What’s your QT Interval?
What does the QT represent? The QT interval measures the complete ventricular contraction and relaxation cycle.
Why do we have to look for the QT Interval?
The longer the QT interval the higher risk of lethal cardiac arrhythmias, specifically Polymorphic Ventricular Tachycardia known at “Torsades de Points”.
Torsades de Pointes
Thousands (5,000 -7,000) of apparently health children and adults die annually due to this under recognized condition.
What are the symptoms? Sudden loss of consciousness (the medical term is 'syncope') and sudden death are the common symptoms and usually occur during physical exertion or emotional excitement like anger, fear or startle, but may occur during sleep, or arousal from sleep. Common startle events include sirens, the telephone and the alarm clock. It is less common for the syncope or sudden death to occur when the person is awake and at rest. The particular trigger for the symptoms depends to some degree on the specific gene abnormality (see the section on genetics). Exercise induced syncope usually occurs right during the exercise, but occasionally occurs within a few seconds or a minute or two after the exertion. In patients who experience syncope the torsade de pointes rhythm reverts spontaneously to normal, usually within about 1 minute or less. When this occurs, the patient quickly regains consciousness, usually without disorientation or residual symptoms, although fatigue may be present. When the torsade rhythm persists for a longer time, however, it degenerates into ventricular fibrillation and the outcome is death unless electrical defibrillation is provided.
Not all patients who have this condition have symptoms; at least one-third, and probably more, never develops any symptoms. In the others, some have just one or two syncopal spells as children, and none thereafter, whereas, some have many episodes over a number of years. The symptoms may begin as early as the first days or weeks of life, or as late as middle age. Most commonly, however, the symptoms first occur during pre-teen and teenage years. The symptoms start earlier in males than females, beginning on average at approximately 8 years in males and 14 years in females. Because many affected persons never have symptoms, the absence of a history of syncope or sudden death in a family does not at all guarantee the absence of LQTS in the family.
How do you get Long QT?
Ionic Channelopathies. “A dysfunction of special heart cells called ion channels” These channels control the flow of ions like potassium, sodium and calcium molecules in and out of the heart cells. This flow produces the electrical activity of the heart.
You can generally get these in two ways.
1. Inherited from genetics, e.g. passed on from mom or dad to child.
2. Acquired through medication use.
There are 8 LQT genotypes that have been identified so far.
LQT1 is the most common type of long QT syndrome, making up about 40 to 55 percent of all cases. The LQT1 gene is KCNQ1 which has been isolated to chromosome 11p15.5. KCNQ1 codes for the voltage-gated potassium channel KvLQT1 that is highly expressed in the heart. It is believed that the product of the KCNQ1 gene produces an alpha subunit that interacts with other proteins (particularly the minK beta subunit) to create the IKs ion channel, which is responsible for the delayed potassium rectifier current of the cardiac action potential.
Mutations to the KCNQ1 gene can be inherited in an autosomal dominant or an autosomal recessive pattern in the same family. In the autosomal recessive mutation of this gene, homozygous mutations in KVLQT1 leads to severe prolongation of the QT interval (due to near-complete loss of the IKs ion channel), and is associated with increased risk of ventricular arrhythmias and congenital deafness. This variant of LQT1 is known as the Jervell and Lange-Nielsen syndrome.
Most individuals with LQT1 show paradoxical prolongation of the QT interval with infusion of epinephrine. This can also unmark latent carriers of the LQT1 gene.
Many missense mutations of the LQT1 gene have been identified. These are often associated with a high risk percentage of symptomatic carriers and sudden death.
The LQT2 type is the second most common gene location that is affected in long QT syndrome, making up about 35 to 45 percent of all cases. This form of long QT syndrome most likely involves mutations of the human ether-a-go-go related gene (HERG) on chromosome 7. The HERG gene (also known as KCNH2) is part of the rapid component of the potassium rectifying current (IKr). (The IKr current is mainly responsible for the termination of the cardiac action potential, and therefore the length of the QT interval.) The normally functioning HERG gene allows protection against early after depolarizations (EADs).
Most drugs that cause long QT syndrome do so by blocking the IKr current via the HERG gene. These include erythromycin, terfenadine, and ketoconazole. The HERG channel is very sensitive to unintended drug binding due to two aromatic amino acids, the tyrosine at position 652 and the phenylalanine at position 656. These amino acid residues are poised so drug binding to them will block the channel from conducting current. Other potassium channels do not have these residues in these positions and are therefore not as prone to blockage.
The LQT3 type of long QT syndrome involves mutation of the gene that encodes the alpha subunit of the Na+ ion channel. This gene is located on chromosome 3p21-24, and is known as SCN5A (also hH1 and NaV1.5). The mutations involved in LQT3 slow the inactivation of the Na+ channel, resulting in prolongation of the Na+ influx during depolarization. Paradoxically, the mutant sodium channels inactivate more quickly, and may open repetitively during the action potential.
