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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 35  |  Issue : 2  |  Page : 364-370

Correlation of blood pressure changes with the functional capacity in patients with heart failure with preserved and midrange ejection fraction


Department of Cardiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt

Date of Submission16-Sep-2021
Date of Decision11-Oct-2021
Date of Acceptance26-Oct-2021
Date of Web Publication27-Jul-2022

Correspondence Address:
Abdulsalam M Algamal
Elteraa Street, Mansoura
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_168_21

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  Abstract 


Objective
To assess different blood pressure (BP) parameters and their changes after 6-min walk test (6-MWT) in patients with heart failure with midrange ejection fraction (HFmEF) and heart failure with preserved ejection fraction (HFpEF) and correlate them with the functional capacity (FC) as assessed by 6-min walk distance (6-MWD).
Background
The 6-MWT reflects the daily activity of patients with HF who develop progressive limitation of FC.
Patients and methods
A total of 40 patients with HFmEF and 50 patients with HFpEF were enrolled. The 6-MWT was performed according to the American Thoracic Society guidelines 2002. Different BP parameters were measured before and after 6-MWT, and 6-MWD was recorded.
Result
The mean 6-MWD was 325.3 ± 56.84 m in all patients, 316.1 ± 61.33 m in HFmEF group, 332.66 ± 52.44 m HFpEF group. The 6-MWD and limited FC showed no significant difference between the two groups. Independent predictors of limited FC assessed by the 6-MWD were lower EF, pulse pressure (PP), and proportionate pulse pressure (PPP) and higher diastolic blood pressure in patients with HFmEF and lower EF in patients with HFpEF. Cutoff points for prediction of limited FC as assessed by 6-MWD less than 300 m included PP less than 32.5 mmHg and PPP less than 30.22% in patients with HFmEF, PP less than 37.5 mmHg and PPP less than 32.67% in patients with HFpEF, and EF less than 42.5% in all patients.
Conclution
A simple bedside measurement of BP parameters correlates with the FC and can predict limited FC represented by 6-MWD less than 300 m in patients with HFmEF and HFpEF.

Keywords: 6-min walk distance, 6-min walk test, functional capacity, heart failure with midrange ejection fraction, heart failure with preserved ejection fraction


How to cite this article:
Algamal AM, Osman AM, Elhusseiny SH, Elshal AM, Salem MA. Correlation of blood pressure changes with the functional capacity in patients with heart failure with preserved and midrange ejection fraction. Menoufia Med J 2022;35:364-70

How to cite this URL:
Algamal AM, Osman AM, Elhusseiny SH, Elshal AM, Salem MA. Correlation of blood pressure changes with the functional capacity in patients with heart failure with preserved and midrange ejection fraction. Menoufia Med J [serial online] 2022 [cited 2024 Mar 29];35:364-70. Available from: http://www.mmj.eg.net/text.asp?2022/35/2/364/352130




  Introduction Top


Heart failure (HF) is a worldwide health condition with high morbidity and mortality associated with limited functional capacity (FC) and impaired quality of life. The American Heart Association/American College of Cardiology and the European Society of Cardiology classified HF according to ejection fraction (EF) into HF with reduced EF (HFrEF) less than 40%, HF with midrange EF (HFmEF) between 40 and 49%, and HF with preserved EF (HFpEF) more than or equal to 50%[1]. Among patients with HF, the prevalence of HFpEF ranges from 33 to 39%, HFmEF from 13 to 15%, and HFrEF from 52 to 47%[2]. Symptoms of HF in patients with HFpEF may be caused by impaired relaxation, decreased compliance, increased filling pressure of the left ventricle, and evidence of subtle abnormalities of the systolic function[3]. Cardiopulmonary exercise testing is the diagnostic gold standard of FC[4]. The 6-min walk test (6-MWT) is a well-tolerated simple clinical test that can be used as an alternative in patients with HF[5]. The normal response of blood pressure (BP) during exercise is an increase in systolic blood pressure (SBP) and a maintained or slightly decreased diastolic blood pressure (DBP)[6]. Low pulse pressure (PP) was found to be an independent predictor of mortality in HF[7]. Proportional pulse pressure (PPP), defined as the ratio of PP and SBP, correlated with FC and identified low cardiac index[8].

