nterval
Schematic representation of normal
ECG trace ( sinus rhythm ), with waves,
segments, and intervals labeled.
In cardiology , the QT interval is a measure of
the time between the start of the Q wave and
the end of the T wave in the heart’s electrical
cycle . The QT interval represents electrical
depolarization and repolarization of the
ventricles . A lengthened QT interval is a
marker for the potential of ventricular
tachyarrhythmias like torsades de pointes and
a risk factor for sudden death.
Correction for heart rate
Like the R-R interval, the QT interval is
dependent on the heart rate in an obvious way
(the faster the heart rate the shorter the R-R
Interval and QT interval) and may be adjusted
to improve the detection of patients at
increased risk of ventricular arrhythmia.
Modern computer-based ECG machines can
easily calculate a corrected QT (QTc), but this
correction may not aid in the detection of
patients at increased risk of arrhythmia. There
are a number of different correction formulas.
The standard clinical correction is to use
Bazett’s formula ,[1] named after physiologist
Bazett, calculating the heart rate-corrected QT
interval (QTcB). Please be ware that Bazett’s
formula is based on observations of only 12
patients in 1920 and does meet current
scientific quality standards. A more robust
method is the Frammingham correction based
on the Framingham Heart study, recent
longterm cohort data of over 5000 subjects.
Bazett’s formula is:
where QTcB is the QT interval corrected for
heart rate, and RR is the interval from the
onset of one QRS complex to the onset of the
next QRS complex, measured in seconds, often
derived from the heart rate (HR) as 60/HR
(here QT is measured in milliseconds).
However, this non-linear formula, obtained
from data in only 39 young men, is not
accurate, and over-corrects at high heart rates
and under-corrects at low heart rates. [2]
Fridericia [3] has published an alternative
correction formula using the cube-root of RR.
There are several other methods, such as
regression-analysis: [4]
Upper limit of normal QT interval, corrected for
heart rate according to Bazett’s formula , [1]
Fridericia’s formula [3] and subtracting 0.02 s
from QT for every 10 bpm increase in heart
rate. [5] Up to 0.42 s (≤420 ms) is chosen as
normal QTc of QT B and QT F in this diagram.
Definitions of normal QTc vary from being
equal to or less than 0.40 s (≤400 ms), [5]
0.41s (≤410ms), [6] 0.42s (≤420ms) [7] or
0.44s (≤440ms). [8] For risk of sudden cardiac
death , “borderline QTc” in males is 431-450
ms, and in females 451-470 ms. An
“abnormal” QTc in males is a QTc above 450
ms, and in females, above 470 ms. [9]
If there is not a very high or low heart rate,
the upper limits of QT can roughly be
estimated by taking QT=QTc at a heart rate of
60 beats per minute (bpm), and subtracting
0.02s from QT for every 10 bpm increase in
heart rate. For example, taking normal QTc ≤
0.42 s, QT would be expected to be 0.42 s or
less at a heart rate of 60 bpm. For a heart rate
of 70 bpm, QT would roughly be expected to
be equal to or below 0.40 s. Likewise, for
80 bpm, QT would roughly be expected to be
equal to or below 0.38 s. [5]
Measurement
The QT interval is most commonly measured
in lead II for evaluation of serial ECGs, with
leads I and V5 being comparable alternatives
to lead II. Leads III, aVL and V1 are generally
avoided for measurement of QT interval.
