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Wikipedia:Osmosis/Long QT syndrome

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Long QT syndrome and Torsade

Author: Tanner Marshall, MS

Editor: Rishi Desai, MD, MPH, Tanner Marshall, MS

On a normal ECG, you’ve got the P, Q, R, S, and T waves. The QT interval spans from the start of the Q to the end of the T wave. Long QT syndrome, or LQTS, is when somebody’s QT interval is longer than normal, which should typically be less than half of a cardiac cycle.

In fact, for a heart rate of 60 beats per minute, the QT interval’s generally considered to be abnormally long when it’s greater than 440 milliseconds in males or 460 milliseconds in females. If you measure someone’s QT interval at a different rate though, say 90 beats per minute and it was 400 milliseconds, you can’t really use that to compare that to these value at 60 beats per minute, since the QT interval changes depending on the rate.

As rate increases, the QT interval decreases. So what we have to do is find the corrected QT interval, or QTc, at the different rate so that you can compare it to the QT interval at 60 beats per minute. Even though there are several formulas you can use, the Bazett’s formula’s probably the simplest, where the corrected QT interval equals the QT interval in milliseconds divided by the square root of the R to R interval in seconds divided by 1 second. As a bit of a side-note, usually this formula’s expressed without the “divide by 1 second” bit, but the astute observer will notice that the units won’t work out if you do that.

Interestingly, the originally formula did include dividing by 1 second to get the units to work out, but for some reason in a paper way back when that step wasn’t included, and basically the version without the 1 second, the sort of unit-incorrect version, has been used ever since!

Anyways, let’s do a quick example of a male with a 400 milliseconds QT interval at a rate of 90 beats per minute. Comparing to the values at 60 beats per minute, 400 milliseconds wouldn’t be considered a long QT, right? If we use our handy formula, though, we’ll plug in 400 for QT and 90 beats per minute or .66 seconds per beat. So we have a QT of 400 milliseconds divided by the square root of 0.66 seconds over 1 second, which is 400 milliseconds divided by 0.81, which is unitless, and we get a corrected QT interval of 493 milliseconds, which is greater than 440, so actually, a 400 milliseconds QT interval at 90 beats per minute is considered long.

Alright so the QT interval’s a little long, what’s wrong with that? Well, the QRS complex corresponds to the ventricles depolarizing and contracting. After they depolarize, they have to repolarize, and that’s captured by the T wave. When someone has a long QT interval, it means that they have an abnormally long repolarization of some of their heart cells, but not all of their heart cells - which is an important point to remember. Specifically some of the heart cells are taking longer than normal to repolarize compared to their neighboring heart cells. Having some cells with an abnormally prolonged repolarization phase is thought to be caused by abnormalities in the movement of ions through ion channels,

which is responsible for both depolarization and repolarization, and each time it depolarizes and repolarizes, it’s called a cardiac action potential, where ions flow in and out of the cell, and this happens in four phases, which we can plot on a graph of membrane potential over time. During phase 2, potassium channels open and let potassium flow out, which tends to wanna make the membrane potential more negative, but L-type calcium channels open and let calcium flow into the cell, which tends to wanna make the cell more positive and therefore it maintains the “plateau” phase. During phase 3, the potassium channels stay open, but now the L-type calcium channels close, which let’s the cell repolarize.

So, it’s thought that dysfunction in the L-type calcium channels is one mechanism that can lead to a long repolarization phase. Specifically, they might let in more calcium during phase 2, making the membrane potential more positive and causing an early after-depolarization, or an EAD.

Other mechanisms involve sodium and potassium ion channels which can also malfunction and cause early after-depolarization as well. If the EAD is large enough it might propagate out and depolarize the ventricles, causing a premature ventricular contraction, or a PVC, in other words an unexpected ventricular contraction. If at this point, some neighboring cells are ready for another depolarization and some aren’t, then the wave of depolarization will go through the ready cells but get blocked on the not-ready cells. Then, at some point when those not ready cells come around, the wave of depolarization can double back, potentially creating a reentrant circuit, which leads to reentrant tachycardia, which are super fast heart rates that could happen because the signals might propagate around in a circular way, over and over and over again.

This becomes a special type of ventricular tachycardia or VT which is associated with Long QT syndrome called Torsade de Pointes, which means “the twisting of points”, because the QRS complexes seem to twist around the isoelectric line, and since the QRSs are different in shape, this is more specifically a type of polymorphic VT. Rates for Torsades range between 150 and 250 beats per minute, the upper end of which is really fast, right? So although these episodes can revert to a normal rhythm spontaneously, they can also be really serious and people with Torsades can feel palpitations, dizziness, syncope—or fainting, and it can even potentially lead to sudden cardiac death.

Alright so with long QT syndrome and Torsades, the cause of these abnormal ion channels is often congenital, meaning it’s present at birth and caused by some genetic abnormality. There’re at least 10 specific gene mutations that are known to be linked to Long QT syndrome, which are referred to as, for example, LQT1, LQT2, and so on, all of which have some effect on one or more ion channels. Aside from congenital causes though, sometimes the QT interval can be prolonged by certain medications which affect ion channels. For example, class IA antiarrhythmic drugs block sodium and potassium channels, while class III block potassium channels. These effects can lead to QT prolongation and an increased risk of Torsade de Pointes in some patients.

Sources

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http://www.uptodate.com/contents/pathophysiology-of-the-long-qt-syndrome

http://www.uptodate.com/contents/genetics-of-congenital-and-acquired-long-qt-syndrome?source=search_result&search=long+qt+syndrome&selectedTitle=3~150

http://emedicine.medscape.com/article/157826-overview#a4

https://www.nhlbi.nih.gov/health/health-topics/topics/qt

http://lifeinthefastlane.com/ecg-library/basics/qt_interval/

https://en.wikipedia.org/wiki/Long_QT_syndrome

http://emedicine.medscape.com/article/1950863-overview#a2