P rospective Clinical Trial Comparing IV Esmolol to IV Metoprolol in CT Coronary Angiography: Effect on Hemodynamic,Technical Parameters and Cost

Abstract

French

Background:

Intravenous [IV] esmolol, an alternative to IV metoprolol for coronary computed tomography angiography [CCTA], has shorter half-life that decreases the risk of prolonged hypotension. The primary aim was to prospectively compare IV esmolol alone to IV metoprolol alone for effectiveness in achieving heart rate [HR] of 60 beats per minute[bpm] during CCTA. The secondary aim was to compare hemodynamic response, image quality, radiation dose and cost.

Materials and Methods:

Institutional Review Board approved prospective randomized study of 28 CCTA patients medicated in a 1:1 blinded match with IV esmolol or IV metoprolol to achieve HR of 60 bpm. Serial hemodynamic response was measured at 6 specified times. Two cardiac radiologists independently scored the image quality.

Results:

Both IV esmolol and IV metoprolol achieved the target HR. IV esmolol resulted in significantly less profound and shorter duration of reduction in systolic blood pressure [BP] than IV metoprolol with a difference of -10, -14 and -9 mm Hg compared to -20, -26 and -25 mmHg at 2, 15 & 30 min respectively. No significant difference in HR at image acquisition, exposure window, radiation dose and image quality. Although IV esmolol was expensive, the overall cost of care was comparable to IV metoprolol due to shortened post CCTA observation period consequent to faster restoration of hemodynamic status.

Conclusion:

Comparison of IV esmolol and IV metoprolol demonstrate that both are effective in achieving the target HR but significantly faster recovery of HR and BP in patients who receive IV esmolol was found.

Keywords

esmolol CT coronary angiography metoprolol

Introduction

Coronary computed tomography angiography [CCTA] is established for non-invasive evaluation of coronary arteries in the appropriate clinical setting.¹ Many centres utilize metoprolol as the drug of choice for heart rate [HR] control during CCTA.^2,3 Intravenous [IV] metoprolol shortens the preparation time for CCTA, is effective and safe, even at high doses.⁴ CCTA is being increasingly used in diverse patient populations who are at risk of sustained bradycardia and hypotension such as elderly, debilitated patients and patients who have impaired cardiac output due to reduced ventricular function. Hence the long plasma half-life of 3-7 hours⁵ for IV metoprolol is of concern. IV esmolol is an attractive alternative to IV metoprolol due to a rapid onset of action of 1-4 minutes and a very short half-life of 4-9 minutes⁶ and has been shown to be effective and safe during CCTA.⁷ However, there has been no direct head to head comparison of these two drugs. The primary aim of this study was to prospectively compare the efficacy of IV esmolol alone to IV metoprolol alone in achieving a target HR of 60 bpm during CCTA. The secondary aims were to compare the HR and blood pressure [BP] response, image quality, patient radiation dose and overall cost of IV esmolol to IV metoprolol.

Materials and Methods

Patient Selection

The study was approved by the Institutional Research and Ethics Board and performed in the Department of Medical Imaging (BLINDED) from January 2017 to June 2017.Written informed consent was obtained from each patient by a study coordinator. Patients clinically referred for CCTA of native coronary arteries were prospectively randomized using a random number generator, to equal cohorts to either of the limb. The randomisation list was known only to a research assistant who was not involved in any other part of the study. Patients were blinded to which beta blocker was administered. The staff supervising the CCTA examination was aware of which drug was administered, but was not involved in any other aspect of the study. Patients were included if they were aged ≥ 18 years, had a HR >60 bpm, had sinus rhythm and normal renal function. Patients were excluded if they were already taking an oral beta blocker or had contraindications to beta blockers,⁸ had a baseline HR <60 bpm, systolic BP < 100 mmHg, or uncontrolled atrial fibrillation. Each patient completed the six item Spielberger State-Trait Anxiety Inventory (STAI) self-evaluation questionnaire prior to the procedure.⁹ This was done to compare both patient cohorts for anxiety levels prior to CCTA. In brief, the STAI has six questions; three questions address high anxiety levels and 3 questions assess low anxiety levels. Each question is scored from 1- 4 where a score of 1 represents strong disagreement and a score of 4 represents strong agreement with a given high or low anxiety level statement.