[10] The accurate measurement of the QT
interval is subjective [11] because the end of
the T wave is not always clearly defined and
usually merges gradually with the baseline. QT
interval in an ECG complex can be measured
manually by different methods such as the
threshold method, in which the end of the T
wave is determined by the point at which the
component of the T wave merges with the
isoelectric baseline or the tangent method, in
which the end of the T wave is determined by
the intersection of a tangent line extrapolated
from the T wave at the point of maximum
downslope to the isoelectric baseline. [12]
With the increased availability of digital ECGs
with simultaneous 12-channel recording, QT
measurement may also be done by the
‘superimposed median beat’ method. In the
superimposed median beat method, a median
ECG complex is constructed for each of the 12
leads. The 12 median beats are superimposed
on each other and the QT interval is measured
either from the earliest onset of the Q wave to
the latest offset of the T wave or from the
point of maximum convergence for the Q wave
onset to the T wave offset. [13]
Abnormal intervals
Prolonged QTc causes premature action
potentials during the late phases of
depolarization. This increases the risk of
developing ventricular arrhythmias or fatal
ventricular fibrillations. [14] Higher rates of
prolonged QTc are seen in females, older
patients, high systolic blood pressure or heart
rate, and short stature. [15] Prolonged QTc is
also associated with EKG findings called
Torsade de Pointes, which are known to
degenerate into ventricular fibrillation,
associated with higher mortality rates. There
are many causes of prolonged QT intervals,
acquired causes being more common than
genetic. [16]
Genetic causes
An abnormally prolonged QT interval could be
due to long QT syndrome , whereas an
abnormally shortened QT interval could be due
to short QT syndrome .
The QTc length is associated with variations in
NOS1AP gene. [17] The autosomal recessive
syndrome of Jervell and Lange-Nielsen is
characterized by a prolonged QTc interval in
conjunction with sensorineural hearing loss .
Due to adverse drug reactions
Prolongation of the QT interval may be due to
an adverse drug reaction. [18] Many drugs such
as haloperidol , [19] vemurafenib , ziprasidone ,
methadone[20] and sertindole [21] can prolong
the QT interval. Some antiarrhythmic drugs,
like amiodarone or sotalol work by getting a
pharmacological QT prolongation. Also, some
second-generation antihistamines, such as
astemizole, have this effect. In addition, high
blood-alcohol concentrations prolongs the QT
interval. [22] A possible interaction between
selective serotonin reuptake inhibitors and
thiazide diuretics is associated with QT
prolongation. [23] Macrolide antibiotics are also
suspected to prolong the QT interval, after it
was discovered recently that azithromycin was
associated with an increase in cardiovascular
death. [24]
Due to pathological conditions
Hypothyroidism , a condition of low function of
the thyroid gland, can cause QT prolongation
at the electrocardiogram . Acute hypocalcemia
causes prolongation of the QT interval, which
may lead to ventricular dysrhythmias.
A shortened QT can be associated with
hypercalcemia. [25]
Use in drug approval studies
Since 2005, the FDA and European regulators
have required that nearly all new molecular
entities be evaluated in a Thorough QT (TQT)
study to determine a drug’s effect on the QT
interval. [26] The TQT study serves to assess
the potential arrhythmia liability of a drug.
Traditionally, the QT interval has been
evaluated by having individual human reader
measure approximately nine cardiac beats per
clinical timepoint. However, a number of recent
drug approvals have used a highly automated
approach, blending automated software
algorithms with expert human readers
reviewing a portion of the cardiac beats, to
enable the assessment of significantly more
beats per timepoint in order to improve
precision and reduce cost. [27] As the
pharmaceutical industry has gained experience
in performing TQT studies, it has also become
evident that traditional QT correction formulas
such as QT F, QT B , and QT LC may not always
be suitable for evaluation of drugs impacting
autonomic tone. [28] Current efforts are
underway by industry and regulators to
consider alternative methods to help evaluate
QT liability in drugs affecting autonomic tone,
such as QT beat-to-beat and Holter-bin
methodologies. [29]
As a predictor of mortality
Electrocardiography is a safe and noninvasive
tool that can be used to identify those with a
higher risk of mortality. In the general
population, there has been no consistent
evidence that prolonged QTc interval in
isolation is associated with an increase in
mortality from cardiovascular disease. [30]
However, several studies[ which? ] have
examined prolonged QT interval as a predictor
of mortality for diseased subsets of the
population.
Rheumatoid arthritis
Rheumatoid arthritis is the most common
inflammatory arthritis. [31] Studies have linked
rheumatoid arthritis with increased death from
cardiovascular disease.[31] In a 2014 study,
[14] Panoulas et al. found a 50 ms increase in
QTc interval increased the odds of all-cause
mortality by 2.17 in patients with rheumatoid
arthritis. Patients with the highest QTc interval
(> 424 ms) had higher mortality than those
with a lower QTc interval. The association was
lost when calculations were adjusted for C-
reactive protein levels. The researchers
proposed that inflammation prolonged the QTc
interval and created arrhythmias that were
associated with higher mortality rates.
