Abstract
Background
The autonomic imbalance and low vagal tone are common characteristic among patients with chronic heart failure (CHF). It is hypothesized that CHF rehabilitation programs targeting autonomic nerves system (ANS) function may offer greater efficacy for CHF management. This trial represents the first attempt to investigate such an approach.
Methods
This is a randomized controlled trial aimed to examine the effectiveness of individualized paced deep breathing training (IBT) in CHF patients, with ANS measures as rehabilitation targets. Patients in the IBT group received an additional 4-week program of IBT alongside their standard rehabilitation care. The cardiopulmonary resonance index (CRI), 6-Minute Walking Distance (6MWD) and the Minnesota Quality of Life Score Questionnaire (MLHFQ) were assessed at baseline (T1) and after 4 weeks (T2).
Results
All 38 participants completed the trial successfully. Participants in the IBT group showed significant improvements in CRI, including enhancements in respiratory stability (RS), cardiopulmonary resonance amplitude (CRA), cardiopulmonary resonance factor (CRF), cardiopulmonary coupling coefficient (CPC), and the Spearman’s Rank Correlation Coefficient between Respiratory Rate and Heart Rate (CRS). Further, improvements in both 6MWD and MLHFQ scores were observed. [Multiple linear regression analysis results showed correlations between RS and white blood cell (r = 0.924), CRF and procalcitonin (r = 0.733) and serum creatinine (r = 0.494), as well as CRS and glycosylated hemoglobin (r = 0.819)].
Conclusions
These findings demonstrate that IBT is a feasible and effective rehabilitation approach for CHF patients with ANS measures as target. The IBT program here also showed therapist efficiency and good patients compliance.
Keywords: Chronic heart failure, Individualized paced deep breathing training, Autonomic nervous function, Cardiopulmonary respiration test
1. Introduction
Autonomic nerve imbalance is a common characteristic in individuals with chronic heart failure (CHF), and its severity is directly associated with the risk of heart failure exacerbation and mortality [[1], [2], [3]]. This imbalance, along with adrenergic receptor overactivity, results in myocytes dysfunction, apoptosis, inflammation, and abnormal nitric oxide synthase signaling, contributing to poor clinical outcomes and decreased survival rates. Rehabilitation programs, including pharmacological and non-pharmacological approaches, have been shown to improve autonomic balance and clinical efficacy in CHF patients [1]. For example, exercise training enhances heart rate variability (HRV) and baroreflex sensitivity (BRS), key indicators of autonomic nervous system (ANS) function, thereby reducing cardiovascular risk. Additionally, rehabilitation programs that include tailored exercise regimens have been associated with reduced hospitalization rates and mortality in CHF patients [4].
Currently, CHF patients often demonstrate low compliance with pharmacological therapies due to their limited efficacy, such as angiotensin-converting enzyme inhibitors, receptor blockers, and beta-blockers. Thus, pharmacological and non-pharmacological approaches are sought to improving autonomic balance. Examples include enhanced electrical stimulation of the vagus nerve and baroreceptor, nerve ablation to reduce sympathetic nerve output, and carotid body resection to reduce the chemoreceptor reflex [1]. However, there is still significant work required in the development of reliable, non-invasive, and clinically applicable methods for autonomic nerves modulation.
Existing autonomic nerve evaluation methods, such as the Cardiovascular Autonomic Reflex Test (CARTs), Heart Rate Variability (HRV), Single Photon Emission CT (SPECT) or Positron Emission Tomography (PET) shows limited clinical applicability [1]. These methods either provide indirect measurements of the ANS or are too complex to effectively capture ANS dynamics. Therefore, there is an urgent need for a quantitative, systematic evaluation and measurement method for ANS assessment that can be easily integrated into rehabilitation programs.
Respiratory Sinus Arrhythmia (RSA), where heart rate increases during inspiration and decreases during expiration, is a physiological phenomenon of cardiopulmonary resonance under autonomic nerve regulation [5]. RSA is frequently employed as an indicator of cardiac vagal tone and plays a primary role in regulation of energy exchange by synchronizing respiratory and cardiovascular processes during metabolic and behavioral changes [6,7]. Modeling and assessment of RSA can be done using the Cardiopulmonary Respiration Test (CRT) [8,9], a 20-minute breathing test that includes free breathing and paced breathing stages, capturing ECG and respiration signals to calculate Cardiopulmonary Resonance Indices (CRI), a quantitative measure of RSA and ANS activity.
