormalities seen on
echocardiogram, although the ejection fraction was
calculated to be 47%.
A working diagnosis of Takotsubo cardiomyopathy
was established. In retrospect, the patient reported
signifi cant life stressors coincident with her present-
ing event. Irbesartan/hydrochlorothiazide and clopi-
dogrel were discontinued, and she was discharged
on metoprolol, atorvastatin, aspirin, and lisinopril.
Repeat echocardiogram at 11 days post-presentation
showed normalization of the ejection fraction (50%)
without any regional wall motion abnormalities. The
motor weakness improved with potassium repletion,
and neurology consultation and work-up revealed no
alternative cause for the neurologic symptoms.
Section III: Concepts
Although there are numerous unusual causes of car-
diac ischemia, this chapter focuses on eight salient
causes: coronary embolism, coronary artery dissec-
tion, aortic dissection with coronary occlusion, con-
genital coronary artery anomalies, carbon monoxide
poisoning, coronary vasospasm, thyrotoxicosis, and
Takotsubo cardiomyopathy.
Coronary embolism
Coronary embolism has long been known as a non-
atherosclerotic cause of cardiac ischemia, fi rst being
described by Virchow in 1856. Embolism may arise
from many sources, including mural thrombi, valvular
vegetations, atherosclerotic plaques, atrial myxomas,
or paradoxically from the systemic veins.
1,2
Depending
on the size of the embolus, symptoms of a coronary
embolism can range from silent and undetected to a
massive myocardial infarction (MI) leading to sudden
death. Emboli are three to four times more likely to
enter the left coronary artery than the right coronary
artery because of its larger diameter.
3,4
Emboli occur acutely in patients, unlike those with
atherosclerotic changes where there is a gradual nar-
rowing. The acute coronary occlusion causes trans-
mural infarction with more extensive areas of damage.
Even small emboli that lodge distally in the coronary
arteries can cause infarction, although the vessel may
SG: Had the case been just slightly different where the
EKG were a little less suggestive of an acute STEMI,
and there were perhaps diffuse ST depressions or
some less specifi c fi nding, this patient might have been
an excellent candidate for a coronary CT scan. When
there is no pressure for emergent catheterization, cor-
onary CT scan may be very useful in helping to rule
out cardiac ischemia completely. Perhaps this may be
the ED test that we need to utilize more routinely in
this patient population, particularly when you have a
concomitant history of a major stressor that may have
precipitated the event.
DB: I like the idea of doing a CT scan of the chest in
this patient, because you may get information about
the aorta and the pulmonary arteries as well as the
coronary arteries. The one contraindication is that
coronary CT is done with the co-administration of
nitroglycerin, and her blood pressure may not toler-
ate this, unless it had responded to the IV fl uid bolus.
Most of these patients with documented Takotsubo
cardiomyopathy tend to improve markedly. It appears
that most of the LV dysfunction is myocardial stun-
ning rather than myocardial infarction.
This is a very interesting case, and serves to highlight
some of the challenges we face in those patients who
present with ST elevations on EKG, but with symp-
toms that are confl icting in terms of the diagnosis. It
is easy, in retrospect, to select the proper test in the
proper order, but when your boots are on the ground
in the ED, it is a lot more challenging. Do we have
any longer follow-up on this patient to get a sense of
whether she proved over time that her ejection frac-
tion came back to normal?
Case resolution
The hypotension evident on admission improved with
intravenous normal saline. During the admission pro-
cess, the patient intermittently experienced chest pain;
repeat cardiac enzymes were elevated with a peak
troponin I of 3.1, and the EKG remained abnormal.
Unfractionated heparin was started in light of the EKG
changes and presumed acute coronary syndrome. An
echocardiogram showed moderate to marked LV
dilatation, a decreased ejection fraction (20%), aki-
nesis of the apical walls, and severe hypokinesis of
the mid-apical anteroseptal, inferolateral and antero-
lateral walls of the LV. There was mild-to-moderate
CHAPTER 4
60
coronary artery dissections consisting of only a small
subset of all myocardial infarctions.
6
Motor vehi-
cle collisions are the most common mechanism of
injury.
6,7
The left anterior descending artery (LAD) is
the most commonly injured artery (71%), followed
by the right coronary artery (RCA) (19%), the left
main artery (7%), and the left circumfl ex artery
(3%).
6
Coronary artery dissection as a result of aortic
dissection will be discussed separately.
