QT syndrome

This article explains long QT syndrome ; but there is also the (much rarer) short QT syndrome .

Classification according to ICD-10
I49.8	LQTS (Long QT Syndrome)
ICD-10 online (WHO version 2019)

ECG with extended QT time (QTc = 477 ms)

The long QT syndrome ( LQTS , "Long QT syndrome", formerly QT syndrome ) is a rare disease that in otherwise healthy people heart to sudden cardiac death can result. It is either inherited ( congenital ) or acquired, then mostly as a result of an adverse drug reaction . The best-known congenital long QT syndromes are Romano-Ward syndrome ( autosomal dominant ; synonym: pseudohypokalaemia syndrome ) and Jervell and Lange-Nielsen syndrome ( autosomal recessive ; JLNS).

The pioneering and eponymous sign of the long QT syndrome is an extension of the QT time in the electrocardiogram (EKG) with a frequency-corrected QT time (QTc, English Corrected QT interval ) of over 440 milliseconds (ms). The long QT syndrome is characterized by a palpitations of the heart ( tachycardia ), often in the form of life-threatening torsade de pointes tachycardia. These arrhythmias can lead to dizziness , sudden loss of consciousness ( syncope ) and cardiac arrest due to ventricular fibrillation . However, many patients do not suffer from any symptoms, so they remain asymptomatic .

Both tachycardias and syncope occur preferentially during physical exertion or in stressful situations. In symptomatic patients, the prognosis is poor without treatment, but today almost all patients can be offered adequate therapy .

Cause and forms

Play media file

Video describes the mechanism of long QT syndrome. English with German subtitles.

Pathogenesis

Long QT syndrome is caused by slight deviations in the process of electrical signal transmission in the cells of the heart muscle ( myocardium ). This is a delayed repolarization , mainly an extension of the phase 2 plateau phase of the action potential . During this time of around 300-400 milliseconds, which was previously often referred to as the vulnerable phase , irregular post-depolarizations can trigger an action potential again, which can then trigger longer-lasting arrhythmias (“ triggered activity ”). In congenital long QT syndromes, the prolongation of the plateau phase is caused by abnormal properties of the ion channels, either in the form of reduced ion transport ( "loss of function" of the potassium ion channel in LQTS1 and LQTS2) or increased transport capacity ( "gain of function." “ Of the sodium ion channel in the LQTS3). In the acquired long QT syndrome, it is primarily attributed to an inhibition of the fast component of the potassium ion current IKr.

Congenital long QT syndromes

Since the mid-1960s, two clinical manifestations ( phenotypes ) of the congenital long QT syndrome have been distinguished: the Romano-Ward syndrome and the Jervell and Lange-Nielsen syndrome. Today, a large number of different syndromes have been identified in molecular biology , with currently six genotypes (LQTS1-LQTS6) being assigned to the Romano-Ward syndrome, two to the JLNS (JLNS1-JLNS2) and one to the Andersen syndrome (LQTS7). What they have in common is a mutation of genes that code the ion channels of the heart muscle cells.

With the congenital forms, all blood relatives should be examined for the presence of QT syndrome.

Classification of congenital long QT syndromes (status 2004) according to molecular genetic criteria

syndrome	Gene location	gene	Inheritance	frequency
LQTS1	11p15.5	KvLQT1 (KCNQ1)	dominant	40-55%
LQTS2	7q35-36	HERG (KCNH2)	dominant	35-45%
LQTS3	3p21-24	SCN5a (hNaV1.5)	dominant
LQTS4	4q25-27	ANKB	dominant	very rare
LQTS5	21q22.1-22.2	MinK (KCNE1)	dominant
LQTS6	21q22.1-22.2	MiRP1 (KCNE2)	dominant
LQTS7	21q22.1-22.2	Kir2.1 (KCNJ2)	dominant
Intermittent QTS	?	HERG?	?
JLN1	11p15.5	KvLQT1 (KCNQ1)	recessive	approx. 6.3%
JLN2	21q22.1-22.2	MinK (KCNE1)	recessive	approx. 0.7%

Jervell and Lange-Nielsen Syndrome

The Jervell-Lange-Nielsen syndrome is an autosomal recessive trait with deafness and QT prolongation. About seven percent of the congenital long QT syndromes are attributed to the JLNS.

