Zespół długiego qt – Etiologia i przyczyny

Zespół długiego qt
Etiologia i przyczyny

Zespół długiego QT (LQTS) to zaburzenie elektrofizjologiczne serca charakteryzujące się wydłużeniem odstępu QT w EKG, co predysponuje do torsade de pointes, omdleń i nagłej śmierci sercowej. Etiologia obejmuje formy wrodzone, związane z mutacjami w genach kodujących kanały jonowe (głównie KCNQ1, KCNH2, SCN5A), oraz nabyte, wywołane przez leki (ponad 100 substancji, m.in. chinidyna, sotalol, erytromycyna), zaburzenia elektrolitowe (hipokaliemia, hipomagnezemia, hipokalcemia) i choroby współistniejące (np. niedoczynność tarczycy, bradyarytmie, infekcje). Wrodzony LQTS występuje z częstością 1:2000–1:10000, a u 25-30% pacjentów mutacje genetyczne pozostają nierozpoznane. Patofizjologia opiera się na zaburzeniach kinetyki kanałów jonowych, prowadzących do wydłużenia repolaryzacji i powstawania wczesnych potencjałów następczych, co sprzyja arytmii typu torsade de pointes. W LQT1 i LQT2 dominuje utrata funkcji kanałów potasowych (IKs, IKr), natomiast w LQT3 – nadmierna aktywacja kanałów sodowych (INa).

Etiologia zespołu długiego QT (zespół długiego qt)

Wrodzony zespół długiego QT
Nabyty zespół długiego QT
Teoria wieloczynnikowa nabytego LQTS
Rola płci w LQTS
Patomechanizm LQTS

Związek z innymi chorobami
Czynniki ryzyka i predyspozycje

Kolejne rozdziały

Etiologia zespołu długiego QT (zespół długiego qt)

Zespół długiego QT (LQTS – Long QT Syndrome) to zaburzenie elektrycznej aktywności serca, charakteryzujące się wydłużeniem odcinka QT w zapisie EKG, co predysponuje do groźnych zaburzeń rytmu serca, w tym częstoskurczu komorowego typu torsade de pointes, omdleń, a nawet nagłej śmierci sercowej. Etiologia zespołu długiego QT jest złożona i obejmuje zarówno czynniki wrodzone (genetyczne), jak i nabyte.¹²

Wrodzony zespół długiego QT

Wrodzony zespół długiego QT jest spowodowany mutacjami genetycznymi, które dziedziczone są głównie w sposób autosomalny dominujący (zespół Romano-Ward) lub rzadziej autosomalny recesywny (zespół Jervell i Lange-Nielsen). Częstość występowania wrodzonego LQTS szacuje się na 1:2000 do 1:10000 osób.²³

Mutacje dotyczą genów kodujących białka kanałów jonowych w błonie komórkowej kardiomiocytów, które są odpowiedzialne za przepływ jonów (potasu, sodu, wapnia) do i z komórek mięśnia sercowego. Te kanały jonowe regulują elektryczną aktywność serca. W LQTS kanały te mogą nie funkcjonować prawidłowo lub może być ich zbyt mało, co zaburza przepływ jonów i wydłuża fazę repolaryzacji komór serca.⁴⁵

Typy genetyczne LQTS

Do tej pory zidentyfikowano co najmniej 15-17 różnych genów związanych z zespołem długiego QT, a wśród nich setki mutacji. Trzy główne typy genetyczne stanowią około 75% wszystkich przypadków wrodzonego LQTS:⁶⁷

LQT1 (30-35% przypadków) – spowodowany mutacjami w genie KCNQ1, który koduje kanał potasowy Kv7.1, odpowiedzialny za wolno aktywujący się prąd potasowy (IKs)⁶⁸
LQT2 (25-40% przypadków) – spowodowany mutacjami w genie KCNH2, który koduje kanał potasowy Kv11.1, odpowiedzialny za szybko aktywujący się prąd potasowy (IKr)⁶⁸
LQT3 (5-10% przypadków) – spowodowany mutacjami w genie SCN5A, który koduje kanał sodowy Nav1.5, odpowiedzialny za prąd sodowy (INa)⁶⁸

Ponadto zidentyfikowano rzadsze formy LQTS:⁹¹⁰

Zespół Jervell i Lange-Nielsen – autosomalnie recesywna forma LQTS z towarzyszącą wrodzoną głuchotą, związana z mutacjami w genach KCNQ1 (JLN1) i KCNE1 (JLN2)¹¹
Zespół Andersena-Tawila (LQT7) – charakteryzujący się nie tylko wydłużeniem QT, ale także okresowymi porażeniami i nieprawidłowościami w budowie twarzy i szkieletu⁹
Zespół Timothyego (LQT8) – w którym wydłużony QT towarzyszy nieprawidłowościom w strukturze serca i zaburzeniom ze spektrum autyzmu⁹

U około 25-30% pacjentów z klinicznie rozpoznanym LQTS nie udaje się zidentyfikować mutacji genetycznej mimo zastosowania nowoczesnych metod diagnostycznych.¹²¹³