Deep and slow-paced breathing improves alveolar ventilation, reduces ineffective lung space, and increases arterial oxygen saturation and venous return [10]. During deep breathing, the relation between respiration and vasomotor function becomes more obvious, creating a significant resonant effect [10]. Paced slow breathing training (BT) may offer a practicable, effective, and beneficial option for home-based rehabilitation in CHF patients [11]. The results of the RESPeRATE study further support the benefits of using BT as a component of cardiorespiratory rehabilitation scheme in patients with CHF [12]. Despite these promising results, there are still significant gaps in the current research. Most existing studies on BT in CHF patients have been limited in terms of oarticipant adherence. Additionally, the optimal frequency, duration, and intensity of BT for maximal benefit in CHF patients remain unclear. Future research should focus on developing digital and tailored breathing training strategies that can be easily implemented in clinical practice, to better understand the full potential of BT in CHF rehabilitation.
In this trial, we aim to develop and evaluate the efficacy of an individualized paced deep breathing training (IBT) program utilizing CRT. IBT provides personalized breathing training prescriptions, supervises and monitors the breathing exercise process in both hospital and home settings, and measures vagal tone dynamics throughout the training. We hypothesize that IBT targeting autonomic nervous function, as measured by CRI, will improve ANS activity, exercise capacity, and quality of life in CHF patients.
2. Material and methods
2.1. Study design
This trial study was a prospective, randomized, controlled trial assessed to examine the efficacy of individualized breathing training on autonomic nervous function among patients with CHF. This trial was approved by the Ethics Committee of Shanghai Tongji Hospital, with (Tong) No. 2021-039. The process flowchart is shown in Fig. 1.
Fig. 1.
The process flowchart of the IBT trail study.
2.2. Participants
The participants of the trial were recruited from patients diagnosed with CHF, according to the diagnostic criteria [13], and hospitalized at Shanghai Tongji Hospital in Shanghai, China, from October 2021 to August 2022, following the inclusion and exclusion criteria. The authors confirm that all patients’ consent forms have been obtained for this article.
The inclusion criteria: Adults aged ≥18 years, diagnosed with CHF with stable clinical symptoms, New York Heart Association (NYHA) heart function level I–III, and receiving standard drug therapy for at least one week.
The exclusion criteria: Patients who couldn’t complete the 6-Minute Walking Distance (6MWD) test; those with lung tumors, pulmonary tuberculosis, acute pulmonary inflammation, COPD or bronchial asthma and exercise-induced asthma; patients with sleep apnea syndrome or cognitive impairment; those unable to exercise due to concomitant disease, behavior, or other limiting factors.
Participants were randomly assigned to either the IBT group or the control group with the ratio of 1:1 using a computer-generated randomization sequence via the RAND function. The trial was conducted in accordance with the Helsinki Declaration as revised in 2013 and its latest amendment. Standard pharmacological treatment remained consistent throughout the study for all participants.
2.3. Data Collection
The sample size of 38 patients was calculated using PASS V15 (NCSS, USA) in this trial, to detect a statistically significant difference in the primary endpoint with a power of 90 % and two-tailed alpha level of 5 %, assuming an effect size of 0.4.
Demographic and clinical data of participants were retrieved from electronic medical records, including gender, age, height, weight, body mass index (BMI), resting systolic and diastolic blood pressure, resting heart rate, left ventricular ejection fraction (LVEF), brain natriuretic peptide (BNP), cardiac function grade (NYHA grade), types of complications, and medications for CHF.
The trial data were collected for all participants at baseline (T1) and 4 weeks (T2), including supine blood pressure, procalcitonin (PCT), creatinine (Cr), glycosylated hemoglobin (HbA1c), white blood cell count (WBC), 6-Minute Walking Distance (6MWD), Minnesota Quality of Life Score Questionnaire (MLHFQ), and Cardiopulmonary Resonance Indices (CRI).
The primary efficacy variable was the improvement of autonomic nerves function in IBT group participants, measured by CRI, obtained using the Cardiopulmonary Respiration Test (CRT). CRI parameters include respiratory stability (RS), cardiopulmonary resonance amplitude (CRA), cardiopulmonary resonance factor (CRF), cardiopulmonary coupling coefficient (CPC), Spearman's Rank Correlation Coefficient between Respiratory Rate and Heart Rate (CRS), and frequency of cardiopulmonary resonance (fA).
