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Comparisons of Dyspnea, Fatigue, and Exercise Intolerance Between Individuals with Heart Failure with High Versus Low Knee Extensor Muscle Strength.

INTRODUCTION

Maintaining muscle strength is problematic for patients with heart failure (HF) in the context of HF symptom management (dyspnea and fatigue) and exercise intolerance. Dyspnea and fatigue reduce ambulation in people with HF, which leads to deconditioning (poor exercise tolerance) and disuse atrophy, which further reduces the muscle strength required for performing daily activities and various physical functions. (1-4) Having adequate strength in the lower extremities (eg, knee extensor muscles) is a prerequisite to walking, standing from a chair, and climbing stairs, and is related to an individual's level of independence in performing activities of daily living. (5) Ultimately, with decreased muscle strength, dyspnea and fatigue become greater during minimal daily activities (4), (6) and impact the quality of life. (7) Despite the importance of muscle strength in relation to dyspnea, fatigue, and exercise intolerance, few studies have examined the relationship between muscle strength and symptoms in patients with HF. The purpose of this study was to compare the differences in symptoms of dyspnea, fatigue, and exercise intolerance between individuals with HF having low vs. high knee extensor muscle strength. Identifying reduced muscle strength early could potentially reverse the process of deconditioning, loss of muscle strength, and worsening HF symptoms.

Heart failure is a syndrome broadly defined as the mechanical failure of the heart to maintain systemic perfusion correspondent to the requirements of metabolizing tissues. (8) The reduced cardiac output and systemic perfusion leads to reduced nutritive blood flow to the active skeletal muscles. This results in reduced physical capacity and endurance for performing activities due to greater dyspnea and fatigue with activity, producing further deconditioning, and subsequently reduced muscle strength. (4), (9-11) However, studies have demonstrated that improvement of HF symptoms and exercise intolerance was not related to central cardiac function, but rather to neurohormonal and peripheral function of skeletal muscles. The 'muscle hypothesis' was devised to explain a vicious cycle of symptoms, exercise intolerance, and muscle weakness and the unique role of the peripheral circulation. (3), (12) Recently, Piepoli and Coats (13) revisited the 'muscle hypothesis' to address its critical role in development and management of HF symptoms and exercise intolerance.

Hypoxia or hypercapnea may occur during exercise, or even with low intensity activities of daily living (ADLs). Studies have reported that compared to a healthy, age- and gender-matched control groups, inspiratory muscle strength in HF was decreased and was associated with greater dyspnea on exertion. (14), (15) Little information is currently available on the association between lower-extremity muscle strength and dyspnea.

Fatigue is a complex symptom that people with HF have described as a loss of energy, thereby limiting independence in performing daily activities. (16) Subsequently, an increase in limb muscle fatigue may have a direct effect on muscle force output. (17), (18) Although fatigue is a subjective symptom reported by subjects indicating that they can't sustain activities, the relationship between skeletal muscle dysfunction (reduced muscle strength) and fatigue with ADLs in people with HF has not yet been fully explored and requires further study. (19)

Maintaining independence in performing ADLs is challenging for many people with HF. Yet, maintaining normal activities is important to preventing physical deconditioning and loss of lower-extremity muscle strength and exercise intolerance. (4), (20) Decreased lower-extremity muscle strength is identified as a predictor of exercise intolerance or limitation of function (eg, walking, climbing stairs, rising from a seated position, etc.) in elderly populations and people with cardiac diseases, including HF. (21), (22) Much of the equipment developed to measure muscle strength (eg, isokinetic devices) is impractical to use in a typical HF clinic. (5), (23) Hand-held dynamometry has been shown to be an accurate and reliable alternative method for assessing muscle strength in the clinical setting. (24), (25) To our knowledge, no studies to date have examined the differences in dyspnea, fatigue, and exercise intolerance between individuals with HF having high and low muscle strength of the knee extensors as measured by hand-held dynamometry.

METHODS

A cross-sectional design was used to examine the differences between two naturally occurring groups of people with HF: those with low knee extensor strength and those with high knee extensor strength. The proposed study was approved by the Committee on Human Subjects Review at the School of Nursing, Case Western Reserve University, and University Hospitals of Cleveland where the study was conducted.

