Clinical Review & Education

JAMA Cardiology Clinical Challenge

A Woman With Recurrent Torsade de Pointes

Cody McCoy, MD; John M. Miller, MD; Tanyanan Tanawuttiwat, MD, MPH

Figure 1. The 12-lead electrocardiogram obtained on day 15 of admission. Alternans in T-wave polarity is evident in most
leads (especially V3-V6) while alternans in T-wave amplitude is seen in leads II and aVF.

A woman in her mid-40s presented to the emergency department after a fall with head
trauma. A head computed tomography showed a 0.9-cm left subdural hematoma with a WHAT WOULD YOU DO NEXT?
mild left to right midline shift. Her ethanol level was 202 mg/dL (to convert to millimoles
per liter, multiply by 0.2171); magnesium, 1.7 mg/dL (to convert to millimoles per liter, mul- A. Discontinue metoprolol, start
tiply by 0.4114); potassium, 4.4 mEq/L (to convert to millimoles per liter, multiply by 1); and sotalol
ionized calcium, 4.6 mg/dL (to convert to millimoles per liter, multiply by 0.25). The pa-
tient developed cardiac arrest due to ventricular arrhythmias in the emergency depart-
B. Start intravenous amiodarone
ment and was successfully resuscitated. Echocardiography demonstrated a left ventricu-
lar ejection fraction of 50% and no regional wall motion abnormalities. She subsequently
underwent embolization of the middle meningeal artery. After embolization, however, a C. Start intravenous magnesium
worsening rightward midline shift was discovered. As a result, on the 11th day of her hos-
pitalization, she had a burr hole evacuation. During day 15 of admission, the patient had 3 D. Emergent implantable
episodes of torsade de pointes (TdP) while receiving 50 mg of metoprolol succinate daily, cardioverter defibrillator implant
and her 12-lead electrocardiogram (ECG) is shown in Figure 1.

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Diagnosis resulting in pseudo QRS widening of the next beat, mimicking pre-
T-wave alternans mature ventricular contractions (PVCs) in a bigeminal pattern. The
simultaneous narrow QRS in V2-V4, when compared with seeming
What to Do Next J waves or QRS widening in other leads, confirmed that the appar-
C. Start intravenous magnesium ent QRS widening was due to T-wave “contamination.” This finding
preceded the development of TdP (Figure 2).
Discussion TWA is defined as a transient beat-to-beat oscillation in
The ECG in Figure 1 shows T-wave alternans (TWA). The beat-to- T-wave timing, axis, morphology, and/or amplitude in sinus rhythm
beat opposite T-wave polarity was obvious in leads V3-V6, but only without associated QRS variability or clinically significant changes
amplitude alternans was noted in leads III and aVF. The T wave, in the RR interval.1 It is considered an indicator of myocardial
with a QTc of 670 milliseconds, extended to the next QRS complex, electrical instability and harbinger of life-threatening ventricular

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 Clinical Review & Education JAMA Cardiology Clinical Challenge

Figure 2. Telemetry tracing recorded shortly after the electrocardiogram ventricular tachycardia diagnosed as torsade de pointes.
diagnosis of T-wave alternans. The telemetry tracing showed polymorphic