Secondary efficacy variables were the improvements in 6MWD and MLHFQ scores after the 4-week IBT intervention.
2.4. Intervention
Each IBT participant was supervised and monitored by a physiatrist, using a personalized paced breathing exercise prescription (TDFIT), in addition to their standard rehabilitation program. The TDFIT prescription had 5 components:
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1.
Weekly frequency: 5 times per week.
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2.
Duration: Set to 15 min.
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3.
Frequency: The resonance frequency with the highest resonant amplitude, which is determined by CRT.
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Inhalation-Exhalation Ratio: Defaulted to 2:3.
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5.
Breathing type: Abdominal breathing with nasal inhalation and mouth exhalation [14].
The IBT APP received the TDFIT prescription by synchronizing with the physician’s digital workstation. According to the prescription, the IBT APP provided reminders, voice guidance, and music during training. Upon completion of the training, a report was generated based on CRI data, calculated from the respiration and ECG data acquired during the training. The home-based training was under the co-supervision of the physicians and patients' family members.
All participants received standard guideline-directed pharmacological therapy for CHF and were instructed to maintain their usual physical activity levels throughout the study. Participants in the control group continued with this standard rehabilitation program alone and did not receive the IBT intervention.
2.5. Cardiopulmonary respiration test (CRT)
CRT is a 20-minute breathing test consisting of four breathing stages: 5 min of free breathing followed by 5 min each of paced breathing stages at frequencies of 0.2 Hz, 0.15 Hz, and 0.1 Hz, respectively. Participants wore a miniaturized device that captured ECG, respiration, and 3D acceleration signals simultaneously. CRI values were calculated for each stage.
The equipment and integrated system for CRT and IBT system was provided by the Institute of Digital Health, Chinese Academy of Sciences, with CFDA Jiangsu Certificate Number 20,222,211,254 and referred to as CPRT. It offers integrated functions from the respiration test to personalized IBT prescription, guided breathing training, training progress reports, and cardiopulmonary resonance indices.
2.6. Statistical analysis
IBM SPSS version 26.0 (IBM Corp., Armonk, NY., USA) was used for statistical analyses. The normality of the distribution was assessed using the Shapiro-Wilk test. Measurement data conforming to the normal distribution are presented as mean ± standard deviation (x ± s), while data that did not follow a normal distribution are presented as median (interquartile range, P25, P75). Counting data are expressed as rates or constituent ratios (%). Descriptive statistics were used to describe the baseline characteristics. The independent t-test was used for between-group comparisons of normally distributed data, while the Mann-Whitney U test was used for non-normally distributed data. Chi-square tests were used to compare categorical variables. Within-group comparisons were conducted using paired t-tests for normally distributed data and Wilcoxon signed-rank tests for non-normally distributed data. Correlation analyses were carried out using multivariate linear regression. A two-tailed significance level was set at 0.05.
3. Results
3.1. Demographic and clinical characteristics
The IBT trial was conducted from October 2021 to August 2022. A total of 38 patients were recruited and the data collections was completed at both T1 and T2. The mean age of the participants was 71.21 years, with the majority being men (65.8 %); a mean body mass index of 24.77 kg/m2 (standard deviation = 6.07); and a mean left ventricular ejection fraction of 57.08 % (standard deviation = 12.93).
The demographic and clinical data statistics of participants at baseline are shown in Table 1. As shown in Table 2, there were no statistically significant differences between two groups (P > 0.05).
Table 1.
The definitions and clinical implications of cardiopulmonary resonance index (CRI).
| Cardiopulmonary resonance index (CRI) | Definition and Implication |
| Respiratory stability (RS) | A numerical performance measure of the APP-guided paced deep breathing exercise. |
| Cardiopulmonary resonance amplitude (CRA) | A numerical measure of RSA, the efficiency of cardiopulmonary metabolic system, characterizing vagus nerves and mental health. |
| Cardiopulmonary resonance factor (CRF) | A measure of cardiopulmonary system with respect to degree of resonance it can reach. It depends on the existence of interferences such as stress and inflammation. |
| Cardiopulmonary coupling coefficient (CPC) | As the name indicated, CPC measures the efficiency of the cardiopulmonary interactions. |
| Spearman's rank correlation coefficient between respiratory rate and heart rate (CRS) | The consistency between respiration signal and the heart rate variations. |
| Frequency of cardiopulmonary resonance (fA) | The central frequency of respiration, about 0.2–0.3 Hz at free breathing, and close to the guided frequency at CRT. |
Table 2.
