Published online Dec 20, 2025. doi: 10.5493/wjem.v15.i4.110904
Revised: July 15, 2025
Accepted: October 22, 2025
Published online: December 20, 2025
Processing time: 184 Days and 12.6 Hours
The six-minute walk test (6MWT) allows to determine, in addition to the main parameters, the time of heart rate recovery (THRR), cardiac function, adaptation index (AI), which characterize the compensatory reserve of patients with chronic heart failure (CHF). At the same time, the significance of these parameters in patients taking beta-blockers for CHF is insufficiently studied, taking into account the negative chronotropic effect of drugs. In this regard, it is relevant to identify factors that can characterize the compensatory capabilities of a patient with CHF during 6MWT, not related to the calculation of heart rate.
To identify hemodynamic indicators of the adaptive capabilities of patients with CHF during paired 6MWT depending on their intake of beta-blockers.
Seventy-four patients with compensated CHF due to coronary
There were no significant associations between adaptation characteristics and DECG parameters or functional class (FC) of CHF in patients of the main group. In the comparison group, the indicators of compensatory reserve were significantly and directly associated with left ventricular ejection fraction (LVEF), and inversely with FC CHF and cardiac cavity size. In both groups, a greater difference in systolic blood pressure between the end of the first and the beginning of the second 6MWT was significantly associated with a higher index of right ventricular systolic dysfunction (Tricuspid annular plane systolic excursion) and LVEF, as well as a smaller left ventricular size and mass, and a lower pulmonary artery systolic pressure in patients in the main group.
Systolic BPV, measured immediately after 6MWT and 20 minutes after its completion, can indirectly characterize the compensatory reserve in patients with CHF, regardless of their beta-blocker intake.
Core Tip: Analysis of hemodynamics was conducted during six-minute walk test (6MWT) of patients with chronic heart failure (CHF). In patients who were taking beta-blockers, assessment of the compensatory reserve using routine methods was not significantly correlated with the severity of CHF. It was found that the assessment of short-term systolic blood pressure variability (BPV), measured immediately after 6MWT and 20 minutes after its completion, can characterize the compensatory reserve in CHF, regardless of whether they are taking beta blockers. Monitoring BPV during routine 6MWT might help doctors personalize recommendations for patients with CHF who are taking beta blockers.
- Citation: Akimova NS, Konshina LE, Runnova AE, Zhuravlev MO, Bogdanova TM, Kiselev AR, Shvarts YG. Short-term blood pressure variability as an indicator of the adaptive capacity of patients with chronic heart failure. World J Exp Med 2025; 15(4): 110904
- URL: https://www.wjgnet.com/2220-315X/full/v15/i4/110904.htm
- DOI: https://dx.doi.org/10.5493/wjem.v15.i4.110904
The 6-minute walk test (6MWT) is a straightforward and efficient tool for evaluating the severity of chronic heart failure (CHF) and the exercise tolerance of patients with this condition. It is a standard practice recommended by international cardiologists for routine clinical use[1-3]. It is worth noting that, in addition to its well-established and widely employed algorithm for determining the functional class (FC) of CHF based on the New York classification and the distance covered during the 6MWT, this procedure can also serve as a valuable tool for examining the functional capacity of CHF patients, assessing their level of physical activity, and determining their adaptive capabilities. These parameters are not only principal from a clinical perspective but also hold significant prognostic value[4]. One of the similar indicators of compensatory reserve is the adaptation index (AI) and cardiac function. To calculate these parameters, a paired 6-minute test is conducted[5], which takes into account the distance covered by the patient and the time it takes for the heart rate to recover during the first and second tests. Based on the results of research on this topic, it can be concluded that with an adequate adaptive reserve to physical exertion in patients with CHF, the heart rate decreases during repeated testing, and the distance covered increases. The greater the adaptive capacity, the better the prognosis for patients with CHF according to literature data[5]. The assessment of patients' adaptive capabilities by this method has several undoubted advantages. These include accessibility, simplicity of implementation and the absence of significant material costs. However, at the same time, it is also important to take into consideration the medication regimen that the patient is receiving.
