Association of common QT-prolonging medications with arrhythmic risk in patients with bundle branch block: A stratified cohort analysis in left bundle branch block vs. right bundle branch block phenotypes

BACKGROUND: Bundle branch block (BBB) affects 11-17% of adults over 80 and is associated with mortality and heart failure. Conventional QTc formulae overestimate repolarization in wide QRS complexes, with clinicians holding symptom-management therapies based on inaccurate measurements. OBJECTIVES: This retrospective study utilized the MIMIC-IV database to examine arrhythmogenic risk by drug class and BBB phenotype. METHODS: Adult ICU admissions with BBB were stratified by drug exposure: amiodarone, high-risk anti-arrhythmics (sotalol, dofetilide, procainamide, ibutilide, quinidine, disopyramide), and common non-cardiac QT-prolonging agents (haloperidol, ondansetron, quetiapine, methadone, levofloxacin, azithromycin). The primary outcome was a composite of ventricular arrhythmia and cardiac arrest; a sensitivity analysis restricted to ventricular arrhythmia was performed. Propensity score matching (1:1) with time-varying Cox regression addressed confounding and immortal time bias. RESULTS: The matched cohort included 1722 admissions (LBBB =1252; RBBB =470). Common non-cardiac agents were not associated with the composite outcome in LBBB (HR 0.96, p = 0.83) or RBBB (HR 0.61, p = 0.24; 28 events, hypothesis-generating). Amiodarone was associated with the composite (LBBB: HR 3.63, p < 0.01; RBBB HR: 3.90, p < 0.01), but not the LBBB sensitivity analysis (HR 1.61, p = 0.19), suggesting confounding by indication. Among patients with QTc >500 ms, common agents remained non-significant. CONCLUSION: Common non-cardiac QT-prolonging medications were not associated with increased risk in patients with BBB, even with prolonged QTc. The divergence between composite and sensitivity results for amiodarone highlights the influence of confounding by indication. Medication alerts should incorporate stratification by drug class rather than QTc alone.