Subjects

A total of 102 subjects were enrolled from HF clinics at University Hospitals, Cleveland, Ohio. Participants were considered eligible for this study if they met the following criteria: (1) at least 21 years of age, (2) diagnosed with stable HF and NYHA Functional Class II through IV, (3) cognitively intact as indicated by being able to describe what participation in the study would involve, and (4) able to speak and read English. Subjects had to be stable on an optimized medication regimen for at least one month before entering the study. Exclusion criteria were: walking or mobility difficulties due to (1) neuro-musculoskeletal conditions (such as lower extremity amputation, severe Parkinson's disease) or (2) severe pain from arthritis or intermittent claudication.

Order of Procedures

After obtaining written informed consent, illness data was collected from the medical records (eg, etiology of HF, medication history, and co-morbidities). In addition, the participants completed the questionnaires of dyspnea and fatigue. Lastly, muscle strength and exercise tolerance were measured.

Measures

Muscle strength was measured with a Nicholas handheld dynamometer (Model 01160, Lafayette, IN). The same dynamometer was used for all testing in the study. The dynamometer was calibrated by the manufacturer and properly "zeroed" by the same investigator prior to each test performed in this study. The dynamometer reading was recorded at the time the subject exerted maximum force against the dynamometer while the examiner applied resistance along the vector of rotation directly opposing the movement of the lower leg. For measuring knee extensor strength, participants sat on the examination table with their hips and knees at 90[degrees] of flexion, legs off the floor, and their hands crossed on the upper chest. The dynamometer was placed against the anterior surface of the lower leg, just proximal to the malleoli. Subjects were asked to extend their knees to 60[degrees] of knee flexion and not allow the examiner to "lower" the leg (i.e., an isometric "make test"). To stabilize the knee, the examiner was positioned in front of the subject with one hand placed on the distal anterior surface of the upper leg. Patients were instructed to avoid explosive contractions and to increase their effort gradually and quickly to a maximum effort after hearing the signal "ready, go" from the examiner. Subjects were told to stop contracting their muscles when the examiner finished counting to 3. All subjects were asked to "push as hard as they could against the dynamometer."

Two measurement trials were conducted on each lower extremity of the subject with a one-minute rest period in between trials. If the second trial measurement was not within 1 kg of the first, a third trial was performed with the greatest of these measurements taken as the maximal voluntary contraction. The peak knee extensor strength produced by each subject (either lower extremity) was used for the data analysis. The dynamometer was mechanically reliable with .8% error. (26) Marino and colleagues (27) reported test-retest reliability from .69 to .80. Prior to data collection, an inter-rater coefficient of .92 was established between the examiner and an expert physical therapist. All measurements were performed by the same examiner. Intra-rater reliability for all muscle strength tests was measured on every tenth subject and agreement was 98%.

Dyspnea was measured by a 10 cm visual analog scale (VAS) for 29 activities: 6 basic ADLs (eg, bathing, dressing), 7 instrumental ADLs (IADLs) (eg, shopping, housework) taken from the Older American Resource Services instrument; (28) and 16 activities required for lower-extremity functioning taken from the functional component of the Late Life Function and Disability Instrument (eg, lifting an object while climbing upstairs, getting up and down a flight of stairs, or walking several blocks). (29) The patients rated self-perceived severity of dyspnea from 0 "not at all" to 10 "dyspnea as bad as it can be." The ratings were summed for 3 separate scales: dyspnea with ADLs, dyspnea with IADLs, and dyspnea with physical functioning. The possible ranges were 0 to 60 for basic ADLs, 0 to 70 for IADLs, and 0 to 160 for the lower-extremity functioning, with higher scores indicating greater dyspnea. In the present study, Cronbach's alphas were .92 for ADLs, .84 for IADLs, and .96 for physical functioning.

Fatigue was measured by the revised behavioral/severity subscale of the Piper Fatigue Scale (PFS). The behavioral/ severity subscale focuses on the perceived impact of fatigue while doing daily activities. (30) Subjects rated items from 0 "no distress or none" to 10 "a great deal of distress" associated with daily activities. The sub-scale scores were calculated by taking the average of the 6 items included in the revised guideline provided by Piper. (30) The possible ranges of sub-scale score were 0 to 10, with higher scores indicating greater fatigue. In the present study, Cronbach's alpha of the subscale was .94.