Romano Ward Syndrome

Around 70 percent of inherited long QT syndromes have one of the autosomal dominant variants without hearing impairment, Romano-Ward syndrome .

Acquired Long QT Syndrome

A prolongation of the QT interval in the ECG can also result from the influence of a large number of drugs , from electrolyte disturbances and possibly as a result of inflammation ( myocarditis ) and circulatory disorders ( ischemia ). If torsades de pointes tachycardia or even syncope occur, one speaks of an acquired long QT syndrome, although it is still unclear to what extent these patients actually have a hidden, congenital long QT syndrome.

In the 1960s, the first reports were published about a prolongation of the QT time by quinidine, which was then very common for the treatment of arrhythmias. Since the 1990s, drug-induced long QT syndrome has received increasing attention as more and more substances dangerous in this regard have been identified. This list now includes more than a hundred, in some cases frequently used, preparations from a wide variety of groups, often only affecting one or two representatives of a substance class. In addition to antiarrhythmics such as quinidine and sotalol, as well as amiodarone , these include many commonly prescribed drugs whose cardiac side effects were not known at all for a long time. Antibiotics such as erythromycin and trimethoprim - sulfamethoxazole , some antihistamines , many psychotropic drugs (especially antidepressants and antipsychotics or neuroleptics such as pimozide , sertindole , haloperidol , ziprasidone , quetiapine and sulpiride ) have also come into focus . In addition, Parkinson's and anti- malaria drugs as well as X-ray contrast media and various opioids . Several preparations (including astemizole , cisapride and clobutinol , LAAM and grepafloxacin ) have therefore already been withdrawn from the market. Other drugs that can prolong the QTc time are the serotonin antagonists ketanserin , probucol, and the migraine drug zolmitriptan , which are used against high blood pressure . A detailed and up-to-date English-language list of noteworthy drugs is maintained at the University of Arizona .

What these substances have in common is that they inhibit the outflow of potassium in the heart muscle cell during repolarization and can thus extend the QT interval. The blocked potassium channel is the HERG channel . The risk of such adverse drug reactions (ADRs) is increased in the case of low pulse rates ( bradycardia ), female sex, low potassium levels in the blood ( hypokalaemia ), thickening of the heart muscle due to arterial hypertension (high blood pressure), heart muscle weakness and high drug concentrations due to pharmacogenetic characteristics.

Frequency and prognosis

Sudden deaths of young and otherwise healthy people attract attention, especially when they occur in front of the public at major sporting events. Statistically , however, such events are rare, and even less often they are the result of long QT syndrome. Overall, for the sudden death of a prevalence assumed that 1-2 per 1,000 population per year in under-30s only about 0.5-1 per 100,000 population per year. About six percent of those who suddenly died showed no signs of an organic heart disease at an autopsy , i.e. they succumbed to a primary arrhythmia. It is believed that around a third of these had long QT syndrome. These partially estimated figures suggest that around ten to twenty people under the age of 30 die of long QT syndrome each year in Germany.

The suspicion that some of the cases of sudden infant death syndrome could also be caused by a congenital long QT syndrome could not be substantiated in a study of 41 cases, at least from a molecular genetic point of view and on the basis of an examination of family members. A more recent meta-analysis, however, assumes a connection between sudden infant death syndrome and long QT syndromes (“LQTS-induced SIDS”).

Congenital long QT syndromes occur with a frequency of 1 in 5,000 to 1 in 15,000 of all live births. About 30-46 percent of these patients develop syncope before the age of 40 . The incidence of sudden cardiac death in adolescents with long QT syndrome is 1.6% within the ten years between ages 10-20. This frequency varies greatly within the different groups of patients and can be reduced significantly through medication.

