Effects of onabotulinumtoxinA on cardiac function following intradetrusor injections

Abstract

OnabotulinumtoxinA intradetrusor injections are considered a highly effective localized therapy for refractory detrusor overactivity. However, despite evidence for distant systemic effects of onabotulinumtoxinA, little is known on potential systemic side effects following intradetrusor injections. Given that onabotulinumtoxinA is a highly potent toxin this is an important safety issue specifically with regard to repeat injections and parallel treatments with botulinum toxin. Hence, it was the purpose of this prospective study to investigate, using heart rate variability (HRV) analysis, whether onabotulinumtoxinA causes systemic effects on cardiac function following intradetrusor injections. Patients with neurogenic detrusor overactivity (NDO) and age-matched healthy controls were recruited. Concomitant medication and diseases affecting the cardio-vascular system were exclusion criteria. A 3-channel resting electrocardiogram (ECG) was recorded in supine position for 15min during four consecutive visits: 1) 2weeks prior onabotulinumtoxinA intradetrusor injections, 2) 10min prior injections, 3) 30min after injections, and 4) 6weeks after injections. NDO patients received intradetrusor injections (300units Botox®) between visits 2 and 3. The control group had no intervention. Short-term (5min) HRV analysis included assessment of frequency and time domain parameters. Statistical analysis was performed using ANOVA with repeated measures and the t-test. Due to multiple comparisons, α was corrected to 0.0125 (Bonferroni method). Twelve healthy volunteers (5♀, 7♂; 46±12years old) and 12 NDO patients (5♀, 7♂; 46±13years old) completed all measurements. Comparing both groups, resting heart rate was significantly higher in the patients group at visit 4 only. No further significant differences in time and frequency domain parameters were discovered. Within the NDO group, standard deviation of the normal to normal intervals (SDNN) in the ECG demonstrated a significant decrease (1.70 to 1.53ms, p=0.003) from visit 3 to 4, whereas the total power (TP) significantly increased (3.05 to 3.29ms², p=0.009) from visit 2 to 3. This increase subsided until visit 4.

Study limitations: single treatment investigation under resting conditions only. In conclusion, onabotulinumtoxinA intradetrusor injections do not seem to affect resting state cardiac function. Short-term changes such as total power might rather result from natural cardio-vascular responses to the procedure itself (e.g. discomfort, stress). Further detailed investigations also under physical stress and repeated injections are necessary to fully exclude systemic cardiac side effects of onabotulinumtoxinA intradetrusor injections.

Keywords: Autonomic cardiac function; Botulinum toxin; Heart rate variability; Intradetrusor injections; Neurogenic detrusor overactivity; Spinal cord injury; Systemic side effects; onabotulinumtoxinA.