Spontaneous coronary artery dissection is rare. It
affects young women (mean age 38) in 80% of cases,
one-third of whom are in their third trimester of
pregnancy or postpartum period, and most of whom
have no cardiac risk factors.
8–11
Men who experience
spontaneous coronary artery dissection tend to be
older, and have one or more risk factors for ASCAD.
The LAD is the most commonly-affected artery with
spontaneous coronary artery dissection; however,
there does seem to be a predilection based on gender.
Women tend to have left-sided dissections, while men
have a higher involvement of the right coronary sys-
tem, with up to two-thirds of men reported to have
RCA dissections.
8,10,11
Men tend to have better sur-
vival rates after spontaneous dissection than women,
although up to 70% of cases are diagnosed at autopsy
after sudden death.
8,9,12
Clinical presentation of coronary artery dissection
can range from asymptomatic to unstable angina, car-
diogenic shock, acute myocardial infarction, or sud-
den death depending on the location, extent, and rate
of dissection.
10
The EKG changes will be consistent
with the myocardial territory of the vessel involved,
with anterolateral involvement correlating to the LAD
being the most common. Traumatic coronary artery
dissection should be considered in patients who com-
plain of ischemic chest pain symptoms in conjunction
with signifi cant blunt trauma to the chest and pres-
ence of large chest wall contusions, sternal or thoracic
vertebral fractures, or mediastinal hematomas. An
EKG should be obtained after the patient is stabi-
lized from a trauma perspective. Spontaneous coro-
nary artery dissection should be strongly considered
in a late pregnancy or postpartum woman with no
ASCAD risk factors who presents with myocardial
ischemia or infarction.
Myocardial injury from coronary artery dissection
is treated similarly to injury with ASCAD with mor-
phine, nitrates, aspirin, oxygen, and anticoagulation.
Fibrinolytic therapy should be avoided in this patient
undergo recanalization, which may lead to angio-
graphically normal coronary arteries.
3
As a result of
the complete occlusion, the EKG most often shows
ST-segment elevation in cases of coronary embolism.
Because the left coronary system is more commonly
affected, ST-segment changes are seen in the anterior
leads most frequently.
History and physical examination fi ndings can
provide clues that the cardiac event was caused by
a coronary embolism instead of atherosclerotic dis-
ease. Patients with coronary embolism historically do
not have preceding angina symptoms. These patients
do not have risk factors for atherosclerotic disease,
but may have a history of atrial fi brillation, left ven-
tricle aneurysm, a prosthetic heart valve, or infective
endocarditis.
4
If embolic infarction is suspected, it is
important to ascertain symptoms that might suggest
emboli to the cerebral and mesenteric vascular beds.
The physical examination may suggest a source of the
embolus; for instance, there may be fi ndings consis-
tent with infective endocarditis, atrial fi brillation, or
deep venous thrombosis.
Treatment for cardiac infarction caused by coro-
nary embolism is similar to that of infarction caused
by atherosclerotic coronary artery disease (ASCAD).
Morphine, aspirin, nitrates, oxygen, and anticoagula-
tion are fi rst line therapies for embolic occlusion. If
the embolus is thought to have originated from the
cardiac valves (either infective endocarditis or from
a prosthetic valve thrombus), fi brinolytic therapy
should be avoided because of the risk of cerebral
embolism.
4,5
Coronary angiography may identify the
embolus and allow for removal or lysis to restore cor-
onary fl ow. A small embolus may undergo spontane-
ous lysis, resulting in normal coronary arteries at the
time of angiography.
Coronary artery dissection
Coronary artery dissection can occur after blunt
chest trauma, as a complication of coronary angiog-
raphy, as an extension of an aortic dissection, or
spontaneously. Similar to coronary embolism, coro-
nary artery dissections may be small and clinically
silent, or may involve the length of the vessel and
cause complete occlusion and massive myocardial
infarction and death.
Myocardial infarction from coronary vessel injury
after blunt trauma is a rare occurrence, with traumatic
UNUSUAL CAUSES OF MYOCARDIAL ISCHEMIA
61
Diagnosis and treatment of aortic dissection with
coronary artery occlusion is vastly different from
ASCAD. One must obtain timely advanced imag-
ing with computed tomography or transesophageal
echocardiography.
14
Pain control and blood pressure
management with morphine and beta-blockers should
be initiated to prevent extension of the dissection, and
to decrease myocardial demand. Anticoagulation and
fi brinolysis are contraindicated, and can signifi cantly
worsen the patient’s condition. Surgery is the defi nitive
treatment strategy for patients with Stanford class A
dissections with coronary involvement, often requiring
CABG to restore myocardial blood fl ow.