However, the mechanism by which C-reactive
protein is associated with the QTc interval is
still not understood.
Type 1 diabetes
Compared to the general population, type 1
diabetes may increase the risk of mortality, due
largely to an increased risk of cardiovascular
disease. [15][32] Almost half of patients with
type 1 diabetes have a prolonged QTc interval
(> 440 ms). [33] Diabetes with a prolonged QTc
interval was associated with a 29% mortality
over 10 years in comparison to 19% with a
normal QTc interval. [15] Anti-hypertensive
drugs increased the QTc interval, but were not
an independent predictor of mortality.[15]
Type 2 diabetes
QT interval dispersion (QTd) is the maximum
QT interval minus the minimum QT interval,
and is linked with ventricular repolarization.
[34] A QTd over 80 ms is considered
abnormally prolonged.[35] Increased QTd is
associated with mortality in type 2 diabetes.
[35] QTd is a better predictor of cardiovascular
death than QTc, which was unassocited with
mortality in type 2 diabetes. [35] QTd higher
than 80 ms had a relative risk of 1.26 of dying
from cardiovascular disease compared to a
normal QTd.
See also
Electrocardiogram
Comprehensive QTc Calculator with 5
formulas at TheCalculator.co
References
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(7): 353–370.
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systole in the electrocardiogram of normal
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Bengston JR, Levy D (1992). “An improved
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rate (the Framingham Heart Study)”. Am J
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Normal ECG Frank G. Yanowitz, MD.
Professor of Medicine. University of Utah
School of Medicine. Retrieved on Mars 23,
2010
6. ^ Loyola University Chicago Stritch School
of Medicine > Medicine I By Matthew Fitz,
M.D. Retrieved on Mars 23, 2010
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ECG Retrieved on Mars 23, 2010
8. ^ Image for Cardiovascular Physiology
Concepts > Electrocardiogram (EKG, ECG) By
Richard E Klabunde PhD
9. ^ medscape.com > QTc Prolongation and
Risk of Sudden Cardiac Death: Is the Debate
Over? February 3, 2006
10. ^ Panicker GK, Salvi V, Karnad DR,
Chakraborty S, Manohar D, Lokhandwala Y,
Kothari S. (2014). “Drug-induced QT
prolongation when QT interval is measured in
each of the 12 ECG leads in men and women
in a thorough QT study.”. J Electrocardiol 47
(47(2)): 155–157. doi : 10.1016/
j.jelectrocard.2013.11.004 .
PMID 24388488 .
11. ^ Panicker GK, Karnad DR, Joshi R, Shetty
S, Vyas N, Kothari S, Narula D (2009). “Z-
score for benchmarking reader competence in a
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12. ^ Panicker GK, Karnad DR, Natekar M,
Kothari S, Narula D, Lokhandwala Y (2009).
“Intra- and interreader variability in QT interval
measurement by tangent and threshold
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52. doi : 10.1016/j.jelectrocard.2009.01.003 .
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13. ^ Salvi V, Karnad DR, Panicker GK,
Natekar M, Hingorani P, Kerkar V, Ramasamy
A, de Vries M, Zumbrunnen T, Kothari S, Narula
D (2011). “Comparison of 5 methods of QT
interval measurements on electrocardiograms
from a thorough QT/QTc study: effect on
assay sensitivity and categorical outliers”. J
Electrocardiol 44 (44(2)): 96–104.
doi: 10.1016/j.jelectrocard.2010.11.010 .
PMID 21238976 .
14. ^ a b Panoulas VF, Toms TE, Douglas KM,
et al. (January 2014). “Prolonged QTc interval
predicts all-cause mortality in patients with
rheumatoid arthritis: an association driven by
high inflammatory burden”. Rheumatology 53
(1): 131–7. doi: 10.1093/rheumatology/
ket338 . PMID 24097136 .
15. ^ a b c d Rossing P, Breum L, Major-
Pedersen A, et al. (March 2001). “Prolonged
QTc interval predicts mortality in patients with
Type 1 diabetes mellitus” . Diabetic Medicine
18 (3): 199–205. doi : 10.1046/
j.1464-5491.2001.00446.x .
