Effects of Cardiac Surgery on Heart Rate Variability and Its Correlation with the Quality of Life

doi:10.21203/rs.3.rs-4684282/v1

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Effects of Cardiac Surgery on Heart Rate Variability and Its Correlation with the Quality of Life

https://doi.org/10.21203/rs.3.rs-4684282/v1

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Objectives

The purpose of this study is to explore the changes in HRV before and after cardiac surgery and the relationship between HRV and quality of life.

Methods

A total of 21 patients who received cardiac surgery were included in this study. All cases were conducted with a five-minute ECG uploaded by a Bluetooth signal three times. The ECGs were measured before the operation (1st), after the operation (2nd), and one month after the operation (3rd). The parameters of HRV included: standard deviation of normal to normal (SDNN), low frequency (LF), high frequency (HF), normalized low frequency (LF %), and LF/HF. In the third ECG measurement, the patients were also required to answer the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF) in the concise Taiwanese version. The parameters of HRV were analyzed with Wilcoxon signed ranked test. The Spearman correlation test analyzed the correlations between the parameters of HRV and quality of life. Informed consent was obtained from all subjects and/or their legal guardian(s).

Results

Compared with the 1st ECG measurement, the SDNN, LF, and LF% decreased significantly in the 2nd ECG. There was a significant increase in SDNN in the 3rd ECG, but there was no significant difference compared with the 1st ECG. There was a significant positive correlation between HRV and the psychological category of quality of life.

Conclusions

Heart rate variability decreased after cardiac surgery, and the slight recovery of heart rate variability one month after surgery was mainly due to the recovery of sympathetic nerves. The psychological category of quality of life after surgery received the lowest score, which may be related to the incomplete recovery of parasympathetic nerve activity after surgery. The objective data of heart rate variability analysis can reflect the subjective psychological category of patients after heart surgery.

Biological sciences/Neuroscience

Health sciences/Cardiology

Health sciences/Neurology

cardiac surgery

heart rate variability

quality of life

psychological category

Among the leading causes of death in Taiwan, heart disease was the second leading causes of death in 2019 (ref 1). Since the first case report in the 1950s, coronary artery bypass surgery has become a mature technique, including the improvements in the peri-operative myocardial protection technologies and related equipment and consumables. All of these aspects have led to an increased successful rate in patient treated with cardiac surgery. However, heart surgery remains a major, risky operation to date, most patients still required median sternotomy with a cardiopulmonary bypass machine. Peri-operative anxiety, wound pain, postoperative usage of ventilator, and rehabilitation therapy, all are the sources of enormous physical and psychological stress to the patients.

Heart rate variability (HRV) analysis is a method of measuring the level of subtle variation between heartbeats within a set of continue and regular heartbeats. It is a simple and non-invasive method to assess the balance of the autonomic nervous system (ANS) and the regulation of the heart by the ANS. The better the ANS activity, the higher the HRV, such in healthy young people. Normal heartbeat fluctuates due to regulation by the ANS. Such fluctuations would decrease or disappear due to dysregulation of the ANS. There are many factors behind these changes. HRV can be affected by age, sex, and level of physical activity. In addition to age and sex, pathological factors such as heart diseases and diabetes may also lead to a decline in HRV.

HRV is an indicator of the balance of the ANS and is related to the overall health status. Cardiac surgery poses a major threat to a patient's physical and mental health as well as social well-being. The level of stress experienced by a patient would affect the ANS regulation of the heart as well as postoperative recovery. Few studies in the past have directly explored the correlation between HRV and the quality of life (QOL) of patients after cardiac surgery. Therefore, the aims of this study were to investigate the changes in HRV in patients before and after cardiac surgery and to explore the correlation between HRV and the QOL of patients after cardiac surgery.

(1) Research subjects

We recruited patients who underwent cardiac surgery in a regional teaching hospital in northern Taiwan from 2019 to 2020 (IRB number: TYGH108010, review agency: Taoyuan Hospital of the Ministry of Health and Welfare, Taiwan). All patients who underwent cardiac surgery with cardiopulmonary bypass machines were selected. Patients who were under the age of 20; those with an extracorporeal support system preoperatively, those with severe heart and lung failure, major postoperative complications, arrhythmia on ECG pre- and post-operatively, and poor ECG signal acquisition were excluded.

