Abstract
Background
Isoproterenol, a non-specific beta agonist, is commonly used during electrophysiology studies (EPS). However, with the significant increase in the price of isoproterenol in 2015 and the increasing number of catheter ablations performed, the cost implications cannot be ignored. Dobutamine is a less expensive synthetic compound developed from isoproterenol with a similar mechanism to enhance cardiac conduction and shorten refractoriness, thus making it a feasible substitute with a lower cost. However, the use of dobutamine for EPS has not been well-reported in the literature.
Objective
To determine the site-specific effects of various doses of dobutamine on cardiac conduction and refractoriness and assess its safety during EPS.
Methods
From February 2020 to October 2020, 40 non-consecutive patients scheduled for elective EPS, supraventricular tachycardia, atrial fibrillation, and premature ventricular contraction ablations at a single center were consented and prospectively enrolled to assess the effect of dobutamine on the cardiac conduction system. At the end of each ablation procedure, measures of cardiac conduction and refractoriness were recorded at baseline and with incremental doses of dobutamine at 5, 10, 15, and 20 mcg/kg/min. For the primary analysis, the change per dose of dobutamine from baseline to each dosing level of dobutamine received by the patients, comparing atrioventricular node block cycle length (AVNBCL), ventricular atrial block cycle length (VABCL) and sinus cycle length (SCL), was tested using mixed-effect regression. For the secondary analysis, dobutamine dose level was tested for association with relative changes from baseline of each electrophysiologic parameter (SCL, AVNBCL, VABCL, atrioventricular node effective refractory period (AVNERP), AH, QRS, QT, QTc, atrial effective refractory period (AERP), ventricular effective refractory period (VERP), using mixed-effect regression. Changes in systolic and diastolic blood pressures were also assessed. The Holm-Bonferroni method was used to adjust for multiple testing.
Results
For the primary analysis there was no statistically significant change of AVNBCL and VABCL relative to SCL from baseline to each dose level of dobutamine. The SCL, AVNBCL, VABCL, AVNERP, AERP, VERP and the AH, and QT intervals all demonstrated a statistically significant decrease from baseline to at least one dose level with incremental dobutamine dosing. Two patients (5%) developed hypotension during the study and one patient (2.5%) received a vasopressor. Two patients (5%) had induced arrhythmias but otherwise no major adverse events were noted.
Conclusion
In this study, there was no statistically significant change of AVNBCL and VABCL relative to SCL from baseline to any dose level of dobutamine. As expected, the AH and QT intervals, and the VABCL, VERP, AERP and AVNERP all significantly decreased from baseline to at least one dose level with an escalation in dobutamine dose. Dobutamine was well-tolerated and safe to use during EPS.
Similar content being viewed by others
Data Availability
The participants of this study did not give written consent for their data to be shared publicly, so due to the sensitive nature of the research, supporting data is not available.
References
Zipes DP, DiMarco JP, Jackman WM, et al. ACC/AHA Task Force Report: Guidelines for Clinical Intracardiac Electrophysiological and Catheter Ablation Procedures. J Am Coll Cardiol. 1995;26(2):555–73.
D’Silva A, Wright M. Advances in imaging for atrial fibrillation ablation. Radiol Res Pract. 2011;2011:714864.
Khot UN, Vogan ED, Militello MA. Nitroprusside and Isoproterenol Use after Major Price Increases. N Engl J Med. 2017;377(6):594–5. https://doi.org/10.1056/NEJMc1700244.
Knight BP. The rising costs of isoproterenol. EP Lab Dig. 2013;17(3).
Tuttle RR, Mills J. Dobutamine: development of a new catecholamine to selectively increase cardiac contractility. Circ Res. 1975;36(1):185–96.
Vanegas DI, Perez CDJ, Montenegro JDJ, et al. Dobutamine use for arrhythmia induction during electrical programmed heart stimulation. Rev Colomb Cardiol. 2006;12(7):479–83.
Cossú SF, Rothman SA, Chmielewski IL, Hsia HH, Vogel RL, Miller JM, Buxton AE. The effects of isoproterenol on the cardiac conduction system: site-specific dose dependence. J Cardiovasc Electrophysiol. 1997;8(8):847–53. https://doi.org/10.1111/j.1540-8167.1997.tb00845.x.
Cismaru G. Arrhythmia induction in the EP lab. 1st ed. Cham, Switzerland: Springer Nature Switzerland AG;2019:71-86.
Gianni C, Sanchez JE, Mohanty S, Trivedi C, Della Rocca DG, Al-Ahmad A, Burkhardt JD, Gallinghouse GJ, Hranitzky PM, Horton RP, Di Biase L, Natale A. High-Dose Dobutamine for Inducibility of Atrial Arrhythmias During Atrial Fibrillation Ablation. JACC Clin Electrophysiol. 2020;6(13):1701–10. https://doi.org/10.1016/j.jacep.2020.07.018.
Piérard LA, Berthe C, Albert A, Carlier J, Kulbertus HE. Haemodynamic alterations during ischaemia induced by dobutamine stress testing. Eur Heart J. 1989;10(9):783–90. https://doi.org/10.1093/oxfordjournals.eurheartj.a059571.
Lu D, Greenberg MD, Little R, Malik Q, Fernicola DJ, Weissman NJ. Accelerated dobutamine stress testing: safety and feasibility in patients with known or suspected coronary artery disease. Clin Cardiol. 2001;24(2):141–5. https://doi.org/10.1002/clc.4960240208.
Mazeika PK, Nadazdin A, Oakley CM. Dobutamine stress echocardiography for detection and assessment of coronary artery disease. J Am Coll Cardiol. 1992;19(6):1203–11. https://doi.org/10.1016/0735-1097(92)90325-h.
Burger AJ, Notarianni MP, Aronson D. Safety and efficacy of an accelerated dobutamine stress echocardiography protocol in the evaluation of coronary artery disease. Am J Cardiol. 2000;86(8):825–9. https://doi.org/10.1016/s0002-9149(00)01100-0.
Masoni A, Alboni P, Malacarne C, Codeca L. Effects of dobutamine on electrophysiological properties of the specialized conduction system in man. J Electrocardiol. 1979;12(4):361–70. https://doi.org/10.1016/s0022-0736(79)80004-7.
Bianchi C, Diaz R, Gonzales C, Beregovich J. Effecto of dobutamine on atrioventricular conduction. Am Heart J. 1975;90(4):474–8.
Dahlberg P, Diamant U, Gilljam T, Rydberg A, Bergfeldt L. QT correction using Bazett’s formula remains preferable in long QT syndrome type 1 and 2. Ann Noninvasive Electrocardiol. 2021;26:12804.
Northwell Health Pharmacy Department. Contracted Price for Isoproterenol and Dobutamine in 2023.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Ethical approval
This study was approved by the Institutional Review Board (IRB #: 19–0934) of Northwell Health and exempted from the investigational new drug (IND) based upon a Food and Drug Administration (FDA) review. This study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.
Informed consent
this study was obtained from all participants included in the study.
Conflict of interest
There was no outside funding for this study. The authors did not receive support from any organization for the submitted work.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Ismail, H., Gabriels, J.K., Chang, D. et al. Site-specific effects of dobutamine on cardiac conduction and refractoriness. J Interv Card Electrophysiol 67, 71–82 (2024). https://doi.org/10.1007/s10840-023-01573-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10840-023-01573-1