PMID 11318840 .
16. ^ Van Noord, C; Eijgelsheim, M; Stricker,
BHC (2010). “Drug- and non-drug-associated
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Clinical Pharmacology 70 (1): 16–23.
doi: 10.1111/j.1365-2125.2010.03660.x .
PMID 20642543 .
17. ^ Arking DE, Pfeufer A, Post W, et al. (June
2006). “A common genetic variant in the NOS1
regulator NOS1AP modulates cardiac
repolarization”. Nature Genetics 38 (6): 644–
51. doi : 10.1038/ng1790 . PMID 16648850 .
18. ^ Leitch A, McGinness P, Wallbridge D
(September 2007). “Calculate the QT interval
in patients taking drugs for dementia” . BMJ
(Clinical Research Ed.) 335 (7619): 557.
doi: 10.1136/bmj.39020.710602.47 .
PMC 1976518 . PMID 17855324 .
19. ^ “Information for Healthcare
Professionals: Haloperidol (marketed as
Haldol, Haldol Decanoate and Haldol
Lactate)” . Archived from the original on
2007-10-11. Retrieved 2007-09-18.
20. ^ Haigney, Mark. “Cardiotoxicity of
methadone” (PDF). Director of Cardiology .
Retrieved 21 February 2013.
21. ^ Lewis R, Bagnall AM, Leitner M (2005).
“Sertindole for schizophrenia”. The Cochrane
Database of Systematic Reviews (3):
CD001715.
doi: 10.1002/14651858.CD001715.pub2 .
PMID 16034864 .
22. ^ Aasebø W, Erikssen J, Jonsbu J, Stavem
K (April 2007). “ECG changes in patients with
acute ethanol intoxication”. Scandinavian
Cardiovascular Journal 41 (2): 79–84.
doi: 10.1080/14017430601091698 .
PMID 17454831 .
23. ^ Tatonetti NP, Ye PP, Daneshjou R,
Altman RB (March 2012). “Data-driven
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Science Translational Medicine 4 (125):
125ra31. doi: 10.1126/
scitranslmed.3003377 . PMC 3382018 .
PMID 22422992 .
24. ^ http://www.fda.gov/Drugs/Drugsafety/
ucm304372.htm [ full citation needed ]
25. ^ Hypercalcemia [full citation needed ]
26. ^ http://www.fda.gov/downloads/
RegulatoryInformation/Guidances/
UCM129357.pdf [full citation needed ]
27. ^ iCardiac Applies Automated Approach to
Thorough QT Study for a Leading
Pharmaceutical Company – Applied Clinical
Trials
28. ^ “Garnett” (PDF). Retrieved 6 June
2014.
29. ^ http://thew-project.org/document/FDA
%20CPI%20project.pdf [ full citation needed ]
30. ^ Montanez A, Ruskin JN, Hebert PR,
Lamas GA, Hennekens CH (May 2004).
“Prolonged QTc interval and risks of total and
cardiovascular mortality and sudden death in
the general population: a review and
qualitative overview of the prospective cohort
studies”. Archives of Internal Medicine 164 (9):
943–8. doi: 10.1001/archinte.164.9.943 .
PMID 15136301 .
31. ^ a b Solomon DH, Karlson EW, Rimm EB,
et al. (March 2003). “Cardiovascular morbidity
and mortality in women diagnosed with
rheumatoid arthritis” . Circulation 107 (9):
1303–7.
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32. ^ Borch-Johnsen K, Andersen PK, Deckert
T (August 1985). “The effect of proteinuria on
relative mortality in type 1 (insulin-dependent)
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doi: 10.1007/bf00281993 . PMID 4054448 .
33. ^ Rossing P, Breum L, Major-Pedersen A,
et al. (March 2001). “Prolonged QTc interval
predicts mortality in patients with Type 1
diabetes mellitus” . Diabetic Medicine 18 (3):
199–205. doi: 10.1046/
j.1464-5491.2001.00446.x .
PMID 11318840 .
