The silent storm: Quinine-induced Torsade de Pointes unmasking a latent KCNH2 variant

Abstract

Quinine, a Cinchona alkaloid and a cornerstone of malaria therapy in resource-limited settings, produces predominant sodium-channel blockade alongside modest inhibition of the rapid delayed-rectifier potassium current (IKr). Although generally safe at the population level, even modest IKr blockade can precipitate life-threatening Torsade de Pointes (TdP) in patients with severely impaired repolarization reserve. We report an 8-year-old boy with severe Plasmodium falciparum malaria who, on the third day of intravenous quinine, developed profound QTc prolongation (730 ms) followed by recurrent TdP. This arose from the convergence of quinine-induced IKr inhibition, hypokalaemia (K 2.9 mmol/L), and an underlying pathogenic KCNH2 variant, which together exhausted repolarization reserve. Although initially haemodynamically stable, the patient's extreme electrical instability proved a sentinel event, prompting identification of latent Long QT Syndrome type 2 (LQT2).

The case highlights the importance of ECG monitoring and electrolyte correction during quinine therapy. It illustrates how drug-induced arrhythmia can represent the phenotypic unmasking of diminished repolarization reserve, in which a pharmacological trigger exposes a silent genetic substrate—here necessitating lifelong beta-blocker therapy and family cascade screening to prevent sudden cardiac death.