Exercise tolerance was measured by the 6-Minute Walk Test (6-MWT). (31) Each subject performed a single 6-MWT using a standardized protocol adapted from the American Thoracic Society (ATS). (32) The subjects were asked to walk as far as they could in 6 minutes at their self-selected pace on flat surface 20 meter long. Although the length of the hallway used in this study for conducting the 6-MWT was shorter than ATS recommendations, a multicenter study found that for straight courses, the length had no significant effect on 6-MWT. (33) Encouragement was provided as per the ATS guidelines. The distance walked in 6 minutes was recorded in meters. The 6-MWT has been shown to have moderate criterion validity with other measures of functional capacity, such as NYHA class (r = -.45), peak oxygen uptake (r = .65), and the MET level (r = -.46) from the Heart Failure Functional Status Inventory that had high test-retest reliability (intra-class correlation coefficient, .82). (31), (34)

Data Analysis

Differences in demographic data and disease severity between high vs. low knee extensor muscle strength group were tested by %2 tests for categorical variables and t-tests for continuous variables. Participants were categorized into strength groups according to a median split of the actual raw knee extensor strength (Mdn = 6.70 kg). Although there is debate over the appropriateness of dichotomizing continuous variables, a median split can be justified in certain situations, when the goal is to aid in interpretation. (35) Scores for the muscle strength measure in the present study were restricted in their variability compared to published data for HF patients. (36) Thus, we were reluctant to use the full range of scores (continuous variable) and chose instead to group individuals based on strength using the median split. Also, because no data concerning normal knee extensor strength were found in individuals with HF, using a median split ensured similar sample sizes across the two groups. Differences in dyspnea, fatigue, and activity tolerance between groups were compared using independent t-tests. All analyses were conducted with SPSS software (v. 21, IBM, Chicago, IL, USA). A p value of less than .05 was considered statistically significant.

All major variables used in this study had normal distributions except for dyspnea with basic ADLs and IADLs, which had standardized scores (Z scores) exceeding 3.29 (p<.001) indicating positive skewness. As skewed distributions may distort the results of statistical tests, these variables were log transformed with improved normal distributions. (37) When the transformed variables were analyzed using the t-test, the findings were the same as with the untransformed variables. Thus, the findings with the untrans-formed scores were presented to aid with interpretability. A follow-up analysis of covariance was conducted to test group differences in the main study variables controlling for gender and NYHA class. Five subjects (4.9%) were unable to complete the 6-MWT, due to shortness of breath, or combination of shortness of breath, tiredness, dizziness, and/or leg discomfort. These subjects were not included in the data analysis for the 6-MWT.

RESULTS

Subject Characteristics

Subject characteristics including demographic data and disease severity are presented based on high (n=49) vs. low knee extensor muscle strength (n=53) in Table 1. No group differences were found in age, body mass index, co-morbidity, duration of HF, ejection fraction, etiology of HF, or medication treatment for HF. There were significantly more women and more participants with class III/IV heart failure in the low muscle strength group.
Table 1. Characteristics of Subjects in High vs. Low Knee
Extensor Muscle Strength Groups

 N (%) N (%) [X.sup.2]-
 test

Gender 3.85*

 Female 21 (42.9) 33 (62.3)

 Male 28 (57.1) 20 (37.7)

Comorbid conditions

 Hypertension 40 (81.6) 37 (69.8) 1.92

 Hyperlipidemia 32 (65.3) 28 (52.8) 1.64

 Myocardial 19 (38.8) 22 (41.5) .08
 infarction

 Arrhythmia 17 (28.6) 21 (39.6) .2 7

NYHA class 4.85*

 II 43 (87.7) 37 (69.8)

 III/IV 6 (12.2) 16 (30.2)

Etiology of HF .08

 Non-ischemic 30 (61.2) 31 (58.5)

 Ischemic 19 (38.8) 22 (41.5)

Medications

 ACE Inhibitor 41 (83.7) 44 (83.0) .00

 Beta Blocker 48 (98.0) 45 (84.9) .2 7

 Diuretics 44 (89.8) 41 (77.4) .51

 Lipid Lowering 31 (63.3) 25 (47.2) 2.66
 Medications

*p < .05


Compared to participants with low knee extensor strength, those with high knee extensor strength had significantly lower dyspnea with ADLs (t=2.50, p<0.01), lower dyspnea with IADLs (t=2.35, p<0.05), lower dyspnea with physical functioning (t=2.65, p<0.01), and greater 6-MWT distance (t = -2.43, p<0.05) (see Table 2). There were no group differences in fatigue. There was a medium effect size for all the main study variables except for fatigue.
Table 2. Differences in Dyspnea, Fatigue, and Exercise
Intolerance between Muscle Strength Groups

