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{{authors|
{{authors|
|mainauthor= [[user:Pgpostema|P.G. Postema, MD]]
|mainauthor= [[user:Drj|J.S.S.G. de Jong, MD]]
|advisor=
|supervisor=
|coauthor= [[user:Drj|J.S.S.G. de Jong, MD]]
|coauthor= [[user:Pgpostema|P.G. Postema, MD]]
|moderator= [[user:Pgpostema|P.G. Postema, MD]]
|moderator= [[user:Pgpostema|P.G. Postema, MD]]
|editor=  
|editor=  
}}
}}
The '''Long QT Syndrome (LQTS)''' is characterized on the ECG by prolongation of the [[Conduction#The_QT_interval|heart rate corrected QT interval]]. This was first recognized by Dr. Jervell and Dr. Lange-Nielsen in 1957. They described 4 children with a long QT interval which was accompanied by hearing deficits, sudden cardiac death and an autosomal recessive inheritance.<cite>Lang1957</cite>


 
The Long QT syndrome may be divided into two distinct forms: congenital Long QT syndrome and acquired Long QT syndrome. These forms may however overlap when QT prolongation due to medication occurs in a patient with congenital Long QT syndrome.
The '''Long QT Syndrome''' is characterized on the ECG by prolongation of the [[Conduction#The_QT_interval|heart rate corrected QT interval]]. This was first recognized by dr. Jervell and dr. Lange-Nielsen in 1957. They described 4 children with a long QT interval which was accompanied by hearing deficits, sudden cardiac death and an autosomal recessive inheritance.<cite>Lang1957</cite>
<gallery>
 
File:acquired_longQT.jpg|A 12-lead ECG of a patient with acquired long QT syndrome. Notice the QT prolongation. The QTc is about 640ms.
The Long QT syndrome may be divided into two distinct forms: congenital Long QT syndrome and acquired Long QT syndrome. These forms may however  
File:Lqts1.png|A 12 lead ECG of a patient with genetically proven LQTS1
 
File:Lqts2.png|A 12 lead ECG of a patient with genetically proven LQTS2
'''Diagnosis'''
File:Lqts3.png|A 12 lead ECG of a patient with genetically proven LQTS3
*The diagnosis is by maesurement of the [[Conduction#The_QT_interval|heart rate corrected QT interval]] on the ECG.
</gallery>
*Sometinmes the QT interval can be difficult to assess. Read the [[Difficult_QT|guidelines for measurement of difficult QT interval]].
===Diagnosis===
*The diagnosis is by measurement of the [[Conduction#The_QT_interval|heart rate-corrected QT interval]] on the ECG, which can be calculated with the [[QTc calculator]].
*Sometimes the QT interval can be difficult to assess. Read the [[Difficult_QT|guidelines for measurement of difficult QT interval]].
*A QTc of > 500ms in patients with Long QT Syndrome is associated with an increased risk for sudden death.<cite>Priori</cite>  
*A QTc of > 500ms in patients with Long QT Syndrome is associated with an increased risk for sudden death.<cite>Priori</cite>  
*In patients suspected of LQTS (e.g. family members of known LQTS patients) a QTc > 430ms makes it likely that a LQTS gene defect is present.<cite>Hofman</cite>
*In patients suspected of LQTS (e.g. family members of known LQTS patients) a QTc > 430ms makes it likely that a LQTS gene defect is present.<cite>Hofman</cite>
*Because the QTc can change with age, it is best to take the ECG with the longest QTc interval for risk stratification.<cite>Goldenberg</cite>
*Because the QTc can change with age, it is best to take the ECG with the longest QTc interval for risk stratification.<cite>Goldenberg</cite>


'''Treatment'''<cite>ACC2006</cite>
===Treatment<cite>ACC2006</cite>===
*"Lifestyle modification":
*"Lifestyle modification":
** No competitive sports in all LQTS patients
** No competitive sports in all LQTS patients
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*[[:w:nl:Internal_Cardiac_Defibrillator|ICD]] implantation in combination with beta-blockers in LQTS patients with previous cardiac arrest or [[syncope]] or [[Ventricular Tachycardia|ventricular tachycardia]] while on beta-blockers.
*[[:w:nl:Internal_Cardiac_Defibrillator|ICD]] implantation in combination with beta-blockers in LQTS patients with previous cardiac arrest or [[syncope]] or [[Ventricular Tachycardia|ventricular tachycardia]] while on beta-blockers.