14,15
Congenital coronary artery anomalies
Congenital coronary artery anomalies are an elusive
cause of myocardial ischemia and infarction. While
coronary anomalies are known to occur in about
1% of the general population, it is not fully known
what role they play in causing relevant clinical
consequences.
19
Coronary anomalies often become
symptomatic in young, otherwise healthy people who
are involved in vigorous activity. They have been
thought to be the cause of sudden death, myocardial
infarction, chest pain, syncope, and rarely reproduc-
ible exercise-induced angina.
19,20
In patients who present to the ED, symptoms are
likely to have resolved with the cessation of vigorous
activity. Look for myocardial ischemia from coronary
anomalies in young athletes who present with exer-
tional chest pain or syncope. Ischemia from coronary
anomalies is thought to be caused by coronary spasm
and lack of collateral fl ow.
19
There are data to suggest
that thrombus formation is not an integral component
of vascular occlusion.
21
Therefore, treatment for these
patients begins with pain control and oxygen therapy,
with coronary angioplasty for defi nitive diagnosis.
Carbon monoxide poisoning
Carbon monoxide (CO) has long been known to
cause myocardial injury, and was fi rst described in
1865.
22
Cardiotoxicity occurs after carbon monoxide
exposure in patients with and without underlying ath-
erosclerotic disease. At carboxyhemoglobin (CoHb)
levels greater than 25%, myocardial ischemia is likely,
although in patients with ASCAD, ischemia can occur
at much lower levels.
23,24
population, as it may cause propagation of the dis-
section by restoring blood fl ow in the false lumen.
10
Distinguishing coronary artery dissection from ath-
erosclerotic occlusion can only be done by coronary
angiography. Placement of coronary stents during angiog-
raphy is becoming more favored, especially with single-
vessel dissections, while coronary artery bypass grafting
(CABG) is being reserved for multi-vessel dissections or
those complicated by atherosclerosis.
10
Medical therapy
alone has also been shown to be successful.
8
Aortic dissection with coronary occlusion
Aortic dissection is a disease that often occurs in
patients who suffer from hypertension and atheroscle-
rosis. Atherosclerotic plaques cause weakness in the
vessel’s intima and media, and false lumens form as a
result of the increased pressure. There is also an asso-
ciation of aortic dissection in patients with connective
tissue disorders such as Marfan’s or Ehlers-Danlos
syndromes. Weakness in the elastin and microfi brils
cause the aorta to be susceptible to the constant pres-
sure and turbulent fl ow of blood through the ascend-
ing aorta.
13
Stanford type A aortic dissection, those involving
the ascending aorta, can potentially propagate in a
retrograde fashion to involve the coronary arteries,
although this is uncommon.
14
When it does occur,
occlusion of the coronary artery leading to ischemia
or infarction may result from direct mural exten-
sion of the dissection, extravasation of blood into
the pericardial and perivascular tissues, or via direct
compression from the expanding hematoma.
15–17
When an aortic dissection does involve the coronary
arteries, it is more likely to involve the right coronary
artery.
15
Classically, aortic dissection has a more acute onset
of sharp, severe tearing chest pain than with the
more dull, insidious pain associated with ASCAD.
Additionally, young patients who have known con-
nective tissue disorders should be suspected of having
aortic dissection with coronary involvement when pre-
senting with coronary ischemia or infarction. Physical
examination fi ndings consistent with ascending aortic
dissection, such as unequal pulses and blood pressure
measurements, neurologic defi cits, a new aortic insuf-
fi ciency murmur, or signs of pericardial tamponade,
as well as with Marfan’s-like physical features, should
be sought.
4,14,18
CHAPTER 4
62
Coronary vasospasm
Coronary vasospasm, also called Prinzmetal’s angina
was fi rst described by Prinzmetal in 1959 as a “vari-
ant” cause of ST-segment elevation and chest pain.
Vasospasm usually occurs at a single site in the blood
vessel, and can occur in patients with and without
underlying ASCAD.
27
While the etiology of Prinzmetal’s
angina is not entirely known, it is hypothesized that it
occurs because of endothelial dysfunction and activa-
tion of the autonomic nervous system, specifi cally the
alpha-adrenergic receptors.