Heart Rate Control

All patients received standard instructions and preparation for CCTA. Once the patient was on the CT table, an 18-gauge IV cannula was placed in a right antecubital vein and three precordial leads were attached and adjusted to maximize the ECG signal. The baseline blood pressure (BP #1) and heart rate (HR#1) were automatically taken and recorded. Patients with HR ≤ 60 bpm were excluded from the study. Patients who were randomized to receive IV metoprolol, received a slow IV bolus of 5 mg over 2 minutes, with a repeat dose of 5 mg every 4 minutes until the target HR of 60 bpm was achieved or until a maximum of 40 mg had been given. Patients randomized to receive IV esmolol were given a slow IV bolus of 100 mg and repeat aliquots of 100 mg over 2 minutes, every 2 minutes until the HR of 60 bpm was reached or a maximum dose of 400 mg had been given. A self-inflating cuff on the left upper arm automatically monitored the systemic blood pressure and HR every 60 s during IV beta blocker administration, to ensure that the systolic BP was maintained >100 mmHg. Following this, 0.3 mg of sublingual nitroglycerine was given for coronary vasodilation. Subsequently BP #2, HR #2, were recorded after the administration of beta blocker and BP #3 and HR #3 were recorded during image acquisition. Following the CCTA, the patient was observed by a nurse for 30 minutes, or until hemodynamic status was restored, and vital signs were monitored. The HR (# 4, 5, 6) and BP (# 4, 5, 6) were taken and recorded at 2 minutes, 15 minutes and 30 minutes respectively following CCTA. The patient was discharged as soon as they felt well and in the absence of systemic hypotension. The cost of the IV beta blocker and the overall cost of care were calculated for each group. The algorithm of patient selection and HR control is summarized in Figure 1.

Figure 1.

Algorithm of patient selection, beta blocker administration and monitoring of HR & BP for CT Coronary Angiogram.

Image Acquisition

All CCTA studies were performed on a wide volume multidetector computed tomography [MDCT] scanner (Aquilion ONE, Canon Medical Systems, Ottawa, Japan) using 280-320 x 0.5 mm detectors and a standard procedure for x-ray dose adaptation to individual patient body habitus to ensure diagnostic image quality.¹⁰ All scans were acquired using prospective ECG gated image acquisition with x-ray exposure window being automatically optimized to the patient’s HR using pre-determined manufacturer settings. 50-70 ml of iodinated, non-ionic water-soluble contrast medium (Iopromide 370 mg iodine/mL) was power injected at 4.5-5.0 mL/s, determined by patient bodyweight, followed by a 20 ml saline push. Image acquisition was triggered using a contrast threshold technique in the descending aorta initiated by a luminal contrast threshold of +130 HU at 120 kV, ensuring acquisition at peak arterial opacification.

Image Analysis

Two radiologists with 3 and 7 years of reading CCTA were blinded to the type of beta blocker administered, and independently scored the image quality of the CCTA. Image quality was analysed using an 18 segment model,^11,12 0.5/0.3 mm trans-axial images, multiplanar reconstructions and curved planar reformatted images. The image quality of each segment was evaluated using a 4 point scale¹³ where 4 = excellent (excellent attenuation of vessel lumen and clear vessel definition with barely perceived image noise), 3 = good (good attenuation of vessel lumen and well- maintained vessel wall definition with minimal image noise), 2 = fair (some limitation in vessel wall definition and contrast resolution with moderate image noise that would affect diagnosis) and 1= poor (impaired image quality with severe image noise). Prior to image analysis, both radiologists participated in a calibration session during which they evaluated a separate series of 10 CCTA examinations that had been independently selected to demonstrate image quality scores from 1-4. Excellent intra observer and interobserver agreement was observed in these assessments. These CCTA studies did not form part of the trial. The number of analysable segments in any particular CCTA was multiplied with a maximum image quality score of 4, to obtain the maximum possible CCTA score for that study. Missing segments or segments smaller than 1.5 mm diameter were excluded from image analysis. Total score for each CCTA was calculated by adding the individual segment quality scores. Diagnostic score for each CCTA is obtained on dividing total score obtained by the maximum possible score for that CCTA (for example, in a CCTA with 17 analysable segments, maximum possible CCTA score is 68. If the total score obtained is 62, then diagnostic score is 62 / 68 = 0.91). Hence the maximum diagnostic score for any CCTA was 1. The mean image quality score per coronary artery segment for each patient was calculated from the separate radiology reads. The nomenclature of the segments was defined by consensus between both radiologists in cases with congenitally abnormal coronary arteries.