With the help of the resting ECG and a molecular genetic examination, patients with a particularly high risk can now be better identified. All patients with a QTc interval of more than 500 ms and the genotypes LQTS1 and LQTS2 as well as LQTS3 in males are considered to be high-risk groups. If left untreated, you have a risk of more than 50 percent of syncope, cardiac arrest, or sudden cardiac death before the age of 40. People who have more than one of the known mutations are also particularly at risk; this is to be expected in just under eight percent of congenital long QT syndromes. These genotypes, known as compound mutations , are more symptomatic (100 vs. 72 percent) and suffer more cardiac arrest (56 vs. 27 percent) than those with fewer than two detected mutations.

About two percent of patients who receive methadone develop a prolonged QT time. For the substitution therapy of opioid addicts, appropriate guidelines were developed by a US panel of experts, which are also of importance for the German-speaking area, since the respective guidelines are still missing here.

A 2013 study found an association between QT prolongation and approaching death in hospital patients. Among all patients for whom an EKG was written, 2% had QT prolongation over 500 milliseconds (frequency corrected). The death rate within this group was 19% for the same period compared to 5% in the group without QT prolongation.

Signs of illness

The prolongation of the QT time itself is usually not noticeable; more than half of the patients with long QT syndrome have no symptoms whatsoever. If symptoms occur, they are already caused by potentially life-threatening (so-called malignant) cardiac arrhythmias, which must be assessed as a serious symptom of the disease. These are persistent (> 30 seconds) or non-persistent (≤ 30 seconds) ventricular tachycardias, mostly of the torsade de pointes tachycardia type. Depending on the duration and pulse rate of the tachycardia, body position and general condition, these tachycardias may not be noticed at all, lead to dizziness or sudden loss of consciousness ( syncope ) or even to cardiac arrest and thus to sudden cardiac death .

Since the tachycardias occur suddenly and preferentially during physical exertion or in stressful situations, the symptoms are often noticed unexpectedly and out of complete well-being in the situations described.

A heart action in the ECG,
the QT interval is marked in gray.

Diagnosis

The pioneering and eponymous finding of the long QT syndrome is the prolongation of the QT interval in the resting ECG.

The QT time measured in milliseconds (ms) is not very meaningful in and of itself, as it can occur in humans. a. of the heart rate is dependent on the age and gender. In order to be able to reliably detect an abnormally long QT time and to be able to meaningfully compare different QT times with one another, a computational correction of the measured QT time is required. The most commonly used is the Bazett formula:

${\displaystyle QTc={QT{\textrm {-Zeit}} \over {\sqrt {RR{\textrm {-Abstand}}}}}}$,
with the QT duration in ms and the RR interval in seconds. For heart rates above 100 per minute, the Bazett correction formula leads to an overcorrection, for heart rates below 60 per minute to an undercorrection. At frequencies above 80 per minute, the Fridericia formula, which has been used more and more frequently in recent years, leads to more precise results:

${\displaystyle QTc={QT{\textrm {-Zeit}} \over {\sqrt[{3}]{RR{\textrm {-Abstand}}}}}}$,
Wherein indicate also the QT interval in ms and the RR interval in seconds.

For scientific purposes, a more accurate correction of the QT time that also takes into account the gender and age of the patient is needed. This is done according to the following formulas (after Pfeufer et al. 2005):

• For men:
  ${\displaystyle QTc{\textrm {[ms]}}=QT{\textrm {[ms]}}-(0{,}152\times {(RR{\textrm {[ms]}}-1000)})-(0{,}318\times {(Alter{\textrm {[a]}}-60)})}$
• For women:
  ${\displaystyle QTc{\textrm {[ms]}}=QT{\textrm {[ms]}}-(0{,}154\times {(RR{\textrm {[ms]}}-1000)})-(0{,}207\times {(Alter{\textrm {[a]}}-60)})-4{,}58}$

The disadvantage of the correction formulas mentioned is the computational step required, which requires a computer or corresponding nomograms. For this reason, many doctors use special “EKG rulers” that indicate the normal QT time for the determined heart rate.