Nabyty zespół długiego QT

Nabyty zespół długiego QT jest znacznie częstszy niż wrodzony i może rozwinąć się w ciągu życia z różnych przyczyn. Najczęstszymi czynnikami wywołującymi są leki, zaburzenia elektrolitowe oraz choroby współistniejące.¹⁴

Leki indukujące LQTS

Ponad 100 leków może powodować wydłużenie odstępu QT i rozwój nabytego zespołu długiego QT (tzw. polekowy zespół długiego QT). Wiele z tych leków działa poprzez blokowanie kanału potasowego kodowanego przez gen hERG (KCNH2), co prowadzi do zahamowania szybkiego prądu potasowego (IKr).¹⁴¹⁵

Do leków często powodujących wydłużenie odstępu QT należą:¹⁶¹⁷

Leki przeciwarytmiczne klasy I i III (np. chinidyna, prokainamid, sotalol, amiodaron)
Antybiotyki (np. erytromycyna, azytromycyna, cyprofloksacyna)
Leki przeciwgrzybicze
Leki przeciwpsychotyczne (np. haloperidol, olanzapina)
Leki przeciwdepresyjne (np. amitryptylina, fluoksetyna)
Leki przeciwhistaminowe
Diuretyki (mogą powodować zaburzenia elektrolitowe)
Leki obniżające poziom cholesterolu
Leki przeciwcukrzycowe

Ryzyko polekowego LQTS jest większe u osób, które mają genetyczne predyspozycje do wydłużenia odstępu QT, nawet jeśli wcześniej nie występowały u nich objawy.¹⁸¹⁹

Zaburzenia elektrolitowe

Zaburzenia elektrolitowe mogą istotnie wpływać na wydłużenie odstępu QT. Najczęściej związane z LQTS są:¹⁵¹⁶

Hipokaliemia (niski poziom potasu) – szczególnie niebezpieczna, często występująca jako skutek stosowania leków moczopędnych, wymiotów lub biegunki
Hipomagnezmia (niski poziom magnezu)
Hipokalcemia (niski poziom wapnia)

Choroby i stany kliniczne

Wiele chorób i stanów klinicznych może prowadzić do nabytego zespołu długiego QT:¹⁶²⁰

Niedoczynność tarczycy (hipotyroza)
Hipotermia (temperatura ciała poniżej 35°C)
Bradyarytmie (zaburzenia funkcji węzła zatokowego, blok przedsionkowo-komorowy II lub III stopnia)
Choroby serca (niedokrwienie mięśnia sercowego, zawał serca z wyraźnymi odwróceniami załamka T)
Choroby neurologiczne (udar mózgu, krwotok śródmózgowy)
Guz chromochłonny nadnerczy (pheochromocytoma)
Zaburzenia odżywiania (anoreksja, bulimia, głodzenie się)
Infekcja COVID-19
Zakażenie HIV
Stan zapalny (zarówno sercowy, jak i ogólnoustrojowy)

Teoria wieloczynnikowa nabytego LQTS

Coraz więcej dowodów wskazuje na tzw. „teorię wieloczynnikową” (multi-hit theory) w patogenezie nabytego zespołu długiego QT. Zgodnie z tą teorią, do klinicznego ujawnienia się LQTS często potrzebne jest współistnienie kilku czynników ryzyka jednocześnie.²¹

Przykładem może być sytuacja, gdy pacjent z genetyczną predyspozycją do LQTS (która sama w sobie może nie powodować objawów) przyjmuje lek wydłużający odstęp QT i jednocześnie ma hipokaliemię spowodowaną wymiotami lub biegunką. Taka kombinacja czynników znacznie zwiększa ryzyko wystąpienia groźnych zaburzeń rytmu serca.¹⁹

Rola płci w LQTS

Płeć również odgrywa rolę w patogenezie zespołu długiego QT. LQTS jest częstszy u kobiet niż u mężczyzn. Kobiety z LQTS są bardziej narażone na omdlenia lub nagłą śmierć sercową podczas miesiączki i wkrótce po porodzie.⁴

W przypadku różnych typów genetycznych LQTS występują różnice w podatności na arytmie w zależności od płci i wieku. W LQT1 objawy pojawiają się zwykle w młodszym wieku, a szczególnie narażeni są chłopcy. Natomiast w LQT2 i LQT3 objawy najczęściej pojawiają się w okresie dojrzewania, a bardziej zagrożone są dziewczęta.²²

Patomechanizm LQTS

Patofizjologia zespołu długiego QT opiera się na zaburzeniach kinetyki kanałów jonowych, co prowadzi do wydłużenia potencjału czynnościowego komórek mięśnia sercowego.⁵

W normalnych warunkach, po każdym skurczu serca, system elektryczny serca „ładuje się ponownie”, przygotowując się do następnego uderzenia. Ten proces obejmuje przepływ jonów przez specjalne kanały w błonach komórkowych kardiomiocytów. U osób z LQTS występuje zaburzenie tego procesu, co powoduje wydłużenie czasu repolaryzacji komór (widoczne jako wydłużenie odstępu QT w EKG).²⁰