===Inborn LQTS===
===Acquired LQTS===
[[Image:lqts1-3.png|thumb| De drie meest voorkomende vormen van het long QT syndrome zijn te herkennen aan '''specifieke ECG afwijkingen''': LQT1 'early onset' T top met brede basis; LQT2 kleine late T top; LQT3 verlengde QT tijd met 'late onset' T golf van normale vorm; LQT8 met alternerende T toppen (LQT8 is zeer zeldzaam).]]
Acquired LQTS is most often caused by drugs that prolong the QT interval. Combined with risk factors (see table) the risk of [[Torsade_de_Pointes|Torsade de Pointes]] increases.
Congenitale LQTS is een erfelijke aandoening waarbij de ventriculaire repolarisatie verlengd is, wat zich onder meer uit in een verlengde QT tijd op het ECG. Syncope en plotse hartdood treedt bij LQTS vaak op tijdens een specifieke ventriculaire ritmestoornis: [[Ritmestoornissen#Torsade_de_pointes|torsade de pointes]]. Hierbij draait de hartas continu, tijdens een ventriculaire tachycardie. Torsades de pointes kan overgaan in ventrikelfibrilleren en plotse hartdood.
 
De prevalentie is ongeveer 1:3000-5000. De symptomen starten vaak in de tienerleeftijd. Niet alle dragers van afwijkende LQTS genen zijn ook ziek. De uiting kan wisselen van extreme QT velenging en regelmatige syncope, tot minimaal verlenge QT tijd, zonder enig symptoom.
{|
|-
|valign="top"|
{| class="wikitable" width="400px"
!Common drugs that can cause [[Torsade_de_Pointes|Torsade de Pointes]] include:<cite>Roden</cite>
|-
|
<ul>
<li>Sotalol</li>
<li>Amiodarone</li>
<li>Erythromycin</li>
<li>Clarithromycin</li>
</ul>
|-
!Less often used drugs include:
|-
|
<ul>
<li>Cisapride</li>
<li>antibiotics: halofantrine, pentamidine, sparfloxacin</li>
<li>Anti-emetics: domperidon, droperidol</li>
<li>Anti-psychotics: chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide</li>
<li>Methadon</li>
<li>Disopyramide</li>
<li>Dofetilide</li>
<li>Ibutilide</li>
<li>Procainamide</li>
<li>Quinidine</li>
<li>Bepridil</li>
</ul>
|-
|[http://www.torsades.org Torsades.org] has an extensive list of drugs that can TdP
|}
|valign="top"|
{| class="wikitable" align="right" width="400px"
!Concomittant risk factors for medication induced [[Torsade_de_Pointes|Torsade de Pointes]]:
|-
|
<ul>
<li>Female sex</li>
<li>Hypokalemia</li>
<li>Bradycardia</li>
<li>Recent conversion of [[Atrial Fibrillation|atrial fibrillation]], especially if QT prolonging drugs were used (sotalol, amiodarone)</li>
<li>Cardiac decompensation</li>
<li>Digoxin treatment</li>
<li>High or overdosing or rapid infusion of a QT prolonging drug</li>
<li>Pre-existing QT prolongation</li>
<li>Congenital long QT syndrome</li>
</ul>
|}
|-
|}


Onderzoek heeft aangetoond, dat de inborn vormen berusten op een genetisch defect in de genen die coderen voor ionenstromen die verantwoordelijk zijn voor de repolarisatiefase van een actiepotentiaal. He meest voorkomende defect berust op die van de '''uitwaartse kaliumstroom'''. Dit leidt tot een verlengde repolarisatie en dus een verlengde QT-tijd. Tevens bestaan er ook defecten in de '''natriumkanalen'''. Er is dan met name sprake van een longre inwaartse natriumstroom. Het gevolg is een longre actiepotentiaal als mede een longre QT-tijd.
===Congenital LQTS===
[[Image:lqts1-3.png|thumb|The three most common forms of LQTS can be recognized by the '''characteristic ECG abnormalities''']]:
*LQT1 'early onset' broad based T wave
*LQT2 small late T wave
*LQT3 prolonged QT interval with 'late onset' T wave with a normal configuration
In congenital LQTS the ventricular repolarisation is prolonged. '''The prevalence is about 1:3000-5000'''.  


Er zijn inmiddels 8 LQTS genen beschreven met ieder verschillende kenmerken: <cite>ACC2006</cite>
More than 10 different types of congenital LQTS have been described. However, only LQTS 1-3 are relatively common.<cite>ACC2006</cite>