Participants' demographic and clinical data statistics at baseline (N = 38).
| Parameter | Intervention group (n = 19) | Control group (n = 19) | t/Z/x2 | P |
|---|---|---|---|---|
| Gender[N(%)] | 0.117 | 0.732 | ||
| Male | 12(63.2) | 13(68.4) | ||
| Female | 7(36.8) | 6(31.6) | ||
| Age | 68.8 ± 9.6 | 73.6 ± 7.5 | − 1.732 | 0.092 |
| Height, cm | 165. 1 ± 8.7 | 166.5 ± 8.1 | −0.541 | 0.592 |
| Weight, kg | 70.3 ± 19.5 | 66. 1 ± 14.5 | 0.763 | 0.450 |
| BMI, kg/m2 | 23.7(22.0,27.7) | 23.4(20.7,27.3) | −0.774 | 0.439 |
| SBP, mmHg | 120.0(110.0, 131.0) | 133.0(115.0, 141.0) | − 1.157 | 0.247 |
| DBP, mmHg | 71. 1 ± 7.5 | 75.2 ± 10.8 | − 1.361 | 0.182 |
| MAP, mmHg | 88.5 ± 9.8 | 93.2 ± 9.5 | − 1.496 | 0.143 |
| HR, bpm | 73.0(65.0,87.0) | 75.0(66.0,80.0) | −0.453 | 0.650 |
| LVEF, % | 63.0(44.0,67.0) | 64.0(45.0,67.0) | 0.000 | 1.000 |
| BNP, pg/mL | 208.6(175.7,402.9) | 334.9(177.3,542.5) | −0.949 | 0.343 |
| NYHA class[N(%)] | 0.182 | 0.913 | ||
| NYHA class I | 6(31.6) | 5(26.3) | ||
| NYHA class II | 8(42. 1) | 8(42. 1) | ||
| NYHA class III | 5(26.3) | 6(31.6) | ||
| CAD, [N(%)] | 8(42. 1 %) | 13(68.4 %) | 0.191 | |
| HBP, [N(%)] | 15(78.9 %) | 16(84.2 %) | 1.000 | |
| Arrhythmia, [N(%)] | 3(15.8 %) | 7(36.8) | 0.269 | |
| Diuretics, [N(%)] | 10(52.6 %) | 12(63.2 %) | 0.743 | |
| ACEI/ARB/ARNI, [N(%)] | 17(89.5 %) | 16(84.2 %) | 1.000 | |
| Beta-blockers, [N(%)] | 8(42. 1 %) | 13(68.4 %) | 0.191 | |
| Antisterone, [N(%)] | 5(26.3 %) | 4(21. 1 %) | 1.000 | |
| RS | 0.512 ± 0.19 | 0.586 ± 0.23 | − 1.085 | 0.285 |
| CRA | 0.357 ± 0.18 | 0.386 ± 0.15 | −0.546 | 0.589 |
| CRF | 0. 140 ± 0.10 | 0.222 ± 0.19 | − 1.624 | 0.113 |
| CPC | 0. 114 ± 0.09 | 0. 166 ± 0.11 | − 1.517 | 0.138 |
| CRS | −0. 119 ± 0.32 | −0. 134 ± 0.32 | 0.146 | 0.885 |
| fA [N(%)] | 0.740 | |||
| 0.2–0.3 Hz | 7(36.8) | 8(42. 1) | ||
| <0.2 Hz or >0.3 Hz |
12(63.2) | 11(57.9) | ||
| 6MWD, m | 370.2 ± 10.04 | 376.2 ± 13.37 | −0.359 | 0.724 |
| MLHFQ | 37.7 ± 14.2 | 41.4 ± 17.4 | −0.725 | 0.473 |
Abbreviations: BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure; HR, heart rate; LVEF, left ventricular ejection fraction; BNP, brain natriuretic peptide; NYHA, New York Heart Association; CAD, coronary artery disease; HBP, high blood pressure; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARNI, angiotensin receptor enkephalase inhibitors; RS, respiratory stability; CRA, cardiopulmonary resonance amplitude; CRF, cardiopulmonary resonance factor; CPC, cardiopulmonary coupling coefficient; CRS, Spearman's Rank Correlation Coefficient between Respiratory Rate and Heart Rate; fA, frequency of cardiopulmonary resonance; 6MWD, 6-Minute Walking Distance; MLHFQ, Minnesota Quality of Life Score Questionnaire.