Wydłużenie QT zwiększa ryzyko wystąpienia wczesnych potencjałów następczych (early afterdepolarizations, EAD), które mogą inicjować częstoskurcz komorowy typu torsade de pointes. Ten rodzaj arytmii może prowadzić do migotania komór i nagłej śmierci sercowej, jeśli nie zostanie natychmiast przerwany.⁵

W zależności od typu LQTS, mechanizm patofizjologiczny różni się:⁶²³

W LQT1 i LQT2 występuje zmniejszenie funkcji kanałów potasowych (loss-of-function), co ogranicza wypływ jonów potasu z komórek i wydłuża repolaryzację
W LQT3 występuje zwiększenie funkcji kanałów sodowych (gain-of-function), co powoduje nadmierny napływ jonów sodu do komórek i również wydłuża repolaryzację

Niektóre czynniki, takie jak zwiększone napięcie układu współczulnego (np. podczas wysiłku fizycznego, stresu emocjonalnego), mogą nasilać te zaburzenia i zwiększać ryzyko wystąpienia groźnych arytmii, szczególnie u pacjentów z LQT1.⁵²⁴

Związek z innymi chorobami

Istnieje coraz więcej dowodów na związek między LQTS a zespołem nagłej śmierci niemowląt (SIDS). Szacuje się, że około 5-10% niemowląt, które zmarły z powodu SIDS, miało zespół długiego QT spowodowany defektem genetycznym.²⁵²⁶

Ponadto, badania wykazują powiązania między stanami autoimmunologicznymi i zapalnymi a wydłużeniem odstępu QT. Zapalenie serca lub ogólnoustrojowe może promować wydłużenie odstępu QT poprzez efekty mediowane przez cytokiny, co może zwiększać ryzyko nagłej śmierci sercowej.¹⁸

Czynniki ryzyka i predyspozycje

Główne czynniki ryzyka rozwoju zespołu długiego QT obejmują:⁴²⁷

Wywiad rodzinny – obecność LQTS lub przypadków nagłej śmierci sercowej w rodzinie
Płeć żeńska – kobiety są bardziej narażone na LQTS i jego powikłania
Choroby serca – kardiomiopatia, wrodzone wady serca
Zaburzenia elektrolitowe – niski poziom potasu, magnezu lub wapnia
Przyjmowanie leków wydłużających odstęp QT
Choroby współistniejące – zaburzenia odżywiania, choroby tarczycy

U osób z genetyczną predyspozycją do LQTS ryzyko wystąpienia objawów może być zwiększone przez dodatkowe czynniki, takie jak wysiłek fizyczny, silne emocje, nagły hałas lub stres – szczególnie u pacjentów z LQT1 i LQT2.²²

Warto zauważyć, że podatność na nabyte wydłużenie odstępu QT może być modyfikowana przez warianty genetyczne, co tłumaczy dlaczego niektóre osoby są bardziej wrażliwe na działanie leków wydłużających QT niż inne.¹⁸