34. ^ Okin PM, Devereux RB, Howard BV,
Fabsitz RR, Lee ET, Welty TK (2000).
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35. ^ a b c Giunti S, Gruden G, Fornengo P, et
al. (March 2012). “Increased QT interval
dispersion predicts 15-year cardiovascular
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population-based Casale Monferrato Study” .
Diabetes Care 35 (3): 581–3. doi: 10.2337/
dc11-1397 . PMC 3322722 .
PMID 22301117 .
Torsades de pointes or torsade de pointes
( TdP or simply torsade(s) ) (French: [tɔʁsad də
pwɛ̃t] , translated as “twisting of the spikes”),
is a specific type of abnormal heart rhythm
that can potentially lead to sudden cardiac
death . It is a polymorphic ventricular
tachycardia that exhibits distinct
characteristics on the electrocardiogram
(ECG). It was described by Dessertenne in
1966. [1]
Signs and symptoms
Most episodes revert spontaneously to a
normal sinus rhythm. Other possible outcomes
include palpitations, dizziness, lightheadedness
(short episodes), fainting (longer episodes),
and sudden cardiac death .
Causes
Common causes for torsades de pointes
include diarrhea, low blood magnesium and
low blood potassium . It is commonly seen in
malnourished individuals and chronic
alcoholics . Certain combinations of drugs
resulting in drug interactions may contribute:
decreasing the metabolism of a medication
causing QT elongation such as clarithromycin
(Biaxin) , levofloxacin, or haloperidol (Haldol) ,
taken concomitantly with a specific cytochrome
P450 inhibitor like fluoxetine (Prozac) ,
cimetidine (Tagamet) ; foods like grapefruit will
result in higher than normal doses of the
medication responsible for the QT elongation.
Since these specific drugs worsen the
elongation of the QT wave in a dose-
dependent manner, inhibition of drug
metabolism raises the risks of developing a
malignant torsades de pointes arrhythmia.
Prescription drug interactions
TdP as a prescription drug side effect has been
a major liability and reason for withdrawal of
medications from the marketplace. [2]
Examples include amiodarone , methadone,
lithium , chloroquine , erythromycin ,
amphetamine , ephedrine, pseudoephedrine,
methylphenidate and phenothiazines. [3] It can
also be the side effect of some antiarrhythmic
medications such as sotalol , procainamide and
quinidine. The gastrokinetic drug cisapride
(Propulsid) was withdrawn from the US market
in 2000 after such interactions led to deaths
caused by long QT syndrome-induced
torsades de pointes. To correct the prolonged
QT interval, magnesium IV 2gm will help
effectively block calcium flow as well as
prevent recurrent Torsade de Pointes.
In September 2011 (subsequently updated in
March 2012 and February 2013), the FDA
issued a warning concerning increased
incidence of QT elongation with doses of the
antidepressant Celexa ( citalopram ) above
40 mg per day, which is considered the
maximum allowable dosage, increasing the risk
of Torsades. [4][5] However, the study,
“Evaluation of the FDA Warning Against
Prescribing Citalopram at Doses Exceeding 40
mg” reported no increased risk of abnormal
arrhythmias thus questioning the merit of FDA
warning. [6]
Risk factors
The following is a list of factors associated
with an increased tendency toward torsades de
pointes: [ medical citation needed ]
Lead II ECG showing torsades being shocked
by an implantable cardioverter-defibrillator
back to the patient’s baseline cardiac rhythm .