*p ≤ 0.05, ** p ≤ 0.01.
3.2. Efficacy of the IBT program
Differences between the IBT and control groups are listed in Table 3.
Table 3.
The Difference IBT made on IBT group in comparison with control group.
| Parameter | IBT group(n = 19) | Control group(n = 19) | t/Z/x2 | P |
|---|---|---|---|---|
| ΔRS | 0.247 ± 0.04 | 0.004 ± 0.05 | 3.909 | 0.000** |
| ΔCRA | 0.213 ± 0.04 | 0.037 ± 0.06 | 2.536 | 0.016* |
| ΔCRF | 0.272(0.160,0.349) | 0. 171(−0.030,0.312) | −2.088 | 0.037* |
| ΔCPC | 0. 104(0.060,0. 129) | 0.023(−0.085,0.066) | −3.256 | 0.001** |
| Δ6MWD, m | 35.60 ± 2.38 | 10.90 ± 2.30 | 7.473 | <0.01** |
| ΔMLHFQ | 6.89 ± 0.48 | 4.37 ± 0.62 | 3.238 | ＜0.01** |
Abbreviations: ΔRS, the difference of respiratory stability between T2 and T1; ΔCRA, the difference of cardiopulmonary resonance amplitude between T2 and T1; ΔCRF, the difference of cardiopulmonary resonance factor between T2 and T1; ΔCPC, the difference of cardiopulmonary coupling coefficient between T2 and T1; Δ6MWD, the difference of 6-Minute Walking Distance between T2 and T1; ΔMLHFQ, the difference of Minnesota Quality of Life Score Questionnaire between T2 and T1.
*p ≤ 0.05, ** p ≤ 0.01.
Regarding primary efficacy, four weeks of individualized paced deep breathing training significantly improved autonomic function in the IBT group, as evidenced by increases in cardiopulmonary resonance indices (CRI). On the contrary, the change of CRI in the control group was negligible. In the IBT group, the respiration stability (RS) increased by 0.247 ± 0.04 (p = 0.000). All 19 participants in the IBT group demonstrated great compliance (100 %), successfully completing the full one-month regimen of paced breathing training. CRA, CRF and CPC increased by 0.213 ± 0.04, 0.272(0.160,0.349) and 0. 104(0.060,0. 129) with p-values of 0.016, 0.037 and 0.01, respectively. The IBT group demonstrated significant improvements in vagal tone, as reflected by the enhanced cardiopulmonary resonance indices, suggesting a potential reduction in sympathetic overactivity.
Improved autonomic function led to gain in exercise capacity and enhanced quality of life. While the 6MWD for both groups increased after the one-month intervention, the gains were significantly larger in the IBT group. Additionally, MLHFQ scores decreased for both groups, with the IBT group showing a greater reduction compared to the control group (P < 0.01).
3.3. Correlation between cardiopulmonary resonance indices and blood biochemical indices
Multiple linear regression analyses were performed between cardiopulmonary resonance indices and blood biochemical indices at baseline (T1). The results are listed in Table 4, revealing a correlation between RS and white blood cell (WBC) (r = 0.924, P < 0.01), CRF and procalcitonin (PCT) (r = 0.733, P < 0.01) and serum creatinine (r = 0.494, P < 0.05), and CRS and glycosylated hemoglobin (HbA1c) (r = 0.819, P < 0.01).
Table 4.
Multiple linear regression analysis results (N = 38).
| Standardization coefficient Beta | t | p | VIF | R2 | ||
|---|---|---|---|---|---|---|
| RS | Constant | −0.315 | −2.496 | 0.041* | ||
| WBC, *109/L | 0.924 | 0.000 | 0.000** | 1.000 | 0.853 | |
| CRF | Constant | 1.178 | 0.283 | |||
| PCT, ng/mL | 0.733 | 5.475 | 0.002** | 1.026 | ||
| Cr, g/L | 0.494 | 3.689 | 0.010* | 1.026 | 0.895 | |
| CRS | Constant | −4.105 | 0.005** | |||
| HbAlc, % | 0.819 | 3.774 | 0.007** | 1.000 | 0.671 | |
Abbreviations: RS, respiratory stability; CRF, cardiopulmonary resonance factor; CRS, Spearman's Rank Correlation Coefficient between Respiratory Rate and Heart Rate; WBC, white blood cell; PCT, procalcitonin;Cr, creatinine; HbAlc, glycosylated hemoglobin.
