<s>
The	O
QT	B-Algorithm
interval	I-Algorithm
is	O
a	O
measurement	O
made	O
on	O
an	O
electrocardiogram	B-Application
used	O
to	O
assess	O
some	O
of	O
the	O
electrical	O
properties	O
of	O
the	O
heart	O
.	O
</s>
<s>
It	O
is	O
calculated	O
as	O
the	O
time	O
from	O
the	O
start	O
of	O
the	O
Q	B-Algorithm
wave	I-Algorithm
to	O
the	O
end	O
of	O
the	O
T	B-Algorithm
wave	I-Algorithm
,	O
and	O
approximates	O
to	O
the	O
time	O
taken	O
from	O
when	O
the	O
cardiac	O
ventricles	O
start	O
to	O
contract	O
to	O
when	O
they	O
finish	O
relaxing	O
.	O
</s>
<s>
An	O
abnormally	O
long	O
or	O
abnormally	O
short	O
QT	B-Algorithm
interval	I-Algorithm
is	O
associated	O
with	O
an	O
increased	O
risk	O
of	O
developing	O
abnormal	B-Application
heart	I-Application
rhythms	I-Application
and	O
sudden	O
cardiac	O
death	O
.	O
</s>
<s>
Abnormalities	O
in	O
the	O
QT	B-Algorithm
interval	I-Algorithm
can	O
be	O
caused	O
by	O
genetic	O
conditions	O
such	O
as	O
long	O
QT	O
syndrome	O
,	O
by	O
certain	O
medications	O
such	O
as	O
sotalol	O
or	O
pitolisant	O
,	O
by	O
disturbances	O
in	O
the	O
concentrations	O
of	O
certain	O
salts	O
within	O
the	O
blood	O
such	O
as	O
hypokalaemia	O
,	O
or	O
by	O
hormonal	O
imbalances	O
such	O
as	O
hypothyroidism	O
.	O
</s>
<s>
The	O
QT	B-Algorithm
interval	I-Algorithm
is	O
most	O
commonly	O
measured	O
in	O
lead	O
II	O
for	O
evaluation	O
of	O
serial	O
ECGs	B-Application
,	O
with	O
leads	O
I	O
and	O
V5	O
being	O
comparable	O
alternatives	O
to	O
lead	O
II	O
.	O
</s>
<s>
Leads	O
III	O
,	O
aVL	O
and	O
V1	O
are	O
generally	O
avoided	O
for	O
measurement	O
of	O
QT	B-Algorithm
interval	I-Algorithm
.	O
</s>
<s>
The	O
accurate	O
measurement	O
of	O
the	O
QT	B-Algorithm
interval	I-Algorithm
is	O
subjective	O
because	O
the	O
end	O
of	O
the	O
T	B-Algorithm
wave	I-Algorithm
is	O
not	O
always	O
clearly	O
defined	O
and	O
usually	O
merges	O
gradually	O
with	O
the	O
baseline	O
.	O
</s>
<s>
QT	B-Algorithm
interval	I-Algorithm
in	O
an	O
ECG	B-Application
complex	O
can	O
be	O
measured	O
manually	O
by	O
different	O
methods	O
,	O
such	O
as	O
the	O
threshold	O
method	O
,	O
in	O
which	O
the	O
end	O
of	O
the	O
T	B-Algorithm
wave	I-Algorithm
is	O
determined	O
by	O
the	O
point	O
at	O
which	O
the	O
component	O
of	O
the	O
T	B-Algorithm
wave	I-Algorithm
merges	O
with	O
the	O
isoelectric	O
baseline	O
,	O
or	O
the	O
tangent	O
method	O
,	O
in	O
which	O
the	O
end	O
of	O
the	O
T	B-Algorithm
wave	I-Algorithm
is	O
determined	O
by	O
the	O
intersection	O
of	O
a	O
tangent	O
line	O
extrapolated	O
from	O
the	O
T	B-Algorithm
wave	I-Algorithm
at	O
the	O
point	O
of	O
maximum	O
downslope	O
to	O
the	O
isoelectric	O
baseline	O
.	O
</s>
<s>
With	O
the	O
increased	O
availability	O
of	O
digital	O
ECGs	B-Application
with	O
simultaneous	O
12-channel	O
recording	O
,	O
QT	O
measurement	O
may	O
also	O
be	O
done	O
by	O
the	O
'	O
superimposed	O
median	O
beat	O
 '	O
method	O
.	O
</s>
<s>
In	O
the	O
superimposed	O
median	O
beat	O
method	O
,	O
a	O
median	O
ECG	B-Application
complex	O
is	O
constructed	O
for	O
each	O
of	O
the	O
12	B-Application
