Diagnosis, management and therapeutic strategies for congenital long QT syndrome

Abstract

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. Growing insights into the genetic background and pathophysiology of LQTS has led to the identification of genotype–phenotype relationships for the most common genetic subtypes, the recognition of genetic and non-genetic modifiers of phenotype, optimisation of risk stratification algorithms and the discovery of gene-specific therapies in LQTS. Nevertheless, despite these great advancements in the LQTS field, large gaps in knowledge still exist. For example, up to 25% of LQTS cases still remain genotype elusive, which hampers proper identification of family members at risk, and it is still largely unknown what determines the large variability in disease severity, where even within one family an identical mutation causes malignant arrhythmias in some carriers, while in other carriers, the disease is clinically silent. In this review, we summarise the current evidence available on the diagnosis, clinical management and therapeutic strategies in LQTS. We also discuss new scientific developments and areas of research, which are expected to increase our understanding of the complex genetic architecture in genotype-negative patients, lead to improved risk stratification in asymptomatic mutation carriers and more targeted (gene-specific and even mutation-specific) therapies.

Acquired Long QT Syndrome (LQTS) Secondary to Electrolyte Imbalance: A Case Report

“…The long QT syndrome (LQTS) is a type of cardiac arrhythmia syndrome characterized with impaired ventricular repolarization manifest as prolongation of QT interval on the ECG [1,2]. This predisposes to the development risk of syncope, ventricular arrhythmias, seizure, and cardiac death to the patient [1,3,4]. LQTS can caused by two conditions, such as inherited disorder in which there are genes changes or mutations of cardiac ion channels on cardiac myocyte and acquired in which malfunction of the cardiac ion channels is caused by medication or electrolyte imbalance, especially hypokalemia, hypomagnesemia, and hypocalcemia [1,3,4,6].…”

“…The long QT syndrome (LQTS) is serious cardiac arrhythmia disorder that driving reason of unexpected cardiac death, characterized with impaired ventricular repolarization manifest as prolongation of the QT interval on the electrocardiogram (ECG) [1,2]. This condition caused by hereditary disorder in sodium and potassium channels on cardiac myocyte and acquired caused by drugs or electrolyte imbalance, especially hypokalemia, hypomagnesemia, and hypocalcemia result in abnormality on the ECG examination as QT interval prolongation and may increase risk of syncope, ventricular arrhythmias, seizure, and cardiac death to the patient [1,3,4]. Long QT syndrome incidences is approximately about 1 in 10.000 to 15.000 peoples and female is more prevalent [5].…”

Left cardiac sympathetic denervation and device implantation in congenital long QT syndrome -- A case series and review.

“…Last but not the least, these devices can reliably identify the cardiac rhythm during future episodes of syncope, if any, and guide further therapy in them. The importance of pacing therapy is being relooked recently with available mounting evidence 19,20 Hence, in patients where ICD implantation is not an optimal therapy possible (reasons provided earlier), epicardial PPI is an effective alternative. The beneficial effects of pacing in high-risk LQTS patients probably relate to the prevention of bradycardia, pauses, and the shortening of long QT intervals -factors that are known to be arrhythmogenic in this syndrome 3 .…”

Critical Appraisal of Cenobamate as Adjunctive Treatment of Focal Seizures in Adults

“…Changes in the QT interval are associated with an increased risk of fatal arrhythmias. 28,29 For this reason, from 2005, formal studies (placebo and active drug-controlled studies conducted in healthy volunteers) are required to evaluate the effect of therapeutic and supratherapeutic doses of any new agent on ECG during clinical drug development. 30 Several ASMs, mainly those that target sodium channels, may alter cardiac repolarization.…”