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Materiały źródłowe

#1 Long QT syndrome – Symptoms and causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/long-qt-syndrome/symptoms-causes/syc-20352518
Long QT syndrome (LQTS) is caused by changes in the heart’s electrical signaling system. It doesn’t affect the shape or form of the heart. […] Some people are born with changes in DNA that cause long QT syndrome. This is known as congenital long QT syndrome. LQTS also can happen later in life due to some health conditions, certain medicines or changes in the levels of body minerals. This is called acquired long QT syndrome. […] Long QT syndrome usually falls into two groups. Congenital long QT syndrome. You’re born with this type of LQTS. It’s caused by changes in DNA that are passed down through families. That means it is inherited. […] Acquired long QT syndrome. This type of LQTS is caused by another health condition or medicine. It usually can be reversed when the specific cause is found and treated.
#2 Long QT Syndrome – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK441860/
The causes of QT interval prolongation can be divided into congenital or acquired. Congenital causes are usually a result of mutations in ion channels (potassium, calcium, or sodium) with more than 15 identified mutations. In contrast, acquired QT interval prolongation may result from electrolyte abnormalities or drugs that affect those ion channels. […] The prevalence of congenital causes, also known as Long QT syndrome (LQTS), is difficult to estimate but may be expected in 1 in 2,500 to 1 in 10,000 individuals. […] Family history is positive for Long QT syndrome in 40% and for sudden cardiac death in 30% of patients. Acquired causes are relatively more common than congenital causes. […] Though rare, this entity results in a high risk of sudden death. So far, mutations of any of 15 genes have been linked to Long QT syndrome, with KCNQ1 being the most common gene mutated and is the cause of Long QT syndrome type 1. […] More commonly, prolongation of QT interval is acquired. As one can expect, disturbances of electrolytes (hypokalemia, hypocalcemia, hypomagnesemia) prolong QT. Also, certain medications affect those ion channels and lead to QT prolongation.
#3 Long QT Syndrome – SADS Foundation
https://sads.org/sads-conditions/long-qt-syndrome/
We estimate that at least 1 in 2000 people in the United States have congenital long QT syndrome (LQTS). […] LQTS is a disturbance of your hearts electrical system. Its caused by abnormalities of microscopic pores (proteins) in the heart cells called ion channels. […] LQTS is an inherited genetic condition, so if someone in your family is diagnosed with LQTS, it is extremely important that the rest of your family be tested for the syndrome. […] The usual treatment involves taking beta-blocker medications daily (preferably nadolol or propranolol). This approach is effective for the majority of those with LQTS. […] If you continue to have symptoms despite appropriate doses of beta-blockers, or are not able to tolerate your beta-blocker therapy, you may need additional medications, surgery (left cardiac sympathetic denervation [LCSD]), or device therapy with an implantable cardioverter defibrillator (ICD).
#4 Arrhythmias – Long QT Syndrome | NHLBI, NIH
https://www.nhlbi.nih.gov/health/long-qt-syndrome
Long QT syndrome (LQTS) is a type of conduction disorder. […] On the surface of each heart muscle cell are tiny pores called ion channels. Ion channels open and close to let electrically charged sodium, calcium, and potassium atoms (ions) flow into and out of each cell. This generates the hearts electrical activity. In people who have LQTS, the ion channels may not work well, or there may be too few of them. This may disrupt electrical activity in the hearts lower chambers, or ventricles, and cause dangerous arrhythmias. […] LQTS is often inherited, which means you are born with the condition and have it your whole life. You also can acquire LQTS. This means you are not born with the disorder but develop it during your lifetime. […] The following factors can raise your risk of LQTS: A family history of LQTS, or if someone in your family has had unexplained fainting or seizures, drowning or near drowning, or unexplained sudden death; Heart conditions such as cardiomyopathy and congenital heart defects; Medical conditions, such as eating disorders, thyroid disease, or serious diarrhea or vomiting, that cause low blood levels of potassium, magnesium, or calcium; Medicines that affect how your hearts ion channels work, including some antibiotics, antidepressants, and antihistamines; Sex: LQTS is more common in women than men. Women who have LQTS are more likely to faint or die suddenly from the disorder during menstruation and shortly after giving birth.
#5 Long QT Syndrome: Practice Essentials, Background, Etiopathophysiology
https://emedicine.medscape.com/article/157826-overview
LQTS results from mutations of genes encoding for cardiac ion channel proteins, which cause abnormal ion channel kinetics. […] In LQTS, QT prolongation can lead to polymorphic ventricular tachycardia, or torsade de pointes, which itself may lead to ventricular fibrillation and sudden cardiac death. […] Torsade de pointes is widely thought to be triggered by reactivation of calcium channels, reactivation of a delayed sodium current, or a decreased outward potassium current that results in early afterdepolarization (EAD), in a condition with enhanced TDR usually associated with a prolonged QT interval. […] Any additional condition that accelerates the reactivation of calcium channels (eg, increased sympathetic tone) increases the risk of EAD.
#6 Genetics of long-QT syndrome | Journal of Human Genetics
https://www.nature.com/articles/jhg201574