arrhythmias. TWA is particularly associated with congenital long QT
syndrome but occurs in a wide range of clinical conditions, such as
alcoholism, cardiomyopathy, electrolyte imbalances, medication ad-
verse effects, and ischemia. Experimental evidence is that abnor-
mal intracellular Ca2+ handling is the ionic basis for TWA.2 In-
creased and unstable cardiac Ca2+ dynamics and suppressed K+
channels (both IKr and IKs) lead to prolonged repolarization in ven-
tricular myocytes, action potential duration alternans, and beat-to-
beat alternation during repolarization giving rise to TWA on the ECG.2
The relationship between TWA and heterogeneity of repolariza-
tion is observed frequently with discordant TWA, when myocytes
in proximity repolarize out of phase, thereby markedly enhancing
heterogeneity of repolarization and establishing the preconditions
for conduction block, reentry, and life-threatening arrhythmias.3
Initial management should focus on TdP prevention. The first-
line therapy is intravenous magnesium sulfate, which can prevent
TdP by suppressing development of early afterdepolarizations that
initiate episodes, regardless of serum magnesium concentration. All
QT-prolonging medications, including amiodarone, should be dis-
continued and avoided. Hypokalemia should be treated to main-
tain serum potassium concentrations in the high-normal range. Iso-
proterenol infusion and/or temporary pacing can be considered to
prevent pause-dependent TdP. Lidocaine and mexiletine can
be used to diminish QT prolongation.4 After TdP is controlled, an
implantable cardioverter defibrillator (ICD) should be considered in
individuals with long QT experiencing sustained ventricular arrhyth-
mias or sudden cardiac arrest despite taking β-blockers.5 After
attempting the above-mentioned conservative treatment, PVC ab-
lation can be taken into consideration in individuals with drug-
refractory, recurrent TdP caused by monomorphic PVCs.
Patient Outcome
Loading doses of intravenous magnesium sulfate and lidocaine were
administered to the patient. Isoproterenol was not given as her in-
trinsic heart rate was 100 to 120 beats/min. Lidocaine infusion was
transitioned to oral mexiletine in the next few days. Even with car-
diac and neurologic stabilization along with a β-blocker and mexi-
letine, her QT prolongation persisted (QTc 580 milliseconds). Ge-
netic testing revealed a heterozygous mutation in the potassium
voltage-gated channel subfamily Q member 1 (KCNQ1) gene at exon
1, c.352A>C. This mutation has been observed in individuals with clini-
cal features of long QT syndrome, but because the available evi-
dence is currently insufficient, it has been classified as a variant of
uncertain significance. She eventually underwent an ICD implant.
At the 3-month follow-up, the patient did not take mexiletine for a
month but continued to take metoprolol. Repeated ECG showed ab-
sence of TWA and a QTc 520 milliseconds. ICD interrogation showed
no ventricular arrhythmia events. Mexiletine was resumed.

ARTICLE INFORMATION REFERENCES the Council on Clinical Cardiology, the Council on

Author Affiliations: Division of Cardiovascular
Medicine, Indiana University, Indianapolis.
Corresponding Author: Tanyanan Tanawuttiwat,
MD, MPH, Division of Cardiovascular Medicine,
Indiana University, 1800 N Capitol Ave, Room
300B, Indianapolis, IN 46202 (ttanawu@iu.edu).
Published Online: January 18, 2023.
doi:10.1001/jamacardio.2022.5094
Conflict of Interest Disclosures: Dr Miller reports
fellowship support and lecture fees from
Medtronic, Boston Scientific, Biosense-Webster,
Abbott Electrophysiology, and Biotronik, Inc.
Additional Contributions: The authors are grateful
to Peng-Seng Chen, MD, for his invaluable
suggestions. We also thank the patient for granting
permission to publish this information.
1. Shimizu W, Antzelevitch C. Cellular and ionic
basis for T-wave alternans under long-QT
conditions. Circulation. 1999;99(11):1499-1507.
doi:10.1161/01.CIR.99.11.1499
2. Bao M, Zhang J, Huang C, Jiang H, Liu J, Zhao D.
Abnormal intracellular calcium handling underlying
T-wave alternans and its hysteresis. Cardiology.
2007;108(3):147-156. doi:10.1159/000096566
3. Nieminen T, Verrier RL. Usefulness of T-wave
alternans in sudden death risk stratification and
guiding medical therapy. Ann Noninvasive
Electrocardiol. 2010;15(3):276-288. doi:10.1111/j.1542-
474X.2010.00376.x
4. Drew BJ, Ackerman MJ, Funk M, et al; American
Heart Association Acute Cardiac Care Committee of
Cardiovascular Nursing, and the American College
of Cardiology Foundation. Prevention of torsade de
pointes in hospital settings: a scientific statement
from the American Heart Association and the
American College of Cardiology Foundation.
Circulation. 2010;121(8):1047-1060. doi:10.1161/
CIRCULATIONAHA.109.192704
5. Al-Khatib SM, Stevenson WG, Ackerman MJ,
et al. 2017 AHA/ACC/HRS Guideline for
Management of Patients With Ventricular
Arrhythmias and the Prevention of Sudden Cardiac
Death: A Report of the American College of
Cardiology/American Heart Association Task Force
on Clinical Practice Guidelines and the Heart
Rhythm Society. J Am Coll Cardiol. 2018;72(14):e91-
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