Heart rate control in paediatric coronary CT angiography using phenylephrine

Abstract

Aims

Obtaining images of diagnostic quality using coronary CT angiography (CCTA) depends, in part, upon a patient’s heart rate (HR) at time of scanning. HR reduction is most commonly achieved with beta blockers. In the paediatric population, the effectiveness of beta blockers is limited by hypotensive effects. Phenylephrine, a pure alpha agonist, raises blood pressure and causes reflex bradycardia so it could be used to reduce patients’ HRs.

Methods and results

We retrospectively reviewed all children at a single centre who underwent sedated CCTA study using phenylephrine between 2019 and 2024. In 25 children (mean age 5.3 ± 2.5 years), HR was reduced from a mean of 94.1 to 73.8 beats per minute (bpm). No adverse effects were reported. Images of diagnostic quality were obtained in all patients.

Conclusion

In this first-of-its-kind study we found that phenylephrine was effective at reducing patients’ HRs prior to CCTA, with an average reduction of 20 bpm.

Graphical Abstract

Graphical Abstract.

(A) Schematic illustration of the mechanism of action of phenylephrine, a selective alpha adrenergic agonist which induces systemic vasoconstriction via activation of alpha-1-adrenergic receptors resulting in increased arterial blood pressure. This pressor response is sensed by carotid baroreceptors and triggers a compensatory, parasympathetically medicated reflex bradycardia. Illustration created with Canva graphic design platform (Canva Pty Ltd., Sydney, Australia). (B) Paired heart rate measurements at baseline and at coronary CT angiography acquisition following phenylephrine administration. Each line represents an individual patient. Phenylephrine exposure was associated with a significant reduction in heart rate (P = 0.0002).

Background

Coronary CT angiography (CCTA) has become an essential tool for the diagnosis of coronary artery disease. Obtaining diagnostic quality images of the coronary arteries on CCTA is facilitated by a slow and regular heart rate (HR), with increased HR being associated with worse image quality.¹

Society of Cardiovascular Computed Tomography recommendations for CCTA in patients with congenital heart disease (CHD) suggest considering beta blockade in paediatric patients to decrease HR.² Beta-blocking agents have preferential effects on beta-1 adrenoreceptors resulting in reduced cardiac contractility and HR. However, utilizing beta blockers for HR control can induce hypotension, particularly in paediatric patients who generally have lower blood pressures (BP) and higher heart rates than adults, and can be contraindicated in some patients with CHD.

Phenylephrine is a pure alpha agonist with minimal effects on beta-adrenergic activity.³ Acting primarily on alpha-1 adrenergic receptors, phenylephrine induces systemic vasoconstriction; the resulting rise in BP stimulates carotid baroreceptors, triggering a compensatory reflex bradycardia mediated by the parasympathetic nervous system (Graphical Abstract A). Despite its pressor effects, phenylephrine has a net neutral impact on coronary arterial tone, as its weak direct coronary vasoconstriction is compensated for by local metabolite mediated vasodilation.⁴ Both the anti-hypotensive and bradycardic effects of phenylephrine may be uniquely suited for CCTA. However, beyond a single case report,⁵ no literature has characterized the efficacy of phenylephrine in the paediatric population undergoing CCTA.

Methods

All paediatric patients who underwent CCTA with phenylephrine between January 2019 and May 2024 at Columbia University Irving Medical Center were retrospectively included in this study. Patients were excluded if they lacked: (i) a baseline recorded HR or BP prior to anaesthesia medication administration, (ii) HR or BP measurement after administration of medications or (iii) were sedated prior to the CCTA encounter. All patients who underwent CCTA and received phenylephrine during the trial period were sedated.

As this was a retrospective trial, no standardized protocol for medication administration was in place. Phenylephrine dose and method of administration, as well as exposure to other medications with potential HR-modifying effects—including dexmedetomidine, esmolol and propofol—were recorded for each patient. Patients were scanned on GE LightSpeed VCT XTe, Revolution, or Discovery CT750 HD scanners. Scans were prospectively ECG-gated (70-80 kV, 145–450 mA).

The primary outcome was change in HR from baseline to HR at time of CCTA acquisition and was compared using paired t-tests. Sub analysis was performed to compare change in HR between bolus and infusion groups. To determine whether change in HR was a result of factors other than phenylephrine administration, linear regression modelling of change in HR as a function of baseline HR, age, esmolol, dexmedetomidine and propofol exposure was performed. Statistical analysis was performed with RStudio (Posit, Boston, MA). The study was approved by Columbia University’s institutional review board.

Results

Twenty-five patients (5.3 ± 2.5 years) with mean baseline HR of 94.1 ± 24.3 were included in the analytic cohort (Table 1). Phenylephrine administration was found to result in a significant mean paired reduction of 20.3 bpm (P = 0.0002, Graphical Abstract B) corresponding to a HR of 73.8 ± 14.4 bpm. When patients were stratified by phenylephrine administration, the mean change in HR was −14.2 bpm for bolus dosed patients and −24.3 bpm for those who received infusion dosing; however, the magnitude of HR reduction did not differ significantly between bolus and infusion administration (P = 0.25).

Table 1.

Patient characteristics, hemodynamics and phenylephrine dosing

Patient characteristics and hemodynamics	Mean (SD)
Age, year	5.3 (2.5)
Baseline Heart Rate, bpm	94.1 (24.3)
Baseline Systolic BP, mmHg	104.9 (13.2)
Baseline Diastolic BP, mmHg	63.7 (13.4)
Post-phenylephrine Systolic BP, mmHg	102.6 (12.9)
Post-phenylephrine Diastolic BP, mmHg	62.1 (15.7)
Heart Rate at CCTA, bpm	73.8 (14.4)
Phenylephrine Dosing
Phenylephrine Bolus Dose	12.6 (13.3)
Phenylephrine Infusion Dose (mL/h)	5.4 (5.7)

bpm, beats per minute; BP, blood pressure; CCTA, coronary CT angiography; SD, standard deviation.