Congenital long QT syndrome (LQTS) is an inherited arrhythmia syndrome characterized by a prolonged QT interval in the 12-lead ECG, torsades de pointes and not negligible prevalence of sudden cardiac death. […] A total of 15 genes have been reported for autosomal-dominant forms of Romano-Ward-type congenital LQTS and 2 genes for autosomal-recessive forms of the Jervell and Lange-Nielsen syndrome. […] Most of the genetic abnormalities identified thus far appear to prolong the duration of action potentials by decreasing the potassium current (loss-of-function mutation) or increasing the sodium or calcium current (gain-of-function mutation), resulting in clinical QT prolongation on the ECG. […] Between 1995 and 1996, three major causative genes were recognized for LQTS and associated with LQTS types 1-3: KCNQ1-encoding Kv7.1 (for LQT1), KCNH2-encoding Kv11.1 (for LQT2) and SCN5A-encoding Nav1.5.
#7 Genetics of long-QT syndrome | Journal of Human Genetics
https://www.nature.com/articles/jhg201574
According to the Heart Rhythm Society/European Heart Rhythm Association Expert Consensus Statement on the State of Genetic Testing for the Channelopathies and Cardiomyopathies, abnormalities of the three LQTS-associated genes are detected in ~75% of clinically definite LQTS, with rates of 30%-35%, 25%-40% and 5%-10% for LQTS types LQT1, LQT2 and LQT3, respectively. […] Beyond the three common LQTS gene variants, several mutations encoding ion-channel subunits, except for those associated with LQT4, LQT9, LQT11, LQT12, LQT14 and LQT15, have also been found. […] Notably, mutations in KCNQ1 (that is, JLN1, also associated with LQT1) and KCNE1 (that is, JLN2, also associated with LQT5) have also been found to be causal in autosomal-recessive forms of the Jervell and Lange-Nielsen syndrome attributable to a decrease in the Iks.
#8 Genetics of long-QT syndrome | Journal of Human Genetics
https://www.nature.com/articles/jhg201574
The LQTS types associated with slowly activating delayed rectifier potassium current (IKs) dysfunction include LQT1, LQT5, LQT11, JLN1 and JLN2, although most are associated with LQT1. […] The LQTS types associated with rapidly activating delayed rectifier potassium current (IKr) dysfunction include LQT2 and LQT6, with the former accounting for the majority of cases. […] The LQTS types with dysfunctional late-activating sodium channels (INa) include LQT3, LQT9, LQT10 and LQT12, although most are LQT3. […] A type of LQTS that is associated with a mutation in KCNJ2 is LQT7, which creates a condition known as Andersen-Tawil syndrome. […] The most severe phenotypic form of LQTS is Timothy syndrome (LQT8). […] Crotti et al. performed exome sequencing in infants with recurrent cardiac arrest and dramatically prolonged QTc intervals, discovering heterozygous de novo mutations in CALM1 and CALM2 encoding calmodulin (that is, LQT14 and LQT15, respectively).
#9 Long QT syndrome – Wikipedia
https://en.wikipedia.org/wiki/Long_QT_syndrome
LQTS can arise from variants in several genes, leading in some cases to quite different features. […] The common thread linking these variants is that they affect one or more ion currents leading to prolongation of the ventricular action potential, thus lengthening the QT interval. […] The most common of these, accounting for 99% of cases, is Romano-Ward syndrome (genetically LQT1-6 and LQT9-16), an autosomal dominant form in which the electrical activity of the heart is affected without involving other organs. […] A less commonly seen form is Jervell and Lange-Nielsen syndrome, an autosomal recessive form of LQTS combining a prolonged QT interval with congenital deafness. […] Other rare forms include Andersen-Tawil syndrome (LQT7) with features including a prolonged QT interval, periodic paralysis, and abnormalities of the face and skeleton; and Timothy syndrome (LQT8) in which a prolonged QT interval is associated with abnormalities in the structure of the heart and autism spectrum disorder.
#10 Diagnosis, management and therapeutic strategies for congenital long QT syndrome | Heart
https://heart.bmj.com/content/108/5/332
Congenital long QT syndrome (LQTS) is characterised by heart rate corrected QT interval prolongation and life-threatening arrhythmias, leading to syncope and sudden death. Variations in genes encoding for cardiac ion channels, accessory ion channel subunits or proteins modulating the function of the ion channel have been identified as disease-causing mutations in up to 75% of all LQTS cases. […] Based on the underlying genetic defect, LQTS has been subdivided into different subtypes. […] In the last 25 years, 17 genes have been associated with LQTS. However, a recent analysis, based on an approach using gene and disease specific metrics designed by the Clinical Genome Resource (ClinGen), reclassified a number of these genes to limited or disputed evidence. This approach left seven genes with definitive or strong evidence for causality.
#11 Long QT syndrome Guide: Causes, Symptoms and Treatment Options
https://www.drugs.com/health-guide/long-qt-syndrome.html
Long QT syndrome is an uncommon inherited conditionâmeaning it’s caused by genes passed on to you from your parents. The electrical activity of heart cells is controlled by a set of channels that pump minerals, such as sodium and potassium, in and out of cells. If you inherit genes that cause alterations in these channels, it can affect the action of heart cells. […] Inherited long QT syndrome is not nearly as common as a prolonged QT interval caused by a medication or an imbalance of certain minerals in the blood stream. Many medications are known to lengthen the QT interval and upset the heart rhythm. […] The two best understood inherited long QT syndromes are the Romano-Ward syndrome and the Jervell and Lange-Nielsen syndrome. Of the two, the Romano-Ward syndrome is more common. It is an autosomal dominant inherited condition â meaning you can have a long QT if you inherit one abnormal gene from either parent. The Jervell and Lange-Nielsen syndrome is rare. People with this syndrome have a very long QT interval and are also deaf. The Jervell and Lange-Nielsen syndrome is an autosomal recessive inherited condition â meaning that you need to inherit two abnormal genes, one from each parent, to get this syndrome.