Radiation Dose

The x-ray tube exposure parameters (kVp, mAs) were determined by patient body habitus, the x-ray exposure window varied with the patient’s heart rate and the scan length varied with the z-axis length of the heart. Together these parameters determined the dose length product [DLP] in mGy.cm, that was recorded from the CT console. The effective dose was calculated as the product of the DLP and an organ weighting factor of 0.014.^14,15

Cost

Although the cost of the IV esmolol was higher than that of IV metoprolol, the cost of nursing supervision in the recovery room following CCTA were less for IV esmolol with a mean cost of $51.15 (30.6) in Canadian dollars [CAD] compared to the mean cost of IV metoprolol CAD $56.79 (20.6) due to faster restoration of hemodynamic status. Therefore, the overall cost of care was comparable for both medications.

Statistical Analysis

The sample size was calculated at 90% power. All continuous variables were assessed for normal distribution and presented as mean ±standard deviation and categorical variables represented as median (interquartile range [IQR]). The difference of the mean between the groups was calculated using the independent T- test. Chi square and Fischer’s exact test were used to determine the significance of the relationship between categorical variables. Cohen’s kappa was calculated to assess the interobserver agreement. A p value of <0.05 was considered statistically significant. Statistical analysis was performed using SPSS version 16.0 for Windows (SPSS, Chicago, IL).

Results

Baseline Characteristics

A total of 28 patients (15 men, 53%), with 14 patients in each arm, were included in the study. The median (IQR) age of the cohort was 53.5 years (16 years). There was no significant difference in age, gender or ethnicity between the two groups as shown in Table 1. There was no statistically significant difference in the pre procedure low anxiety score between the two groups. The high anxiety score was higher in the metoprolol group than in the esmolol group, but this was not statistically significant. The mean (standard deviation [SD]) dose of IV esmolol and IV metoprolol used in this study was 217.86 mg (132.44 mg) and 26.79 mg (15.01 mg) respectively.

Table 1.

Comparison of Demographic Characteristics, Radiation Dose, Image Quality, Cost of Beta Blocker Between the IV Esmolol and IV Metoprolol Cohorts.

Demographic Characteristics	Entire cohort	Esmolol group (n=14)	Metoprolol group (n=14)	P value
Age [Mean(SD)]	55.18(12.63) Median:53.5 IQR:16	54(12.89)	56.36(12.72)	0.63
Gender	Females:13 Males:15	Females:6 Males:8	Females:7 Males:7	0.144
Race	White: 23 South Asian: 4 Caribbean:1	White: 11 South Asian: 2 Caribbean:1	White: 12 South Asian: 2	0.999
Low Anxiety score	9.29 (2.43)	9.64 (2.65)	8.93 (2.23)	0.448
High anxiety score	4.86 (1.84)	4.21(1.42)	5.5 (2.02)	0.064
Dose length product(mGy.cm)	384.13 (192.82)	404.25 (192.46)	364.04 (198.25)	0.591
Effective radiation dose(mSv)	5.37 (2.69)	5.65 (2.69)	5.09 (2.77)	0.591
Average dose (mg)		217.86 (132.43)	26.79 (15.01)	< 0.001
Cost of beta blocker alone used for CCTA (CAD)	18.59 (11.96)	23.25 (13.77)	13.92 (7.8)	0.039
Cost of beta blocker + cost of nursing care and observation during recovery	54.07 (25.56)	51.15 (30.6)	56.79 (20.6)	0.584
Image quality score for entire study(maximum possible score =1)		0.91(0.05)	0.92(0.94)	0.801