leads	I-Application
.	O
</s>
<s>
The	O
12	O
median	O
beats	O
are	O
superimposed	O
on	O
each	O
other	O
and	O
the	O
QT	B-Algorithm
interval	I-Algorithm
is	O
measured	O
either	O
from	O
the	O
earliest	O
onset	O
of	O
the	O
Q	B-Algorithm
wave	I-Algorithm
to	O
the	O
latest	O
offset	O
of	O
the	O
T	B-Algorithm
wave	I-Algorithm
or	O
from	O
the	O
point	O
of	O
maximum	O
convergence	O
for	O
the	O
Q	B-Algorithm
wave	I-Algorithm
onset	O
to	O
the	O
T	B-Algorithm
wave	I-Algorithm
offset	O
.	O
</s>
<s>
The	O
QT	B-Algorithm
interval	I-Algorithm
changes	O
in	O
response	O
to	O
the	O
heart	O
rate	O
-	O
as	O
heart	O
rate	O
increase	O
the	O
QT	B-Algorithm
interval	I-Algorithm
shortens	O
.	O
</s>
<s>
These	O
changes	O
make	O
it	O
harder	O
to	O
compare	O
QT	B-Algorithm
intervals	I-Algorithm
measured	O
at	O
different	O
heart	O
rates	O
.	O
</s>
<s>
To	O
account	O
for	O
this	O
,	O
and	O
thereby	O
improve	O
the	O
reliability	O
of	O
QT	O
measurement	O
,	O
the	O
QT	B-Algorithm
interval	I-Algorithm
can	O
be	O
corrected	O
for	O
heart	O
rate	O
(	O
QTc	B-Algorithm
)	O
using	O
a	O
variety	O
of	O
mathematical	O
formulae	O
,	O
a	O
process	O
often	O
performed	O
automatically	O
by	O
modern	O
ECG	B-Application
recorders	O
.	O
</s>
<s>
The	O
most	O
commonly	O
used	O
QT	O
correction	O
formula	O
is	O
the	O
Bazett	O
's	O
formula	O
,	O
named	O
after	O
physiologist	O
Henry	O
Cuthbert	O
Bazett	O
(	O
1885	O
–	O
1950	O
)	O
,	O
calculating	O
the	O
heart	O
rate-corrected	O
QT	B-Algorithm
interval	I-Algorithm
(	O
QTcB	O
)	O
.	O
</s>
<s>
Bazett	O
's	O
formula	O
is	O
often	O
given	O
in	O
a	O
form	O
that	O
returns	O
QTc	B-Algorithm
in	O
dimensionally	O
suspect	O
units	O
,	O
square	O
root	O
of	O
seconds	O
.	O
</s>
<s>
where	O
QTcB	O
is	O
the	O
QT	B-Algorithm
interval	I-Algorithm
corrected	O
for	O
heart	O
rate	O
,	O
and	O
RR	O
is	O
the	O
interval	O
from	O
the	O
onset	O
of	O
one	O
QRS	B-Algorithm
complex	I-Algorithm
to	O
the	O
onset	O
of	O
the	O
next	O
QRS	B-Algorithm
complex	I-Algorithm
.	O
</s>
<s>
This	O
mathematically	O
correct	O
formula	O
returns	O
the	O
QTc	B-Algorithm
in	O
the	O
same	O
units	O
as	O
QT	O
,	O
generally	O
milliseconds	O
.	O
</s>
<s>
However	O
,	O
reporting	O
QTc	B-Algorithm
using	O
this	O
formula	O
creates	O
a	O
"	O
requirement	O
regarding	O
the	O
units	O
in	O
which	O
the	O
original	O
QT	O
and	O
RR	O
are	O
measured.	O
"	O
</s>
<s>
Fridericia	O
had	O
proposed	O
an	O
alternative	O
correction	O
formula	O
(	O
QTcF	B-Algorithm
)	O
using	O
the	O
cube-root	O
of	O
RR	O
.	O
</s>
<s>
Definitions	O
of	O
normal	O
QTc	B-Algorithm
vary	O
from	O
being	O
equal	O
to	O
or	O
less	O
than	O
0.40s	O
( ≤400ms	O
)	O
,	O
0.41s	O
( ≤410ms	O
)	O
,	O
0.42s	O
( ≤420ms	O
)	O
or	O
0.44s	O
( ≤440ms	O
)	O
.	O
</s>
<s>
For	O
risk	O
of	O
sudden	O
cardiac	O
death	O
,	O
"	O
borderline	O
QTc	B-Algorithm
"	O
in	O
males	O
is	O
431	O
–	O
450ms	O
;	O
and	O
,	O
in	O
females	O
,	O
451	O
–	O
470ms	O
.	O
</s>
<s>
An	O
"	O
abnormal	O
"	O
QTc	B-Algorithm
in	O
males	O
is	O
a	O
QTc	B-Algorithm
above	O
450ms	O
;	O
and	O
,	O
in	O
females	O
,	O
above	O
470ms	O
.	O
</s>
<s>