(2) Instruments

1. Wearer electrocardiogram (ECG)

This is a two-lead patch that can continuously record the electrocardiogram, which can be uploaded wirelessly for analysis through a mobile phone connected via Bluetooth. The wearable ECG is a research instrument that is under development, with the wireless transmission part certified by the National Communications Commission (NCC) in Taiwan and the Federal Communications Commission (FCC).

2. The Taiwan version of the Quality of Life Scale, developed using the World Health Organization – Brief Version (WHOQOL-BREF) (WHOQOL Group, 1998), was simplified into four main categories with 26 questions, including seven questions on physical health, six questions on mental health, four questions on social relations, and nine questions on the environment. In addition, two local-level questions, namely ‘diet’ and ‘reputation’ were added to make up a total of 28 questions. The questionnaire was mainly designed to understand the patients' perceptions of health-related quality of life in the past 2 weeks, and the responses to the questions was scored using a Likert five-point scale, with scores ranging from 1 to 5 points (Yao, 2005). A higher score indicated a better quality of life. The distribution of each category was symmetrical for complete coverage with good reliability and validity. The questionnaire was concise, and the test duration was short, approximately 15 minutes (Yao, 2002) (Annex 1). The Health Promotion Administration of the Ministry of Health and Welfare, Taiwan included health-related quality of life in the first National Health Interview Survey in 2001 and has established a norm for the Taiwanese population. The use of this questionnaire has been authorized (Annex II).

(3) Methods

The study protocol was shown in Fig. 1. A five-minute ECG was obtained by using the wearer ECG. The first measurement was conducted after the patient was hospitalized but before the surgery (measurement 1), the second measurement was done after the patient was transferred to the general ward postoperatively and before discharge with the analgesic and inotropic discontinued (measurement 2), and the third measurement was done at least 1 month postoperatively in out-patient department (measurement 3). All measurements were recorded in a quiet environment after the patients had rested with emotional and hemodynamic stable. The ECG waveform was wirelessly uploaded to the server via Bluetooth and a mobile phone for HRV analysis. The patient was also filled in the WHOQOL-BREF-Taiwan version at time of measurement 3. The parameters of HRV analysis in this study included standard deviation of normal to normal (SDNN), low frequency (LF), high frequency (HF), normalized low frequency (LF%), and ratio of low and high frequency (LF/HF).

(4) Statistical analysis

Wilcoxon signed-rank test was used to compare the categorical factors. Numerical values were expressed as mean ± SD and were compared using the Student’s t-test. Spearman’s correlation coefficient analysis was performed to explore the correlation between the five indicators of HRV and the four categories of quality of life. A p < 0.05 is defined as statistical significance. All statistical analyses were performed using SPSS 18.0 for Windows (SPSS, Inc., Chicago, IL).

(1) Patients demographics

A total of 31 patients were enrolled; however, seven patients with poor ECG signal acquisition, one patient with an abnormal response in the questionnaire (outside the observed range), and two patients with major comorbidities (one patient died and one patient was dependent on a respirator), were excluded. A total of 21 cases were finally included in the analysis. Among the 21 patients, 12 were male, and the average age was 61.1 years. The educational level was primary school for six patients, junior high school for nine patients, high school for four patients, college for one patient, and graduate degree for one patient. Most patients (17 patients, 84%) were married; one patient was unmarried, one patient was divorced, and two patients were widowed. In terms of past medical history, 14 patients had hypertension, six had diabetes, and five had chronic kidney disease. Five patients had no history of hypertension, diabetes, or chronic kidney disease (CKD). Ten patients had one chronic comorbid disease (hypertension, diabetes, or CKD), three had two chronic diseases, and three had all three chronic diseases. The mean European System for Cardiac Operative Risk Evaluation (EuroSCORE) of the patients was 2.35%, and the mean ejection fraction (EF) was 63.3%. Further, 53% (10 patients) and 47% (9 patients) had undergone heart valve surgery (aortic, mitral, tricuspid valve replacement or repair surgery) and coronary artery bypass, respectively. One patient underwent aortic repair surgery and one underwent two a combination of two surgeries (coronary artery bypass graft and valve surgery). The average intensive care unit (ICU) duration was 5.1 days, and the average total hospitalisation duration was 14.1 days (Table 1).