^a CAD –Canadian dollar

Hemodynamic Parameters

A comparison of the hemodynamic response in the IV esmolol group and IV metoprolol cohort is presented in Table 2. Although the IV metoprolol patients had higher BP and HR at baseline, the response to IV beta blockade was comparable with 15 subjects (54%) achieving a target HR of 60 bpm at the time of image acquisition; 7 patients (50%) received IV esmolol and 8 patients (57%) received IV metoprolol. There was no significant difference in the mean (SD) HR between the groups, at the time of image acquisition; esmolol: 64 (7); metoprolol: 62 (8) (p =0.45) [Figure 2]. Both IV esmolol and IV metoprolol resulted in a similar reduction in systolic BP of 11-12 mmHg prior to CCTA. IV esmolol resulted in a significant (p < 0.05) and quicker restoration of baseline systolic BP than IV metoprolol with a difference (baseline - time point) of -10, -14 and -9 mmHg compared to -20, -26 and -25 mmHg at 2, 15 and 30 min respectively. There was also quicker restoration of baseline heart rate in the IV esmolol group compared to the IV metoprolol group with a difference (baseline – time point) of -0.4, -0.5 and -0.5 bpm compared to -12, -11 and -13 bpm respectively at 2, 15 and 30 mins respectively. At 2 minutes, 12 (84%) patients in the IV esmolol group had restoration of the baseline HR compared to 4 (28%) patients in the IV metoprolol group, and at 30 minutes, 13 (93%) patients in the IV esmolol group had restoration of baseline HR compared to 5 (36%) patients in the IV metoprolol group. No adverse event occurred in either group.

Table 2.

Comparison of Mean of Hemodynamic Parameters Between the Groups.

Hemodynamic parameters	Esmolol group (n=14)	Metoprolol group (n=14)	p value
Baseline
Systolic BP	129 (12)	142 (25)	0.111
Diastolic BP	76 (8)	81 (11)	0.247
Heart rate	72 (7)	80 (13)	0.06
After administration of beta blocker
Systolic BP	117 (10)	131 (21)	0.039
Diastolic BP	74 (9)	78 (9)	0.184
Difference in systolic BP	-12 (10)	-11 (10)	0.713
Difference in diastolic BP	-3 (4)	-2 (7)	0.867
Heart rate	66 (9)	66 (8)	0.931
Difference in heart rate	-6 (10)	-15 (9)	0.022
At the time of image acquisition
Heart rate	64 (7)	62 (8)	0.45
Difference in heart rate	-9 (7)	-19 (11)	0.006
2 minutes post CCTA
Systolic BP	119 (17)	122 (9)	0.674
Diastolic BP	68 (9)	71 (8)	0.287
Difference in systolic BP	-10 (14)	-20 (12)	0.066
Difference in diastolic BP	-8 (6)	-9 (8)	0.741
Heart rate	72 (7)	68 (7)	0.161
Difference in heart rate	-0.4 (6)	-12 (11)	0.002
15 minutes post CCTA
Systolic BP	115 (12)	115 (20)	0.982
Diastolic BP	69 (9)	69 (8)	0.892
Difference in systolic BP	-14 (13)	-26 (17)	0.039
Difference in diastolic BP	-7 (4)	-11 (9)	0.17
Heart rate	73 (8)	69 (11)	0.307
Difference in heart rate	0.4 (6)	-11 (12)	0.003
30 minutes post CCTA
Systolic BP	120 (14)	116 (19)	0.548
Diastolic BP	70 (7)	69 (7)	0.708
Difference in systolic BP	-9 (11)	-25 (15)	0.003
Difference in diastolic BP	-6 (6)	-11 (9)	0.077
Heart rate	72 (9)	68 (10)	0.241
Difference in heart rate	0.5 (5)	-13 (11)	0.002

Figure 2.

Heart rate at image acquisition of CCTA in two groups.

Comparison of heart rate, systolic BP and diastolic BP between the two groups at baseline, after administration of IV beta-blocker, at the time of image acquisition (for HR only), 2 min, 15 min and 30 min after CCTA image acquisition with confidence intervals are demonstrated in Figure 3A-C.

Figure 3.

