###### Created: 2024-06-12 19:57 ###### Areas & Topics: #medicine ###### Note Type: #permanent ###### Connected to: [[Torsades de Pointes]] [[Tachycardias]] [[Peri-Arrest Rhythms]] [[Acute Coronary Syndrome (ACS)]] - Long QT Syndrome is characterised by a prolonged QT interval due to delayed repolarisation of the ventricles. - It has multiple causes, but is normally due to gene mutations which either cause the condition or pre-dispose someone to develop it in certain conditions. - A normal QT interval is less than 430 milliseconds in males and 450 milliseconds in females. ### Epidemiology - More common in females ### Causes of Long QT Syndrome #### Congenital - Jervell-Lange-Nielsen Syndrome (a rare autosomal recessive disorder characterised by bilateral sensorineural hearing loss and a long QT interval due to dysfunctional potassium channels in the heart and cochlea) - Romano-Ward Syndrome (an autosomal dominant disorder causing an inherited long QT interval) #### Pharmacological A: Amiodarone S: Sotalol, SSRIs (especially citalopram) T: Terfenadine H: Haloperidol M: Methadone, Macrolides (erythromycin) A: Antiarrhythmics class 1a (e.g. flecainide, propafenone and other sodium channel blockers) T: Tricyclic antidepressants O: Ondansetron C: Chloroquine N.B. a useful mnemonics for drugs causing long QT syndrome is ASTHMATOC #### Other - Electrolyte Disturbances (hypocalcaemia, hypokalaemia, hypomagnesaemia) - Myocardial Infarction (myocardial ischaemia leading to a long QT) - Hypothermia - Subarachnoid Haemorrhage (due to the haemorrhage causing sudden catecholamine release affecting the heart) ### Pathophysiology - The duration of the QT interval entirely depends on how quickly an action potential can pass through the ventricles. - This process is mostly dependant on ion channels in the heart allowing for depolarisation or repolarisation. - Congenital or acquired causes can lead to disturbances in these ion channels. #### Congenital - Gene mutations coding for ion channel proteins cause the ion channels to malfunction, leading to prolongation of the QT interval. - The most common gene mutated is KCNQ1, causing Long QT Syndrome Type 1. #### Acquired - The main acquired causes of Long QT Syndrome are electrolyte disturbances and medication use. - Electrolyte disturbances cause long QT through changes in the concentration of ions in the membranes of the heart. - Virtually all the medications which cause long QT Syndrome do so by blocking the outward rapid delayed rectifier potassium current (also known as the IKr). - This current is mediated by the potassium channel coded by the KCNH2 gene. ### Sub-Types of Long QT Syndrome **Long QT Syndrome Type 1** - The most common subtype caused by a mutation of the KCNQ1 gene. - Causes a loss of function of the alpha-subunit of the slow delayed rectifier potassium channel. - Cardiac events with this type typically occur due to exercise (e.g. swimming) or emotion. **Long QT Syndrome Type 2** - The second most common subtype caused by a mutation of the KCNH2 gene. - Also causes a loss of function of the alpha-subunit of the slow delayed rectifier potassium channel. - Cardiac events with this type typically occur due to sudden arousal (e.g. auditory stimuli, emotion etc.) **Long QT Syndrome Type 3** - Caused by a mutation of the SCN5A gene. - Causes a gain of function in the alpha-subunit of the cardiac sodium ion channel. - Cardiac events with this type typically occur during rest or sleep. ### Clinical Features - Long QT syndrome is typically picked up on routine ECG or following screening from a positive family history. - Syncope is the most common symptom. - Other symptoms include cardiac arrest or seizures. N.B. In 10 to 15% of patients, death is the first sign of long QT syndrome. ### Management General Advice 1. Avoid drugs and precipitants which prolong the QT interval. Medical Interventions 1. [[Beta Blockers]] (other than sotalol) are 1st line pharmacological management. 2. Implantable Cardioverter Defibrillator (ICD) can be used for high-risk patients or those who cannot take beta-blockers. ### Resources Al-Akchar M, Siddique MS. Long QT Syndrome. [Updated 2022 Dec 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441860/ Wallace, Eimear et al. “Long QT Syndrome: Genetics and Future Perspective.” _Pediatric cardiology_ vol. 40,7 (2019): 1419-1430. doi:10.1007/s00246-019-02151-x Long QT Syndrome - NHS https://www.nhs.uk/conditions/long-qt-syndrome/ Groffen AJ, Bikker H, Christiaans I. Long QT Syndrome Overview. 2003 Feb 20 [Updated 2024 Mar 21]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1129/ Long QT Syndrome - PassMed High Yield Textbook Pabba K, Chakraborty RK. Jervell and Lange-Nielsen Syndrome. [Updated 2023 Aug 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537300/ Romano-Ward Syndrome - ScienceDirect https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/romano-ward-syndrome