Our prospective and single-center study was conducted according to the declaration of Helsinki and was approved by our local institutional ethics board (No. D 549/19). All patients gave their informed consent in written form prior to inclusion.
Patients:
From December 2019 to January 2022, a total of 60 patients receiving elective CCTA to exclude CAD in our department were included in our study and separated into two groups: with biofeedback (W-BF) and without biofeedback (WO-BF). Biofeedback was applied in 30 patients before CCTA (W-BF), and another 30 patients constituted the control group without the use of biofeedback (WO-BF). Group assignments were randomized and occurred before the pre-examination interview (before MTP 1).
Study population data:
In W-BF, 14 (46.7%) subjects were female with a mean age of 59.2 ± 12.9 years, and in the control group (WO-BF) 17 subjects were female (56.7%) with a mean age of 58 ± 11.8 years. All demographic data (age, weight, body mass index, and gender) and clinical characteristics of our patient are summarized in Table 1.
Table 1
Demographic and clinical data of our study population. Metric data are given as mean and standard deviation, p-values are calculated using Students-t-test. For nominal data absolute and relative frequencies are shown.
|
W-BF (n = 30)
|
WO-BF (n = 30)
|
p-value
|
Demographic data
|
|
|
|
Female gender, n (%)
|
14 (46.7)
|
13 (43.3)
|
|
Age (years)
|
59.2 [12.9]
|
58.0 [11.8]
|
0.716
|
Weight (kg)
|
81.3 [17.8]
|
83.7 [20.3]
|
0.636
|
Height (cm)
|
174 [9.8]
|
172 [8.9]
|
0.316
|
BMI (kg/m²)
|
26.7 [4.6]
|
28.1 [5.3]
|
0.266
|
Clinical data
|
|
|
|
Thoracal pain, n (%)
|
10 (33.3)
|
12 (40)
|
|
Dyspnoe, n (%)
|
15 (50)
|
14 (46.7)
|
|
Post-infect, n (%)
|
2 (6.7)
|
4 (13.3)
|
|
Positive family history, n (%)
|
16 (53.3)
|
16 (53.3)
|
|
Asthma/COPD, n (%)
|
2 (6.7)
|
3 (10)
|
|
hypertension, n (%)
|
15 (50)
|
17 (56.7)
|
|
permanent use of beta-blocker, n (%)
|
9 (30)
|
7 (23.3)
|
|
psychopharmaceuticals, n (%)
|
4 (13.3)
|
8 (26.7)
|
|
Nicotine abuse, n (%)
|
9 (30)
|
7 (23.3)
|
|
Performing sportive activities, n (%)
|
16 (53.3)
|
15 (50)
|
|
Performing Yoga, biofeedback or autogenous training, n (%)
|
5 (16.7)
|
3 (10)
|
|
Employed person, n (%)
|
20 (66.7)
|
16 (53.3)
|
|
stressful activity before examination, n (%)
|
3 (10)
|
6 (20)
|
|
Consume of coffee, black tea or chocolate before examination, n (%)
|
19 (63.3)
|
18 (60)
|
|
Patient evaluation:
Following CCTA, all patients evaluated their subjective perceptions or stress levels before and during the examination, satisfaction, and perceived hospital atmosphere. These issues were rated on a scale from 1 to 6.
HRV biofeedback:
In our study, we used a commercially available and mobile biofeedback device ("Qiu", BioSign GmbH, Ottenhofen, Germany), which is a medical device and complies with all requirements of the Medical Device Directive 93/42/EEC (Supplementary file 1).