Hypokalemia (low blood potassium)
Hypomagnesemia (low blood magnesium)
Hypocalcemia (low blood calcium)
Bradycardia (slow heartbeat)
Heart failure
Left ventricular hypertrophy
Hypothermia
Subarachnoid hemorrhage
Hypothyroidism
The following is a list of drugs known to
induce Torsades de pointes, (possibly along
with QTc interval prolongation):
Ciprofloxacin (antibiotic)
AZD9291 (chemotherapy drug currently in
clinical trials; may be particularly dangerous in
combination with the above-cited
Ciprofloxacin)
Diagnosis
The ECG tracing in torsades demonstrates a
polymorphic ventricular tachycardia with a
characteristic illusion of a twisting of the QRS
complex around the isoelectric baseline (peaks
which are at first pointing up are seen to be
pointing down for subsequent “beats” when
looking at ECG traces of the “heartbeat”). It is
hemodynamically unstable and causes a
sudden drop in arterial blood pressure, leading
to dizziness and fainting . Depending on their
cause, most individual episodes of torsades de
pointes revert to normal sinus rhythm within a
few seconds, but may also persist and
possibly degenerate into ventricular fibrillation ,
which will lead to sudden death in the absence
of prompt medical intervention. Torsades de
pointes is associated with long QT syndrome ,
a condition whereby prolonged QT intervals are
visible on the ECG. Long QT intervals
predispose the patient to an R-on-T
phenomenon, where the R wave representing
ventricular depolarization occurs during the
relative refractory period at the end of
repolarization (represented by the latter half of
the T-wave). An R-on-T can initiate torsades.
Sometimes pathologic T-U waves may be seen
in the ECG before the initiation of torsades. [7]
A “short-coupled variant of torsade de
pointes”, which presents without long QT
syndrome, was also described in 1994. [8]
Drastic rotation of the heart’s electrical axis
Prolonged QT interval ( LQTS) – may not be
present in the short-coupled variant of torsade
de pointes
Preceded by long and short RR-intervals –
not present in the short-coupled variant of
torsade de pointes
Triggered by a premature ventricular
contraction (R-on-T PVC)
Treatment
Treatment is directed at withdrawal of the
offending agent, infusion of magnesium sulfate ,
[9][10] antiarrhythmic drugs , and electrical
therapy such as a temporary pacemaker as
needed.
Because of the polymorphic nature of torsades
de pointes, synchronized cardioversion may
not be possible, and the patient may require
an unsynchronized shock (or defibrillation ).
History
The phenomenon was originally described in a
French medical journal by Dessertenne in
1966, when he observed this cardiac rhythm
disorder in an 80-year-old female patient with
complete intermittent atrioventricular block . In
coining the term, he referred his colleagues to
the “Dictionnaire Le Robert,” a bilingual French
English dictionary, of which his wife had just
given him a copy. Here “torsade” is defined as
(a)a bundle of threads twisted in a helix or
spiral, for ornamental purposes, as in an Aran
sweater ; (b) long hair twisted together, or (c)
an ornamental motif as seen on architectural
columns.
The singular and plural forms ( torsade de
pointes and torsades de pointes) have both
often been used. The question of whether
either one is “correct” and the other “incorrect”
has repeatedly arisen. Among major medical
dictionaries, one enters only the plural form,
another enters the plural form as the
headword but lists the singular as a variant,
and another enters the singular form as the
headword and gives a usage comment saying
that the plural is not preferred. One group of
physicians suggests[11] that it would make
sense to use the singular form as the general
entity name (whether comprising a single or
repeated episodes) and that one might best
reserve the plural form for describing repeated
twistings during a single episode. Regarding
the natural language variation, they conclude
good-naturedly, “Wasn’t it the French who
coined the term ‘vive la difference?'” [11]
References
1. ^ Dessertenne, F. (1966). “La tachycardie
ventriculaire a deux foyers opposes variables”.
Archives des maladies du coeur et des
vaisseaux (in French) 59 (2): 263–272.
ISSN 0003-9683 . PMID 4956181 .
Prepaired by Rahel farhad
2. ^ Labant, MaryAnn (November 15, 2014).
“Weaving a Stronger Drug Safety Net”. Gen.
Eng. Biotechnol. News (paper) 34 (20). p. 1.
3. ^ “Drugs That Prolong the QT Interval or
Induce Torsades de Pointes” . Point of Care
Quick Reference . American Academy of
Pediatrics. March 11, 2010. Archived from the
original on March 7, 2014.
Case Report
A Case of QT Prolongation
Associated with Panhypopituitarism
Dilek Arpaci, Mustafa Volkan
Demir , Tayfun Garip, and Ali Tamer
Department of Internal Medicine,
Sakarya Education and Research
Hospital, 54290 Sakarya, Turkey
Received 10 March 2013; Accepted 17
April 2013
Academic Editors: H. Hattori, H. Ikeda,
and R. Murray
Copyright © 2013 Dilek Arpaci et al. This
is an open access article distributed
under the Creative Commons Attribution
License , which permits unrestricted use,
distribution, and reproduction in any
medium, provided the original work is
properly cited.