A, B, C, Comparison of the hemodynamic response to IV esmolol group and IV metoprolol. A, Comparison of mean heart rate with confidence intervals between the two groups at baseline, after administration of IV beta-blocker, at the time of image acquisition (for HR only), 2 mins, 15mins and 30 mins after CCTA image acquisition. B, Comparison of mean systolic BP with confidence intervals between the two groups at baseline, after administration of IV beta-blocker, 2 min, 15mins and 30 mins after CCTA image acquisition. C, Comparison of mean diastolic BP with confidence intervals between the two groups at baseline, after administration of IV beta-blocker, 2 min, 15mins and 30 mins after CCTA image acquisition.

Radiation Dose

The x-ray exposure windows used in these patient cohorts were determined by the manufacturer settings according to the patient HR and included the following ranges: 73-77%, 70-80%, 60-80%, 40-80% and 35-80% phases of the R-R interval. The 70-80% exposure window was used in 57% of the IV esmolol group and in 64% of the IV metoprolol group as demonstrated in Figure 4, with no significant difference between the two groups (p =0.81) . The mean (SD) radiation dose (mGy.cm) and the mean (SD) effective radiation dose (mSv) received by the IV esmolol patients was 404 (192) mGy.cm and 5.7(2.3) mSv; and by the IV metoprolol patients was 364 (198) mGy.cm and 5.1(2.7) mSv respectively, with no significant difference between the two groups (p= 0.59).

Figure 4.

Exposure window used during image acquisition in two groups.

Image Quality

113 (22%) coronary segments from a total of 504 potential segments were excluded from the study as they were absent or too small to analyse (<1.5 mm). All of the evaluated coronary segments were of diagnostic image quality. There was no significant difference in the image quality of the coronary segments between the two groups with mean (SD) diagnostic scores for esmolol of 0.912 (0.05) and for metoprolol of 0.919 (0.94) as shown in Table 3. There was moderate to strong inter observer agreement in the image quality scoring between the two radiologists. There was a statistically significant strong inter observer agreement, in the following coronary segments: left main, proximal RCA, the first and second diagonal branches, the second obtuse marginal branch and the ramus intermedius.

Table 3.

Image Quality Score Between the Two Groups and Interobserver Agreement for the Cohort.

Segments	Esmolol group (Median [IQR])	Metoprolol group (Median [IQR])	p value	Interobserver agreement	p value
Proximal RCA	4 (0)	4 (0)	0.828	0.711	< 0.001
Mid RCA	3.5 (0)	3.75 (1)	0.15	0.579	< 0.001
Distal RCA	4 (1)	4 (0)	0.999	0.765	< 0.001
RPDA	3.5 (0)	4 (1)	0.288	0.6	0.001
RPLB	4 (1)	4 (1)	0.555	0.661	0.001
Left main	4 (0)	4 (0)	0.999	1	< 0.001
Proximal LAD	4 (0)	4 (0)	0.481	0.627	< 0.001
Mid LAD	4 (0)	4 (0)	0.834	0.521	0.006
Distal LAD	3.25 (1)	3.75 (1)	0.999	0.675	< 0.001
D1	3.5 (1)	4 (1)	0.44	0.708	< 0.001
D2	3 (1)	3.5 (0.5)	0.087	0.72	< 0.001
Proximal LCx	4 (0)	4 (0)	0.999	0.523	0.026
Mid/Distal LCx	3.5 (1)	4 (0.5)	0.151	0.592	< 0.001
OM1	4 (1)	4 (1)	0.999	0.564	0.006
OM2	3.75 (1)	4 (0)	0.765	0.75	< 0.001
LPDA	-	-	-	1	< 0.001
LPLB	-	-	-	1	< 0.001
Ramus Intermedius	3.75 (1)	3.75 (1)	0.524	0.849	0.002
Diagnostic score [Mean(SD)]	0.912 (0.05)	0.919 (0.94)	0.801

^a RCA – right coronary artery; ^bRPDA – right posterior descending artery; ^cRPLB – right posterolateral branch; ^dLAD – left anterior descending artery; ^eD1 – first diagonal branch; ^fD2 –second diagonal branch; ^gLCx- left circumflex artery; ^hOM1- first obtuse marginal branch; ⁱOM2 - second obtuse marginal branch; ^jLPDA – left posterior descending artery; ^kLPLB – left posterolateral branch

Discussion

This is the first prospective randomized control trial to compare the clinical effectiveness and image quality of IV esmolol alone to IV metoprolol alone, without prior administration of oral beta blocker, for CCTA. This study has highlighted that both medications have comparable efficacy in achieving the target heart rate of 60 bpm but that the significantly shorter half-life of IV esmolol results in a faster restoration of heart rate and systolic blood pressure towards baseline values.