*p ≤ 0.05, ** p ≤ 0.01.
4. Discussion
Previous research has shown that breathing training, as an adjunct to standard CHF treatment, may increase blood oxygenation level, improve exercise performance, lower NYHA levels and systolic pulmonary artery pressure, and thereby improve quality of life [[15], [16], [17], [18]].
This IBT trial study offers a digital and tailored breathing training strategy using CPRT system, an integrated system tailored for both testing and training based on cardiopulmonary resonance indices. CPRT provides personalized breathing training prescriptions, supervises and monitors breathing exercise processes either in the hospital or at home, and measures the vagus tone during training. In other words, we have enacted an optimization methodology, wherein breathing techniques are personalized using CRI assessments prior to patient prescription.
The IBT trial study has shown that using CRI as a rehabilitation target, facilitated by CPRT, leads to notable compliance and significant improvements in autonomic function, exercise capacity, and quality of life in the IBT group, summarized as follows:
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(1)
IBT trial program resulted in an overall improvement in vagus nerve.
Autonomic nerve imbalance is commonly seen in CHF patients, the degree of this imbalance correlates with the severity of cardiac failure. This is the first IBT trial program to use CRI as rehabilitation target for CHF, showing improvements in autonomic nervous functions, particularly in vagal nerve tone. We propose that cardiovascular autonomic neuropathy, especially low vagal nerve tone, can be both a cause and a symptom of CHF. CRI, as a quantitative measure of autonomic function, is thus an ideal target for CHF rehabilitation.
The advantages of using CRI as rehab target are supported by significant improvements in CRI parameters, including RS, CRA, CRF, CPC, and CRS (see Table 2). CRI reflects autonomic regulation within the cardiopulmonary metabolic system, and its improvement is related to vagal nerve function, metabolic system efficiency and adaptation [19,20], as well as stress response.
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(2)
Significant improvement in 6MWD
Improvements in 6MWD and MLHFQ scores in CHF patients of the IBT group were observed in the study. These improvements might be attributed to the effects of respiratory cardiovascular oscillation, specifically through vagal-mediated mechanisms such as the Hering-Breuer reflex. This reflex coordinates respiratory and circulatory systems by modulating lung volume and heart rate. During deep inhalation, pulmonary stretch receptors activate the vagus nerve, which inhibits further inspiration and promotes expiration, preventing lung overinflation [21,22]. This reflex also influences heart rate variability (HRV) through the nucleus ambiguus, leading to transient increases in heart rate during full lung inflation [23].
Breathing, when performed at the frequency corresponding to the highest resonant amplitude, enhances ventilation-perfusion (V/Q) matching by synchronizing respiratory and cardiovascular rhythms. During inhalation, intrathoracic negative pressure increases, expanding blood vessel diameter and improving oxygen perfusion to tissues. Conversely, exhalation reduces perfusion, leading to cyclic variations in arterial blood pressure [23]. This synchronization has a potential effect on reducing physiological void space, improving lung gas exchange efficiency, minimizes energy consumption, and enhances overall cardiopulmonary function [15]. Future studies could further explore the combined effects of slow breathing and exercise training on ANS indices in CHF patients.
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The advantages of the IBT trial program
The advantages of the IBT trial program can be summarized as follows:
The IBT trial program is the first to use vagal nerve-related measures, specifically CRI, as targets for CHF rehabilitation, leading to significant improvements in autonomic function, as well as exercise capacity and quality of life.
With the integrated testing and training system CPRT combined, this offers a seamless rehabilitation process, which consists of a cardiopulmonary respiration test assessing autonomic function and metabolic system, personalized breathing training prescription, voice and music guided paced deep breathing training, and real-time report of the training—all with CRI as the primary target.
The IBT trial program was highly efficient, requiring minimal therapist involvement, and was associated with excellent patient compliance, as all participants completed all scheduled training sessions.