Abstract
We describe a 37-year-old patient with
panhypopituitarism who experienced
symptoms and signs of hormonal
insufficiency and QT prolongation on
electrocardiogram without electrolyte
disturbances. After hormonal (steroidal
and thyroid) replacement therapy
electrocardiographic findings were
normalized. Hormonal disorders should
be considered as a cause of long QT
intervals which may lead to torsade de
pointes, even if plasma electrolyte levels
are normal, because life-threatening
arrhythmia is treatable by
supplementation of the hormone that is
lacking.
1. Introduction
QT prolongation has various causes,
including drug toxicity, electrolyte
abnormality, myocarditis,
cerebrovascular disease, chromosomal
abnormalities of cardiac ion channels,
and hormonal disorders such as
hypopituitarism, hypothyroidism, and
adrenal insufficiency [1 –5 ]. It is well
known that QT prolongation can be
associated with polymorphic ventricular
tachycardia (VT), which is usually
resistant to antiarrhythmic drug
therapy.
We experienced a case of long QT
intervals associated with
panhypopituitarism that developed
idiopathically as a result of empty sella.
2. Case Report
A 37-year-old woman was admitted to
our hospital because of amenorrhea and
infertility. She also suffered from
fatigue, numbness, and swelling in
hands and foot. Her systolic blood
pressure was found to be <90 mmHg.
She had mild myxedema without
acromegalic phenotype. No galactorrhea
was described. Her past history was
remarkable. She had a traffic accident at
14 years of age. She had regular
menstrual cycles until 20 years of age.
After 20 years of age, no menstrual
bleedings have yet occurred nowadays.
She also complained from mild headache
around eyes. Polydipsia and polyuria
were not defined.
Laboratory tests include serum
biochemistry, and hormones revealed
glucose: 86 mg/dL (70–105 mg/dL), urea:
17.1 mg/dL (18–45 mg/dL), creatinine:
0.7 mg/dL (0.57–1.11 mg/dL), calcium:
8.8 mg/dL (8.4–10.2 mg/dL),
phosphorus: 3.3 mg/dL (2.5–4.5 mg/dL),
magnesium: 2.1 mg/dL (1.7–3.1 mg/dL)
Na: 141 mmol/L (136–145 mmol/L), K:
4.7 mmol/L (3.5–5.1 mmol/L), fT3: 2.12
pmol/L (2.63–5.70 pmol/L), fT4: 5.81
pmol/L (9.01–19.04 pmol/L), TSH: 1.28
IU/mL (0.35–4.94 IU/mL), LH: 0.02 mIU/
mL, FSH: 0.06 mIU/mL, PRL: 1.81 ng/mL
(5.18–26.53 ng/mL), oestrogen: 24 pg/
mL, progesterone: 0.1 ng/mL, cortisol:
0.01 μg/dL (3–19 μg/dL), and ACTH:
10.9 pg/mL (22.5–95.3 pg/mL). She was
hypotensive without any electrolyte
imbalance. We administered stress-dose
steroid and then reduced to replacement
dose by titration. At followup,
hypotension was improved. Thyroid
function tests displayed lower fT3 and
fT4 and normal TSH levels which was
thought to be secondary hypothyroidism.
We gave her levothyroxine (LT4)
replacement. Urine-specific gravity was
1011 and fluid intake and urine output
were normal. She had no menstrual
bleedings for seventeen years, and also
serum progesterone level, was low so
called hypogonadism. She was consulted
with gynecologist and endometrial wall
thickness was lower, so she was offered
to take estrogen progesterone
replacement treatment. With all these
findings, we suspected
panhypopituitarism. Hypophyseal
magnetic resonance imaging (MRI) was
taken and was shown as hypophyseal
hypoplasia with dimensions of 4.6 mm
height and 8.5 mm width. And also
posterior pituitary bright spot was seen
on MRI. Twelve-lead electrocardiogram
was taken (Figure 1 ).