A large number of mutations have been characterized as leading to or predisposing LQT3. Calcium has been suggested as a regulator of SCN5A, and the effects of calcium on SCN5A may begin to explain the mechanism by which some these mutations cause LQT3.
is an autosomal dominant relatively uncommon form of LQTS. It involves mutations in the gene KCNE1 which encodes for the potassium channel beta subunit MinK. In its rare homozygous forms it can lead to Jervell and Lange-Nielsen syndrome
is an autosomal dominant relatively uncommon form of LQTS. It involves mutations in the gene KCNE2 which encodes for the potassium channel beta subunit MiRP1, constituting part of the IKr repolarizing K+ current.
Andersen-Tawil syndrome is an autosomal dominant form of LQTS associated with skeletal deformities. It involves mutation in the gene KCNJ2 which encodes for the potassium channel protein Kir 2.1. The syndrome is characterized by Long QT syndrome with ventricular arrhythmias, periodic paralysis and skeletal developmental abnormalities as clinodactyly, low-set ears and micrognathia. The manifestations are highly variable.
Timothy's syndrome is due to mutations in the calcium channel Cav1.2 encoded by the gene CACNA1c. Since the Calcium channel Cav1.2 is abundant in many tissues, patients with Timothy's syndrome have many clinical manifestations including congenital heart disease, autism, syndactyly and immune deficiency.
A number of syndromes are associated with LQTS.
In untreated individuals with JLNS, about 50 percent die by the age of 15 years due to ventricular arrhythmias.
Romano-Ward syndrome is an autosomal dominant form of LQTS that is not associated with deafness.
What Drugs Prolong the QT interval?
Please ask yourself, have I ever given these drugs to my patient. These are very common drugs.
These drugs have a risk of Torsades de Pointes *,**
*As of 3/02/2006 ** From www.qtdrugs.org
Drugs that prolong the QT interval and/or induce Torsades De Pointes
Is the QT interval hard to Identify? No, it only takes about 5 seconds to measure the QT interval. A simple QT measurement can help you recognize the precursor to LQTS and prevent life threatening problems.
How do you measure the QT interval?
The QT interval should be less than half of the R-R interval. This is generally accurate for regular rates between 65 and 90. If you have a rate less than 65 and have a prolonged QT interval consider a 12 lead ecg. This doesn’t work on irregular rhythms.
1) Measure the QT interval.
2) Compare the QT interval to the R to R interval
3) If the QT interval is greater than 50% of the R to R, it suggests LQTS.
4) Notify the MD in charge.
5) Request a 12 lead EKG to monitor for QTc > 440ms in men and >450/ms in women and suggest cardiology screen for LQTS.
Long QT Work up
In 12% of patients with LQTS, sudden death was the first manifestation of the disease and in 4% this happened in the first year of life. This point alone
mandates the treatment of all those diagnosed as affected, even if there are no symptoms. In most cases, several members of the same family are gene-carriers. Low penetrance exists in LQTS, which means that gene-carriers may not show the clinical phenotype and may have a normal QT interval. Therefore a normal QT in the parents does not rule out familial LQTS. In addition, approximately 30% of cases are due to 'de novo' mutations which imply unaffected parents and no family history. 'De novo' LQTS mutations have been demonstrated in infant victims of cardiac arrest and sudden death diagnosed as Sudden Infant Death Syndrome.
Even though relatively few LQTS patients have cardiac events during the first year of life, the vast majority become symptomatic later on, either during childhood or adolescence according to genetic subgroups. Therefore treatment must continue. Beta-blockers are the first choice therapy in LQTS and are effective in preventing recurrences in 80% of already symptomatic
patients; different degrees of protection exist according to genetic subgroups. If beta-blockers are unable to prevent new cardiac events, additional drug therapy, left cardiac sympathetic denervation, pacemakers or the implantable cardioverter defibrillator should be considered based on evidence, with due consideration for body size.
It is well understood that the likelihood of having LQTS increases with increasing QTc; however, since a small percentage of LQTS patients has a QTc <440 ms, the correlation between QT prolongation and the presence of the syndrome is not absolute. Therefore, the following discussion is presented as guidelines based upon experience and current knowledge, and is likely to be updated frequently. Given the life-threatening potential of the disease, once the diagnosis of LQTS becomes probable, it is recommended that these infants are referred to a specialist as soon as possible.
First ECG: QTc above 440 ms, the upper limit of normal.
