Clinical Review & Education
Challenges in Clinical Electrocardiography
Abnormal Electrocardiogram in a Woman
With Atrial Fibrillation and Recent Care Transition
Katie E. Raffel, MD; Nora Goldschlager, MD
A woman in her 80s with a history of severe symptomatic aortic
stenosis and recent transfemoral transcatheter aortic valve replace-
ment (TAVR) presented with a change in mental status character-
ized by lethargy, blurred vision, nausea, and diarrhea. Her other co-
morbidities included persistent (chronic) atrial fibrillation (AF),
moderate mitral stenosis (peak and mean transvalvular gradients of
12 mm Hg and 5 mm Hg, respectively, with valve area 1.4 cm2) and
left intraventricular conduction delay.
Her TAVR procedure, performed 1 week prior to presentation,
had been complicated by transient complete atrioventricular (AV)
block requiring temporary transvenous pacing, and hypoxemic re-
spiratory failure owing to acute pulmonary edema caused by the
rapid ventricular rate from AF, and exacerbated by her mitral ste-
nosis. Her cardiopulmonary decompensation improved with diure-
sis and ventricular rate control with metoprolol, diltiazem, and di-
goxin. Her discharge medications included these plus clopidogrel,
apixaban, bumetanide, pravastatin, and omeprazole.
On presentation, she was afebrile with a regular heart rate of
60 beats per minute, blood pressure was 119/53 mm Hg. Cardiopul-
monary examination revealed a regular rhythm with crisp A2 and
II/VI systolic murmur best heard at left upper sternal border. An
opening snap and diastolic mitral murmur were unappreciable. Elec-
trolyte panel results showed normal serum potassium and renal
function. ECG is shown (Figure).
Questions: What is the most likely etiology of her symptom-
atology and ECG findings? What would you do next?
Clinical Course
The ECG demonstrates a regularized ventricular rate of 60 beats per
minute despite the underlying AF, which would be expected to be
Figure. Electrocardiographic Results at Admission
I aVR V1
II aVL V2
III aVF V3
V1
880 ms
II
V5
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associated with an irregularly irregular ventricular rate. A regular
ventricular rate in the presence of AF indicates complete AV block
with junctional or ventricular foci of origin of the QRS rhythm. In this
ECG, one sees several QRS morphologies: her baseline left intraven-
tricular conduction delay (IVCD) (red arrowheads) followed by QRS
complexes having a right IVCD morphology (black arrowheads) with
mean frontal plane rightward axis, as well as a possible fusion beat
between the 2 sites of origin of the QRS rhythm (blue arrowhead)
(Figure). The R-R intervals between the left IVCD QRS morphology
are approximately 880 ms and 960 ms, while the R-R interval be-
tween the right IVCD QRS morphology is 1040 ms. This suggests that
the R IVCD morphology with rightward axis QRS complexes repre-
sents an escape rhythm, possibly from the AV junction or the
His-Purkinje (left anterior fascicular) system, distal to the origin of
the left IVCD focus. Notably, this is not a junctional rhythm. In the
context of the patients other symptoms of altered mental status,
vision changes, and nausea, there was a high suspicion for toxic af-
fects associated with digoxin. Indeed, it was then recognized that
the patient had been inadvertently prescribed 10 times the appro-
priate dose of digoxin (625 mcg per day), a result of a transcription
error at her retail pharmacy. Her initial digoxin level on presenta-
tion was 2.3 ng/mL (reference range 0.5-2.0 ng/mL, therapeutic
range 0.5-0.8 ng mL).
The team treating the patient discussed the utility of adminis-
tering digoxin immune antigen-binding fragments (Digibind) to
bind molecules of digoxin and allow their excretion from the kid-
neys. However, given the stability of her rhythm and blood pres-
sure and her improving mental status, Digibind was not given.
Notably, this conservative treatment with telemetry and symptom
and digoxin level monitoring, may be appropriate in the setting of
Atrial fibrillation (best seen in V1) with
regularized ventricular rate owing to
V4 complete heart block. Patient has
baseline left intraventricular
conduction delay morphology (red
arrowheads) with a likely His-Purkinje
V5 (fascicular) escape rhythm with right
intraventricular conduction delay
morphology (black arrowheads) and
V6 a vertical mean frontal plane QRS
axis. Notably, the R-R interval
between L IVCD morphology is
880 ms and 960 ms whereas the R-R
1040 ms
interval between the R IVCD
morphology is 1040 ms. The seventh
beat is likely a fusion beat (blue
arrowhead) based on the narrowed
QRS duration of approximately
60 ms and its intermediate
morphology between right- and
left-sided conduction delays.