Few previous studies have evaluated the correlation of different BP parameters before and after the 6-MWT with FC represented as 6-min walk distance (6-MWD). The aim of this study was to assess different BP parameters and their changes after the 6-MWT in patients with HFmEF and HFpEF and correlate them with the FC of the patients assessed by the 6-MWD.


  Patients and methods Top


This is a single-center prospective study that enrolled patients who presented with clinical manifestations of HF and were admitted to the Cardiology Department from November 2020 to July 2021 and given optimal medical therapy. The main presentations included dyspnea on exertion and at rest, orthopnea, paroxysmal nocturnal dyspnea, fatigue, chest tightness, lower limb edema, jugular venous distention, and pulmonary rales. There were no significant differences in the clinical manifestations among patients with HFrEF, HFmEF, and HFpEF. After echocardiography, patients with HFmEF (EF between 40 and 49%) and HFpEF (EF ≥50%) were included in the study. The diagnosis of HFpEF was challenging and determined by the objective demonstration of structural and/or functional alterations that link the clinical presentation to HFpEF. To diagnose HFpEF, we relied on echocardiographic criteria, which included left atrial volume index more than 34 ml/m2, left ventricular mass index more than or equal to 149 g/m2 for males and more than or equal to 122 g/m2 for females, relative wall thickness more than 0.4, early diastolic transmitral flow velocity to early diastolic mitral annular tissue velocity ratio (E/e′) more than or equal to 15, septal early diastolic tissue Doppler velocities (e′) less than 9 cm/s, lateral e′ less than 10 cm/s, tricuspid regurge peak velocity more than 2.8 m/s, pulmonary artery systolic pressure more than 35 mmHg, and reduced global longitudinal strain less than 16%[9]. Patients without an objective evidence of cardiac functional or structural alterations as the underlying mechanism of symptoms of HF were excluded from the study. We excluded patients refusing to participate in the study, patients with HFrEF (EF <40%), patients with chronic obstructive lung disease, patients with renal or hepatic impairment, and patients with diseases affecting walking such as musculoskeletal diseases or morbid obesity.

Sample size calculation

The calculated sample size of the study was 66 participants at 5% level of significance and 90% power of the study, using the following formulas[10]: C = 0.5 × ln[(1 + r)/(1 − r)]=0.4847 and total sample size = N=[(Zα+Zβ)/C]2 + 3 = 66 (the standard normal deviate for α=Zα=2.58, the standard normal deviate for β=Zβ=1.26, and the expected correlation coefficient for PP and pulse wave velocity in patients with HF (r = 0.45)[11]). The sample size was increased by 20% attrition rate to be 90 participants to compensate for incomplete data and to increase the study power.

After admission and control of the symptoms of patients, BP less than 140/90 mmHg, and heart rate less than 100 beats per minute, an informed consent was obtained from each patient. All participants in the study were subjected to full history taking, stressing on cardiovascular risk factors and clinical presentation, thorough clinical examination stressing on HF signs, 12-lead resting ECG, and two-dimensional transthoracic echocardiography with ECG gating according to standard techniques using a General Electric Vivid E9 XD clear dimensions ultrasound system (GE Healthcare, USA) North Richland Hills, TX 76180, United States Phone: using the M5Sc transducer.