Intersubjective variability in the effectiveness of beta blockers has been previously described¹⁶ and ethnic background has been demonstrated to influence the responsiveness to oral beta blockers predominantly due to variation in liver activation of the inactive oral compound.¹⁷ The IV preparation does not have similar limitations.

There are two previous studies that have demonstrated the safety and efficacy of using IV esmolol in achieving a target heart rate for CCTA.^18,7 Degertekin et al [18] performed CCTA in 391 patients using 64 MDCT and IV esmolol with retrospective data acquisition. The target heart rate of 65 bpm was achieved in 52% of the patients using a mean (SD) dose of 158 mg (55 mg) of IV esmolol with a mean effective radiation dose of 5.7 (2.3) mSv. Wang J D [6] performed CCTA in 232 patients using a dual source CT system and IV esmolol. In their study, the target heart rate of 65 bpm was achieved in 85% of the patients using a mean (SD) dose of 57.26 (15.39) mg of IV esmolol with a mean effective radiation dose of 2.28 (0.02) mSv. In both of these studies, the safety of IV esmolol was established in a large cohort of patients, however neither study provided a head-head comparison of IV metoprolol to IV esmolol.

The current study demonstrated a significantly faster restoration of the baseline hemodynamic parameters in the IV esmolol group compared to the IV metoprolol group. The difference between the baseline heart rate and heart rate at 30 mins after CCTA showed a significantly prolonged bradycardia (<60 bpm) in 2 (14%) patients in the IV metoprolol group compared to none in the IV esmolol group with a mean heart rate of 68 bpm in the IV metoprolol group compared to 72 bpm in the IV esmolol group at 30 minutes. There was prolonged hypotension (systolic BP < 100 mmHg) in 3 patients (21%) in the IV metoprolol group compared to none in the IV esmolol group. In a larger cohort study of 1871 patients done to assess the safety of IV metoprolol in CCTA, one patient had an adverse event requiring hospital admission.^19,20 Sustained and symptomatic bradycardia has been reported following the administration of IV metoprolol.^20,21 For the majority of patients having CCTA, the difference in hemodynamic response between IV esmolol and IV metoprolol is unlikely to be clinically significant; however, for elderly patients and patients with impaired left ventricular function who are at increased risk of falling from the dampened systolic BP and heart rate recovery, IV esmolol may provide a safer alternative to IV metoprolol due to the quicker restoration of baseline hemodynamic parameters.

In the current study, both IV beta blockers were equally effective in achieving the target heart rate at the time of image acquisition. This is contrary to the study by Maurovich-Horvat et al,²¹ where 89% of patients receiving IV esmolol achieved the target heart rate of 65 bpm compared to 78% of patients given IV metoprolol. The dose of IV esmolol used was 100-500 mg with a mean (SD) dose of 325.6 (158.4) mg compared to 5- 20 mg of IV metoprolol with a mean dose of 10.7 (6.3) mg. The dose of IV esmolol used was higher compared to the current study (217.86 [132.44] mg) whereas the dose of IV metoprolol was lower compared to the current study (26.79 [15.01] mg).

In the current study, although the heart rate at the time of image acquisition was similar in both groups, the reduction in HR from baseline was more pronounced in the IV metoprolol group compared to the IV esmolol cohort due to a higher pre-study HR in the metoprolol group. This could be related to the higher pre-test anxiety scores in the metoprolol group.

Although the shorter half-life of IV esmolol is favoured for improved patient safety from reduced risks of hypotension and bradycardia following CCTA, the shorter duration of action necessitates that the CCTA scan is performed during the peak action time of IV esmolol and necessitates an efficient clinical operation.