If	O
there	O
is	O
not	O
a	O
very	O
high	O
or	O
low	O
heart	O
rate	O
,	O
the	O
upper	O
limits	O
of	O
QT	O
can	O
roughly	O
be	O
estimated	O
by	O
taking	O
QT	O
=	O
QTc	B-Algorithm
at	O
a	O
heart	O
rate	O
of	O
60	O
beats	O
per	O
minute	O
(	O
bpm	O
)	O
,	O
and	O
subtracting	O
0.02s	O
from	O
QT	O
for	O
every	O
10bpm	O
increase	O
in	O
heart	O
rate	O
.	O
</s>
<s>
For	O
example	O
,	O
taking	O
normal	O
QTc≤	O
0.42s	O
,	O
QT	O
would	O
be	O
expected	O
to	O
be	O
0.42s	O
or	O
less	O
at	O
a	O
heart	O
rate	O
of	O
60bpm	O
.	O
</s>
<s>
Prolonged	O
QTc	B-Algorithm
causes	O
premature	O
action	O
potentials	O
during	O
the	O
late	O
phases	O
of	O
depolarization	O
.	O
</s>
<s>
This	O
increases	O
the	O
risk	O
of	O
developing	O
ventricular	O
arrhythmias	B-Application
,	O
including	O
fatal	O
ventricular	O
fibrillation	O
.	O
</s>
<s>
Higher	O
rates	O
of	O
prolonged	O
QTc	B-Algorithm
are	O
seen	O
in	O
females	O
,	O
older	O
patients	O
,	O
high	O
systolic	O
blood	O
pressure	O
or	O
heart	O
rate	O
,	O
and	O
short	O
stature	O
.	O
</s>
<s>
Prolonged	O
QTc	B-Algorithm
is	O
also	O
associated	O
with	O
ECG	B-Application
findings	O
called	O
Torsades	B-Algorithm
de	I-Algorithm
Pointes	I-Algorithm
,	O
which	O
are	O
known	O
to	O
degenerate	O
into	O
ventricular	O
fibrillation	O
,	O
associated	O
with	O
higher	O
mortality	O
rates	O
.	O
</s>
<s>
There	O
are	O
many	O
causes	O
of	O
prolonged	O
QT	B-Algorithm
intervals	I-Algorithm
,	O
acquired	O
causes	O
being	O
more	O
common	O
than	O
genetic	O
.	O
</s>
<s>
An	O
abnormally	O
prolonged	O
QT	B-Algorithm
interval	I-Algorithm
could	O
be	O
due	O
to	O
long	O
QT	O
syndrome	O
,	O
whereas	O
an	O
abnormally	O
shortened	O
QT	B-Algorithm
interval	I-Algorithm
could	O
be	O
due	O
to	O
short	O
QT	O
syndrome	O
.	O
</s>
<s>
The	O
QTc	B-Algorithm
length	O
is	O
associated	O
with	O
variations	O
in	O
the	O
NOS1AP	O
gene	O
.	O
</s>
<s>
The	O
autosomal	O
recessive	O
syndrome	O
of	O
Jervell	O
and	O
Lange-Nielsen	O
is	O
characterized	O
by	O
a	O
prolonged	O
QTc	B-Algorithm
interval	O
in	O
conjunction	O
with	O
sensorineural	O
hearing	O
loss	O
.	O
</s>
<s>
Prolongation	O
of	O
the	O
QT	B-Algorithm
interval	I-Algorithm
may	O
be	O
due	O
to	O
an	O
adverse	O
drug	O
reaction	O
.	O
</s>
<s>
In	O
addition	O
,	O
high	O
blood	O
alcohol	O
concentrations	O
prolong	O
the	O
QT	B-Algorithm
interval	I-Algorithm
.	O
</s>
<s>
Hypothyroidism	O
,	O
a	O
condition	O
of	O
low	O
function	O
of	O
the	O
thyroid	O
gland	O
,	O
can	O
cause	O
QT	O
prolongation	O
at	O
the	O
electrocardiogram	B-Application
.	O
</s>
<s>
Acute	O
hypocalcemia	O
causes	O
prolongation	O
of	O
the	O
QT	B-Algorithm
interval	I-Algorithm
,	O
which	O
may	O
lead	O
to	O
ventricular	O
dysrhythmias	O
.	O
</s>
<s>
Since	O
2005	O
,	O
the	O
FDA	O
and	O
European	O
regulators	O
have	O
required	O
that	O
nearly	O
all	O
new	O
molecular	O
entities	O
be	O
evaluated	O
in	O
a	O
Thorough	O
QT	O
(	O
TQT	O
)	O
or	O
similar	O
study	O
to	O
determine	O
a	O
drug	O
's	O
effect	O
on	O
the	O
QT	B-Algorithm
interval	I-Algorithm
.	O
</s>
<s>
The	O
TQT	O
study	O
serves	O
to	O
assess	O
the	O