Six-min walk test

SBP and DBP before the 6-MWT (SBP 1 and DBP 1) were recorded. Moreover, we calculated mean BP, PP, and PPP before the 6-MWT (mean BP 1, PP 1, and PPP 1), where PP = SBP–DBP, mean BP = SBP + PP/3, and PPP = PP/SBP. The 6-MWT was performed according to the American Thoracic Society guidelines 2002[12] with patients wearing comfortable clothing and walking on a 30-m flat obstacle-free corridor. Patients were requested to walk unaccompanied as far as they can for 6 min. The test was stopped if the patients felt unwell or developed chest pain or dyspnea. All patients completed the test. In HFmEF group, two (5%) patients requested one rest stop and six (15%) patients experienced mild breathing difficulty, whereas, in HFpEF group, one (2%) patient requested one rest stop and four (8%) patients experienced fatigue. After the 6-MWT, patients were seated and BP was measured. SBP and DBP after the 6-MWT (SBP 2 and DBP 2) were recorded. Moreover, mean BP, PP, and PPP after the 6-MWT (mean BP 2, PP 2, and PPP 2) were calculated. The changes in SBP, DBP, mean BP, PP, and PPP after the 6-MWT were calculated. Moreover, we recorded abnormal BP response to exercise (ABPRE), defined as a decrease, no increase, or an increase of the SBP after exercise by less than 20 mmHg[13]. In our study, we defined limited FC as a 6-MWD less than 300 m as in agreement with most studies, which showed that 6-MWD less than 300 m was predictive of total or cardiovascular mortality and hospitalization for worsening HF[14].

Statistical analysis

Data were analyzed using the Statistical Package of the Social Sciences (SPSS) IBM Corp., Armonk, New York, USA program for Windows (standard version 21). The normality of data was first tested with one-sample Kolmogorov–Smirnov test. Qualitative data were presented as number and percent and analyzed by χ2 test. Continuous variables were presented as mean ± SD for normally distributed data. The two groups were compared with Student t test for normal data. Pearson correlation was used to correlate continuous variables. Significant variables were entered into logistic regression model using the enter statistical technique to predict the most significant determinants and to control for possible interactions and confounding effects. Sensitivity and specificity at different cutoff points were tested by the receiver operating characteristic (ROC) curve. The results were considered significant when P vaue less than or equal to 0.05. The smaller the P value obtained, the more significant are the results.

Ethical consideration

The study protocol was approved by the Institutional Research Board of Mansoura, Faculty of Medicine (ID number R.20.11.1068). Informed consent was obtained from each patient. Confidentiality and personal privacy were respected at all levels of the study. Collected data will not be used for any other purpose.


  Results Top


The study included 90 patients with HF divided according to EF into two groups: 40 patients with HFmEF and 50 patients with HFpEF. [Table 1] shows the clinical characteristics, resting BP parameters, 6-MWD, and BP changes after 6-MWT in both study groups. Patients with HFpEF had significantly higher age, hypertension, SBP 2, PP 2, PPP 2, PP change, PPP change, and SBP change and significantly lower diabetes, DBP 2, DBP change, and ABPRE. There was no significant difference between the two groups regarding the FC represented by 6-MWD or limited FC represented by 6-MWD less than 300 m.
Table 1: Clinical characteristics and blood pressure parameters of all patients

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In patients with HFmEF, 6-MWD showed a significant positive correlation with EF, SBP 1, PP 1, and PPP 1 and a significant negative correlation with DBP 1, PP change, PPP change, and SBP change [Table 2]. After multivariate regression analysis and adjustment for confounding factors, predictors of limited FC represented by 6-MWD less than 300 m were lower EF, PP 1, and PPP 1 and higher DBP 1 [Table 3]. In patients with HFpEF, 6-MWD showed a significant positive correlation with EF, SBP 1, PP 1, PPP 1, and DBP change and a significant negative correlation with DBP 1, mean BP 1, PP change, PPP change, and SBP change [Table 2]. After multivariate regression analysis and adjustment for confounding factors, predictors of limited FC represented by 6-MWD were lower EF [Table 3].
Table 2: Correlation between 6-min walk distance and clinical characteristics

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Table 3: Linear regression analysis for prediction of limited functional capacity indicated by 6-min walk distance <300 m in HFmEF and HFpEF

