Noura Darwish, PhD & Miley Nguyen, PharmD
- Supraventricular tachycardia (SVT) is a common arrhythmia requiring medical intervention.
- Treatment with antiarrhythmic drugs is often unpredictable, with a high variability in patient response and risk of adverse effects.
- Pharmacogenomics offers a path to personalize SVT treatment by considering genetic factors that affect how individuals respond to medications.
Supraventricular tachycardias (SVTs) are a type of arrhythmia that cause rapid heart rhythms (Mayo Clinic, 2025). Symptoms may include a racing heartbeat, palpitations, shortness of breath, chest discomfort, and occasional fainting. While SVTs are often manageable, their treatment is complicated by individual variability in disease susceptibility and drug response. Pharmacogenomics (PGx) examines how variations in a person’s genetic makeup affect their response to medications. Applying the PGx approach to SVT care could increase treatment effectiveness, reduce the likelihood of side effects, and support more personalized cardiac care.
PGx-guided dosing helps optimize medications like flecainide. Flecainide is a potent Class IC agent for SVT that can be life-saving but carries a risk of toxicity. It is primarily metabolized by the polymorphic CYP2D6 enzyme (Palmen et al., 2023). Patients with certain CYP2D6 genotypes that cause them to clear flecainide more slowly may experience higher drug levels and potential toxicity. International guidelines now recommend starting flecainide at 50–75% of the usual dose and closely monitoring drug levels in the blood and ECGs in these patients (Palmen et al,. 2024).
Furthermore, variants in cardiac ion channels and regulatory genes such as SCN5A (encoding the cardiac sodium channel) have been linked to SVT risk. An SCN5A mutation might predispose someone to arrhythmia and signals a higher proarrhythmic potential if flecainide is given (Palmen et al., 2023). Recognizing such genetic factors enables a more informed choice of therapy for each individual patient.
Despite these insights, PGx testing remains underutilized in SVT care, and clinical guidelines are limited. Incorporating SVT-relevant genetic markers into PGx testing panels could help bridge this gap offering clinicians a safer, effective, and individualized treatment.
- Mayo Clinic. Supraventricular tachycardia: Diagnosis & treatment. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/supraventricular-tachycardia/diagnosis-treatment/drc-20355249. Accessed July 3, 2025.
- Palmen R, Sandritter T, Malloy-Walton L, Follansbee C, Wagner JB. Case report: Use of therapeutic drug monitoring and pharmacogenetic testing as opportunities to individualize care in a case of flecainide toxicity after fetal supraventricular tachycardia. Front Pediatr. 2023;11:1168619. Published 2023 Jun 28. doi:10.3389/fped.2023.1168619
- Palmen R, Walton M, Wagner J. Pediatric flecainide pharmacogenomics: a roadmap to delivering precision-based care to pediatric arrhythmias. Front Pharmacol. 2024;15:1477485. doi:10.3389/fphar.2024.1477485