#12 Diagnosis, management and therapeutic strategies for congenital long QT syndrome | Heart
https://heart.bmj.com/content/108/5/332
However, further optimisation of treatment strategies is pertinent, in particular in two specific patient categories. […] Despite all progress in genetic screening methods, the yield of finding a potential pathogenic variant in a LQTS patient with a clear phenotype is at most 75%-80%. […] Important additional scientific inquiries in this field are the unravelling of the genotype in the 25%-30% genotype elusive cases and the role of additional genetic and other factors in determining the arrhythmia risk. […] In summary, congenital LQTS is an inheritable entity characterised by a prolonged heart-rate corrected QT interval, and it associates with malignant arrhythmias at young age. It is caused by a decrease in repolarising cardiac ion currents in a complex polygenic composition and interacting with multiple other factors such as sex, age, comorbidities and triggers such as drugs.
#13 Long QT Syndrome | Advancing Genomic Medicine | Perelman School of Medicine at the University of Pennsylvania
https://www.med.upenn.edu/agm/long-qt-syndrome
Long QT syndrome (LQTS) is a cardiac electrophysiologic disorder, characterized by QT prolongation and T-wave abnormalities on the EKG that are associated with tachyarrhythmias. […] There are known acquired and hereditary causes of LQTS. […] The main genes associated with LQTS are KCNQ1, KCNH2, and SCN5A, and contribute to approximately 75% of all cases. […] There are additional genes identified that account for 5-10% of cases. […] Approximately 25% of individuals with LQTS will not have a genetic cause identified on genetic testing. […] LQTS is usually inherited in an autosomal dominant pattern. There are rare causes of LQTS that are inherited in an autosomal recessive pattern.
#14 Acquired Long QT Syndrome and Electrophysiology of Torsade de Pointes | AER Journal
https://www.aerjournal.com/articles/acquired-long-qt-syndrome-and-electrophysiology-torsade-de-pointes
Congenital long QT syndrome (LQTS) has been the most investigated cardiac ion channelopathy. […] Acquired LQTS is by far, more prevalent than congenital LQTS. The vast majority of acquired LQTS is the result of the adverse effect of drugs and/or electrolyte abnormalities, which, in the majority of cases, interact with the human ether- -go-go-related gene (hERG) encoding the pore-forming subunits (Kv11.1) of the rapidly activating delayed rectifier current, IKr. […] The vast majority of acquired LQTS is the result of adverse effects of drugs that interact with the hERG gene, and the IKr. However, although most drugs that cause TdP do so via hERG channel blockade, TdP is not necessarily a potential consequence of all drugs blocking the hERG pathway. […] Other causes of acquired LQTS include electrolyte abnormalities (hypokalaemia, hypomagnesaemia, and hypocalcaemia), hypothyroidism, hypothermia, and marked bradycardia.
#15 Long QT syndrome – Symptoms and causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/long-qt-syndrome/symptoms-causes/syc-20352518
Many genes and gene changes have been linked to long QT syndrome (LQTS). […] A medicine or other health condition can cause acquired long QT syndrome. […] If a medicine causes acquired long QT syndrome, the disorder may be called drug-induced long QT syndrome. More than 100 medicines can cause prolonged QT intervals in otherwise healthy people. […] Health conditions that can cause acquired long QT syndrome include: Body temperature below 95 degrees Fahrenheit (35 degrees Celsius), a condition called hypothermia. Low calcium, also called hypocalcemia. Low magnesium, also called hypomagnesemia. Low potassium, also called hypokalemia. A tumor of the adrenal gland that usually is not cancer, called pheochromocytoma. Stroke or brain bleed. Underactive thyroid, also called hypothyroidism.
#16 Causes of long QT syndrome – UpToDate
https://www.uptodate.com/contents/image?imageKey=CARD/57431
Diuretic therapy via electrolyte disorders, particularly hypokalemia and hypomagnesemia […] Herbs […] Cinchona (contains quinine), iboga (ibogaine), licorice extract in overuse via electrolyte disturbances […] Medications […] High risk […] The „high risk” category includes drugs with evidence of likely or probable association with TdP or clinically significant QT prolongation typically defined as a mean QTc increase of >60 msec from baseline and/or a QTc increased to >500 msec in a significant proportion of patients […] Moderate risk […] The „moderate risk” category includes drugs with evidence of a possible association with TdP or moderate QT prolongation typically defined as a mean QTc increase of 20 to 59 msec from baseline and/or an increase to a QTc of 460 to 499 msec in a significant proportion of patients
#16 Causes of long QT syndrome – UpToDate
https://www.uptodate.com/contents/image?imageKey=CARD/57431
Some reported causes and potentiators of the long QT syndrome […] Congenital […] Jervell and Lange-Nielsen syndrome (including „channelopathies”) […] Romano-Ward syndrome […] Idiopathic […] Acquired […] Metabolic disorders […] Hypokalemia […] Hypomagnesemia […] Hypocalcemia […] Starvation […] Anorexia nervosa […] Liquid protein diets […] Hypothyroidism […] Bradyarrhythmias […] Sinus node dysfunction […] AV block: second or third degree […] Other factors […] Myocardial ischemia or infarction, especially with prominent T-wave inversions […] Intracranial disease […] HIV infection […] Hypothermia […] Toxic exposure: organophosphate insecticides […] Androgen deprivation therapy […] GnRH agonist/antagonist therapy […] Bilateral surgical orchiectomy
#17 Long QT Syndrome: Symptoms, Causes, Treatment, and Life Expectanc
https://www.healthline.com/health/long-qt-syndrome