Table 1

Basic demographic data (N = 21)
	Mean	Standard deviation	Min	Max
Age	61.1	11.8	40	78
BSA	1.71	0.23	1.30	2.32
EuroSCORE	2.35	1.46	0.67	6.00
EF	63.3	11.7	36	80
Pump time	165	57	30	300
X-clamp time	108	37.9	0	167
ICU days	5.1	2.2	3	12
Total hospitalisation duration (days)	14.1	7.9	8	37

(2) Statistical results

A significant decline was observed in the SDNN, LF, and LF%, of HRV between the second measurement and the first measurement (median SDNN, 22.40–7.87; median LF, 4.02–2.75; median LF%, 52.80–39.10; all p < 0.05), while there was no significant difference in HF and LF/HF, as shown in Table 2. A significant increase in the SDNN of HRV was observed when comparing measurement 3 with measurement 2 (median, 7.87–13.80, p < 0.05), while no significant differences were observed in LF, LF%, HF, and LF/HF. Moreover, no significant differences in HRV were identified when comparing measurement 3 with measurement 1, as shown in Table 3.

Table 2

Preoperative, postoperative, and measurement 3 HRV (N = 21)
	Mean	Median	Standard deviation	Min	Max
Preoperative
SDNN	22.52	22.40	10.34	6.00	51.00
LF	3.70	4.02	1.59	-0.20	6.76
HF	3.11	3.17	1.51	0.66	6.07
LF%	55.24	52.80	23.04	6.50	93.90
LF/HF	0.59	0.48	1.22	-2.30	3.07
Postoperative
SDNN	10.22	7.87	5.65	3.32	21.00
LF	2.21	2.75	1.83	-1.60	5.45
HF	2.43	2.29	1.10	0.85	5.24
LF%	40.27	39.10	28.77	2.77	93.50
LF/HF	-0.22	-0.10	1.69	-3.40	2.73
Measurement 3
SDNN	20.44	13.80	15.50	5.58	68.90
LF	3.21	2.72	1.80	0.40	6.22
HF	2.97	2.74	1.15	1.27	5.63
LF%	50.91	60.00	27.91	4.03	90.00
LF/HF	0.24	0.73	1.47	-3.00	2.42
HRV, heart rate variability

Table 3

Results of the Wilcoxon signed-rank test of preoperative vs. postoperative HRV vs. HRV at measurement 3 (N = 21) HRV, heart rate variability
	Z	P (two-tailed)
Preoperative vs. postoperative
SDNN	-3.6	< 0.001
LF	-2.6	0.009
HF	-1.8	0.073
LF%	-2.1	0.035
LF/HF	-1.9	0.063
Preoperative vs. measurement 3
SDNN	-1.16	0.244
LF	-1.62	0.106
HF	-0.54	0.590
LF%	-0.57	0.566
LF/HF2	-0.38	0.702
Postoperative vs. measurement 3
SDNN	-3.46	0.001
LF	-1.76	0.079
HF	-1.50	0.135
LF%	-1.30	0.192
LF/HF2	-1.03	0.259

The average scores of the four categories of the QOL questionnaire were as follows: physiological category – 68.9 ± 8.7, psychological category – 60.6 ± 12.5, social relations – 66.1 ± 10.77, environmental category – 67.1 ± 9.03. Among these categories, the psychological category score was the lowest (Table 4). The Spearman coefficients of the correlation between the third measurement of HRV and the quality of life categories revealed that SDNN, LF, LF%, and LF/HF were significantly positively correlated with the psychological category (r = 0.458, 0.535, 0.551, 0.521; all p < 0.05), while no correlation was identified with HF. LF and LF% were found to be significantly positively correlated with the environment category (r = 0.528, 0.458; all p < 0.05), while no correlation was identified for SDNN, HF, and LF/HF. HRV indicators were not correlated with the physiology and social relations categories of the quality of life, as shown in Table 5.

