Optimized heart rate for 320-row cardiac CT can be feasibly predicted from prescan parameters

Patients

This study was approved by the institutional review board, and was performed in accordance
with the ethical standards laid down in the 1964 Declaration of Helsinki and its later
amendments. The requirement for informed consent to participate in this study was
waived, because of the retrospective design. The patients’ records and information
were made anonymous before starting the analysis.

The records of 791 consecutive patients (470 men, 321 women; mean age 65.5 ± 13.9 years,
range 8–94 years) who underwent cardiac CT angiography from August 2011 to July 2013
were retrospectively reviewed. The patients were suspected of having coronary artery
disease, had a history of myocardial infarction, or had a complex cardiac anomaly.
The exclusion criteria were arrhythmia, such as atrial fibrillation and flutter (n = 43),
premature ventricular contraction during HR recording (n = 16), premature atrial contraction
during HR recording (n = 4), complete left bundle branch block (n = 4), complete right
bundle branch block (n = 1), proxysmal supraventricular tachycardia (n = 1), sick
sinus syndrome (n = 1), and sustained ventricular tachycardia (n = 1); presence of
pacemakers (n = 7); wide-volume scanning in patients who underwent coronary artery
bypass surgery (n = 88); expiratory scanning for ablation planning (n = 9); irregular
protocol for concurrent evaluation of the pulmonary artery or right ventricle (n = 8);
pediatric patients (n = 2); and inaccurate ECG-recording (n = 43).

The final study group included 563 patients (311 men, 252 women; mean age 65.2 ± 12.9 years,
age range 18–94 years; body weight 61.3 ± 14.4 kg, range 32–142 kg). Medications that
could possibly influence HRs were beta blockers in 290 patients (51.5 %), digitalis
derivatives in 110 patients (19.5 %), Calcium channel blockers in 86 patients (15.3 %),
nifedipine in 21 patients (3.7 %), anti-arrhythmcs in seven patients (1.2 %), and
alpha-blockers in three patients (0.5 %).

CT data acquisition

All examinations were performed by 320-detector CT scanner (Aquilion ONE Vision Edition:
Toshiba, Tochigi, Japan) with prospective ECG gating axial scans.

The scanning parameters were as follows: detector configuration, 320 × 0.5 mm; gantry
rotation time, 275, 300, 320 or 350 ms depending on breath hold HR; tube potential,
120 kV; and tube current, from at 250 to 760 mA depending on body habitus. Acquisition
window and number of scans were determined based on the experience of attending radiologists
(EM, NT, KY, and SK). Patients received 22.2 mgI/kg of Iopamidol 370 mgI/mL (Iopamiron
370: Bayer, Osaka, Japan); the mean volume administered was 45.7 ± 10.4 mL (range,
25–96 mL) over 14 s. Bolus tracking was performed using thresholds of 100 (HU) in
the left ventricle and 260HU in the descending aorta. Patients were assigned to breathe
in and hold their breaths after the first threshold. The scan was immediately started
after the second threshold.

As a baseline medication, oral ?-blocker was administered to 116 patients. For 173
outpatients with HRs higher than 75 bpm, 20–40 mg of metoprolol (Lopresor: Novartis,
Tokyo, Japan), was administered. The patients were instructed to take the medicines
2 h prior to the examination. In 2013, we started to use an intravenous ?-blocker,
landiolol at 0.125 mg/kg (Corebeta; Ono Pharmaceutical, Osaka, Japan) for patients
with HRs higher than 75 bpm. Eighteen patients received injection before the test
breath hold, and were scanned 4–7 min after injection. Before 2013, no additional
?-blocker was used when the HR was higher than 75 bpm at the time of the examination.
No patients who were administered ?-blockers had contraindications, such as hypotension,
more than grade II atrioventricular block, severe pulmonary hypertension causing right-sided
cardiac failure, severe cardiac failure, and allergy to ?-blockers. There were no
side effects from ?-blockers recorded. All patients received 2.5 mg sublingual isosorbide
dinitrate (Nitorol; Eisai, Tokyo, Japan) before imaging. No nitrates were administered
to patients with contraindications, such as severe hypotension, closed angle glaucoma,
and allergy to nitrates.

Acquisition of heart rate

HR was recorded in terms of RR interval on ECG (IVY Model 3000; Chronos, Chiba, Japan).
Mean HR during free breathing for 10 s (HRrest) was immediately recorded prior to
giving instructions for the test breath hold; the actual test breath hold lasted for
10 s. HRtest was defined as the average HR of four beats, with the first beat designated
as the one occurring at 5 s of the test breath hold. HRscan was defined as the average
HR of four consecutive beats, with the second beat corresponding to the first CT cardio
angiogram scan (Fig. 1).

Fig. 1. Definition of the four beats and the timing of exposure. HRscan was defined as the
average HR of consecutive four beats (arrow), with the second beat corresponding to the first CT cardio angiogram scan. The scan
duration took place during the RR interval within the gray box. The beginning of the scan was the left edge of the gray box, and the end of the scan was the right edge of the gray box

Statistical analysis

All statistical analyses were performed using JMP Pro software (version 10.0.2; SAS,
Cary, NC). Quantitative variables were expressed as mean ± standard deviation.

The differences in HRrest, HRtest, and HRscan were determined by the Bland–Altman
method and were analyzed in the entire population as well as in the groups of patients
in whom the HRtest decreased from the HRrest (Group Dec) and those in whom the HR
test increased from the HRrest (Group Inc). This analysis based on groups was performed
to determine whether the behavior of HR during breath hold was related to the behavior
of HR after contrast injection; for this purpose, multiple regression analysis was
performed after extracting patients in whom the HRtest decreased from the HRrest.
The ratios of changes in HRscan in both groups were analyzed using Fisher’s exact
test.

Multiple regression analysis was based on data acquired during odd-numbered months.
The derived multiple regression predictive formula was then applied to data acquired
during even-numbered months, to assess accuracy of prediction. This analysis was performed
on the entire study population, Group Dec, but not on Group Inc because the number
during the even-numbered months (n = 36) was too small to calculate the 5 % assessment
of feasibility. The prediction was evaluated as accurate when less than 5 % of the
actual HRscan exceeded the predicted HRscan by ±5 bpm; this criterion was based on
the fact an error of ±5 bpm will result in inadequate 1-beat scan or unnecessary 2-beat
scan when the predicted HR was 70–75 bpm. A p value of 0.05 was determined as significant.

The accurate formula was applied to the HRrest and HRtest to calculate the estimated
HRscan. A theoretical acquisition window based on the predictive formula and percentage
of RR interval was determined from the estimated HRscan and was compared with the
actual acquisition window. If the actual acquisition window was longer than the theoretical
acquisition window, the examination was determined to have an excessive acquisition
window. The percentage of examinations with excessive acquisition window in the concerned
group was estimated.

Clinical parameters, such as sex, age, weight, height, body mass index, amount of
contrast material, speed, ?-blockers used, history of diabetes mellitus, and standard
deviation of HR at rest were compared between the Groups Dec and Inc. The same parameters
were also compared between the patients whose HRscan decreased from HRtest vs HRscan
increased from HRtest, in Group Dec and Group Inc respectively. For comparison, Student’s
t test was applied for quantitative parameters and Fisher’s exact test was applied
for categorical data. The significance level was adjusted by Bonferroni to 0.05/10 = 0.005.