LQTS can be either inherited or acquired, meaning that something beyond genetics causes it. […] Seven types of inherited LQTS exist. They are numbered LQTS 1, LQTS 2, and so on. Researchers have identified more than 15 different types of genetic mutations that can lead to LQTS. […] Acquired LQTS can be due to taking certain medications, including: antiarrhythmics, antibiotics, antihistamines, antipsychotics, cholesterol-lowering medicines, diabetes medications, diuretics. […] Several other things can cause LQTS, especially those that cause a loss of potassium or sodium from your bloodstream, such as: severe diarrhea or vomiting, anorexia nervosa, bulimia, malnutrition, hyperthyroidism.
#18 Acquired Long QT Syndrome and Electrophysiology of Torsade de Pointes | AER Journal
https://www.aerjournal.com/articles/acquired-long-qt-syndrome-and-electrophysiology-torsade-de-pointes
Several recent reports from this laboratory have provided strong evidence for a pathogenic role of autoimmune and inflammatory conditions in the development of QTc prolongation. […] In summary, cardiac or systemic inflammation promotes QTc-interval prolongation via cytokine-mediated effects and this may increase SCD risk. […] The susceptibility to acquired QT interval prolongation can be influenced by genetic variations. […] The overall incidence of drug-induced LQTS in a given population is difficult to estimate. […] QT prolongation is one of the most common reasons for drug withdrawal from the market, despite the fact that these drugs may be beneficial for certain patients and not harmful in every patient.
#19 Vomiting, electrolyte disturbance, and medications; the perfect storm for acquired long QT syndrome and cardiac arrest: a case report | Journal of Medical Case Reports | Full Text
https://jmedicalcasereports.biomedcentral.com/articles/10.1186/s13256-021-03204-7
Ondansetron is known to prolong the QT interval in a dose-dependent manner, it is recommended to be used with caution in patients who may develop prolongation of QTc, such as patients with electrolyte abnormalities. […] Fluoxetine is also known to cause prolonged QT interval. […] Although metoclopramide on its own is not listed as a QT prolonging medication, and no warnings about QT prolongation exist on its product information, there is evidence that it can contribute to QT prolongation. […] This case serves as an important reminder that vomiting leads to both electrolyte disturbances and the prescription of antiemetics, which here led to a quadruple hit (hypokalemia, hypomagnesemia, ondansetron, metoclopramide) causing TdP and cardiac arrest. […] SSRIs are so commonly prescribed, that 1 in 6 patients may have this preexisting risk factor for TdP, as this patient did, contributing to the multiple hits required for clinical manifestations of acquired LQTS.
#20
https://www.amerikanhastanesi.org/mayo-clinic-care-network/mayo-clinic-health-information-library/diseases-conditions/long-qt-syndrome
Acquired long QT syndrome. This type of LQTS is caused by another health condition or medicine. It usually can be reversed when the specific cause is found and treated. […] Many genes and gene changes have been linked to long QT syndrome (LQTS). […] A medicine or other health condition can cause acquired long QT syndrome. […] If a medicine causes acquired long QT syndrome, the disorder may be called drug-induced long QT syndrome. More than 100 medicines can cause prolonged QT intervals in otherwise healthy people. […] Health conditions that can cause acquired long QT syndrome include: Body temperature below 95 degrees Fahrenheit (35 degrees Celsius), a condition called hypothermia. Low calcium, also called hypocalcemia. Low magnesium, also called hypomagnesemia. Low potassium, also called hypokalemia. A tumor of the adrenal gland that usually is not cancer, called pheochromocytoma. Stroke or brain bleed. Underactive thyroid, also called hypothyroidism.
#20
https://www.amerikanhastanesi.org/mayo-clinic-care-network/mayo-clinic-health-information-library/diseases-conditions/long-qt-syndrome
Long QT syndrome (LQTS) is a heart rhythm disorder that causes fast, chaotic heartbeats. The irregular heartbeats can be life-threatening. LQTS affects the electrical signals that travel through the heart and cause it to beat. […] Some people are born with changes in DNA that cause long QT syndrome. This is known as congenital long QT syndrome. LQTS also can happen later in life due to some health conditions, certain medicines or changes in the levels of body minerals. This is called acquired long QT syndrome. […] Long QT syndrome (LQTS) is caused by changes in the heart’s electrical signaling system. It doesn’t affect the shape or form of the heart. […] Long QT syndrome usually falls into two groups. […] Congenital long QT syndrome. You’re born with this type of LQTS. It’s caused by changes in DNA that are passed down through families. That means it is inherited.
#21 Vomiting, electrolyte disturbance, and medications; the perfect storm for acquired long QT syndrome and cardiac arrest: a case report | Journal of Medical Case Reports | Full Text
https://jmedicalcasereports.biomedcentral.com/articles/10.1186/s13256-021-03204-7
Acquired long QT syndrome is an important and preventable cause of cardiac arrest. Certain medications and electrolyte disturbance are common contributors, and often coexist. […] Acquired LQTS is commonly caused by medications, electrolyte abnormalities, structural heart disease, bradyarrhythmias, starvation, hypothermia, toxins, endocrine disease, liver disease, human immunodeficiency virus infection, and inflammation. […] The multi-hit theory suggests that more than one risk factor is required to cause clinical or electrocardiographic manifestations of acquired LQTS. […] This case report highlights the perfect storm of electrolyte disturbance (potassium, magnesium) and medication effects (fluoxetine, ondansetron, and metoclopramide), leading to acquired long QT syndrome and cardiac arrest.
#22 Diagnosis, management and therapeutic strategies for congenital long QT syndrome | Heart
https://heart.bmj.com/content/108/5/332