The mean patient radiation dose in the current study was slightly higher than previous studies which were performed using a similar CT platform.^22,23 This difference is likely to reflect a difference in the body habitus of the study population and a difference in heart rate at the time of image acquisition. Twenty-one per cent of the current study population had a heart rate above 70 bpm at the time of image acquisition resulting in a wider exposure window; a multi heart beat acquisition was used in 8 patients. Tomizawa et al recorded a similar experience using 320 MDCT to perform cardiac CT in 123 patients with 23 (18.6%) patients requiring multiple heart beat acquisitions due to a heart rate >75 bpm.²⁴ In the current study, all of the examinations were of diagnostic image quality despite the high heart rate in one fifth of the patient cohort.

There are a few limitations to this study. The trial was performed in a single tertiary centre, hence multi centre trial will be required for further validation of results. The study has a relatively smaller sample size; and a larger patient cohort may produce different results. The sample size might affect the power to detect a statistically significant difference in the acquisition time HR between IV metoprolol and IV esmolol cohorts. We believe that this difference would not be clinically significant as the haemodynamic responses observed during this study are as expected from the known pharmacokinetics of the medications and in line with previous publications.

Conclusion

IV esmolol and IV metoprolol are equally effective in achieving a target heart rate of 60 bpm for CCTA but there is a significantly faster recovery of heart rate and systolic blood pressure in patients who receive IV esmolol. There is no significant difference in the image quality and radiation dose from use of the two medications. The shorter recovery time for restoration of hemodynamic status with IV esmolol is reflected in a reduced cost of nursing care for post procedural observation. Hence, IV esmolol can be used as a safer, cost effective alternative to IV metoprolol while performing CCTA in patients at risk of prolonged bradycardia and hypotension.

Footnotes

Authors’ Note

Leena Robinson Vimala is also affiliated with Department of Radiology, Christian Medical College, Vellore, Tamil Nadu, India.

Acknowledgements

The authors acknowledge the cardiothoracic imaging fellows and technologists in CT Cardiac suite of Toronto General Hospital, for their help and support during the research.

Authors acknowledge the technologists in cardiac CT suite in Toronto General Hospital for their help during the research.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Leena Robinson Vimala, DMRD, MD

References

Taylor

Cerqueira

Hodgson

, et al. Accf/scct/acr/aha/ase/asnc/scai/scmr 2010 appropriate use criteria for cardiac computed tomography. A report of the American college of cardiology foundation appropriate use criteria task force, the society of cardiovascular computed tomography, the American college of radiology, the American heart association, the American society of echocardiography, the American society of nuclear cardiology, the society for cardiovascular angiography and interventions, and the society for cardiovascular magnetic resonance. Circulation 2010;122(21): e525–e555. Corrected version Circulation 2010;122(25):e642–e643.

Jiménez-Juan

Nguyen

Wintersperger

, et al. Failed heart rate control with oral metoprolol prior to coronary CT angiography: effect of additional intravenous metoprolol on heart rate, image quality and radiation dose. Int J Cardiovasc Imaging 2013;29(1):199–206.

Abbara

Blanke

Maroules

, et al. SCCT guidelines for the performance and acquisition of coronary computed tomographic angiography: a report of the society of cardiovascular computed tomography guidelines Committee: Endorsed by the North American Society for Cardiovascular Imaging (NASCI). J Cardiovasc Comput Tomogr 2016;10(6):435–449.

Kassamali

Kim

Patel

, et al. Safety of an i.v. β-adrenergic blockade protocol for heart rate optimization before coronary CT angiography. AJR Am J Roentgenol 2014;203(4):759–762.

Pannu

Alvarez

Jr Fishman

. Beta-blockers for cardiac CT: a primer for the radiologist. AJR Am J Roentgenol 2006;186(6): S341–S3455.

Sabarudin

Sun

. Beta-blocker administration protocol for prospectively ECG-triggered coronary CT angiography. World J Cardiol 2013;5(12):453–458.

Wang

J-D

Zhang

H-W

Xin

, et al. Safety and efficacy of intravenous esmolol before prospective electrocardiogram-triggered high-pitch spiral acquisition for computed tomography coronary angiography. J Geriatr Cardiol. 2014;11(1):39–43.