27
Prinzmetal’s angina has
been associated with other vasospastic disorders such as
Raynaud’s disease and migraines; the vasospasm may
be provoked by cocaine, alcohol, or nicotine abuse;
hyperventilation; beta-blocker overdoses; and rapid eye
movement sleep.
27–29
Often, the ST-segment elevation seen on the EKG
can be resolved with nitroglycerin, thus aborting the
coronary vasospasm and preventing cardiac necro-
sis. However, myocardial infarction can result if the
vasospasm occurs at the site of an atherosclerotic
plaque, leading to complete occlusion; more com-
monly, myocardial infarction occurs if the spasm
leads to endothelial injury, platelet aggregation, and
thrombus formation.
30
In addition to ischemia and
infarction, Prinzmetal’s angina is also associated
with sudden death and various dysrhythmias dur-
ing periods of ST-segment elevation, including ven-
tricular tachycardia, third-degree heart block, and
asystole.
27
Coronary vasospasm typically occurs in young
females whose only cardiac risk factor is tobacco
smoking.
27,31
The pain often occurs at rest in a circa-
dian pattern, developing in the early morning hours.
The pain is not affected by myocardial demand, and
thus cannot be provoked with exercise stress testing.
Historical clues of the timing of symptoms, other
vasospastic symptoms such as headache patterns
and cold intolerance with skin changes, or recent
cocaine use, may aid in differentiation from typical
ASCAD.
Medical therapy is the mainstay of treatment for
Prinzmetal’s angina. Nitroglycerin and calcium chan-
nel blockers are both highly effective at resolving the
patient’s chest pain and EKG changes associated
with coronary vasospasm.
27,29
Aspirin and mor-
phine are reasonable adjuncts. Beta-blockers should
be avoided in patients with suspected coronary
Carbon monoxide exerts its damage to the myocar-
dium through multiple mechanisms. It has been shown
to cause diffuse and punctuate hemorrhages involving
the pericardium and endocardium, as well as myo-
cardial fi ber degeneration and necrosis.
22,23
While CO
can act directly on the coronary arteries to reduce vas-
cular resistance, it appears as though the subendocar-
dial blood fl ow only marginally increases, resulting in
tissue that remains hypoperfused.
25
Myocardial con-
tractility is also decreased after CO exposure. This is
due to a combination of tissue hypoxia from reduced
oxygen delivery, as well as from direct myocardial
depression and mitochondrial dysfunction.
22,23,26
There are various EKG changes that can be seen
with CO poisoning, ranging from sinus tachycardia
to nonspecifi c ST-segment changes to ST-segment ele-
vation. Cardiac biomarkers and an EKG should be
obtained in all patients with signifi cant CO exposure.
A study by Satran, et al. fi nds that 30% of patients
presenting with CO toxicity have ischemic EKG
changes.
26
Of these patients, 64% have positive bio-
markers. Overall, 35% of patients in this study had
positive biomarkers, with 53% of them revealing
ischemic EKG changes.
26
Obtaining historical clues for CO poisoning will
help differentiate patients with CO-induced myocar-
dial ischemia. CO poisoning should be considered in
patients who additionally complain of dyspnea, head-
ache, nausea, or altered sensorium, or who present in
clusters from the same environment. Patients without
a history of cardiac disease who have cardiac isch-
emia from CO toxicity tend to be younger and have
more profound CO poisoning (Glasgow Coma Scale
[GCS] ⬍14) and global left ventricular involvement.
Those patients with known ASCAD tend to be older,
and have a normal GCS with regional wall motion
abnormalities.
26
There may be a history of worsening
anginal symptoms in patients with previously stable
angina.
Treatment of cardiac ischemia from CO poison-
ing requires early recognition. Aspirin and aggres-
sive oxygen therapy should be initiated, followed by
hyperbaric oxygen treatments. Hyperbaric oxygen
is indicated for patients with ischemic chest pain,
elevated biomarkers, ischemic EKG changes, or sig-
nifi cant dysrhythmias. For those patients with known
ASCAD who suffer ischemia after CO poisoning,
there may be benefi t in coronary angiography and
revascularization after hyperbaric therapy.
UNUSUAL CAUSES OF MYOCARDIAL ISCHEMIA
63
Similarly, they may be differentiated from those
patients with Prinzmetal’s angina in the timing of
their symptoms; those with thyrotoxicosis-induced
vasospasm have no association with the time of day,
while those with Prinzmetal’s angina have symptoms
that most often occur in the early morning hours.