(Reprinted) JAMA Internal Medicine April 2017 Volume 177, Number 4 575
 Clinical Review & Education Challenges in Clinical Electrocardiography

bradycardia because it is not per se a life-threatening arrhythmia;
this treatment strategy would not be appropriate in the setting of
significant and/or unstable ventricular arrhythmias, such as ven-
tricular tachycardia (VT). Her diltiazem and metoprolol were held
in order to avoid additional AV nodal blockade. Over the next 2
days, her neurologic and gastrointestinal symptoms resolved as
did her regular ventricular rhythm, her AF then being accompa-
nied by the expected irregularly irregular ventricular rhythm with
average rate of 85 beats per minute. Her diltiazem and metoprolol
were slowly resumed, and she was discharged. Digoxin was
discontinued.
Discussion
A study among Veterans Health Administration practitioners evalu-
ating early AF management and prescribing practices revealed that
digoxin prescribing has decreased by more than 50% over the past
decade (2002-2011).1 This decreased digoxin use has also been
demonstrated in populations with a diagnosis of systolic heart
failure.2 This trend may be related to a significantly increased use of
B-blockers, awareness of digoxin toxic effects, or an aging popula-
tion. Despite this shift in prescribing patterns in AF and heart failure
with reduced ejection fraction, the rate of ED visits and hospitaliza-
tions owing to digoxin-associated adverse events has remained
stable.2,3 Among women and the elderly, the demographic features
of this patient, these rates of ED visits, and hospitalizations were
doubled compared with their male counterparts or those younger
than 85 years.3
At therapeutic concentrations (0.5-0.8 ng/mL), the affects of
digoxin on cardiac function include increased contractility and
slowed conduction through the AV node through increased vagal
tone and antiadrenergic affects.4 However, at concentrations above
1.2 ng/mL, digoxin is associated with nonspecific multiorgan dys-
function, as seen in this case, causing gastrointestinal symptoms
including nausea, vomiting, and diarrhea, visual disturbances, and
neurologic changes including altered mental status, weakness, and
reduced level of consciousness. These often precede cardiac
manifestations.5-7
Atrial and ventricular ectopy are the most common cardiac ar-
rhythmias associated with digoxin use and are thought to be owing
to increased automaticity. Classic (and less commonly seen) arrhyth-
mias include regularized atrial fibrillation, atrial tachycardia with AV
block (usually 2:1), and accelerated junctional rhythm. Ventricular
tachycardia, including bidirectional VT, are also associated, and po-
tentially fatal, arrhythmias.8 This patients ECG demonstrated AF with
slow, regularized rate and ventricular and/or His-Purkinje escape
rhythms.
In addition to highlighting the risk of digoxin-related toxic ef-
fects among the elderly, this case also emphasizes the risk of tran-
sitions of care. It is estimated that nearly 20% of patients experi-
ence an adverse event surrounding the time of discharge.9 This
incidence is particularly troubling when coupled with the fact that
unrecognized adverse drug effect is a common etiology of diagnos-
tic error.10 Even in this era of decreased digoxin use, it is important
that physicians remain familiar with the clinical symptoms and car-
diac arrhythmias associated with digoxin-induced toxic effects.
Take-Home Points
While digoxin prescribing and use has decreased over time, rates
of digoxin-associated toxic effects have not; women and the
elderly remain at highest risk for digoxin-related toxic effects. Con-
sideration should be given to discontinuing digoxin in elderly
patients who are also prescribed other AV-nodal blocking agents
for rate-control.
Exposure to digoxin and new neurologic, GI, or cardiac (arrhyth-
mia) symptoms should raise clinical suspicion for digoxin-related
toxic effects; serum digoxin concentration does not always corre-
late with toxicity.
Digoxin-associated toxic effects can cause a diffuse array of car-
diac arrhythmias including AV nodal blockade, regularized ventricu-
lar rate when the atrial rhythm is atrial fibrillation, and potentially
or actually lethal ventricular arrhythmia.
Digoxin immune antigen-binding fragments should be adminis-
tered in the setting of hemodynamically unstable arrhythmias,
end-organ dysfunction, or hyperkalemia.

ARTICLE INFORMATION
Author Affiliations: Internal Medicine Residency,
University of California San Francisco, San Francisco
(Raffel); Zuckerberg San Francisco General Hospital,
Division of Cardiology, University of California
San Francisco, San Francisco (Goldschlager).
Corresponding Author: Katie Raffel, MD, Internal
Medicine Residency, University of California
San Francisco, 505 Parnassus Ave, Rm 987,
San Francisco, CA 94143-0119
(katie.raffel@ucsf.edu).
Section Editors: Zachary D. Goldberger, MD, MS;
Nora Goldschlager, MD; Elsayed Z. Soliman, MD,
MSc, MS.
Published Online: February 13, 2017.
doi:10.1001/jamainternmed.2016.9356
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Conflict of Interest Disclosures: None reported. 5. Kastor JA, Yurchak PM. Recognition of digitalis 10. Schiff GD, Hasan O, Kim S, et al. Diagnostic error
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