To date, it remains unclear whether the calculated parameters of exercise test, which take into account heart rate (HR), time of HR recovery (THRR) and speed of HR recovery (which is another indicator characterizing adaptive reserve and the severity of CHF, defined as the difference between the maximum HR during physical activity and the HR one minute after the completion of the 6MWT, that also have prognostic value)[6-8], have the same high clinical and prognostic significance when taking beta-blockers (HR-lowering and used for CHF with evidence level A). According to the findings of Budnevsky et al[5], the use of beta-blockers appears to enhance the outcomes of 6MWT by increasing the distance covered, while simultaneously reducing the rate of HR recovery.
It is evident that in order to mitigate the impact of beta-blockers on the outcomes of 6MWT, a temporary suspension of their administration may be proposed. However, this recommendation may not always be feasible. In such circumstances, it would be relevant to explore the use of an alternative parameter that does not rely on HR calculations but retains appropriate clinical and predictive significance[6-8].
In recent times, there has been a growing interest among researchers and practicing cardiologists in the area of blood pressure variability (BPV)[9]. The fluctuations in BP observed during exercise tests may provide insights into the hemodynamic response to physical activity[10]. It is noteworthy that the relationship between BP changes during 6MWT and the severity of CHF characteristics, as well as the parameters measured during this test, remains underexplored.
The aim of the study was to conduct a comparative analysis of hemodynamic parameters, including BP, HR, BPV during the 6MWT, in patients with CHF, with and without beta-blocker therapy, and to identify which parameters can characterize the compensatory capacity of these patients.
The study was conducted at the University Clinical Hospital No. 1 named after S.R. Mirotvortsev in Saratov and was of an observational nature. A total of 46 individuals with compensated CHF II-III FC were included in the main group, which occurred against the background of existing coronary heart disease (CHD) and/or hypertension (HT) as underlying conditions. Their age ranged from 42 to 65 years. All patients in the main group received standard treatment for CHF, including beta-blockers, as well as treatment for CHD and/or HT according to current clinical guidelines[3,11,12]. The patients' beta-blocker regimen was as follows: They took the medication once a day at the individual maximum tolerated dosage in order to achieve the target HR range. Most patients in the main group received bisoprolol as their beta-blocker medication. The minimum daily dosage of the drug was 5 mg and the maximum dosage was 10 mg. One patient received nebivolol at a daily dose of 5 mg. Three patients received metoprolol succinate at a daily dosage of 100 mg each.
The exclusion criteria were as follows: Limitation of the distance traveled during 6MWT due to significant musculoskeletal system diseases; acute myocardial infarction, cardiovascular surgery or percutaneous coronary intervention within 3 months prior to participation; unstable angina pectoris within 1 month; registration of the following values before the test: HR above 120 bpm at rest, systolic BP (SBP) above 180 mmHg, and diastolic BP (DBP) over 100 mmHg; any pathological condition that might prevent participation in the study, such as blindness, deafness, and speech problems, etc.; life-threatening or uncontrolled heart rhythm disturbances, including those with clinical manifestations, or persistent ventricular tachycardia or atrial fibrillation, flutter; taking medications other than beta-blockers that can affect HR; current or previous malignancies of any organ system, except localized basal cell carcinoma of the skin; any other disease/condition of the patient, which, in the opinion of the researcher, could increase the patient's risk to their health during participation in the study or prevent them from complying with the study requirements or completing the study.
