1. Definition and background

The QT interval is the period from the start of the QRS complex to the end of the T wave.

It corresponds to the total duration of ventricular excitation and reveals itself as prolonged or shortened in different pathologies [1].

The beginning of the QRS complex as well as the end of the T wave is determined in each of the 12 channels.

The earliest point in time of the beginning of a QRS complex in a channel is defined as start of "Q". Accordingly, the latest point in time of a T wave end in a channel is defined as the end of "T". Channels that supply non-plausible, significantly deviating results compared to the points in time of the other channels, are ignored to make sure that disturbed channels do not falsify the result. Basically, this procedure can be applied to any single beat. In order to minimize disturbances, the so-called summary complex is measured in a resting ECG.

The sum complex (cumulative complex) results from averaging the normal beats of equal morphology of the last 10 seconds of the first section.

Figure 1 - Progress of a cardiac excitation

2. Diagnostic significance of the QT interval

The QT interval is the period of de- and repolarisation of the ventricles. QT prolongations indicate a disturbance of these processes. Basically, acquired and congenital QT prolongations can be distinguished.
Acquired QT prolongations are frequently caused by certain drugs such as antiarrhythmic agents (class I and II e.g. quinidine, sotalol and others), tricyclic antidepressants as well as antibiotics. They can prolong the QT interval and the repolarisation of the heart and increase the risk for dangerous cardiac arrhythmia.
Congenital QT prolongations can often be attributed to genetic causes. Some known diseases are the Jervell and Lange-Nielsen Syndrome (JLNS) or the Romano-Ward Syndrome (RWS).
Cardinal symptoms are hearing loss (JLNS), syncope with stress, effort or cold as well as a considerably prolonged QT interval (>500ms), frequently associated with tachy-arrhythmia (ventricular tachycardia, episodes of Torsades de Pointes (TdP) with polymorphic ventricular tachycardia and ventricular fibrillation), which may result in syncope or sudden death.
If the QT interval is prolonged, normally further risk factors are given such as heart diseases, drug interactions, a genetic predisposition or electrolyte imbalances.

3. Determination of the QT interval

• Determination of the start of a QRS complex per channel
  On the basis of the maximum deflection of the complex search is made towards the left, until the ECG merges with the isoelectric line. The start of the QRS complex is defined as the point in the ECG that has the largest distance to a straight line defined by 2 points: the first point is located on the isoelectric line before the point in time when the ECG merges with the isoelectric line. The second point lies above the first positive or below the first negative deflection of the QRS complex.

• Determination of the end of the T wave for each channel
  In analogy with the determination of the start of the QRS complex, search is made towards the right on the basis of the maximum or minimum of the T wave, until the ECG merges with the isoelectric line. The end of the T wave is defined as the point in the ECG that has the largest distance to a straight line defined by 2 points: the first point lies on the isoelectric line behind the point in time when the ECG merges with the isoelectric line. The second point lies above the T wave maximum or below the T wave minimum.

4. QTc - the heart rate-corrected QT interval

As the QT interval depends on the heart rate - with high heart rate the QT interval is shorter and vice versa - a heart rate-adjusted, standardised QT interval is used for diagnostics, the so-called QTc interval. The QTc value shows which value the measured QT interval would have if it had been determined at a heart rate of 60/min, i.e. a R-R interval of 1s.
In custo diagnostic, the formulas according to Bazett and Fridericia are used.

Bazett:
Named after the English physiologist Henry Cuthbert Bazett (1885-1950). The Bazett formula is an empirically determined, mathematical equation for calculating the physiological QT interval at different heart rates and/or for calculating the heart rate-corrected QT interval (QTc) (https://flexikon.doccheck.com/de/Bazett-Formel).

The formula for calculating the heart rate-corrected QT interval according to Bazett is the following:

It undercorrects at heart rates <60/min and overcorrects at heart rates >80/min.

Fridericia:
Like the Bazett formula, the Fridericia formula is empirically determined and serves for calculating the physiological QT interval at different heart rates and/or for calculating the heart rate-corrected QT interval (QTc).