Variables High muscle Low muscle t-test Effect
 strength strength size
 group (n = group (n
 49) =53)

 mean (SD) mean (SD)

Knee Extensor 7.88 (.90) 5.83 (.68) NA NA
force (kg)

Dyspnea

 ADLs 5.79 (8.56) 1 1.54 2.45* .50
 (12.74)

 IADLs 10.26 1 6.25 2.35* .48
 (10.04) (12.32)

 Physical 53.84 73.10 2.65** .54
 (35.75) (34.47)

 Functioning

Fatigue 3.72 (3.09) 4.22 (2.77) 0.85 .17

6-Minute Walk 336.50 287.07 -2.43* .50
(meters) (91.23) (108.37)

Effect size = Cohen's d statistic

*p < .05; **p < .01


After controlling for NYHA class, the current study findings were maintained for dyspnea with ADLs [F (1, 101) = 6.47, p =.01], IADLs [F (1, 101) = 5.05, p =.03], physical function [F (1, 101) = 6.01, p =.02], and exercise intolerance [F (1, 96) = 4.41, p =.04]. After controlling for gender, the findings were still significant for dyspnea with ADLs [F (1, 101) = 4.73, p =.03], IADLS [F (1, 101) = 4.03, p =.04], and physical function [F (1,101) = 5.12, p =.03]; but no longer statistically significant for exercise tolerance between the low vs. high knee extensor muscle strength groups [F (1, 96) = 3.34, p =.07].

DISCUSSION

The findings from this study showed that individuals with HF and lower knee extensor muscle strength had greater dyspnea and exercise intolerance compared to individuals with higher knee extensor muscle strength. However, the present finding of no significant difference in fatigue between low and high knee extensor strength highlights the complexity of fatigue as a symptom and requires further study.

Based on our best knowledge, the present study was one of the first studies in HF to assess differences in dyspnea with a broad range of activities by leg muscle strength. In this study, dyspnea was measured in relationship to ADLs (e.g., bathing, dressing), IADLs (e.g., shopping, housework), and physical function (e.g., lifting an object while climbing upstairs, getting up and down a flight of stairs, or walking several blocks). Dyspnea with all of these activities was significantly greater in subjects with low muscle strength compared to subjects with higher muscle strength. These participants with mild, stable and early HF reported relatively low levels of dyspnea with ADLs and IADLs, and moderate levels of dyspnea with physical function. Thus, even with low to moderate levels of dyspnea, muscle strength may be already reduced relatively early in the trajectory of HF. These findings suggest that a routine assessment of changes in muscle strength of the lower extremities and dyspnea with various activities is useful for early identification of physical deconditioning in patients with HF.

Present findings show that participants with higher knee extensor strength were able to achieve greater distances in the 6-MWT. This supports previous observations that patients with chronic HF have decreased knee extensor strength related to limitations in physical function and functional capacity. (38), (12) In addition, the present findings are similar to findings from Clark et al (12) and Sullivan and Hawthorne (39) of individuals with systolic HF, where reduced knee extensor muscle strength (measured isokinetically) was related to decreased exercise tolerance (measured by peak oxygen consumption). It is also consistent with the finding from Manini et al (40) in older adults where reduced knee extensor strength was related to walking difficulty. Findings among older adults that knee extensor strength is associated with the performance of ADLs are consistent with the present findings that dyspnea was greater in patients with HF with low knee extensor strength. (5), (22)

The 6-MWT has been used to assess exercise tolerance in HF patients. Ingle et al (41) reported that increasing walking distance by 55 meters on the 6-MWT is associated with improvement in HF symptoms. In the present study, the average difference in 6-MWT of 49.5 meters between groups suggests that assessment of single knee extensor strength in the clinical setting may be a valid tool to assess improvements in exercise tolerance after HF treatment is initiated.