The comparison group comprised 28 individuals aged between 41 and 65 who had not been taking beta-blockers at the time of 6MWT and for at least one month prior to the study. Typically, these patients had discontinued beta-blocker therapy on their own initiative, as revealed during routine follow-up consultations. Following 6MWT, participants were advised to resume beta-blocker treatment. The remaining criteria for inclusion and exclusion from the comparison group remained consistent with those of the primary group. A comprehensive overview of the clinical characteristics of these patients is provided in Table 1.
| Indicator | Main group (n = 46) | Comparison group (n = 28) | Significance of differences, |
| Age (years) | 60 (56.0,64.0) | 60.0 (55.0,65.0) | 0.975 |
| Male | 30 (65.22) | 18 (64.29) | 0.934 |
| Female | 16 (34.78) | 10 (35.71) | 0.769 |
| Height (cm) | 166.8 ± 7.7 | 167.1 ± 6.6 | 0.885 |
| Body weight (kg) | 86.2 (74.3-94.2) | 82.7 (70.2-90.3) | 0.921 |
| BMI (kg/m2) | 32.07 (25.64-35.14) | 29.13 (28.12-30.22) | 0.806 |
| FC CHF | 0.309 | ||
| II FC | 16 (34.7) | 12 (42.9) | |
| III FC | 30 (55.3) | 16 (57.1) | |
| DECG parameters | |||
| LVEDD (cm) | 5.08 (4.7-5.2) | 5.2 (4.8-5.3) | 0.578 |
| LVESD | 3.22 (2.9-3.6) | 3.13 (3.1-3.6) | 0.888 |
| LAESD | 3.7 (3.5-4.1) | 3.7 (3.6-4.1) | 0.527 |
| LVEF (%) | 64.0 (58.0-66.0) | 61.0 (59.0-67.0) | 0.737 |
| LVMMI (g/m2) | 108.0 (99.0-128.0) | 105.0 (94.0-150.0) | 0.283 |
| SPAP (mmHg) | 28.0 (25.0-36.0) | 27.0 (24.0-27.0) | 0.052 |
| TAPSE (cm) | 2.12 (2.0-2.22) | 2.1 (2.0-2.2) | 0.599 |
| 6MWT parameters | |||
| Distance covered, test 1 (meters) | 362.0 (310.0-440.0) | 394.0 (375.0-451.0) | 0.328 |
| Distance covered, test 2 (meters) | 390.0 (307.0-471.0) | 416.0 (395.0-487.0) | 0.205 |
| THRR, test 1 (second) | 94.0 (41.0-197.0) | 62.5 (45.0-68.0) | 0.403 |
| Adaptation index | 1.05 (1.02-1.1) | 1.07 (1.03-1.1) | 0.317 |
| SBP initial (before starting 6MWT) (mmHg) | 127.9 (117-139) | 129.6 (109,136) | 0.783 |
| SBP1 (immediately after 6MWT) (mmHg) | 137.6 (116-151) | 140.1 (123-154) | 0.728 |
| SBP2 (20 minutes after 6MWT) (mmHg) | 120.2 (110-129) | 120.9 (108-126) | 0.896 |
| SBPV1-2 6MWT (mmHg) | 36.0 (25.0-41.0) | 32.0 (26.0-43.0) | 0.709 |
As shown in Table 1, the main characteristics of the study groups were homogeneous and comparable. In particular, there are no statistically significant differences in terms of age, gender and structural and functional parameters related to CHF severity between the groups. After obtaining informed consent and undergoing a standard clinical examination, all study participants underwent echocardiography using Doppler techniques (DECG), as well as a paired 6MWT. During DECG, parameters such as the left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left atrium end-systolic dimension (LAESD), left ventricular ejection fraction (LVEF), left ventricular myocardial mass index (LVMMI), systolic pulmonary arterial pressure (SPAP), as well as tricuspid annular plane systolic excursion (TAPSE), were measured. 6MWT was conducted in accordance with established clinical guidelines[1].