The formula for calculating the heart rate-corrected QT interval according to Fridericia is the following:

With higher heart rates (> 80/min) in particular, the rate correction according to Fridericia is considered to be more suitable than the formula according to Bazett.

Further formulas for heart rate-adjusted, QT-dependent considerations can be found in literature (see e. g. [6]). The formulas according to Bazett and Fridericia were developed around 1920 / 1937 (Hegglin). Since 2012, the Framingham formula has become available which has been determined on the basis of a considerably larger patient collective.
The formula for calculating the heart rate-corrected QT interval (QTc) in milliseconds according to Framingham is: QTc [ms] = QT interval [ms] + (0.154 * (1000 - R-R interval [ms]).

5. QT dispersion

The duration of the QT interval varies from lead to lead and is the longest in the precordial chest leads. The difference between the longest and the shortest QT interval is called QT dispersion. People with a healthy heart have a QT dispersion around 50ms (+/- 18ms), values exceeding 80ms have to be considered as pathologic and indicate an electrical inhomogeneity of the ventricles with an increased risk for heart rhythm-related events, particularly the sudden cardiac death [2].

The measurement of the QT interval with prominent U wave can be difficult or even impossible (in case of T-U merges). From a pathophysiological point of view, it makes sense to consider and measure also the complete repolarisation, which means including the U wave. [2].

6. Normal ranges of the QT interval

QT intervals are measured in milliseconds. The normal range for QTc is 350ms to 430ms, the average value in women being significantly higher, with 421ms versus 409ms in men [2]. According to Gertsch (2008), slightly shortened or slightly prolonged QT intervals may also occur in people with a healthy heart, however the QTc interval should not exceed 460ms [3].
In custo diagnostic, the measured value table indicates a percentage value in addition to QTc interval. This is based on the formula by Hegglin and Holzmann (1937) for calculating a heart rate-corresponding QT target value.
The formula is: QT target value = 0.39 x (square root of R-R interval +/- 0.04 sec) [4].
The result is a heart rate-corrected QTc target value of 390ms (+/- 40ms). The percentage indication in custo diagnostic specifies the deviation from this (average) target value (390ms) in percent.

As limits for a QT prolongation, the values specified in Lewalter & Lüderitz (2010) are used. When using the Bazett formula, the authors differentiate as follows:

QTc limits for men, women and children (from 1 to 15 years):

Table 1 QTc limit values [5]

7. Measurement of the QT interval in custo diagnostic

First of all, the determination of the QT interval is explicitly regulated in the DIN EN 60601-2-51 standard, i.e. there is a clearly defined requirement that has to be observed.
The above-mentioned standard literally states the following:
"…The global intervals of P, QRS and T are physiologically defined as the earliest start in a LEAD and the latest end of another LEAD. (Due to the different dispersion of wave progressions, the starts and ends of the wave progressions are not necessarily visible in all LEADS simultaneously.) Figure FF.2 shows an example where P start is determined by LEAD II, P end by LEAD G I, QRS start by LEAD V1 and LEAD G V3, QRS end by LEAD G V5 and T end by LEAD G V2 and V3…"

Figure 2 Definition and determination of global intervals [8]

The measurement of the QT interval in the resting and stress ECG is based on the exact calculation of the summary complex over all 12 channels. It is possible for the examining physician to check the markings automatically set by our software for start and end of the each complex and to correct them if required. For determining the QT interval, the QT segment in the summary complex is measured by means of the QT segment of the maximum interval, i.e. the intervals from Q to T determined via all leads.

In the result, this maximum interval then starts at the "earliest" Q and ends at the "latest" T. However, it has to be considered that due to the different projection of the wave progressions, the beginnings and ends of the wave progressions are not necessarily visible in all leads simultaneously. This procedure complies exactly with the requirements of the DIN EN 60601-2-51 standard.

The only difference between resting and stress ECG is that there is one QT interval in the result in the resting ECG and one QT interval per load step in the stress ECG. Here, as a standard, the last 10 seconds of the corresponding load step are taken into consideration for measurement, which can however be changed by the physician. From the measured QT intervals, the QTc intervals according to Bazett (1920) or Fridericia (1920) can be calculated, too.
In custo diagnostic the QTc interval will be classified as pathologic if it exceeds 440ms.