Fatigue did not differ significantly between groups, which is different from previous studies with HF patients. (12), (42) The discrepancy between the present finding and previous findings may be related to the instrument used to measure fatigue in the current study. The current study used only one subscale, the behavioral/severity subscale, of the PFS. Because fatigue is multidimensional, (30), (43) it may be that other dimensions of fatigue, such as the sensory component, would be more sensitive for capturing the degree to which fatigue is associated with decreased muscle strength. The second issue is that the PFS is designed to measure the impact of fatigue on doing daily activities within a restricted time frame (today and now). Patients with HF may perceive fatigue differently based on various situations, including types and amount of activities and treatment factors (i.e., swollen legs, more dyspnea, change in medications, etc.). In addition, it is likely that levels of fatigue increase slowly and imperceptibly over a long period of time in HF. Future studies are needed to determine the most appropriate measure of fatigue in people with HF.

LIMITATIONS

Convenience sampling limits the generalizability of the study because subjects received care from heart failure specialists whose medical managements may differ from other generalists. The study was also limited by the use of cross-sectional data, so causation cannot be implied. Because a large majority of the subjects were classified as NYHA functional class II indicating having slight limitations during physical activity but not at rest, the results cannot be generalized to all individuals with HF.

Prior studies in non-HF populations have used body weight to normalized muscle strength because muscle strength has been shown to be dependent on the size of the individual measured. (44) However, for several reasons the present study used the raw knee extensor strength, not body weight normalized knee extensor strength for the data analysis. First, all subjects had a diagnosis of HF and their current body weight may not reflect accurate dry weight as their fluid levels are highly variable due to water retention (ie, edema in legs, lungs, liver). Secondly, there is no standard protocol for reporting muscle strength raw scores or normalized scores in HF patients. We did examine group differences in lower vs. higher knee extensor muscle strength using normalized knee extensor strength scores and found no differences between the groups in the main study variables. However, the normalized scores were restricted in their variability.

IMPLICATIONS FOR PRACTICE

The present study demonstrated that in people with HF, knee extensor muscle strength using a hand-held dynamometer was easily and objectively assessed. Since high vs. low knee extensor strength groups exhibited significant differences in dyspnea and exercise tolerance, knee extensor strength may be a key muscle group to screen routinely to monitor for patients' current status of muscle weakness or detect responsiveness of treatment in HF. This would allow health care professionals to identify individuals at greater risk of developing muscle weakness or worsening of HF symptoms, including exercise intolerance.

Furthermore, the present study suggests the need for testing interventions aimed at maintaining muscle strength through resistance training programs to subsequently delay the point where muscle weakness impacts dyspnea and exercise intolerance. Resistance training incorporated into the standard, aerobic exercise-based rehabilitation regimens may be advised.

CONCLUSION

People with HF who have lower knee extensor muscle strength also reported more dyspnea with ADLs, IADLs, and physical function, and less exercise tolerance compared to those with higher knee extensor muscle strength. Knee extensor muscle strength, as assessed by hand-held dynamometer, is recommended to identify individuals who may have greater dyspnea and exercise intolerance in clinical practice. Future larger-scale studies are needed to examine the effects of muscle strengthening intervention on symptoms and function in people with HF.

ACKNOWLEDGEMENTS

This research was supported by Grant P20 NR011404 from the National Institute of Nursing Research, National Institute of Health and by Sigma Theta Tau International, Alpha Mu chapter and by Case Western Reserve University, Frances Payne Bolton School of Nursing Alumni Association.

The authors would like to express their appreciation to the participants, research associates, and administrative support staff that made it possible to complete this study.

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Yaewon Seo, (1) Bernice C. Yates, (1) Joseph F. Norman, (2) Bunny Pozehl, (1) Kevin Kupzyk (1)

(1) College of Nursing, University of Nebraska Medical Center, Omaha, NE

(2) Division of Physical Therapy Education, University of Nebraska Medical Center, Omaha, NE

Address correspondence to: Yaewon Seo, College of Nursing, University of Nebraska Medical Center, Omaha, NE 68198 (yaewonseo@unmc.edu).
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Author:Seo, Yaewon; Yates, Bernice C.; Norman, Joseph F.; Pozehl, Bunny; Kupzyk, Kevin
Publication:Cardiopulmonary Physical Therapy Journal
Article Type:Author abstract
Date:Mar 1, 2014
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