Retraction: The following abstract from the Physiology 2016 meeting, Dublin, Ireland published as Proc Physiol Soc 37 PCB010 has been retracted by agreement between the authors and The Physiological Society:
High-dose Isoprenaline Infusion as a method of arrhythmia induction in man; a placebo controlled experiment in humans with varying arrhythmic risk
- W. Bowers, M. R. Ginks, K. Rajappan, Y. Bashir, R. N. Balasubramaniam, M. Sopher, T. R. Betts, J. R. Paisey
The abstract has been retracted for the following reason:
The study (NRES ref: 14/SC/1171) was inspected as part of a routine Medicines and Healthcare Products Regulatory Agency (MHRA) Good Clinical Practice (GCP) inspection at the Royal Bournemouth Hospital in July 2018 as the Sponsor for the study. It was identified that the control mechanisms in place to protect the blinding for the study were insufficient. The study cannot therefore be described as being conducted in a double-blind fashion as is described in the abstract.
Isoprenaline has long been used, in conjunction with pacing manoeuvres, to induce arrhythmia in patients as part of clinical cardiac electrophysiology procedures. More recently, high-dose isoprenaline infusion alone has been reported to be effective for induction of the arrhythmia atrial fibrillation(1). Studies suggesting this have failed to exclude confounding factors and are subject to significant selection bias making their conclusions difficult to interpret when considering the use of the technique in clinical practice. These experiments robustly characterise, against placebo, the ability of an infusion of isoprenaline to induce an episode of arrhythmia in man. Consenting human volunteers were administered intravenous infusions of high-dose isoprenaline or placebo in a double blind fashion (NRES ref. 14/SC/1171). Subjects were randomised in blocks based on their background susceptibility to spontaneous atrial fibrillation defined by prior history. Interim analysis results are presented. 115 study infusions (50 isoprenaline, 65 placebo) were delivered to 74 subjects. High-dose isoprenaline (up to 25 mcg/min) was found to be safe and well tolerated with no statistically significant difference between placebo and active drug arms when comparing the number of infusions which needed to be discontinued prematurely for safety or participant comfort reasons (p=0.079). 8 of the 16 high susceptibility participants in the isoprenaline arm of the study experienced an episode of atrial fibrillation during the infusion protocol. This compared to none from the 18 participants in the placebo arm (p=0.001, 95% CI for difference in proportion 21.8% to 72%). In the low susceptibility participants there was no difference between the isoprenaline and placebo arms in the proportion of subjects who experienced an episode of either atrial fibrillation (p=1.000) or any arrhythmia (p=1.000) during the infusion. Using inducibility by isoprenaline infusion as a test for atrial fibrillation would have a sensitivity of between 28% and 72%, a specificity of between 80.6% and 100%, a positive predictive value of between 67.6% and 100% and a negative predictive value of between 46.7% and 82%. These data demonstrate, with the most robust scientific method, that an infusion of high-dose isoprenaline is able to provoke an episode of atrial fibrillation in a proportion of individuals with high susceptibility to that arrhythmia. However, that proportion is likely to be lower than previously suggested. The high specificity and positive predictive value of provocation of atrial fibrillation by isoprenaline infusion mean that it may have a future role as part of a screening tool for the arrhythmia especially where there is clinical suspicion but a lack of electrocardiographic evidence.