• Settings in the custo ServiceCenter (4.x) (see annex)
  In the custo ServiceCenter, the value from which a notice for a QT prolongation is to be indicated can be set under "Einstellungen" (settings), limit for women / men. If required, modifications can be made here.

• Modifications since custo diagnostic 4.3 and subsequent versions
  Since custo diagnostic version 4.3, the criterion for a QT prolongation has been set slightly stricter as it had been chosen too generously in previous versions (up to diag 4.1 and before). In the older versions, a warning notice was issued at a prolongation of about 120% of the QTc interval (related to the average value of 390ms). It became effective at QTc intervals of approx. 470ms and the notice "QT prolongation" was not indicated before. However, 470ms are too long, this is why the notice is now issued at approx. 112% already (which corresponds to approx. 440ms).

• in custo diagnostic, 5 the settings are as described in the previous section. An adaptation can be made as described in annex 2.

8. Summary

The QT interval in custo diagnostic is measured according to the normative requirements of DIN EN 60601-2-25 (VDE 0750-2-25):2016-08.
This standard exactly stipulates how start and end of a QT interval have to be determined and how the measurement over a 12-channel ECG has to be carried out. custo diagnostic strictly observes these regulations. For the calculation of the corrected QT interval, the QTc interval, various formulas can be used such as the Bazett or the Fridericia formula.
For the definition of the pathologic limits, custo diagnostic refers to the current scientific literature, currently Lewalter & Lüderitz (2010).
Furthermore, the limits can also be defined by the physician him- or herself - if this appears to be necessary. These modifications will be noted and are reserved for the medical expert (physician).

Important notice:
The contents made available here have been generated to the best of our knowledge and belief. We do not assume any responsibility for damages resulting from the use of the information contained herein. All liability claims are invalid. The readers are advised to check the accuracy of all product-related information.

9. Literature

[1] von Olshausen, Klaus (). EKG-Information: Vom Anfänger zum Profi. 8., überarbeitete und erweiterte Auflage. Darmstadt: Steinkopff, S. 80.

[2] Rosskamm, H.; Neumann, F.-J.; Kalusche, D.; Bestehorn, H.-P. (2004). Herzkrankheiten. Pathophysiologie, Diagnostik, Therapie, 5. Auflage., Springer-Verlag: Berlin Heidelberg. New York, S. 1373.

[3] Gertsch, M. (2008). Das EKG, 2. Auflage. Springer Medizin Verlag: Berlin, Heidelberg, S. 638.

[4] Gonska, B.D.; Heinecker, R. (1999): EKG in Klinik und Praxis. Das Referenzwerk zur elektrokardiographischen Diagnostik, 14. Auflage. Georg Thieme Verlag: Stuttgart New York, S. 7705.

[5] Lewalter, T.; Lüderitz, B. (2010). Herzrhythmusstörungen. Diagnostik und Therapie, 6. Auflage. Springer Medizin Verlag, S.277.

[6] Rabkin, S.W.; Szefer, E. & Thompson, D.J.S. (2017): A new QT interval correction formulae to adjust for increase in heart rate. Journal of the American College of Cardiology: Clinical Electrophysiology 3 (7): 756-766 (incl. 10 pages of Appendix).

[7] Ulmer, H. E. (2013): Das Das Long-QT-Syndrom (LQTS). In: herzblatt, Sonderdruck: Das Long-QT-Syndrom (LQTS)Über den lebenslangen Umgang mit einer genetisch bedingten Herzerkrankung. Kinderherzstiftung der Deutschen Herzstiftung e. V.: Frankfurt/Main, S. 2.

[8] DIN EN 60601-2-25 (VDE 0750-2-25):2016-08, S.57.

10. List of abbreviations:

11. Table of figures

Figure 1 Progress of a cardiac excitation
Figure 2 Definition and determination of global intervals

12. Tables:

Table 1 QTc limit values

13. Annex

Annex 1: Settings in custo diagnostic 4.x

Servicecenter → Einstellungen → Ruhe-EKG → Befund → "AdultFemaleQTcLimit", bzw. "AdultMaleQTcLimit"

Annex 2: Settings in custo diagnostic 5.x