Factors associated with clinically diagnosed long QT syndrome in Korean adults: a nationwide case-control study

Long QT syndrome (LQTS) is a major substrate for malignant ventricular arrhythmias, yet population-level evidence on its clinical, pharmacological and metabolic correlates in Asian adults remains limited.

Using Korean National Health Insurance Service claims linked to national health screening data (2012-2022), we conducted a 1:1 age- and sex-matched case-control study to characterize factors associated with LQTS in a nationwide adult population. Cases were identified by LQTS-related diagnostic codes with concurrent electrocardiographic procedure claims, and controls were individuals without any arrhythmia diagnosis. Adjusted odds ratios (aORs) with 95% confidence intervals were estimated by multivariable conditional logistic regression for comorbidities, QT-prolonging drug exposure, and metabolic and laboratory factors, with prespecified subgroup analyses by sex and age.

The study included 335,693 cases and 335,693 matched controls (mean age 54.6 years; 48.6% male). Cardiovascular comorbidities, including chronic heart failure and peripheral arterial disease, were among the factors most strongly associated with LQTS. The strength of association increased progressively with the number of concurrently used QT-prolonging drugs, with aORs of 6.70, 11.63 and 15.08 for one, two, and three or more drugs, respectively. Hyperkalaemia, calcium imbalance, central obesity, elevated blood pressure, dyslipidaemia and impaired renal function were also independently associated with LQTS. Associations with hyperkalaemia and thyroid dysfunction were numerically stronger in women, and the drug-related gradient was steepest in older adults.

These nationwide findings characterize the comorbidity, electrolyte and cumulative drug-exposure factors associated with clinically diagnosed LQTS in Korean adults, and may complement Western-derived tools such as CredibleMeds to inform population-specific pharmacovigilance of QT-prolonging drugs.