QT interval

File:SinusRhythmLabels.svg

Schematic representation of normal ECG trace (sinus rhythm), with waves, segments, and intervals labeled.

File:Ecgqt.png

The qt-time is normal, when it is less than half the rr-time.

In medicine, specifically 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. A prolonged QT interval is a risk factor for ventricular tachyarrhythmias and sudden death.

Measurement

QT interval can be measured 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 line extrapolated from the isoelectric baseline and the tangent line which touches the terminal part of the T wave at the point of maximum downslope. The QT interval generally represents electrical depolarization and repolarization of the left and right ventricles.

Correction For Heart Rate

File:QT interval corrected for heart rate.png

Upper limit of normal QT interval, corrected for heart rate according to Bazett's formula, Fridericia's formula and subtracting 0.02s from QT for every 10bpm increase in heart rate. Up to 0.42s (≤420ms) is chosen as normal QTc of QTf in this diagram.

The QT interval is dependent on the heart rate in an obvious way (the faster the heart rate, the shorter the 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, but this correction may not aid in the detection of patients at increased risk of arrhythmia.

The standard clinical correction is to use Bazett's formula, named after physiologist Henry Cuthbert Bazett, calculating the heartrate-corrected QT interval QTc.

Bazett's formula is as follows:

<math>QTc = \frac{QT}{\sqrt {RR} }</math>,

where QTc 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 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.

Definitions of normal QTc varies around being equal to or less than 0.40 s (≤400ms), 0.41s (≤410ms), 0.42s (≤420ms) or 0.44s (≤440ms). 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 isn't 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 10bpm increase in heart rate. For example, taking normal QTc ≤ 0.42s, QT would be expected to be 0.42s or less at a heart rate of 60bpm. For a heart rate of 70 bpm, QT would roughly be expected to be equal to or below 0.40s. Likewise, for 80 bpm, QT would roughly be expected to be equal to or below 0.38s.

Fridericia has published an alternative adjustment:

<math>QT_F = \frac{QT}{RR^{1/3} } </math>.

There are several other methods as well. For example a regression-based approach that had been developed by Sagie et al., as follows:

<math>QT_{LC} = QT + 0.154(1-RR)</math>.n

Abnormal intervals

If abnormally prolonged or shortened, there is a risk of developing ventricular arrhythmias. Preferably 3 consecutive measurements of the QT interval are recorded, mainly in lead II or a long lead. Then, the mean is calculated. If lead 2 is not suitable, then leads in the sequence of V5 V4 V3 V2 are selected.

Genetic causes

An abnormal prolonged QT interval could be due to Long QT syndrome, whereas an abnormal shortened QT interval could be due to Short QT syndrome.

The length of the interval was found to associate 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 and methadone can prolong the QT interval. Some antiarrhythmic drugs, like amiodarone or sotalol work by getting a pharmacological QT prolongation. Also some second generation of antihistamines, like astemizole, has this effect.

Due to pathological conditions

Hypothyroidism, a condition of low function of the thyroid gland, can give QTc prolongation at the electrocardiogram.

A shortened QT can be associated with hypercalcemia.

Use in Drug Studies for FDA Approval

Since 2005, the FDA has required that new molecular entities are evaluated in a Thorough QT (TQT) study to determine a drug's effect on the QT interval. The TQT study serves to assess the potential arrhythmia liability of a drug. As the pharmaceutical industry has gained experience in performing TQT studies, it has become evident that traditional QT correction formulas such as QTcF, QTcB, and QTcI 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.

See also

• Electrocardiogram

External links

• Cardiac safety section in the Biopharmaceutical network

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