As part of their anaesthesia protocols, patients also received concomitant HR affecting medications, including dexmedetomidine in 21/25 patients (84%), propofol in 17/25 (68%), and esmolol in 15/25 (60%). In adjusted analyses including these medications, none were independently associated with HR change following phenylephrine administration (all P > 0.20), while higher baseline HR remained the dominant determinant of significant HR reduction (Figure 1).

Figure 1.

Adjusted effects on heart rate changes from baseline to CT. Forest plot showing adjusted effect estimates for variables associated with change in heart rate (ΔHR, baseline to CT scan acquisition) among patients receiving phenylephrine. Negative values indicate a greater reduction in HR. The model was adjusted for age, baseline HR, and exposure to esmolol, dexmedetomidine, and propofol. Baseline HR was the strongest independent predictor of HR reduction, whereas exposure to other HR–active medications was not significantly associated with ΔHR.

No reported adverse effects were reported for any patient in the study including bradycardia, reflex hypertension or arrhythmia. No significant differences were found in systolic and diastolic blood pressures before and following phenylephrine administration. All scans were of diagnostic quality.

Discussion

Paediatric patients are challenging to image with CCTA due to high HR and increased HR variability, particularly in patients with underlying CHD.⁶ In this non-randomized, retrospective study, we found: (ⅰ) phenylephrine was effective in achieving target HR, (ⅱ) no statistical difference was reported in mode of phenylephrine administration and (ⅲ) no adverse safety events occurred.

In this first-of-its-kind study analyzing use of phenylephrine in a population of paediatric patients, we found that HR was reduced on average by 20 bpm without any compromise in patient safety. Importantly, no statistical differences between modes of administration in phenylephrine allows for flexibility in clinical implementation of using phenylephrine in patients undergoing CCTA.

The present study is not without limitations. Our data were obtained retrospectively without randomization. Moreover, our sample size was relatively small, which could have prevented finding significance. Our patient population was primarily composed of younger patients, and further work is needed to examine its use in older children and non-sedated children. Nevertheless, this is the first study to date to examine the use of phenylephrine for pre-CCTA HR reduction in paediatric patients and we have demonstrated that phenylephrine was effective in lowering HR without the need for additional beta blockade.

Conclusions

Obtaining adequate HR control in paediatric patients who at baseline often have high HRs is difficult. This study has demonstrated the efficacy of phenylephrine use in these patients achieving an average reduction of 20 bpm prior to CCTA. Future studies building on this are needed to characterize the optimal approach for HR control in paediatric CCTA and compare the additive values of premedication with beta blockers, phenylephrine and other agents such as ivabradine, which has only been studied in adults.⁷

Author contributions

Yosef A Cohen (MD, MS (Conceptualization [supporting]; Data curation [equal]; Formal analysis [equal]; Methodology [equal]; Writing—original draft [equal]; Writing—review & editing [equal])), Luca Bremner (BA (Writing—original draft [equal])), Mrinali Shetty (MD (Writing—original draft [equal])), Charrisa Chou (BA (Writing—original draft [equal])), Michelle Castillo (BS (Data curation)), Margarita Chernovolenko (MD (Formal analysis)), Kanwal M Farooqi (MD (Formal analysis [equal]; Methodology [equal]), Amee M Shah (MD (Writing—review & editing [equal]), Anjali Chelliah (MD (Writing—review & editing [equal])), and Andrew Einstein (MD, PhD (Conceptualization [lead]; Data curation [lead]; Formal analysis [lead]; Methodology [lead]; Writing—original draft [lead]; Writing—review & editing [lead]))

Funding

The authors received no funding for the completion of this study.

Data availability

The data underlying this article cannot be shared publicly due to HIPAA-protected patient-level information but may be available from the corresponding author upon reasonable request and with appropriate institutional approvals.

Lead author biography

Andrew J. Einstein is a cardiologist, cardiac imager, and researcher at Columbia University Irving Medical Center and NewYork-Presbyterian Hospital. He serves as Director of Nuclear Cardiology, Cardiac CT, and Cardiac MRI, Director of the Advanced Cardiac Imaging Fellowship, and a tenured Professor of Medicine, with primary appointment in the Department of Medicine and secondary appointment in the Department of Radiology. Dr. Einstein's clinical activities are centered on cardiovascular PET, SPECT, CT, and MRI, and he serves on the attending physician staff in the Heart Institute. His research, which uses each of these modalities, focuses on improving the use of imaging in cardiovascular medicine, with particular interests and current funded projects in quality of healthcare, radiation safety, global health, amyloidosis, artificial intelligence, and device development. It is funded by multiple NIH grants, the International Atomic Energy Agency, and industry. Dr. Einstein is the author or coauthor of over 300 papers and abstracts, in leading journals including the New England Journal of Medicine, JAMA, Lancet, and Nature. For it, Dr. Einstein has received the American College of Cardiology's Douglas P. Zipes Distinguished Young Scientist Award, the Society of Nuclear Medicine and Molecular Imaging's Hermann Blumgart Award, the American Federation for Medical Research's Junior Physician Investigator Award, and the Lewis Katz Cardiovascular Research Prize for a Young Investigator, and has been elected to the American Society for Clinical Investigation and the Association of University Cardiologists. He is Chair of the Young Investigators Awards committee of the American College of Cardiology and President-Elect of the American Society of Nuclear Cardiology. Dr. Einstein has served as a mentor to over 50 trainees at various stages ranging from high school to junior faculty.