Long QT Syndrome

In a patient with syncope, polymorphic ventricular tachycardia, aborted cardiac arrest, or marked QT prolongation, obtain a 12-lead ECG and immediately review all prescribed, over-the-counter, and administered drugs for QT-prolonging exposure. Acquired long QT may result from medications, electrolyte abnormalities, eating disorders, coronary artery disease, and bradyarrhythmia; these conditions must be addressed before interpreting QTc as evidence of congenital LQTS. NatureNatureIon channel traffic jams: the significance of trafficking deficiency in long QT syndrome | Cell Discovery

Document the presenting rhythm whenever possible. Torsades de pointes is a diagnostic component of the Schwartz score, but do not double-count torsades and syncope in that score because they are mutually exclusive criteria. ScienceDirectScienceDirectQTc Interval - an overview A history of syncope during stress carries more diagnostic weight than syncope without stress, supporting an adrenergically mediated inherited arrhythmia phenotype. ScienceDirectScienceDirectQTc Interval - an overview

Patients with known or suspected congenital LQTS warrant particular caution with ondansetron and other QT-prolonging agents because congenital LQTS is a recognized substrate for drug-associated torsades. annemergmedannemergmedOndansetron and the Risk of Cardiac Arrhythmias If QT-prolonging therapy cannot be avoided, reassess the ECG and correct modifiable acquired factors before exposure.

Obtain a high-quality resting 12-lead ECG after reversible acquired causes have been addressed. Bazett correction is commonly used: QTc equals QT divided by the square root of the RR interval. ScienceDirect+1ScienceDirectQTc Interval - an overviewScienceDirectLong QT Syndrome and Perioperative Torsades de Pointes In pediatric diagnostic assessment, measure QT across multiple leads and average RR intervals over several beats; computer QT measurement is unreliable for this purpose. ScienceDirectScienceDirectRR Interval - an overview

Apply the Schwartz score only when ECG findings are not explained by medications or disorders that alter repolarization. QTc of at least 480 ms scores 3 points; QTc 460 to 470 ms scores 2 points; and QTc 450 ms scores 1 point. Torsades de pointes scores 2 points, T-wave alternans and notched T waves in three leads each score 1 point, and resting heart rate below the second percentile for age scores 0.5 point. ScienceDirectScienceDirectQTc Interval - an overview

A Schwartz score of 4 or greater indicates high probability, 2 to 3 intermediate probability, and 1 or less low probability of LQTS. ScienceDirectScienceDirectQTc Interval - an overview Clinical history modifies the result: stress-related syncope scores 2 points, nonstress syncope 1 point, congenital deafness 0.5 point, a family member with definite LQTS 1 point, and unexplained sudden death before age 30 years in an immediate family member 0.5 point. ScienceDirectScienceDirectQTc Interval - an overview

Do not dismiss a patient with a normal baseline QTc when the phenotype is compelling. Approximately 25% of patients with a pathogenic LQTS variant may have normal QTc intervals. ScienceDirectScienceDirectRR Interval - an overview Exercise testing or epinephrine infusion can support assessment of concealed LQTS, but neither provocative approach has adequate sensitivity or specificity to establish the diagnosis in isolation. ScienceDirectScienceDirectRR Interval - an overview

Prioritize the three major autosomal-dominant phenotypes—LQT1, LQT2, and LQT3—during inherited-arrhythmia assessment. LQT1 is associated with KCNQ1, LQT2 with KCNH2, and LQT3 with SCN5A; these three subtypes account for approximately 80% to 90% of LQTS cases. jacc+1jaccCongenital Long QT SyndromeNatureIon channel traffic jams: the significance of trafficking deficiency in long QT syndrome | Cell Discovery The remainder includes less common genes, while at least 30% of clinically clear LQTS can remain genotype-elusive. Nature+1NatureIon channel traffic jams: the significance of trafficking deficiency in long QT syndrome | Cell DiscoveryNatureClinical utility gene card for: Long-QT syndrome