32
Additional symptoms of thyrotoxicosis may be elic-
ited such as unintentional weight loss, hair loss, palpi-
tations, insomnia, or tremor. Examination fi ndings of
exophthalmos and thyroid tenderness, enlargement,
or bruit will support thyrotoxicosis as the cause of
coronary ischemia.
Initial treatment of patients with myocardial isch-
emia from thyrotoxicosis should include the standard
treatment for ASCAD-associated ischemia (aspirin,
morphine, oxygen, and anticoagulation). If thyro-
toxicosis as the cause of myocardial ischemia is not
thought of and sought, and left untreated, the patient
is at increased risk of thyroid storm.
33
Initial beta-
blocker treatment will decrease myocardial oxygen
demand, and may improve underlying vasospasm.
Coronary angiography is useful in patients with
suspected thyrotoxicosis-induced ischemia because
of the potentially increased risk of thrombosis in
those with underlying ASCAD as well as those with
potential vasospasm. In most cases, treatment of the
thyrotoxic state with antithyroid treatment (such as
propylthiouracil and Lugol’s solution) will reverse the
cardiac effects.
Takotsubo cardiomyopathy
Recognized relatively recently, another clinical entity
that presents virtually indistinguishably from acute cor-
onary syndrome is Takotsubo cardiomyopathy (TC),
also known as apical ballooning syndrome, stress car-
diomyopathy, “broken heart” syndrome, and ampulla
cardiomyopathy.
37,38
Originally described in 1990 in
the Japanese literature, it has now been reported across
the globe and has been recognized by the American
Heart Association since 1996 as a primary acquired
cardiomyopathy.
38
The name “tako-tsubo” derives
from the Japanese fi shing term for a round-bottomed,
narrow-necked pot used to trap octopi (tako, “octo-
pus” and tsubo, “jar”). This jar bears a striking resem-
blance to the systolic images of the left ventricle during
cardiac catheterization in patients with TC, where the
cardiac apex “balloons” out despite contraction of the
hyperkinetic cardiac base.
38,39
vasospasm because the unopposed alpha-adrenergic
activity can worsen the spasm.
28
Anticoagulation and
fi brinolysis may be of benefi t if the patient’s symp-
toms and ST-segment elevations do not resolve with
nitroglycerin because of the potential for thrombus
formation after prolonged vasospasm. Defi nitive
diagnosis should be made with coronary angiogra-
phy. Not only can provocative testing be done of sus-
pect vasospastic arteries with ergonovine, but also
it is important that underlying ASCAD be identifi ed
and treated.
27,29
Thyrotoxicosis
Thyrotoxicosis is a complex disease with multiple
pathologic effects that increase one’s risk for cardiac
disease, including congestive heart failure, dysrhyth-
mias, and myocardial ischemia. Similar to the other
unusual causes of myocardial ischemia, thyrotoxicosis
can affect those patients with and without underly-
ing atherosclerosis. Exercise intolerance and anginal
complaints are common in this patient population.
32,33
Even those with only mild hyperthyroidism have a
higher cardiovascular mortality than those who are
euthyroid.
34
In the thyrotoxic state, there is an increase in cardiac
output and myocardial contractility, leading to higher
myocardial oxygen demand. Increases in circulating
blood volume cause increased wall stress on the heart
and decreased contractile reserve, which may signifi -
cantly affect the left ventricular workload, especially
during exercise.
35
These factors can cause an other-
wise insignifi cant atherosclerotic plaque to become
symptomatic. Coronary spasm is well known to occur
during thyrotoxicosis, although the mechanism is not
clear. Vasospasm can affect both normal and diseased
vessels. It is thought that there is increased sensitiv-
ity of the coronary arteries to catecholamines and
higher concentrations of beta-adrenergic receptors,
with a down regulation of alpha-adrenergic recep-
tors limiting vasodilation and promoting vasocon-
striction.
33
Additionally, elevated levels of fi brinogen
have been found during hyperthyroid states, which
may contribute to increased risk of thrombosis and
coronary events.
36
Historically, patients with angina secondary to thy-
rotoxicosis have a more rapid progression of their
angina symptoms, and have more episodes occur-
ring at rest than those patients with typical ASCAD.
32
CHAPTER 4
64
Absence of obstructive coronary disease or angio-2
graphic evidence of acute plaque rupture;
New electrocardiographic abnormalities (either ST- 3
segment elevation or T wave inversion) or modest
elevation in cardiac troponin level;
Absence of pheochromocytoma and myocarditis.4
The EKG in TC (Figure 4-1) traditionally demon-
strates fi ndings consistent with STEMI.