Figure 1: Twelve-lead
electrocardiogram on
admission shows long
QT intervals and
inverted T waves.
At cardiac auscultation murmur was
heard. Patient was consulted with a
cardiologist. A two-dimensional
transthoracic echocardiography was
taken it showed normal left ventricular
systolic function with 65% ejection
fraction, left atrium enlargement, and
mild mitral and tricuspid regurgitation.
A 24-hour rhythm holter
electrocardiography (ECG) was taken
(Figure 2 ); it showed that basic rhythm
was sinusal rhythm, minimal heart rate
was 44/min, mean heart rate was 62/
min, maximal heart rate was 107/min,
and no ventricular/supraventricular
tachycardia or pause was detected.
Maximal QT/QTc interval was 549 ms.
Figure 2: Some
significant ECG events
and minimal heart
rate ECG record
which were detected
at 24-hour rythm
holter ECG.
We considered that QT prolongation may
be caused by hypopituitarism. Steroid
replacement therapy was started on the
5th hospital day and thyroid
replacement therapy on the 11th hospital
day. Three weeks after starting steroid
replacement therapy, the levels of
cortisol and thyroid hormone were
normalized. Two-dimensional
echocardiography showed normal
cardiac wall and valve motions. Also, an
ECG showed QT normalization (Figure
3 ). QT/QTC interval was measured
364/392 ms.
Figure 3: Four weeks
after starting steroid
and thyroid
replacement therapy,
twelve-lead
electrocardiogram
demonstrates normal
QT intervals.
3. Discussion
We described a case of QT prolongation
associated with anterior hypopituitarism
without plasma electrolyte abnormality.
The cause of hypopituitarism could not
be defined in our patient. QT
prolongation may result from electrolyte
disturbances, the use of various
antiarrhythmic drugs, phenothiazines or
tricyclic antidepressants, liquid protein
diets, intracranial events,
bradyarrhythmias, and hormonal
disorders. In our patient, no drug use
was described what mentioned above.
But hormonal disorders
(hypocortisolemia and hypothyroidism)
were found in our patient.
QT prolongation may lead to torsade de
pointes a form of polymorphic
ventricular tachycardia which can cause
sudden cardiac death. In the literature,
there is only one report that described a
case of an association between torsade
pointes and hypopituitarism [6 ].
Electrocardiographic abnormalities
commonly associated with
hypopituitarism are low QRS voltage, ST-
segment depression, inverted T waves,
and a prolonged QT interval [7 , 8 ].
Although the mechanism remains
unclear, glucocorticoid deficiency, an
intracellular-extracellular electrolyte
imbalance of myocytes, and
histopathological changes in the
myocardium are thought to play a role in
this disorder. Recently, it was reported
that glucocorticoids upregulate Kv 1.5 K
channel gene expression in the rat
ventricle [9 ]. Iga et al. [10 ] suggested that
catecholamine release induced by
hypoglycemia might cause arrhythmia or
abnormal wall motion of the left
ventricle in patients with adrenal
insufficiency. In our patient, QT
prolongation without any arrhythmias
occurred in the absence of hypoglycemia
or plasma electrolyte abnormalities.
Some previous reports [4 , 11 ] have
suggested that hypomagnesemia induced
by adrenal insufficiency might cause
myocytic intracellular-extracellular
electrolytic imbalance, resulting in
shortening of the effective refractory
period and prolongation of the relative
refractory period. In our patient, serum
magnesium level was normal. Inverted T
waves and prolonged QT intervals seen
in our patient might be mediated by a
hormonal modulation of ion channels of
cardiac cells, which could contribute to
QT prolongation and lead to
polymorphic ventricular tachycardia
before plasma electrolyte abnormality.
But in our patient, polymorphic
ventricular tachycardia did not occur.
We found lower serum thyroid hormone
levels and plasma cortisol levels. After
steroid and thyroid hormone
replacement therapy, the QT interval
was normalized and no further VT
developed.
In conclusion, hormonal disorders must
be examined as a cause of polymorphic
ventricular tachycardia associated with
long QT intervals even if plasma
electrolyte levels are normal, because
supplementation of insufficient hormone
may permanently cure life-threatening
arrhythmia.
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