{| border="1" cellpadding="2" cellspacing="0" bordercolor="#6EB4EB" style="font-size:100%;" class="plainlinks" class="wikitable"
{| border="1" cellpadding="2" cellspacing="0" bordercolor="#6EB4EB" style="font-size:100%;" class="plainlinks" class="wikitable"
|- style="text-align:center;background-color:#6EB4EB;"
|- style="text-align:center;background-color:#6EB4EB;"
| type
| '''Type'''
| chromosoom
| '''Chromosome'''
| gen
| '''Gene'''
| protein
| '''Protein'''
| ionchannel
| '''Ionchannel'''
| frequentie<cite>priori</cite>
| '''Frequency<cite>priori</cite>'''
| SCD incidence<cite>Shah2005</cite>
| '''SCD incidence<cite>Shah2005</cite>'''
| oververving
| '''Inheritance'''
| ECG kenmerken
| '''ECG characteristics'''
| Trigger
| '''Trigger'''
| Eponiem
| '''Eponyme'''
| [[w:OMIM|OMIM&trade;]] link
| '''[[w:OMIM|OMIM&trade;]] link'''
|-
|-
! LQTS1
! LQTS1
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| I''ks''
| I''ks''
| ~50%
| ~50%
| 0.30%/jaar
| 0.30%/year
| AD, AR
| AD, AR
| 'early onset' T top met brede basis
| broad base 'early onset' T wave
| inspanning, m.n. zwemmen
| exercise, especially swimming
| JLN1 indien homozygoot, LQTS1 indien heterozygoot
| JLN1 if homozygous, LQTS1 if heterozygous
| {{OMIM2|607542}}  
| {{OMIM2|607542}}  
|-
|-
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| I''kr''
| I''kr''
| 30-40%
| 30-40%
| 0.60%/jaar
| 0.60%/year
| AD
| AD
| kleine late T top
| small late T wave
| adrenerge prikkels, m.n. nachtelijk lawaai
| adrenergic triggers, especially nightly noise
| JLN2 indien homozygoot, LQTS2 indien heterozygoot
| JLN2 if homozygous, LQTS2 if heterozygous
| {{OMIM2|152427}}
| {{OMIM2|152427}}
|-
|-
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| 3p21
| 3p21
| SCN5A
| SCN5A
| NA kanaal
| NA channel
|
|
| 5-10%
| 5-10%
| 0.56%/jaar
| 0.56%/year
| AD
| AD
| 'Late onset' T golf van normale vorm
| 'Late onset' T wave with normal configuration
|
|
|
|
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|-
|-
! LQTS4
! LQTS4
| 4q25
| 4q25-q27
| ANK2
| ANK2
| Ankyrin B
| Ankyrin B
|
| I''Na,K''
| <1%
| <1%
| unknown
|  
| AD
| AD
|
|
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|-
|-
! LQTS5
! LQTS5
| 21q22
| 21q22.1
| KCNE1
| KCNE1
| minK  
| minK  
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|-
|-
! LQTS6
! LQTS6
| 21q22
| 21q22.1
| KCNE2
| KCNE2
| MiRP1
| MiRP1
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| {{OMIM2|603796}}
| {{OMIM2|603796}}
|-
|-
! LQTS7
! LQTS7 = ATS1
| 17q23
| 17q23
| KCNJ2
| KCNJ2
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| {{OMIM2|600681}}
| {{OMIM2|600681}}
|-
|-
! LQTS8
! LQTS8 = TS1
| 6q8A
| 12p13.3
| CACNA1C
| CACNA1C
|  
| Ca<sub>v</sub>1.2
| I''Ca-L''
| I''Ca-L''
| <1%
| <1%
| unknown
| unknown
|  
|  
| alternerende T golven
| alternating T waves
|
|
| Timothy syndrome
| Timothy syndrome
| {{OMIM2|114205}}
| {{OMIM2|601005}}
|-
|-
! LQTS9
! LQTS9
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| CAV3
| CAV3
| Caveolin 3
| Caveolin 3
|  
| I''Na''
|  
|  
| unknown
| unknown
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| 11q23.3
| 11q23.3
| SCN4B
| SCN4B
| Navb4
| Na<sub>v</sub>1.5 b4
|  
|  
| 1 family
| 1 family
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|  
|  
| {{OMIM2|608256}}
| {{OMIM2|608256}}
|-
! LQTS11
| 7q21-q22
| Akap9
| AKAP
| I''ks''
| 1 family
| unknown
|
|
|
|
| {{OMIM2|611820}}
|}
|}
;LQTS: Long QT syndrome
;LQTS: Long QT syndrome
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;SCD: Sudden Cardiac Death
;SCD: Sudden Cardiac Death
   