The upper limit value is a QTc of 440 ms, from 500 ms a high risk can be assumed. For the evaluation of the "measured" QT time and thus also the calculated QTc, knowledge of the sources of error in the method is important. Particularly in the case of low amplitudes of the T waves and occasionally subsequent U waves, the end of the T wave and thus the end point of the measurement is not exactly defined and is subject to the subjective perception of the examiner. In addition, the QT intervals determined from one, three or twelve simultaneously derived ECG lines differ significantly , so that the measurement method should be taken into account when making comparisons.

Estimation of the QT time from the resting ECG

If QT <1/2 RR then QT is normal

A prolonged QT time can be recognized relatively easily in the resting ECG if one considers the RR distance between two neighboring QRS spikes. If the QT time is longer than half the RR interval, the QT time is definitely longer.

Score to estimate the likelihood of a LQT syndrome

EKG signs without a history of triggering drug or other known cause
QTc ≥ 480 ms (calculated using Bazzet's formula )	3 pts.
QTc 460-479 ms	2 pts.
QTc 450-459 (men)	1 point
QTc> 480 ms (4 min after load)	1 point
Torsade de pointes without subsequent syncope	2 pts.
T-wave alternation	1 point
T-wave notches in 3 leads	1 point
Low heart rate (below the 2nd age- adjusted percentile )	0.5 pts.
Personal history
Syncope , stress-induced	2 pts.
Syncope, other cause	1 point
Inner ear hearing loss, congenital	0.5 pts.
Family history
LQTS in family member	1 point
Unexplained sudden cardiac death <30 LJ	0.5 pts.

With a score of 1, there is a low, with a score up to 3 a medium, and above 4 a high probability of the presence of a long QT syndrome.

therapy

Since the frequency of serious cardiac arrhythmias is clearly reduced under treatment with beta-blockers , they are part of the standard therapy for congenital long QT syndrome. Patients who still experience syncope and those who have survived cardiac arrest should receive an implantable defibrillator (ICD) as a precaution . Patients at particularly high risk may benefit from having an ICD implanted before they develop symptoms.

In the case of long QT syndrome caused by medication, immediate discontinuation of the substance is the main focus. In contrast to the congenital form, beta blockers are considered contraindicated here because they cause or exacerbate bradycardia and thus increase the risk of threatening arrhythmias. In addition to compensating for any hypokalemia, the supply of magnesium has proven itself ; in the case of bradycardia, an increase in the heart rate through medication (e.g. orciprenaline ) or temporary pacemaker stimulation is recommended.

Exercise is problematic for patients with long QT syndrome. There is an increased risk of threatening arrhythmias, especially with an abrupt start or end of exercise, cold, pressure fluctuations and loud noises. For this reason, sports like basketball , hockey , bodybuilding , surfing / surfing, swimming , diving and snorkeling discouraged in principle, as the competition moderate running , weight lifting , biking , squash - and playing tennis . Regular, moderate physical activity such as jogging , walking and skating, on the other hand, is advocated, and there is little objection to bowling and weightlifting if it is not performance-oriented. Children are often exempted from school sport , as this is subject to grading ( risk of being overwhelmed ), but a decision can be made individually about other recreational sports.

literature

• W. Haverkamp et al. a .: QT syndromes: aspects of pathogenesis, molecular genetics, diagnostics and therapy. In: Deutsches Ärzteblatt . (1997) 94, pp. A667-A672.
• W. Haverkamp et al. a .: Drug-induced QT prolongation and torsades de pointes: a multidisciplinary problem . In: Deutsches Ärzteblatt. (2002) 99, pp. A1972-A1979.
• L. Crotti, G. Celano, F. Dagradi, PJ Schwartz: Congenital long QT syndrome. In: Orphanet J Rare Dis. 2008, July 7; 3, p. 18. Review. PMID 18606002 , PMC 2474834 (free full text)
• Pfeufer u. a .: Common variants in myocardial ion channel genes modify the QT interval in the general population: results from the KORA study. In: Circ Res . 2005 April 1; 96 (6), pp. 693-701.