The interval between the two testing sessions was 20 minutes during which the subject remained at rest. Prior to and following each test pulse oximetry was conducted, Borg scale was completed, immediately before and after the end of each 6MWT HR and BP were recorded, and the AI, THRR, pulse pressure, and difference in systolic and diastolic BP were calculated both before and after the initial and subsequent 6-minutes probes, as well as in comparison between them.
The study employed a range of statistical techniques, including one-way analysis of variance, parametric and nonparametric correlation analyses, depending on the nature of the data Kendall tau coefficients and Spearman's rank correlation coefficients were employed for nonparametric analyses. The article presents only statistically significant correlations. Given the extensive nature of the analyzed data, a multivariate analysis utilizing a generalized normalized logarithmic model was also conducted, with the Wald criterion taken into consideration. The statistical analysis was performed using the Statistica 10.0 software.
The following findings were obtained from the study. During the repeated exertional stress tests, the patients in the primary group covered an average distance of 362 meters during the first trial and 394 meters during the second. The patients in the control group covered an average of 394 and 416 meters, respectively. After the first 6MWT, the average THRR of the patients in the primary group was higher than that of the control group; however, after the second trial, the average values were nearly equal. The AI values calculated for both the primary and control groups were similar.
Through a paired correlation analysis, it has been established that during dual 6MWT in patients not taking beta-blockers, there is a significant correlation between THRR, AI and LVEF, FC CHF. Specifically, a higher LVEF is associated with a higher AI and a lower THRR, with correlations of r = 0.38 and -0.42 respectively, CHF FC is inversely correlated with the AI, with an R value of -0.34. Furthermore, patients in the control group exhibited significant inverse correlations between the AI and LVESD, LVEDD, LAESD and LVMMI, with R = -0.33, R = -0.34, R = -0.66, and R = -0.33, respectively. Additionally, there was a positive correlation between the AI and TAPSE, with an R of 0.37. Moreover, a longer THRR was associated with an increase in LVESD, LVEDD, LAESD and LVMMI (r = 0.68; r = 0.49; r = 0.51; r = 0.46). These findings are consistent with previous research and confirm the reduced compensatory capacity in patients with advanced CHF.
With regard to the patients in the primary group who were taking beta-blockers, no reliable correlation was observed between the AI and THRR, as well as the parameters of DECG and FC CHF. It is evident that the assessment of compensatory reserve, using the standard method, which involves calculating THRR and AI during 6MWT with the use of medications affecting HR, may not be completely accurate. In order to improve the evaluation of the adaptive capacity of patients with heart failure during 6MWT, we calculated the difference in HR at several time points: Before and after the first and second 6-minute walking sessions; before the first test and after the completion of the second test; and after the first test and just prior to starting the second one. However, we did not find any significant correlations with the indicators that characterize the severity of CHF, as well as the distance covered during the test.
At the subsequent stage, for analogous time points, we calculated the divergence (variability) in BP levels, specifically, SBP and DBP separately, for patients in the main group and those in the control group. The correlation analysis revealed a multitude of statistically significant correlations between short-term fluctuations in BP and parameters of heart failure severity. The highest number of statistically significant correlations were observed regarding the difference in SBP (SBP variability - SBPV) between the end of the first 6MWT and the beginning of the second one, 20 minutes following the completion of the initial test (SBPV1-2 6MWT).
It was determined that in the patients of the primary cohort, a higher level of SBPV1-2 6MWT was correlated with lower values of LVEDD, LVESD, LVMMI, SPAP and CHF FC (R = -0.62, R = -0.72, R = -0.56, R = -0.36, and R = -0.34 respectively), while a positive correlation was observed with LVEF and TAPSE (r = 0.68, r = 0.36). In the control group, there was a positive association between SBPV1-2 6MWT and TAPSE (r = 0.37), as well as LVEF (r = 0.55).