38–41
More
recently, a spectrum of EKG changes have been elu-
cidated. One series of 59 patients fi nds anterior
ST-segment elevation to be the most common fi nding
(56%), with T wave inversion being next most com-
mon (17%)
43
; another series of 105 patients fi nds
ST-segment elevation/new left bundle branch block,
T wave inversion (⬎3 mm in three contiguous leads),
and nonspecifi c ST-T abnormalities. A normal EKG is
present about one-third of the time.
44
The possibility
that these variants are actually different electrocardio-
graphic evolutionary stages is supported by Mitsuma
and colleagues, who fi nd four distinct electrocardio-
graphic phases when following daily serial tracings
in nine patients: (1) ST-segment elevation, (2) T wave
inversion (days 1–3), (3) transient improvement in T
wave inversion (days 2–6), (4) deeper T wave inver-
sion (up until about 2 months), followed by recovery.
45
ST-segment elevation appears typically in the precordial
leads, but may occur in the inferior or lateral leads.
38
Q waves and reciprocal changes are not the rule but
may appear; QT prolongation occurs, but also tends to
resolve over time.
38
Electrocardiographic presentation
does not seem to predict outcomes.
44
Cardiac troponins
are invariably elevated, although the degree of eleva-
tion is generally less than that seen with STEMI.
38,43
The diagnosis is made at cardiac catheterization.
Takotsubo cardiomyopathy typically features nonob-
structive coronary artery disease or normal vessels;
obstructive disease is rare. Hypokinesis or akinesis
of the mid and apical segments of the left ventricle
are seen on ventriculogram, while systolic function at
the cardiac base is either spared or hyperkinetic. Wall
motion abnormalities extend beyond the territory of a
single coronary vessel. Right ventricular involvement
is seen in roughly 30% of patients, and portends a
more severe clinical course. Other imaging modalities
may capture the characteristic ventricular fi ndings,
including echocardiography, computed tomography,
and magnetic resonance imaging; echocardiography
is useful to detect clinically signifi cant left ventricular
outfl ow tract obstruction.
38,46
Although the true incidence is still unknown, it
is estimated that, among individuals with an initial
diagnosis of acute coronary syndrome or myocardial
infarction, 1–2% are actually due to TC. Roughly
90% of cases occur in women, most of whom are post-
menopausal, with an estimated 3% of cases occurring
in women under 50 years of age.
38,40
Correspondingly,
a hormonal-protective effect has been advanced to
explain this age and gender bias.
38
Pathophysiology
of the disease is still incompletely understood; vari-
ous considerations include catecholamine-mediated
myocardial stunning, epicardial microvascular spasm,
and myocarditis, although the latter is considered
unlikely.
37–40
A critical feature of the disease is the
absence of signifi cant obstructive coronary disease
at cardiac catheterization, despite clinical evidence
of acute coronary syndrome, manifested by patient
symptoms, electrocardiographic changes, and serum
cardiac enzyme elevations. A recent case registry
demonstrates an increase in occurrence during the
summer months (contrary to that seen in traditional
acute MI), although cases do present throughout the
year.
41
On clinical presentation, TC presents like an acute
coronary syndrome; bedside differentiation is not reli-
ably possible. Anginal symptoms (chest pain, dysp-
nea) predominate, with or without clinical evidence of
congestive heart failure. Syncope and prehospital car-
diac arrest are unusual. Hypotension may be evident,
but frank hemodynamic compromise is not the norm.
The hypotension may be due to systolic reduction in
stroke volume or dynamic obstruction of the left ven-
tricular outfl ow tract. A prior history of hypertension
and an antecedent stressful event (e.g., argument or
altercation, signifi cant medical illness—thus the term
“stress cardiomyopathy”) are more commonly associ-
ated, but not universal.
38,40–42
The classic presentation
would be a postmenopausal woman presenting with
chest pain or dyspnea after a stressful exchange, with
electrocardiographic changes.
The Mayo Clinic criteria for TC are widely ref-
erenced for syndrome defi nition; they include the
following
38
:
Transient hypokinesis, akinesis, or dyskinesis of the 1
left ventricular mid-segments with or without api-
cal involvement; the regional wall motion abnor-
malities extend beyond a single epicardial vascular
distribution; a stressful trigger is often, but not
always present;