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 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, 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, named after physiologist Bazett, calculating the heart rate-corrected
QT interval QTB. Bazett's formula is:
where QTB 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 as 60/HR. However, this nonlinear 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. Fridericia has published an alternative correction
formula using the cube-root of RR.
There are several other methods, such as regression-analysis:
Definitions of normal QTc vary from being equal to or less than 0.40 s, 0.41s, 0.42s
or 0.44s. 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. 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, 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. Measurement
The measurement of QT interval is subjective 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. 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.
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. Higher rates of prolonged QTc are seen in
females, older patients, high systolic blood pressure or heart rate, and short stature.
Genetic causes An abnormally prolonged QT interval could
be due to long QT syndrome, whereas an abnormal shortened QT interval could be due to short
QT syndrome. The QTc length is associated with variations
in NOS1AP gene. Due to adverse drug reactions
Prolongation of the QT interval may be due to an adverse drug reaction. Many drugs such
as haloperidol, vemurafenib, ziprasidone, methadone and sertindole 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, alcohol in high blood concentrations prolongs the QT interval. A
possible interaction between selective serotonin reuptake inhibitors and thiazide diuretics
is associated with QT prolongation. 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. Due to pathological conditions
Hypothyroidism, a condition of low function of the thyroid gland, can give 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.
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 study
to determine a drug's effect on the QT interval. 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. As the pharmaceutical industry has gained experience in performing
TQT studies, it has also become evident that traditional QT correction formulas such as
QTF, QTB, and QTLC may not always be suitable for evaluation of drugs impacting autonomic
tone. 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. 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. However, several studies 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. Studies have linked rheumatoid
arthritis with increased death from cardiovascular disease. In a 2014 study, 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 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. Almost half of patients with type
1 diabetes have a prolonged QTc interval. Diabetes with a prolonged QTc interval was
associated with a 29% mortality over 10 years in comparison to 19% with a normal QTc interval.
Anti-hypertensive drugs increased the QTc interval, but were not an independent predictor
of mortality. Type 2 diabetes
QT interval dispersion is the maximum QT interval minus the minimum QT interval, and is linked
with ventricular repolarization. A QTd over 80 ms is considered abnormally prolonged.
Increased QTd is associated with mortality in type 2 diabetes. QTd is a better predictor
of cardiovascular death than QTc, which was unassocited with mortality in type 2 diabetes.
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 References
External links Cardiac safety section in the Biopharmaceutical
network