Table 4

Means and standard deviations of scores on different categories of quality of life (N = 21)
	Mean	Standard deviation	Min	Max
Physical	68.86	8.70	56	81
Psychological	60.57	12.50	31	88
Social relations	66.14	10.77	44	94
Environment	67.10	9.03	44	81

Table 5

Correlation analysis of HRV and quality of life of patients after cardiac surgery (N = 21)
Correlation coefficient and significance
	SDNN	r	.029	.458	.218	.398
	SDNN	p	.901	.037^✽	.343	.082
	LF	r	.128	.535	.347	.528
	LF	p	.579	.013^✽	.123	.014^✽
	HF	r	.035	.112	-0.24	.273
	HF	p	.881	.629	.918	.231
	LF%	r	.137	.551	.293	.458
	LF%	p	.553	.010^✽	.198	.037^✽
	LF/HF	r	.125	.521	.273	.406
	LF/HF	p	.588	.015^✽	.231	.068
✽p < 0.05
HRV, heart rate variability

Many previous studies on HRV were mainly focused on diabetes and heart diseases. The HRV of the diabetic patients was worse than that of normal people. Long-term poor glycemic control may lead to a decrease or even loss of autonomic regulation (Guo, 2016).

Low HRV has been reported in patients with severe coronary artery disease, heart failure, angina pectoris, and sudden cardiac arrest (Binkley, 2017). Five-minute (short-term) HRV analysis may be used to predict such heart diseases and may be clinically applied in patients with a higher risk of death (Bonaduce et al., 1999). In cardiology, HRV is considered to be a useful tool for the assessment of pre-admission and post-discharge risks to the patients. A study by Lombardi showed that HRV was an important indicator of the physiological status of patients with heart diseases (Lombardi et al., 2001). Several studies have shown that single surgical procedures such as mitral valve surgery (Lakusic et al., 2008) and coronary artery bypass surgery (Mironova et al., 2017) may lead to a short-term reduction in HRV, and that the HRV analysis may also be used to predict the onset of surgical complications (Nenna et al., 2017).

Many studies have discussed the impact of interventional therapy on HRV, such as cardiac catheterisation, deep breathing relaxation, meditation, and exercise. For example, cognitive behavioural therapy can improve the quality of life and overall HRV in patients who undergo cardiac surgeries (Beresnevaitė et al., 2016). In recent years, there have also been studies on the association between HRV and the quality of life. For example, a decline in the quality of life would increase the risk of cardiovascular diseases. Moreover, a significant reduction in HRV was observed in healthy adults with a low quality of life (Lu et al., 2016). Salmoirago-Blotcher et al. (2019) mentioned that although optimism was not associated with coronary artery disease, a decreases in HRV was observed in patients who were less optimistic, and that these patients had an increased risk of coronary artery disease. Depression significantly contributed to autonomic dysfunction (Bassett, 2016). Moreover, depression may increase the risk of cardiovascular morbidities after cardiac surgeries (Tully, 2012). In patients with acute coronary heart disease, reduced HRV was found to be directly related to negative emotions such as stress, anxiety, and depression (Harris, 2014). In addition to changes in physical conditions, such as pain, the disease itself, and incomplete symptom resolution, patients undergoing cardiac surgeries often experience anxiety. Their worries about physical health and stress may develop into depression, resulting in decreased HRV. In addition, the onset of depression after cardiac surgery may be associated with decreased parasympathetic regulation (Patron, 2012).

However, the following questions arise: How is the quality of life of patients after cardiac surgery? Can the HRV of patients after cardiac surgery be used to reflect the patient's quality of life? The QOL would affect not only the postoperative recovery of patients but also their overall health status. The health status of patients (including physical and mental health as well as social well-being) and the quality of life of patients who undergo cardiac surgery are the concerns of not only cardiologists but also the entire care team and even medical staff at all levels.