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Receiver operating characteristic curve analyses showed that the ideal cutoff values for prediction of limited FC as indicated by 6-MWD less than 300 m included PP 1 less than 32.5 mmHg and PPP 1 less than 30.22% in patients with HFmEF [Table 4],[Figure 1]a and PP 1 less than 37.5 mmHg and PPP 1 less than 32.67% in patients with HFpEF [Table 4],[Figure 1]b and EF less than 42.5% in all patients [Table 4],[Figure 1]c.
Figure 1: Receiver operating characteristics (ROC) curve for prediction of limited functional capacity indicated by 6-MWD less than 300 m: (a) HFmEF (n = 40) (PP, PPP). (b) HFpEF (n = 50) (PP, PPP). (c) All patients (n = 90) (EF). 6-MWD, 6-min walk distance, HFmEF, heart failure with midrange ejection fraction; HFpEF, heart failure with preserved ejection fraction, EF, ejection fraction; 1, before 6-min walk test; PP, pulse pressure; PPP, proportionate pulse pressure.

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Table 4: Receiver operating characteristic curve for prediction of limited functional capacity indicated by 6-min walk distance <300 m

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  Discussion Top


Exercise tolerance and FC of patients with HF can be assessed by a simple clinical test as 6-MWT[3]. We investigated the BP changes with 6-MWT in patients with HFmEF and HFpEF, correlated these changes with the FC of the patients assessed by 6-MWD, and investigated the predictors of limited FC of patients defined as 6-MWD less than 300 m. In our study, ABPRE occurred in 28 (31.1%) patients and occurred significantly more in patients with HFmEF than in those with HFpEF. Previous studies showed that ABPRE occurred in 36% of patients with HF[15].

In our study, patients with HFpEF compared with patients with HFmEF were significantly older with significantly higher prevalence of hypertension and lower prevalence of diabetes but no significant difference regarding sex distribution. In other studies, HFpEF was more prevalent in older age patients, hypertensive patients, and women[16],[17]. Branca et al.[18] found that HFmEF was more prevalent in hypertensive patients and women. However, Webb et al.[19] found no significant difference between patients with HFpEF and those with HFmEF regarding age, sex distribution, and diabetes but significantly higher prevalence of hypertension in HFpEF.

In our study, there was no significant difference between the two groups regarding different BP parameters before 6-MWT; this was owing to the control of BP after admission to the hospital and before starting the 6-MWT. Patients with HFmEF had significantly higher DBP 2, DBP change, and ABPRE and significantly lower SBP 2, PP 2, PPP 2, PP change, PPP change, and SBP change. In HFmEF group, the mean 6-MWD was 316.1 ± 61.33 m, and 17 (42.5%) patients had 6-MWD less than 300 m. In HFpEF group, the mean 6-MWD was 332.66 ± 52.44 m, and 17 (33%) patients had 6-MWD less than 300 m. There was no significant difference between the two groups regarding the FC represented by 6-MWD or limited FC represented by 6-MWD less than 300 m. The average 6-MWD in patients with HFpEF showed high variability in different studies, for example, 262 m by Domínguez et al.[20], 352 m by Guazzi et al.[5], and 427 m by Rostagno et al.[21]. No previous studies evaluated 6-MWD in patients with HFmEF.

Few previous studies evaluated different BP parameters before and after 6-MWT and their correlation with the FC of patients with HF. Our study showed that in patients with HFmEF, 6-MWD showed a significant positive correlation with EF, SBP 1, PP 1, and PPP 1 and a significant negative correlation with DBP 1, PP change, PPP change, and SBP change. In patients with HFpEF, 6-MWD showed a significant positive correlation with EF, SBP 1, PP 1, PPP 1, and DBP change and a significant negative correlation with DBP 1, mean BP 1, PP change, PPP change, and SBP change. In our study, independent predictors of limited FC represented by 6-MWD less than 300 m were lower EF, PP 1, and PPP 1 and higher DBP 1 in patients with HFmEF and lower EF in patients with HFpEF.