Exclude other causes of acquired QT interval prolongation and obtain a detailed family history for the possibility of familial LQTS. Episodes of early sudden death, fainting spells, and seizures epilepsy should alert to this possibility. The ECG should be repeated after a few days to confirm the abnormal finding. Subsequent management depends on
1. presence or absence of family history suggestive for LQTS,
2. the degree of QT interval prolongation.
The presence of complex ventricular arrhythmias would have additional importance. The following stepwise approach involves infants with and without a family history for LQTS (see Figure 4 of the
original guideline document).
If family history is positive, then, as LQTS is an autosomal dominant disease, the infant has a 50% probability of being affected and complete diagnostic procedures should be performed, as always with LQTS families.
The second ECG is normal.
If the first QTc was <470 ms, dismiss the case. If the first QTc was less than or equal to 470 ms, then plan a third ECG after 1-2 months to remain on the safe side.
The second ECG shows a QTc between 440 and 470 ms.
In these cases with persistent borderline QT prolongation, electrolytes, including calcium and magnesium, should be checked. Clinical history of autoimmune disease and plasma titres of maternal antibodies (anti Ro/SSA and antiLa) should be performed. T wave morphology may be
helpful; for example, the presence of notches on the T wave in the precordial leads further suggests the presence of LQTS. Additionally, mild bradycardia can also be found in LQTS. ECGs should be obtained from the parents and siblings of the neonate. In the absence of family history of LQTS, symptoms or arrhythmias, a 24-hour Holter monitoring should be obtained to look for T wave alternans, complex ventricular arrhythmias or marked QTc prolongation, and the ECG should be periodically checked during the first year. No treatment is currently recommended. With a positive family history, the probability of LQTS becomes high. Additional diagnostic procedures (24-hour Holter monitoring, echocardiogram and genetic screening) should be performed and initiation of therapy could be considered.
The second ECG shows a QTc greater than or equal to 470 and <500 ms.
All diagnostic procedures listed above should be performed and a third ECG should be planned within a month. In case of a positive family history, therapy should be initiated. Even without a family history, therapy should be considered. Even in infants with a very prolonged QTc in the first month of life, the ECG may normalize. If subsequent ECGs and diagnostic procedures do
not confirm the presence of LQTS, it is logical to progressively withdraw therapy and to return to periodic observations.
The second ECG shows a QTc greater than or equal to 500 ms.
Infants with a QTc >500 ms are very likely to be affected by LQTS and become symptomatic. All diagnostic procedures listed above should be performed and these infants should be treated.
Highest risk. The presence of QTc close to 600 ms, or of T wave alternans, or of 2:1 AV block secondary to major QT prolongation, or of hearing loss, identify infants at extremely high risk.
ST segment elevation
Work-up: Whenever the underlying cause has been identified, it should be
treated. If the Brugada syndrome is suspected, careful family history should be collected, 24-hour Holter monitoring obtained, and the patient should be referred to a specialist.
Frequently asked Questions.
Q. What does the QTc mean?
A. The QT interval corrected for the rate.
Q. Why does the QT interval need to be corrected for the rate?
A. The faster the rate the more narrow the QT interval.
The slower the rate the wider the QT interval.
The QT interval is not a static number that we can tell you to look for.
Q. Where do you find the QTc?
A. The QTc is calculated by all 12 lead EKG machines and is in the same area that contains all other measurements on a 12 lead EKG. (e.g. Rate, axis, PR interval, QRS interval etc… QTc is included in the same area; just look for it and you will find it).
Q. What is normal QTc?
A. Normal QTc; less than 440ms in men
less than 450ms in women.
If your pt has a prolonged QTc generally it’s a cardiology evaluation to rule out Long QT syndrome. We don’t panic for QTc’s that are a little long. The longer the QTc gets the more concern we have.
Example; A QTc of 580ms is definitely a cause for concern and needs a cardiology evaluation along with a review of current medications. A QTc of 450ms is less of a concern but still could be enough to consider a cardiology evaluation.
Q. Do you need to document Qt interval and QTc?
A. Yes, and also document that you informed the MD in charge of the pt’s care and pass it on to your co-workers in shift change report.
Q. What formula is used to calculate QTc?
A. Bazett's formula:
QT interval corrections in the literature use Bazett's formula, defined as the observed QT interval divided by the square root of the R-R interval in seconds. A corrected QT interval of > 440 ms is defined as generally defined as abnormal. Bazett's formula corrects or normalizes the measured QT interval for a heart rate of 60 BPM. Thus, the QT is measured at the given heart rate, and the QTc estimates what the QT interval would be if the heart rate were 60. Bazett's formula works reasonably well at "normal" heart rates, but is less accurate when the heart rate is slow or fast.
A more accurate method to correct the QT interval for the rate was developed by Rautaharju et al., who developed the formula. This method is not widely used by clinicians.
Some great websites: www.qtsyndrome.ch