Kassamali

Kim

Patel

, et al. Safety of an i.v. β-adrenergic blockade protocol for heart rate optimization before coronary CT angiography. AJR Am J Roentgenol 2014;203(4):759–762.

Marteau

Bekker

. The development of a six-item short-form of the state scale of the Spielberger State—Trait Anxiety Inventory (STAI). Br J Clin Psychol. 1992;31(3):301–306.

10.

Odedra

Blobel

Alhumayyd

Jimenez-Juan

Durand

Paul

. Image noise-based dose adaptation in dynamic volume CT of the heart: dose and image quality optimisation in comparison with BMI-based dose adaptation. Eur Radiol. 2014;24(1):86–94.

11.

Raff

Abidov

Achenbach

, et al. SCCT guidelines for the interpretation and reporting of coronary computed tomographic angiography. J Cardiovasc Comput Tomogr. 2009;3(2):122–136.

12.

Achenbach

Paul

Laurent

, et al. Comparative assessment of image quality for coronary CT angiography with iobitridol and two contrast agents with higher iodine concentrations: iopromide and iomeprol. A multicentre randomized double-blind trial. Eur Radiol. 2017;27(2):821–830.

13.

Rybicki

Otero

Steigner

, et al. Initial evaluation of coronary images from 320-detector row computed tomography. Int J Cardiovasc Imaging. 2008;24(5):535–546.

14.

Tomizawa

Maeda

Akahane

, et al. Coronary CT angiography using the second-generation 320-detector row CT: assessment of image quality and radiation dose in various heart rates compared with the first-generation scanner. Int J Cardiovasc Imaging. 2013;29(7):1613–1618.

15.

Hausleiter

Meyer

Hermann

, et al. Estimated radiation dose associated with cardiac CT angiography. JAMA. 2009;301(5):500–507.

16.

Jack

Quarterman

Zaman

Kendall

. Variability of beta-blocker pharmacokinetics in young volunteers. Eur J Clin Pharmacol. 1982;23(1):37–42.

17.

Zhou

Silberstein

Koshakji

Wood

. Interindividual differences in beta-receptor density contribute to variability in response to beta-adrenoceptor antagonists. Clin Pharmacol Ther. 1989;45(6):587–592.

18.

Degertekin

Gemici

Kaya

, et al. Safety and efficacy of patient preparation with intravenous esmolol before 64-slice computed tomography coronary angiography. Coron Artery Dis. 2008;19(1):33–36.

19.

Clayton

Raju

Roobottom

Morgan-Hughes

. Safety of intravenous β-adrenoceptor blockers for computed tomographic coronary angiography. Br J Clin Pharmacol. 2015;79(3):533–536.

20.

Khan

Cummings

Gutierrez

, et al. Contraindications and side effects of commonly used medications in coronary CT angiography. Int J Cardiovasc Imaging. 2011;27(3):441–449.

21.

Maurovich-Horvat

Károlyi

Horváth

, et al. Esmolol is noninferior to metoprolol in achieving a target heart rate of 65 beats/min in patients referred to coronary CT angiography: A randomized controlled clinical trial. J Cardiovasc Comput Tomogr. 2015;9(2):139–145.

22.

Wong

DTL

Soh

BSH

, et al. Superior CT coronary angiography image quality at lower radiation exposure with second generation 320-detector row CT in patients with elevated heart rate: a comparison with first generation 320-detector row CT. Cardiovasc Diagn Ther. 2014;4(4):299–306.

23.

Shen

Dai

Luo

, et al. Image quality and radiation dose of CT coronary angiography with automatic tube current modulation and strong Adaptive Iterative Dose Reduction Three-Dimensional (AIDR3D). PLoS One. 2015;10(11): e0142185.

24.

Tomizawa

Maeda

Akahane

Torigoe

Kiryu

Ohtomo

. Coronary CT angiography using the second-generation 320-detector row CT: assessment of image quality and radiation dose in various heart rates compared with the first-generation scanner. Int J Cardiovasc Imaging. 2013;29(7):1613–1618.