In healthy participants and hypertensive patients, Ramos et al.[22] found that 6-MWD was inversely associated with mean BP, SBP, DBP, and PP, whereas Scott et al.[23] found that shorter 6-MWD was associated with older age, but PP was not significantly related to 6-MWD. In patients with HF, Zotter-Tufaro et al.[3] found a significant negative correlation between 6-MWD and age. In other studies, 6-MWD showed a significant negative correlation with male sex and age[24],[25]. Other studies showed a significant negative correlation between 6-MWD and age, female sex, and diabetes[26]. Ibrahimi et al.[27] found no correlation between 6-MWD and age, sex, or diabetes. Curtis et al.[28] found a significant positive correlation between 6-MWD and DBP. Some studies showed a uniformly weak correlation between 6-MWD and EF[29], whereas other studies found no correlation between 6-MWD and EF[5],[27]. Kawamata et al.[15] showed that ABPRE correlated with reduced exercise tolerance in HF. Kitai et al.[8] showed that postexercise PPP in chronic HF had better correlations with exercise capacity. In BIOSTAT-CHF study, independent predictors of a 6-MWD less than 300 m included older age and female sex[25].

In our study, the cutoff values for prediction of limited FC as indicated by 6-MWD less than 300 m included PP 1 less than 32.5 mmHg and PPP 1 less than 30.22% in patients with HFmEF, PP 1 less than 37.5 mmHg and PPP 1 less than 32.67% in patients with HFpEF, and EF less than 42.5% in all patients. Tokitsu et al.[11] concluded that PP less than 45 and more than 75 mmHg was closely associated with HFpEF prognosis, indicating the clinical significance of PP for risk stratification of HFpEF. Contrary to our results, Kitai et al.[8] found that higher PPP more than 38.0% was associated with increased mortality risk in patients with HFpEF. No previous studies evaluated PPP in patients with HFmEF. In patients with HFrEF, PPP less than 25% identified cardiac index less than or equal to 2.2[30].


  Conclusion Top


The mean 6-MWD for all patients was 325.3 ± 56.84 m, and 37.8% of patients had 6-MWD less than 300 m. In the HFmEF group, the mean 6-MWD was 316.1 ± 61.33 m, and 42.5% of patients had 6-MWD less than 300 m. patients with HFpEF, the mean 6-MWD was 332.66 ± 52.44 m, and 33% of patients had 6-MWD less than 300 m. ABPRE affected 28 (31.1%) of patients and was significantly higher in patients with HFmEF than in patients with HFpEF. There was no significant difference between the two groups regarding the FC represented by 6-MWD or limited FC represented by 6-MWD less than 300 m. Predictors of limited FC represented by 6-MWD were lower EF, PP 1, and PPP 1 and higher DBP 1 in patients with HFmEF and lower EF in patients with HFpEF. Cutoff points for prediction of limited FC as indicated by 6-MWD less than 300 m included PP 1 less than 32.5 MMHG and PPP 1 less than 30.22% in patients with HFmEF, PP 1 less than 37.5 MMHG and PPP 1 less than 32.67% in patients with HFpEF, and EF less than 42.5% in all patients.

Clinical applications and recommendations

The 6-MWT is well tolerated by patients with HF and easy to perform in clinical practice. A simple bed-side measurement of SBP and DBP and calculation of mean BP, PP, and PPP may be used to assess the FC of patients with HFmEF and those with HFpEF. Cutoff points of EF, PP, and PPP at rest can predict limited FC of patients with HFmEF and those with HFpEF as indicated by 6-MWD less than 300 m.

Future studies are needed to emphasize the role of BP measurements at rest and their change with exercise in the assessment of FC of patients with HF. Moreover, the studies should assess the possible use of BP values and their changes with exercise for follow-up of the FC of patients with HF and assessment of the response to different therapies.

Limitation of the study

This was a single-center study with relatively small number of patients.

Acknowledgements

The manuscript has been read and approved by all authors, and each author believes that the manuscript represents honest work.

All authors contributed to the idea formulation, study design, enrollment of patients, data collection, statistical analysis, manuscript editing, and final review.

Abdulsalam M. Algamal (guarantor) takes the responsibility for the integrity of the work as a whole from inception to published article.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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