These remaining genes all encode for ion channels involved in cardiac repolarisation, their modulatory subunits or proteins regulating or modulating the function of ion channels. […] A positive genotype result, which is obtained in up to 75% of individuals with a clear phenotype, is of importance because it significantly contributes to risk and different aspects of the treatment strategy. […] The first two subtypes (LQT1 and 2) are based on functional loss-of-function variants in the potassium channel genes KCNQ1 and KCNH2, respectively. […] LQTS type 3 is based on gain-of-function variants in SCN5A, the gene encoding the fast inward cardiac sodium current (I Na). […] The age of onset of arrhythmias is typically younger in LQT1 patients and in particular LQT1 males are at risk, whereas most LQT2 and LQT3 patients who become symptomatic experience their first symptoms around puberty and here particular females are at risk.
#23 Long QT syndrome with mutations in three genes: A rare case | Revista Portuguesa de Cardiologia (English edition)
https://www.revportcardiol.org/en-long-qt-syndrome-with-mutations-articulo-S217420491500077X
Congenital long QT syndrome (LQTS) is a rare hereditary disease, with an incidence of 1 in 2000, characterized by prolonged ventricular repolarization and malignant ventricular tachyarrhythmias. […] Molecular genetic testing identified three mutations in heterozygosity in the KCNH2, KCNQ1 and SCN5A genes, which is a rare finding and is associated with worse prognosis. […] Mutations have been identified in several genes and new cases are frequently reported. The genes most often affected are KCNQ1 (LQT1), KCNH2 (LQT2) and SCN5A (LQT3). […] The first two lead to loss of function of potassium channels and the third causes gain of function in sodium channels. […] Most mutations have an autosomal dominant inheritance pattern. […] Our patient presented mutations in three different genes. The p.Gly262AlafsX98 mutation in the KCNH2 gene has been described in patients with LQTS and is known to be a cause of the condition.
#24 Long QT Syndrome | UCI Health | Orange County, CA
https://www.ucihealth.org/medical-services/cardiology/cardiac-arrhythmia/long-qt
Long QT syndrome is a rare heart rhythm disorder that creates a fast, uncontrolled heartbeat (arrhythmia). […] Long QT syndrome disrupts your hearts electrical system and can be fatal if you dont seek treatment. […] In some cases, strenuous exercise, stress, shock and fright can trigger Long QT syndrome. […] Doctors classify Long QT syndrome in two ways: genetic or acquired. […] A faulty gene you inherit from a parent can cause this condition. […] In some cases, you can get Long QT syndrome from taking certain medications. These include antibiotics, some heart medicines, antidepressants, antihistamines, antipsychotics, and diuretics. […] An electrocardiogram is the primary way we diagnose Long QT syndrome. […] Beta blockers are the first line treatment for LQTS. […] While genetic factors certainly influence illness, we encourage you to take your lifestyle choices into account too.
#25 Long QT Syndrome | Cardiology | Mercy Health
https://www.mercy.com/health-care-services/heart-vascular/conditions/long-qt-syndrome
Long QT syndrome occurs when the time it takes your heart to recharge between heartbeats becomes prolonged and causes arrhythmias. The QT interval becomes prolonged due to abnormalities in the hearts electrical system the hearts electrical activity is produced by the flow of particles such as calcium, sodium, potassium and chloride into and out of the heart. […] Long QT syndrome can be inherited or acquired. […] Many people with long QT syndrome are born with the condition and live with it their entire lives. Faulty genes that cause the body to produce too few ion channels, ion channels that dont work well or both can cause inherited long QT syndrome. […] Research shows a link between sudden infant death syndrome (SIDS) and long QT syndrome. An estimated 5 to 10 percent of babies who pass away from SIDS had long QT syndrome caused by a genetic defect.
#26 Long QT syndrome | Apollo Hospitals
https://www.apollohospitals.com/diseases-and-conditions/long-qt-syndrome/
So far, there are at least 17 genes that are associated with Long QT Syndrome, and there are hundreds of mutations within these genes that have been identified. Mutations in just three of these genes account for almost 75 percent of Long QT Syndrome cases, while the mutations in the other minor genes contribute to a very small percent of Long QT Syndrome cases. […] There are supposedly two forms of inherited Long QT Syndrome: Romano-Ward Syndrome. This is a more common form that occurs in people who inherit only a single variant of genes from one of their parents. […] Apparently, scientists have been investigating a possible link between long QT syndrome and sudden infant death syndrome (SIDS). They supposedly have discovered that almost five to ten percent of babies affected by the SIDS had either genetic defects or mutation for long QT syndrome.
#27 Long QT Syndrome (LQT) | Borderline Prolonged QT Internal Causes
https://www.radcliffecardiology.com/articles/case-illustrations-long-qt-syndrome?language_content_entity=en
Risk factors for drug-induced torsades de pointes are female sex, hypokalemia, bradycardia, recent conversion of atrial fibrillation especially with QT-prolongation drug, congestive heart failure, baseline QT prolongation, subclinical LQTS, and ion-channel polymorphisms. […] The second and third cases were eventually diagnosed as congenital LQTS, but not at first presentation. […] LQT1 is the most common form of this syndrome. […] The prevalence of congenital LQTS is around 1:2,000 to 1:5,000 LQTS. […] An accurate measurement of the QT interval is valuable in the diagnosis of LQTS, as highlighted in the cases discussed above. […] When a prolonged QTc is identified after a syncopal event in the absence of acquired causes of QT prolongation, a diagnosis of LQTS can be made. […] Prolonged QT syndrome is a rare condition with variable clinical presentation. Physicians need to be highly vigilant and consider LQTS in the clinical evaluation of syncope.