The correlations observed between the indicators identified and calculated during the paired 6-minute exercise test were not likely to be coincidental. The parameters for adaptive characteristics calculated by using classical formulas that consider THRR, assuming that patients are not taking beta-blockers, were reliably associated with measures of heart failure severity, which indirectly supports their significant prognostic significance. Conversely, the use of medications with a negative chronotropic effect significantly alters the situation, necessitating the assessment of other measures to determine the compensatory abilities of patients with CHF.
The findings of this investigation provide compelling evidence that the identification of short-term fluctuations in BP during exercise testing can serve as a valuable parameter in clinical practice. Notably, in the present study, it was the reduction in short-term BPV that showed a significant correlation with the more severe indicators of CHF. There is a substantial body of research literature suggesting that increased BPV in HT is an independent risk factor for cardiovascular risk[12]. However, there are also studies which indicate that in patients with CHF it is the decrease in BPV that is often associated with a more severe degree of cardiac and extracardiac pathology[9].
It is reasonable to postulate that the rise in BP induced by physical activity diminishes more rapidly following its cessation, the more robust and efficient the compensatory mechanisms of the circulatory system remain. This accounts for the significant disparity in the observed measurements, namely, the variability in BP levels.
According to previous studies, the use of beta blockers, such as bisoprolol, metoprolol succinate, and nebivolol, among others, may affect BPV in patients[13-16]. When these drugs were used in patients with HT and CHF, there was a significant reduction in the standard deviation and amplitude of SBP and DBP fluctuations during both short- and long-term BP monitoring. This indicates a decrease in BPV during treatment with these medications. It should be noted that bisoprolol, nebivolol, and metoprolol succinate are highly selective beta-1 blockers. However, nebivolol also has an additional vasodilating effect due to its modulation of nitric oxide. These differences in pharmacokinetic and pharmacodynamic properties may lead to different effects on BPV[15]. Considering that only one patient in the main group received nebivolol and only three patients took metoprolol succinate, while the rest used bisoprolol, it seems unlikely that this would have affected the results of our study. Additionally, with regard to the results of our research, the short-term variability in SBP, measured immediately after the 6-minute exercise test and 20 minutes of rest after its completion, was significantly associated with indicators of CHF severity, both in the group of patients who received beta blockers and in those in the control. Thus, the results of our study do not seem to be influenced by the use of beta blockers by patients. However, it is worth noting that, unlike in the control group, in the main group the indicators of VAD studied are associated not only with echocardiographic parameters but also with clinical ones (FC CHF), which characterize the severity of heart failure. Perhaps this connection may be explained by the specific influence of beta-blockers on hemodynamics, although this hypothesis requires further investigation and confirmation.
Reduced SBPV1-2 6MWT level in patients with CHF, both those taking and not taking beta-blockers, may reflect left and right ventricular systolic dysfunction, including through its association with DECG characteristics in the main group of patients. Additionally, it may serve as an unfavorable prognostic indicator in patients with CHF with CHD and HT.
There are several limitations to the study that should be noted. Firstly, the small sample size and single-center design may limit the generalizability of the results. Secondly, the predictive value of BVP for long-term outcomes such as rehospitalization and mortality has not been fully established, indicating a need for further research in this area. Finally, in clinical practice, it is important to explore how BVP can be incorporated into routine heart failure management, including determining specific thresholds and operational procedures.
While this hypothesis requires additional confirmation through a larger prospective observational study, the findings from this pilot project provide a high degree of confidence in these conclusions.
The evaluation of BPV during 6MWT, and particularly the difference in SBP immediately after 6MWT and 20 minutes following its completion, can indirectly characterize the compensatory capacity of patients with CHF regardless of beta-blocker use. Such short-term BPV during 6-minute probe also hold potential for prognostic value. Further prospective studies on a larger patient cohort are required to answer this question definitively. It is anticipated that monitoring of BPV during routine 6MWT could assist physicians in more precisely assessing the health status of patients on beta-blockers and personalizing clinical recommendations to enhance the quality of life and long-term prognosis for patients with CHF.
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