Two methods were used for HRV analysis: (1) Time domain analysis and (2) frequency domain analysis. In the time domain analysis, the level of dispersion of the heartbeat intervals was calculated using the continuous ECG waveform obtained through the measurements. This was done to detect the interval between each QRS complex in the continuous ECG; the interval between adjacent R waves indicated the heartbeat cycle, namely the R-R interval, which was expressed in milliseconds (ms). The time change of the continuous R-R interval represented the HRV, and relevant statistical methods were applied to quantify the variability. In the frequency domain analysis, Fourier transform was used to convert the time series of heartbeat intervals into a frequency series, which was expressed as power spectral density or spectral distribution. A five-minute stable heartbeat recording was generally used for the frequency domain analysis of HRV (approximately 200–500 beats). The data were mainly divided into an HF range (0.15–0.40 Hz) and an LF range (0.04–0.15 Hz), with frequencies less than 0.04 Hz classified as extremely LF. The HF range usually reflected the activity of the parasympathetic nervous system, while the LF range was regulated by both the sympathetic and parasympathetic nervous systems.

The following HRV indices were analyzed: (1) Standard deviation of normal to normal (SDNN), i.e., the square root of variability, where a higher standard deviation indicated greater HRV. SDNN was expressed in milliseconds (ms) and was used in the time domain analysis. (2) Low frequency (LF): the amplitude of the low frequency range of normal heartbeat intervals reflected the joint regulation of sympathetic nerves and parasympathetic nerves. LF was expressed in millisecond square (ms²) and was used in frequency domain analysis. (3) High frequency (HF): the amplitude of the high frequency range of normal heartbeat intervals was expressed in millisecond square (ms²) and was regulated by the parasympathetic nerves (representing parasympathetic nerve activity). HF was used in the frequency domain analysis. (4). Normalized low frequency (LF%): LF%, i.e., low frequency/(total power - very low frequency) × 100, reflected the sympathetic nerve activity and was used in frequency domain analysis. (5) LF/HF: This ratio indicates the balance of sympathetic and parasympathetic nerve activities as well as sympathetic nerve regulation. LF/HF was used in frequency domain analysis.

Among these indicators, the natural logarithms of LF, HF, and LF/HF were used since these three indicators were not normally distributed (Kuo, 1999). While no action was performed for SDNN and LF%.

In this study, a significant decrease in all parameters of HRV was observed from measurement 2 to measurement 1, indicating that cardiac surgery had a significant effect on both sympathetic and parasympathetic nerve activities, a result that was similar to studies from other researchers (Lakusic et al., 2008; Mironova et al., 2017). However, no significant difference in HRV was observed between measurement 3 and measurement 1, indicating that the HRV of patients who received cardiac surgery recovered slightly 1 month postoperatively. This indicated a decline in all HRV indicators after cardiac surgeries. However, after 1 month of recovery, despite the fact that the overall HRV had not fully recovered, the median LF% and LF/HF were higher than the preoperative values, but the recovery of sympathetic nerves was found to be higher than that of parasympathetic nerves. The activity of the parasympathetic system may need to be followed for a long period of time, such as more than 6 months postoperatively, before drawing conclusions.

HRV may change with stress, and the HRV analysis may be used as an objective assessment for the mental health status and the level of stress in general adults (Kim et al., 2017). Mischke et al. (2018) found an association between HRV and psychological stress in healthy adults, where those with high HRV experienced reduced psychological stress. In our study, the median HF of patients 1 month after cardiac surgery was still lower than the preoperative levels, indicating the incomplete recovery of the parasympathetic nerves. Furthermore, the decrease in the psychology category scores indicated that the patients still experienced immense psychological pressure at this time.

The following conclusions regarding HRV may be drawn based on the results of previous studies: (1) HRV decreased after cardiac surgery; (2) the quality of life of patients declined after cardiac surgery; (3) quality of life was positively correlated with HRV and negatively correlated with the risk of heart diseases; and (4) quality of life and HRV can be improved by interventional therapies/measures. The main findings of this study were as follows: (1) HRV significantly decreased in patients after cardiac surgery; (2) HRV slightly recovered at more than 1 month postoperatively, mainly due to the recovery of the sympathetic system; and (3) patients who underwent cardiac surgeries scored the lowest in the psychological category on the QOL questionnaire 1 month postoperatively. Moreover, a significant positive correlation was identified between HRV and the psychological score, which may be related to the fact that the parasympathetic nerve activity had not yet recovered after cardiac surgery.

