Clinical Review & Education
Challenges in Clinical Electrocardiography
Electrocardiography Evolution in a Woman Presenting
With Alcohol Withdrawal Seizures and Cocaine Use
Jonathan Chou, MD, PhD; Lisa R. Beutler, MD, PhD; Nora Goldschlager, MD
A postmenopausal woman with a history of alcohol abuse compli-
cated by withdrawal seizures (last occurring 4 months prior), crack
cocaine abuse, and depression was brought into the emergency de-
partment for altered mental status after 3 witnessed seizures. Her
partner stated that the evening prior, she did not drink alcohol but
did snort cocaine.
She was afebrile and arousable but not oriented. Her heart rate
was 85 beats per minute and blood pressure was 135/90 mm Hg. Car-
diopulmonary examination results were within normal limits, and neu-
rologic examination revealed no focal deficits. Results from com-
plete blood cell count and electrolyte panel were normal, and a urine
toxicology screen was positive for cocaine. Results from a noncon-
trast head computed tomographic (CT) scan were normal. Her initial
electrocardiography (ECG) test showed normal sinus rhythm with Q
waves in the anterior leads and early repolarization (Figure, A). Over
the next 7 hours, her mental status improved, and she remained sei-
zure-free. The patient was about to be discharged when ST-segment
elevations were noted on the MCL3 telemetry lead. A 12-lead ECG
demonstrated ST-segment elevations in leads V3 to V6 (Figure, B). On
further questioning, the patient reported a 1-day history of mild, con-
stant, nonradiating, nonnitroglycerin-responsive chest ache at rest
but denied exertional chest pain. Her troponin level, drawn when the
ST-segment elevations were noted, was 3.2 ng/mL.
Questions: What is your differential diagnosis of the ST-
segment elevations in this context, and what would you do next?
Clinical Course
Despite these ECG changes, the patient denied any crushing or pres-
sure-like chest pain and was in no acute distress. Bedside ultraso-
nography demonstrated dyskinesis of the left ventricular apex. She
was transferred to the cardiology service for monitoring, given as-
pirin, 325 mg, atorvastatin, 80 mg, and begun on a heparin drip. She
was not taken emergently to cardiac catheterization, given the
atypical history and quality of chest discomfort and the ultrasono-
graphic finding of left apical ballooning, which was highly suspi-
cious, but not diagnostic for stress (takotsubo) cardiomyopathy. Re-
peated ECG 4 hours later demonstrated persistent ST-segment
elevations in V3, as well as new T-wave inversions (TWIs) in leads V4
to V6 (Figure, C). The troponin level decreased to 2.6 ng/mL. A trans-
thoracic echocardiogram revealed akinesis of the left ventricular
apex, apical ballooning, and a hyperdynamic base; the ejection frac-
tion was 40% to 45%. The patient underwent coronary angiogra-
phy the next morning, which demonstrated diffuse nonobstruc-
tive coronary disease without evidence of vasospasm. Given these
findings, the patients clinical presentation was consistent with stress
cardiomyopathy, and the heparin drip was discontinued. Another
ECG 48 hours after initial presentation demonstrated deepening and
more diffuse TWIs and a prolonged QT interval (Figure, D).
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Over the next day, the patient was free of chest pain. Further
medical history revealed that she was under considerable family and
financial stress, and was being evicted from her apartment. She had
recently increased her alcohol consumption and crack cocaine use
to help deal with these issues. At discharge, the patient was pre-
scribed metoprolol succinate, 25 mg, and lisinopril, 5 mg, and coun-
seled regarding her polysubstance abuse. Given her poor medica-
tion compliance, she was not prescribed anticoagulation drugs. An
echocardiogram performed 3 months later demonstrated com-
plete normalization of the left ventricular wall motion and ejection
fraction.
Discussion
This patient was intoxicated and encephalopathic in the setting of
alcohol withdrawal seizures and cocaine use. Her ECG on presenta-
tion revealed Q waves and early repolarization but no ST-segment
elevations. Over the course of several hours, her ECGs were remark-
ably dynamic, revealing new ST-segment elevations in leads V3 to
V6 with evolving and deepening TWIs. In addition, there was sig-
nificant QT interval prolongation, which occurs in approxi-
mately 50% of patients with stress cardiomyopathy.1 To our knowl-
edge, this series of dynamic ECG changes has not been previously
illustrated and demonstrates the natural electrocardiographic evo-
lution of stress cardiomyopathy. Notably, this case differs from our
prior report2 of stress cardiomyopathy which showed TWIs that be-
came upright with the onset of chest pain, and then inverted again
with chest pain resolution (pseudonormalization).
Stress cardiomyopathy is an acute cardiac syndrome first de-
scribed in Japan in 1990 and characterized by transient left ven-
tricular dysfunction affecting more than 1 coronary artery territory.3,4
It occurs predominantly in postmenopausal women, and rates of
neurologic and psychiatric comorbidities (including seizures, mi-
graines, mood, and anxiety disorders) are approximately 50%.1,3
Takotsubo cardiomyopathy, which features apical dyskinesis and
ballooning that resembles an octopus pot, accounts for most stress
cardiomyopathy cases (>80%). However, other echocardio-
graphic patterns, including midventricular dyskinesis (15%) and basal
dyskinesis (2%), are also seen.1 Additional diagnostic criteria for stress
cardiomyopathy include angina, ECG changes (ST-segment eleva-
tions or TWIs), lack of substantial obstructive coronary artery dis-
ease, and the absence of conditions such as pheochromocytoma or
myocarditis.3
The pathophysiologic mechanisms of stress cardiomyopathy are
thought to involve systemic catecholamine surges. Because the api-
cal area of the left ventricle has a higher density of -adrenergic re-
ceptors compared with the base, it is more sensitive to circulating
catecholamines.5 High concentrations of catecholamines cause a
switch from a stimulatory to an inhibitory secondary messenger
(Reprinted) JAMA Internal Medicine Published online March 28, 2016 E1
 Clinical Review & Education Challenges in Clinical Electrocardiography