Use the clinical trigger pattern to guide evaluation of a borderline phenotype. LQT1 commonly shows marked QTc prolongation with exercise, making exercise testing with extended recovery particularly useful when baseline ECG is nondiagnostic. ScienceDirectScienceDirectRR Interval - an overview LQT3 is linked to SCN5A and has bradycardia-triggered arrhythmia mechanisms, so review resting rate, sleep/rest events, and bradyarrhythmia as part of phenotype assignment. jaccjaccClinical Spectrum of SCN5A Mutations: Long QT Syndrome, Brugada Syndrome, and Cardiomyopathy

Order genetic testing in clinically probable LQTS and in selected high-suspicion concealed cases, with pre- and post-test counseling. A pathogenic variant can clarify diagnosis and permit cascade evaluation of relatives; however, a variant of uncertain significance does not independently establish disease, and a negative result does not exclude LQTS. Nature+1NatureClinical utility gene card for: Long-QT syndromeScienceDirectRR Interval - an overview Evaluate relatives of affected patients because phenotype may be absent at a single assessment despite genetic predisposition. cdn clinicaltrialscdn clinicaltrials1 IRAS: 330619 Version 4 Date: 02/04/2024

Initiate beta-blocker therapy for congenital LQTS as the core preventive treatment strategy; beta-blocker efficacy has been evaluated in high-risk LQT1 and LQT2 populations and is incorporated in U.S. ventricular-arrhythmia guidance. jaccjacc2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society In infants and children, the paradoxical use of beta-blockers for LQTS is specifically directed at prevention of ventricular arrhythmias. neoreviews aappublicationsneoreviews aappublicationsEvaluation and Management of Common Neonatal ... Select agent and dose through electrophysiology or inherited-arrhythmia care because the cited evidence does not provide a universal dose regimen.

Define a breakthrough cardiac event as syncope, sustained ventricular arrhythmia, aborted cardiac arrest, or other clinician-adjudicated LQTS-associated event occurring despite effective pharmacotherapy. Such events should trigger confirmation of adherence, reassessment for QT-prolonging drugs and acquired contributors, review of genotype and trigger pattern, and referral for treatment intensification. AHA Journals+2AHA JournalsLeft Cardiac Sympathetic Denervation Monotherapy in Patients With Congenital Long QT Syndrome | Circulation: Arrhythmia and ElectrophysiologyAHA JournalsLeft Cardiac Sympathetic Denervation Monotherapy in Patients With Congenital Long QT SyndromeNatureIon channel traffic jams: the significance of trafficking deficiency in long QT syndrome | Cell Discovery

For LQT3, mexiletine has gene-specific evidence for reducing arrhythmic events in affected patients. jaccjaccClinical Spectrum of SCN5A Mutations: Long QT Syndrome, Brugada Syndrome, and Cardiomyopathy Use this as genotype-directed management rather than empiric therapy for unclassified QT prolongation, and monitor treatment response within an inherited-arrhythmia program.

Construct a three-generation pedigree that specifically captures definite LQTS, unexplained sudden death before age 30 years, syncope, seizures of uncertain cause, and resuscitated cardiac arrest. The Schwartz score assigns points for definite LQTS in a family member and young unexplained sudden death in an immediate relative, making family history diagnostically consequential rather than merely descriptive. ScienceDirectScienceDirectQTc Interval - an overview

Offer clinical and genetic evaluation to relatives when a familial pathogenic variant or convincing clinical phenotype is present. Concealed inherited arrhythmia syndromes may remain undiagnosed because phenotype can be absent at the time of assessment, and LQTS may manifest around physiologic autonomic changes such as immediately after exercise. cdn clinicaltrialscdn clinicaltrials1 IRAS: 330619 Version 4 Date: 02/04/2024 Repeat phenotype assessment should be guided by age, symptoms, family genotype, and inherited-arrhythmia specialist recommendations.

Do not apply blanket sports exclusion solely from the diagnostic label. Return-to-play decisions for athletes with LQTS require individualized assessment within national and international guidance, integrating clinical events, treatment adherence, QT phenotype, genotype, sport setting, and emergency-action planning. jaccjaccReturn-to-Play for Athletes With Long QT Syndrome or Genetic Heart Diseases Predisposing to Sudden Death