Guideline sources The following summarized guidelines for the evaluation and management of long QT syndrome are prepared by our editorial team based on guidelines from the European Society of Cardiology (ESC 2022; 2018), the Global Initiative for Asthma (GINA 2022), the American Heart Association (AHA 2020), the American Academy of Neurology (AAN 2019), the American Heart Association (AHA/HRS/ACC 2018), the Asia Pacific Heart Rhythm Society (APHRS/EHRA/HRS 2013), and the European Heart Rhythm Association (EHRA/HRS 2011). 1 2 3 4 5 6 7 8 Calculator Calculator NYHA functional classification f Schwartz's diagnostic criteria fo Guidelines https://web.pathway.md/diseases/rec8oldky8LvB8hTJ 1/6 6/29/23, 5:54 AM Long QT syndrome Pathway 1. Screening and diagnosis Diagnostic criteria: As per ESC 2022 guidelines, diagnose long QT syndrome with either QTc 480 ms in repeated 12-lead ECGs with or without symptoms or long QT syndrome diagnostic score > 3. B Show 2 more As per EHRA 2013 guidelines: Diagnose long QT syndrome in the presence of the following: long QT syndrome risk score 3.5 in the absence of a secondary cause for QT prolongation and/or unequivocally pathogenic mutation in one of the long QT syndrome genes or QT interval corrected for HR using Bazett's formula (QTc) 500 ms in repeated 12-lead ECG and in the absence of a secondary cause for QT prolongation. B Consider diagnosing long QT syndrome in the presence of a QTc of 480-499 ms in repeated 12-lead ECGs in patients with unexplained syncope in the absence of a secondary cause for QT prolongation and in the absence of a pathogenic mutation. C 2. Classification and risk stratification Risk assessment: As per ESC 2022 guidelines, consider calculating the arrhythmic risk before initiation of therapy based on the genotype and duration of QTc interval in patients with long QT syndrome. C As per EHRA 2013 guidelines, refer patients with long QT syndrome wishing to engage in competitive sports to a clinical expert for risk assessment. A 3. Diagnostic investigations Electrocardiogram: consider obtaining ambulatory ECG monitoring, exercise treadmill testing, and/or recording the ECG lying and immediately on standing for establishing a diagnosis and monitoring the response to therapy in patients with suspected long QT syndrome. C Epinephrine challenge testing: do not obtain routine epinephrine challenge testing in patients with long QT syndrome. D Genetic testing: As per ESC 2022 guidelines, obtain genetic testing and provide genetic counseling in patients with clinically diagnosed long QT syndrome. B As per AHA 2018 guidelines: Provide genetic counseling and obtain genetic testing in patients with clinically diagnosed long QT syndrome. B Provide genetic counseling and obtain mutation-specific genetic testing in first-degree relatives of patients having a causative mutation for long QT syndrome. B https://web.pathway.md/diseases/rec8oldky8LvB8hTJ 2/6 6/29/23, 5:54 AM Long QT syndrome Pathway As per HRS 2011 guidelines, obtain comprehensive or LQT1-3 (KCNQ1, KCNH2, and SCN5A) targeted long QT syndrome genetic testing in any patient with an established strong clinical index of suspicion for long QT syndrome based on clinical history, family history, and expressed ECG (resting 12-lead ECGs and/or provocative stress testing with exercise or catecholamine infusion). A Show 4 more 4. Diagnostic procedures Electrophysiology study: As per ESC 2022 guidelines, do not obtain invasive electrophysiologic testing in patients with long QT syndrome. D As per AHA 2018 guidelines, do not obtain electrophysiologic testing for risk stratification for ventricular arrhythmia in patients with long QT syndrome. D 5. Medical management Avoidance of triggers/aggravators: As per ESC 2022 guidelines, avoid using QT-prolonging drugs in patients with QT syndrome. Avoid and correct electrolyte abnormalities. Avoid genotype-specific triggers for arrhythmias. D As per GINA 2022 guidelines, obtain an ECG for long QTc before initiating long-term azithromycin in patients with persistent symptomatic asthma, and reassess after a month on treatment. B As per AAN 2019 guidelines, monitor QTc interval when prescribing ER guanfacine in patients with a history of cardiac conditions, taking other QT-prolonging agents, or with a family history of long QT syndrome. A As per AHA 2018 guidelines, do not use QT-prolonging medications in patients with long QT syndrome. D As per EHRA 2013 guidelines: Avoid using QT-prolonging drugs in all patients with long QT syndrome. D Identify and correct electrolyte abnormalities likely to occur during diarrhea, vomiting, metabolic conditions, or imbalanced diets for weight loss. A Beta-blockers: As per ESC 2022 guidelines: Initiate -blockers, ideally nonselective -blockers (nadolol or propranolol), to reduce the risk of arrhythmic events in patients with long QT syndrome with documented QT interval prolongation. B Consider initiating -blockers in patients with a pathogenic mutation and a normal QTc interval. C https://web.pathway.md/diseases/rec8oldky8LvB8hTJ 3/6 6/29/23, 5:54 AM Long QT syndrome Pathway As per AHA 2018 guidelines, initiate -blockers in patients with long QT syndrome with a resting QTc > 470 ms. B Show 4 more As per ESC 2018 guidelines, initiate -blocker therapy, if not contraindicated, as a first-line therapy in patients with long QT syndrome and suspected arrhythmic syncope. A As per EHRA 2013 guidelines: Initiate -blocker therapy in asymptomatic patients with long QT syndrome with QTc 470 ms. A Consider initiating -blocker therapy in asymptomatic patients with long QT syndrome with QTc 470 ms. B Initiate -blocker therapy in symptomatic patients with long QT syndrome with syncope or documented VT/VF. A Sodium channel blockers: As per ESC 2022 guidelines, initiate mexiletine in patients with long QT syndrome type 3 with a prolonged QT interval. B As per EHRA 2013 guidelines, consider initiating sodium channel blockers as add-on therapy in patients with long QT syndrome type 3 with a QTc > 500 ms shortening the QTc by > 40 ms following an acute oral drug test with one of these compounds. C Intravenous magnesium: consider administering magnesium for the treatment of polymorphic VT associated with a long QT interval (torsades de pointes). C 6. Therapeutic procedures Implantable cardioverter-defibrillator: As per ESC 2022 guidelines, perform ICD placement in addition to -blockers in patients with long QT syndrome in cardiac arrest. B Show 3 more As per AHA 2018 guidelines, perform ICD placement, left cardiac sympathetic denervation, and/or initiate additional medications (guided by consideration of the particular long QT syndrome type) for intensification of therapy in high-risk patients with symptomatic long QT syndrome, if -blocker therapy is ineffective or not tolerated. B Show 2 more As per ESC 2018 guidelines, consider performing ICD placement in patients with long QT syndrome and suspected arrhythmic syncope on -blocker therapy or intolerant to -blocker therapy. C As per EHRA 2013 guidelines, perform ICD placement in patients with long QT syndrome survived a cardiac arrest. A Show 2 more 7. Surgical interventions https://web.pathway.md/diseases/rec8oldky8LvB8hTJ 4/6 6/29/23, 5:54 AM Long QT syndrome Pathway Left cardiac sympathetic denervation: As per ESC 2022 guidelines: Perform left cardiac sympathetic denervation in patients with symptomatic long QT syndrome when: ICD therapy is contraindicated or declined patient is on -blockers and genotype-specific drugs with an ICD and experiences multiple shocks or syncope due to ventricular arrhythmia. B Consider performing either ICD placement or left cardiac sympathetic denervation in patients with symptomatic long QT syndrome when -blockers and genotype-specific therapies are not tolerated or contraindicated at therapeutic doses. C As per AHA 2018 guidelines, perform left cardiac sympathetic denervation, ICD placement, and/or initiate additional medications (guided by consideration of the particular long QT syndrome type) for intensification of therapy in high-risk patients with symptomatic long QT syndrome, if -blocker therapy is ineffective or not tolerated. B Show 2 more As per ESC 2018 guidelines, consider performing left cardiac sympathetic denervation in patients with long QT syndrome and recurrent syncope of suspected arrhythmic mechanism failed or intolerant to -blocker therapy. C As per EHRA 2013 guidelines: Perform left cardiac sympathetic denervation in high-risk patients with long QT syndrome if ICD therapy is contraindicated or refused and/or -blockers are either not effective in preventing syncope/arrhythmias, not tolerated, not accepted, or contraindicated. A Consider performing left cardiac sympathetic denervation in patients with long QT syndrome experiencing breakthrough events while on therapy with -blockers/ICD. C Clinical findings Symptoms Past medical history Palpitations Andersen-tawil syndrome Pre-syncope Brugada syndrome Syncope Hypothyroidism Timothy syndrome Vital signs Cardiac exam Bradycardia body temperature Cardiac arrest Lab findings ECG findings Hypocalcemia Prolonged QT interval Hypokalemia Prolonged QTc interval Hypomagnesemia Ventricular arrhythmia https://web.pathway.md/diseases/rec8oldky8LvB8hTJ 5/6 6/29/23, 5:54 AM Long QT syndrome Pathway Genetic testing Kcnh2 gene mutation Kcnq1 gene mutation Scn5a gene mutation References 1. Katja Zeppenfeld, Jacob Tfelt-Hansen, Marta de Riva et al. 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J. 2022 Aug 26;ehac262. Open 2. Silvia G Priori, Arthur A Wilde, Minoru Horie et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm. 2013 Dec;10 12 1932 63. Open 3. Sana M Al-Khatib, William G Stevenson, Michael J Ackerman et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2018 Sep 25;138 13):e272-e391. Open 4. Michael J Ackerman, Silvia G Priori, Stephan Willems et al. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society HRS and the European Heart Rhythm Association EHRA . Heart Rhythm. 2011 Aug;8 8 1308 39. Open 5. Pringsheim T, Okun MS, M ller-Vahl K et al. Practice guideline recommendations summary: Treatment of tics in people with Tourette syndrome and chronic tic disorders. Neurology. 2019 May 7;92 19 896 906. Open 6. Ashish R Panchal, Jason A Bartos, Jos G Caba as et al. Part 3 Adult Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2020 Oct 20;142 16_suppl_2 S366 S468. Open 7. Michele Brignole, Angel Moya, Frederik J de Lange et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J. 2018 Jun 1;39 21 1883 1948. Open 8. Global Initiative for Asthma. Global strategy for asthma management and prevention. GINA. 2022. Open 9. P J Schwartz, A J Moss, G M Vincent et al. Diagnostic criteria for the long QT syndrome. An update. Circulation. 1993 Aug;88 2 782 4. Open https://web.pathway.md/diseases/rec8oldky8LvB8hTJ 6/6