Figure. Electrocardiography Images

A Noon Day 1

B 7:00 PM Day 1

C 11:00 PM Day 1

A, Initial electrocardiography (ECG)

on presentation demonstrating Q
waves in V2 and V3 and early
repolarization in V4 (arrowhead);
B, ECG demonstrating borderline
tachycardia and ST-segment
elevations in leads V3 to V6, 7 hours
D Noon Day 3
after initial presentation while the
patient was asymptomatic;
C, ECG demonstrating persistent
ST-segment elevations in lead V3,
with new T-wave inversions in the
lateral leads V4 to V6, 11 hours after
initial presentation;
D, ECG demonstrating deepening and
more diffuse T-wave inversions in V3
to V6 as well as the inferior leads II,
III, and aVF, 48 hours after initial
presentation. The QTc interval
calculated from lead V5 is
significantly prolonged at 600
milliseconds.

pathway within cardiomyocytes, leading to a negative inotropic and The patient described herein had several identifiable stressors
stunning effect.3,6 The loss of the sympatholytic effects of estro- leading to an elevated catecholamine state: alcohol withdrawal, co-
gen in postmenopausal women, which reduces inotropic and chro- caine use, and life stress, each of which has been associated with
notropic response to catecholamines, also plays a role.3 stress cardiomyopathy.7,8

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 Challenges in Clinical Electrocardiography Clinical Review & Education

Notably, long-term morbidity and mortality are higher than pre-
viously recognized, with rates of major adverse cardiac and cerebro-
vascularevents(ie,strokeand/ortransientischemicattack,recurrence,
and death) reaching nearly 10% per patient-year.1 Patients should be
monitored carefully for signs of heart failure and cardiogenic shock,
including pulmonary edema and hypotension. Left ventricular dyski-
nesis results in relative hemostasis and thus increased risk of cardio-
embolic complications. No guidelines exist regarding anticoagulation,
but anticoagulation should be considered.9 Furthermore, -blockers
and angiotensin-converting enzyme (ACE) inhibitors are thought to
be cardioprotective, although data supporting their use are also
limited.10 Finally, counseling should be provided to reduce triggering
events and minimize recurrence of stress cardiomyopathy.
Take Home Points
Stress cardiomyopathy is a bona fide pseudoinfarct syn-
drome that can present with ST-segment elevation and dynamic
T-wave inversions on ECG, chest pain, and often troponin eleva-
tion, findings that generally trigger activation of the cardiac
catheterization laboratory. Alternative diagnoses, including
coronary vasospasm, pericarditis, Brugada syndrome, and stress
(takotsubo) cardiomyopathy, should be considered, but are
diagnoses of exclusion.
Patients with stress cardiomyopathy have nonobstructive coro-
nary disease on cardiac catheterization and transient left ven-
tricular dysfunction in more than 1 coronary artery territory,
leading to apical, midventricular, or basal dyskinesis. Other diag-
nostic criteria include the absence of conditions such as pheo-
chromotyoma and myocarditis, and resolution of the wall
motion abnormalities and ejection fraction in a short amount of
time.
Takotsubo cardiomyopathy specifically describes the subtype of
stress cardiomyopathy with apical dyskinesis. Other echocardio-
graphic patterns of stress cardiomyopathy, including midventricu-
lar and basal dyskinesis, can also be seen.
Cocaine use and alcohol withdrawal seizures are high catechol-
amine states that can trigger stress cardiomyopathy.
Treatment of stress cardiomyopathy should include a -blocker and
angiotensin-converting enzyme (ACE) inhibitor, but data show-
ing survival benefit from these interventions are limited. Oral an-
ticoagulation can be considered in appropriate patients to reduce
cardioembolic stroke risk, and patients should be counseled to
avoid triggering events.

ARTICLE INFORMATION
Author Affiliations: Department of Medicine,
University of California, San Francisco (Chou,
Beutler, Goldschlager); Division of Cardiology,
Department of Medicine, San Francisco General
Hospital, San Francisco, California (Goldschlager).
Section Editors: Zachary D. Goldberger, MD, MS;
Nora Goldschlager, MD; Elsayed Z. Soliman, MD,
MSc, MS.
Published Online: March 28, 2016.
doi:10.1001/jamainternmed.2016.0278.
Corresponding Author: Jonathan Chou, MD, PhD,
Department of Medicine, University of California,
505 Parnassus Ave, PO Box 0119, San Francisco, CA
94143 (Jonathan.Chou@ucsf.edu).
Conflict of Interest Disclosures: None reported.
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