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The potential mechanisms of IBT on autonomic function
As shown in Section 3.3, we have discovered correlations between CRI parameters and biochemical markers such as WBC, PCT, serum creatinine, and HbA1c. Notoriously, elevated WBC levels are often indicative of an inflammatory response, which is a common feature in CHF. Improved respiratory stability, as measured by RS, may reflect better autonomic regulation, which in turn could contribute to reduced inflammation. Our findings align with studies that have shown a link between autonomic dysfunction and systemic inflammation in CHF. Several studies have shown [24,25] and demonstrated that interventions aimed at improving autonomic function can reduce inflammatory markers in CHF patients. Our results further support this by showing a strong correlation between RS and WBC. Similarly, the correlation between CRF and PCT indicates that enhanced cardiopulmonary resonance may be linked to reduced inflammatory markers, further supporting the role of autonomic modulation in improving overall health status.
The observed correlation between CRF and serum creatinine is supported by studies that have shown a relationship between cardiopulmonary efficiency and renal function. A study by Kirkman [26] reported that interventions that improve cardiopulmonary function can also enhance renal outcomes in CHF patients.
To sum up, IBT could be mediated through enhanced vagal activity, which has anti-inflammatory effects and promotes better cardiopulmonary and renal function. On the contrary, IBT may reduce sympathetic overactivity, leading to decreased inflammation and improved organ function. Simultaneously, enhanced cardiopulmonary resonance may improve oxygenation and metabolic efficiency, which in turn can reduce inflammation and support better renal function.
While our study has focused on the effects of IBT on ANS function in CHF patients, we recognize the potential benefits of combining exercise with paced breathing training. Exercise training is a well-established component of CHF rehabilitation, with strong recommendations for improving exercise capacity, quality of life, and reducing hospitalizations [27]. It has also been shown to enhance ANS function, which is a critical aspect of CHF management [27]. Future studies should explore the combined effects of exercise and paced breathing training on ANS-related indices. This integrated approach could offer additional benefits by addressing both the cardiovascular and respiratory aspects of CHF rehabilitation.
However, the IBT trial study is preliminary. Further research should expand to larger cohorts of CHF patients and explore applications for other cardiac conditions.
5. Conclusions
In conclusion, our study demonstrates that IBT significantly improves ANS function in patients with CHF, as evidenced by enhanced cardiopulmonary resonance indices. These findings highlight the potential benefits of incorporating IBT into CHF rehabilitation programs to enhance clinical outcomes. Future research should explore the combined effects of IBT and other interventions, such as exercise training, to further optimize rehabilitation strategies. Additionally, the role of psychological factors in modulating these effects warrants further investigation. Overall, our study underscores the importance of addressing autonomic dysfunction in CHF management and provides a foundation for developing comprehensive rehabilitation approaches.
CRediT authorship contribution statement
Xiaoling Liu: Writing – original draft, Visualization, Validation, Methodology. Ziwei Shan: Visualization, Methodology, Data curation. Ting Shen: Methodology, Conceptualization. Megan Lo: Writing – review & editing. Lin Luo: Methodology, Conceptualization. Qifan Sun: Methodology, Conceptualization. Lemin Wang: Supervision, Conceptualization. Guanghe Li: Methodology, Conceptualization. Yumei Jiang: Methodology, Conceptualization. Dejie Li: Methodology, Conceptualization. Mengyi Zhan: Methodology, Conceptualization. Liang Zheng: Writing – review & editing, Validation, Methodology, Conceptualization. Jiankang Wu: Writing – review & editing, Validation, Supervision, Software, Conceptualization. Yuqin Shen: Writing – review & editing, Supervision, Methodology, Funding acquisition, Conceptualization.
Funding
This work was supported by the Key Research and Development Special Project of the Autonomous Region (2022B03023-3); the Shanghai Hospital Development Center Foundation — Shanghai Municipal Hospital Rehabilitation Medicine Specialty Alliance (SHDC22023304); and the Key Supported Discipline of Health System in Shanghai (2023ZDFC0302).
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
We would like to thank all the authors who provided important contributions to this trial. Xiaoling Liu drafted and revised the manuscript. Ziwei Shan carried out the trial. Ting Shen designed the clinical trial protocol. All the authors participated in the design of the clinical trial and gave the manuscript their final approval.
Contributor Information
Jiankang Wu, Email: jkwu@ucas.ac.cn.
Yuqin Shen, Email: sy_1963@126.com.
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