The Qiu is ball-shaped and can be optimally placed in the palm of the hand. An optical pulse sensor on the Qiu measures HR at the fingertip or palm. The Qiu is also equipped with a large light that can display a color spectrum from green, to yellow and orange, to red, depending on the HRV detected. When HRV is high, the Qiu lights up green, indicating a low stress level. In depressed HRV, the color of the Qiu changes from yellow to red, indicating an increased stress level. An additional blue light-emitting diode (LED) display on the Qiu shows breathing rate and speed, which was set to 6–7 breaths per minute for the present study. Patients were encouraged by the LED display to breathe deeply and slowly to increase the HRV and receive a green light on Qiu. These exercises were performed for a duration of 15 min in the W-BF group before CCTA.
Study design, procedure, and physiological recording:
The measurement timeline is shown in Fig. 1. Blood pressure and HR were assessed in both groups at five measurement time points (MTP):
MTP 1: During the pre-examination interview
MTP 2: After the patient was positioned on the CT table
MTP 3: Immediately before CCTA, while practicing breath holding maneuver, decision to beta-blocker administration
MTP 4: During the CCTA image acquisition
MTP 5: After completing the CCTA examination
The patients in the W-BF group used the biofeedback device independently for 15 min between MTP 1 and MTP 2, whereas the WO-BF group waited this time without biofeedback. Otherwise, all examination steps were the same for the W-BF and WO-BF groups. If a beta-blocker was administered, post procedure surveillance time was prolonged to 30 min.
CCTA Examination:
All prospective, ECG-triggered CCTA examinations were performed using a 2x128-section multi-detector CT (SOMATOM Definition Flash, Siemens Healthcare GmbH, Forchheim, Germany) with the following acquisition parameters: 128x0.6 collimation, 0.28 s gantry rotation time, 120 kVp tube voltage, adapted mA tube current (range 35–800), and 1-mm-thick reconstructed images. An automated attenuation-based dose modulation (CARE Dose, Siemens Healthcare GmbH, Forchheim, Germany) was used in all patients. The total dose and injection rate of the iodine-based contrast medium (Imeron 350, Bracco, Milan, Italy) depended on the respective body mass index (BMI < 25: 5 ml/s, 65 ml; BMI 25–30: 5,5 ml/s, 70 ml; BMI > 30: 6 ml/s, 75 ml). CCTA datasets were acquired in all patients with a 4- to 6-s trigger delay while the bolus tracker was placed in the ascending aorta.
The breath-holding maneuver for subsequent CCTA image acquisition was briefly practiced with each patient at MTP 3. In patients with cardiac arrhythmia or/and with a HR above 65 bpm at MTP 3, a beta-blocker (Metoprolol®) with a dose ranging from 1–15 mg was administered gradually until the target (desired) HR was achieved. Each patient received 0.8 mg nitrolingual spray 3–4 min before the CCTA examination.
Image reconstruction and analysis:
All examinations were analyzed in consensus by two board-certified radiologists (P. L. and A. L.), each with at least 7 years of experience interpreting cardiac CT images. For analysis of CCTA images, multiplanar and three-dimensional reconstructions were created. The commercially available clinical software SyngoVia (Siemens Healthcare, Forchheim, Germany) was used to analyze the images, to evaluate the CAD-RADS (Coronary Artery Disease – Reporting and Data System) and to determine the Agatston Score [15]. The image quality was evaluated by using an image quality scoring scale of 1 to 4:
Grade 1: Good, without artifacts
Grade 2: Moderate, some artifacts not influencing ability to make diagnosis
Grade 3: Poor, artifacts influencing ability to make diagnosis, but still possible to make approximate assessment
Grade 4: Nondiagnostic
Statistical analysis:
Normality was tested for all metric variables by using the Shapiro-Wilk test. If normality was given data were reported as mean and standard deviation (SD), if not, median with interquartile are shown. To compare group values, we used the t-test for normally distributed data, whereas for data without normality and for ordinal data the Mann Whitney U-Test was performed. To analyze dependencies of nominal data we used X² test or Fisher’s exact test if sample size was too small. Statistical significance for all tests was set at a level of p < 0.05. Statistical analysis was performed using the jamovi project, version 2.5.5 for Windows (Sydney, Australia, 2021).