According to the results of this study, the patients’ psychological scores were the lowest at 1 month after cardiac surgery, indicating the presence of high psychological stress postoperatively. Therefore, the clinical staff should pay attention to the psychological status of the patients after open heart surgery and implement early intervention and prevention measures to improve the quality of care of these patients.

We attempted to link the objective HRV and subjective questionnaire responses to assess patients' subjective feelings. Our data can help physicians gauge the mental health status of patients even before consultation through HRV analysis and thus determine whether the psychological support provided to the patients was sufficient. Furthermore, HRV analysis is even more important for patients who cannot fully express their subjective feelings. HRV analysis can be used to assess the mental health status and stress level of patients after cardiac surgery and convert subjective feelings into objective data for improved follow-up management.

HRV would be significantly reduced in patients after cardiac surgery. At one month after cardiac surgery, despite the general recovery, HRV still did not return to preoperative levels. Therefore, although the surgery itself can alleviate the heart disease of patients, it can cause a decline in the patient's mental health status. This study also showed that the HRV analysis data reflected the mental health status of patients after cardiac surgery. Postoperative physiological problems may have psychological impacts and lead to a decrease in HRV. Therefore, as per our findings, when objective clinical indicators are insufficient for determining the subjective feelings of patients after cardiac surgery, the objective data from HRV analysis may be used for this purpose.

Sternotomy is required in traditional cardiac surgeries, and the postoperative pain would be the strongest in the first 3 days, with most patients experiencing complete pain relief by the second to third month postoperatively. However, in this study, measurement 3 of HRV analysis was performed 1 month after cardiac surgery along with the QOL questionnaire survey. Some patients may still feel pain or discomfort from the wound at this time, and the questionnaire responses may be affected by these aspects. Future studies could use long-term tracking to determine the changes in HRV and the quality of life after cardiac surgery over a longer time span. The HRV analysis was based on the small variation of the R-R interval between normal heartbeats under normal sinus rhythm. However, among the enrolled patients, as many as six patients with arrhythmia were excluded. Many patients who undergo cardiac surgery suffer from arrhythmia preoperatively, which is unavoidable, and this resulted in a small sample size. A larger sample size in future studies can help increase the statistical power of the results.

Cardiac surgery is a major operation, and the psychological pressure and burden on patients affects their mental health status. Early intervention is recommended to improve the quality of care for patients receiving cardiac surgery. HRV analysis has high sensitivity and is characterized by the ease of operation and non-invasiveness. HRV analysis can easily and rapidly reflect the postoperative psychological changes in patients, with high economic efficiency and applicability. Future research with a large number of patients and extended assessment duration may provide important information in this area of research.

Author Contribution

Li-Chiu Lee and Huai-Jen Chang wrote the main manuscript text and prepared figures 1 and table 1-5. Chih-Cheng Hsieh, Terry B.J. Kuo, Mei-Yin Chen, Hsin-Wei Lin and Po-Chun Lo shared and collected candidate information. All authors reviewed the manuscript.

Ethics Statement

The study was approved by the local ethics committee, Medical Ethics and Institutional Review Board of Taoyuan General Hospital, Ministry of Health and Welfare and was performed in accordance with the ethical standards of the 1964 Declaration of Helsinki. Informed consent was obtained from all subjects and/or their legal guardian(s).

Statement of competing interests

All the authors have no conflict of interest to declare.

Funding

The research received no specific grant from any funding agency in the public, commercial , or not-for-profit sectors.

Data Availability Statement

Data is provided within the manuscript or supplementary information files. The datasets used and analyzed during the current study available from the corresponding author on reasonable request.

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No competing interests reported.

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Effects of Cardiac Surgery on Heart Rate Variability and Its Correlation with the Quality of Life

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Version 1

Abstract

Objectives

Methods

Results

Conclusions

Figures

Introduction

Materials and Methods: (建議順序: Materials (Populations), Instruments, Methods, Statistical Analysis)

(1) Research subjects

(3) Methods

(4) Statistical analysis

Results

Discussion

Conclusions

Limitations

Study Suggestions

Declarations

Author Contribution

References

Additional Declarations

Status:

Version 1