potential	O
arrhythmia	B-Application
liability	O
of	O
a	O
drug	O
.	O
</s>
<s>
Traditionally	O
,	O
the	O
QT	B-Algorithm
interval	I-Algorithm
had	O
been	O
evaluated	O
by	O
having	O
an	O
individual	O
human	O
reader	O
measure	O
approximately	O
nine	O
cardiac	O
beats	O
per	O
clinical	O
timepoint	O
.	O
</s>
<s>
As	O
the	O
pharmaceutical	O
industry	O
has	O
gained	O
experience	O
in	O
performing	O
TQT	O
studies	O
,	O
it	O
has	O
also	O
become	O
evident	O
that	O
traditional	O
QT	O
correction	O
formulas	O
such	O
as	O
QTcF	B-Algorithm
,	O
QTcB	O
,	O
and	O
QTcLC	O
may	O
not	O
always	O
be	O
suitable	O
for	O
evaluation	O
of	O
drugs	O
impacting	O
autonomic	O
tone	O
.	O
</s>
<s>
Electrocardiography	B-Application
is	O
a	O
safe	O
and	O
noninvasive	O
tool	O
that	O
can	O
be	O
used	O
to	O
identify	O
those	O
with	O
a	O
higher	O
risk	O
of	O
mortality	O
.	O
</s>
<s>
In	O
the	O
general	O
population	O
,	O
there	O
has	O
been	O
no	O
consistent	O
evidence	O
that	O
prolonged	O
QTc	B-Algorithm
interval	O
in	O
isolation	O
is	O
associated	O
with	O
an	O
increase	O
in	O
mortality	O
from	O
cardiovascular	O
disease	O
.	O
</s>
<s>
However	O
,	O
several	O
studies	O
have	O
examined	O
prolonged	O
QT	B-Algorithm
interval	I-Algorithm
as	O
a	O
predictor	O
of	O
mortality	O
for	O
diseased	O
subsets	O
of	O
the	O
population	O
.	O
</s>
<s>
found	O
a	O
50ms	O
increase	O
in	O
QTc	B-Algorithm
interval	O
increased	O
the	O
odds	O
of	O
all-cause	O
mortality	O
by	O
2.17	O
in	O
patients	O
with	O
rheumatoid	O
arthritis	O
.	O
</s>
<s>
Patients	O
with	O
the	O
highest	O
QTc	B-Algorithm
interval	O
(	O
>424ms	O
)	O
had	O
higher	O
mortality	O
than	O
those	O
with	O
a	O
lower	O
QTc	B-Algorithm
interval	O
.	O
</s>
<s>
The	O
researchers	O
proposed	O
that	O
inflammation	O
prolonged	O
the	O
QTc	B-Algorithm
interval	O
and	O
created	O
arrhythmias	B-Application
that	O
were	O
associated	O
with	O
higher	O
mortality	O
rates	O
.	O
</s>
<s>
However	O
,	O
the	O
mechanism	O
by	O
which	O
C-reactive	O
protein	O
is	O
associated	O
with	O
the	O
QTc	B-Algorithm
interval	O
is	O
still	O
not	O
understood	O
.	O
</s>
<s>
Almost	O
half	O
of	O
patients	O
with	O
type	O
1	O
diabetes	O
have	O
a	O
prolonged	O
QTc	B-Algorithm
interval	O
(	O
>440ms	O
)	O
.	O
</s>
<s>
Diabetes	O
with	O
a	O
prolonged	O
QTc	B-Algorithm
interval	O
was	O
associated	O
with	O
a	O
29%	O
mortality	O
over	O
10	O
years	O
in	O
comparison	O
to	O
19%	O
with	O
a	O
normal	O
QTc	B-Algorithm
interval	O
.	O
</s>
<s>
Anti-hypertensive	O
drugs	O
increased	O
the	O
QTc	B-Algorithm
interval	O
,	O
but	O
were	O
not	O
an	O
independent	O
predictor	O
of	O
mortality	O
.	O
</s>
<s>
QT	B-Algorithm
interval	I-Algorithm
dispersion	O
(	O
QTd	O
)	O
is	O
the	O
maximum	O
QT	B-Algorithm
interval	I-Algorithm
minus	O
the	O
minimum	O
QT	B-Algorithm
interval	I-Algorithm
,	O
and	O
is	O
linked	O
with	O
ventricular	B-Application
repolarization	I-Application
.	O
</s>
<s>
QTd	O
is	O
a	O
better	O
predictor	O
of	O
cardiovascular	O
death	O
than	O
QTc	B-Algorithm
,	O
which	O
was	O
unassociated	O
with	O
mortality	O
in	O
type	O
2	O
diabetes	O
.	O
</s>