   
Nog voordat deze genen bekend waren, waren er al enkele syndromen beschreven, die gepaard gingen met een long QT tijd.  
Long before the genes involved were known, two syndromes  associated with a prolonged QT interval on the ECG had been described.
* Anton Jervell and Fred Lange-Nielsen uit Oslo beschreven in 1957 een autosomaal recessief overervend syndrome dat gepaard ging met QT verlenging, doofheid en plotselinge hartdood. Sindsdien heet dit syndrome '''Jervell-Lange-Nielsen syndrome'''. <cite>Lang1957</cite>
* Anton Jervell and Fred Lange-Nielsen from Oslo described in 1957 an autosomaal recessive syndrome that was associated with QT interval prolongation, deafness and sudden death: the now called '''Jervell-Lange-Nielsen syndrome'''. <cite>Lang1957</cite>
* '''Romano-Ward syndrome''' is een long QT syndrome met normale gehoorfunctie en erft i.t.t. de anderen autosomaal dominant over. Inmiddels is bekend dat ook deze syndromen berusten op afwijkingen in bovenstaande genen.
* '''Romano-Ward syndrome''' is a long QT syndrome with normal auditory function and autosomal dominant inheritance.  
* In a genotype–phenotype study by Moss et al. that studied type-1 LQTS, it was found that mutations located in the transmembrane portion of the ion channel protein and the degree of ion channel dysfunction caused by the mutations are important independent risk factors influencing the clinical course of this disorder.<cite>moss</cite>
* In a genotype–phenotype study by Moss et al. that studied type-1 LQTS, it was found that mutations located in the transmembrane portion of the ion channel protein and the degree of ion channel dysfunction caused by the mutations are important independent risk factors influencing the clinical course of this disorder.<cite>moss</cite>
===Verworven LQTS===
Verworven long QT syndrome wordt veroorzaakt meestal veroorzaakt door medicijnen. In combinatie met een aantal risicofactoren neemt het risico op ritmestoornissen toe, met name ook weer [[Arrhythmias#Torsade_de_pointes|Torsade de Pointes]].
{| class="wikitable" align="right" width="400px"
!Medicijnen die [[Arrhythmias#Torsade_de_pointes|Torsade de Pointes]] kunnen veroorzaken:<cite>Roden</cite>
|-
|
<ul>
<li>Sotalol</li>
<li>Amiodarone</li>
<li>Erythromycine</li>
<li>Clarithromycine</li>
</ul>
|-
!Minder vaak gebruikte medicijnen:
|-
|
<ul>
<li>Cisapride</li>
<li>antibiotica: halofantrine, pentamidine, sparfloxacin</li>
<li>Anti-emetica: domperidon, droperidol</li>
<li>Anti-psychotica: chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide</li>
<li>Methadon</li>
<li>Disopyramide</li>
<li>Dofetilide</li>
<li>Ibutilide</li>
<li>Procainamide</li>
<li>Quinidine</li>
<li>Bepridil</li>
</ul>
|-
|Zie ook [http://www.torsades.org Torsades.org] voor een uitgebreide lijst
|}
{{clr}}
{| class="wikitable" align="right" width="400px"
!Risicofactoren voor medicijngeïnduceerde [[Arrhythmias#Torsade_de_pointes|Torsade de Pointes]]:
|-
|
<ul>
<li>Vrouwelijk geslacht</li>
<li>Hypokaliemie</li>
<li>Bradycardie</li>
<li>Recente conversie van [[Arrhythmias#Atrial fibrillation|atrial fibrillation]], in het bijzonder als er een QT-verlengend medicijn is gebruikt (sotalol, amiodarone)</li>
<li>Decompensatio cordis</li>
<li>Digitalis behandeling</li>
<li>Hoge of overdosering of snelle intraveneuze toediening van één van bovengenoemde medicamenten</li>
<li>Bestaande QT verlenging vóórdat het medicament werd toegediend</li>
<li>Subklinisch long QT syndrome</li>
<li>Bepaalde ion-kanaal polymorphismen</li>
</ul>
|}
{{clr}}


==External links==
==External links==
#LongQT.org [http://www.longqt.org/images/Long%20QT%20Syn%20Feb-2002.pdf Powerpoint presentatie over long QT syndrome]
#[http://www.torsades.org Torsades.org has a list of QT prolonging drugs]
#[http://www.torsades.org Torsades.org met een lijst met QT verlengende medicatie]
#[http://qtdrugs.org QTdrugs.org, another list of QT prolonging drugs]
#[http://qtdrugs.org QTdrugs.org, met een lijst van QT verlengende medicatie]
#[http://www.sads.org Sudden Arrhythmia Death Syndrome Foundation]. LQTS patient group.
#[http://www.cardiogenetica.nl Cardiogenetica.nl]
#[http://www.sads.org Sudden Arrhythmia Death Syndrome Foundation]. Een Amerikaanse vereniging o.a. voor LQTS patiënten.
#[http://www.fsm.it/cardmoc/ Inherited Arrhythmias Database]
#[http://www.fsm.it/cardmoc/ Inherited Arrhythmias Database]


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#priori pmid=12736279
#priori pmid=12736279
#Hofman pmid=17090615
#Hofman pmid=17090615
#Roden pmid=18184962
</biblio>
</biblio>
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