Web links

• How stress gets the heart out of sync . Effect of cortisol on mutated IKs channels in LQT syndrome; Scinexx, Springer-Verlag, Heidelberg 2008

Individual evidence

1. ↑ Drugs That Prolong the QT Interval and / or Induce Torsades de Pointes . ( Memento from April 4, 2009 in the Internet Archive )
2. ^ BP Delisle et al. a .: Biology of Cardiac Arrhythmias: Ion Channel Protein Trafficking. In: Circ Res. (2004) 94, pp. 1418-1428. PMID 15192037 .
3. ↑ Torsten Kratz, Albert Diefenbacher: Psychopharmacotherapy in old age. Avoidance of drug interactions and polypharmacy. In: Deutsches Ärzteblatt. Volume 116, Issue 29 f. (July 22) 2019, pp. 508-517, p. 512.
4. ↑ azcert.org ( Memento of December 24, 2010 in the Internet Archive ) Drugs That Prolong the QT Inrerval and / or Induce Torsades de Pointes
5. ↑ H. Löllgen et al. a .: Sudden cardiac death in sports. In: Emergency Med. (2003) 29, pp. 148-158.
6. ↑ H. Wedekind et al. a .: Sudden infant death syndrome and long QT syndrome: an epidemiological and genetic study. In: Int J Legal Med. , 2005, pp. 1-9. PMID 16012827 .
7. ↑ Sudden infant death syndrome due to long QT syndrome: a brief review of the genetic substrate and prevalence . PMC 5348737 (free full text)
8. ↑ JB Hobbs et al. a .: Risk of aborted cardiac arrest or sudden cardiac death during adolescence in the long QT syndrome In: JAMA , 2006 Sep 13; 296 (10), pp. 1249-1254.
9. ↑ SG Priori u. a .: Risk Stratification in the Long-QT Syndrome. In: New Engl J Med . , 2003, 348, pp. 1866-1874. PMID 12944579 .
10. ↑ P. Westenskow u. a .: Compound Mutations - A Common Cause of Severe Long-QT Syndrome. In: Circulation , 2004, 109, pp. 1834–1841. PMID 15051636 .
11. ↑ QT time screening for methadone - US guideline 2009 ( Memento of the original from August 15, 2009 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. 
12. ↑ Kristina H. Haugaa, J. Martijn Bos, Robert F. Tarrell, Bruce W. Morlan, Pedro J. Caraballo, Michael J. Ackerman: Institution-Wide QT Alert System Identifies Patients With a High Risk of Mortality. In: Mayo Clinic Proceedings. 88, 2013, pp. 315-325. doi: 10.1016 / j.mayocp.2013.01.013 .
13. ^ HC Bazett: An analysis of time relations of electrocardiograms. In: Heart. 1920; 7, pp. 353-367
14. ↑ LS Fridericia: The systole duration in the electrocardiogram in normal people and in heart patients. In: Acta Med Scand. 1920; 53, pp. 469-486.
15. ↑ NE Azie u. a .: Comparing methods of measurement for detecting drug-induced changes in the QT interval: implications for thoroughly conducted ECG studies. In: Ann Noninvasive Electrocardiol. (2004) 9 (2), pp. 166-174. PMID 15084215 .
16. ^ PJ Schwartz, AJ Moss, GM Vincent, RS Crampton: Diagnostic criteria for the long QT syndrome. To update . In: Circulation . tape 88 , no. 2 , August 1993, ISSN  0009-7322 , pp. 782–784 , PMID 8339437 ( ahajournals.org [PDF; accessed October 6, 2017]).
17. ↑ A. Koch, B. Schmidt: Sudden death of father and sister - diagnosis based on anamnesis and EKG? In: Der Kardiologe , 5/2017
18. ^ BJ Maron u. a .: Recommendations for Physical Activity and Recreational Sports Participation for Young Patients With Genetic Cardiovascular Diseases. In: Circulation. (2004) 109, pp. 2807-2816. PMID 15184297 .

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !

This version was added to the list of articles worth reading on January 29, 2006 .