Maximal effort test is the gold standard method for the assessment of functional capacity.1 The six-minute walk test (6MWT), however, has become equally important to this end, and has been used as a simple, reproducible and feasible alternative. Since the 80's, the 6MWT has been widely used in clinical practice to evaluate functional capacity in heart failure (HF) patients, especially since the publication of the Studies of Left Ventricular Dysfunction (SOLVD),2 showing that the distance walked was an independent predictor of mortality in patients with New York Heart Association (NYHA) classes II and III.

Functional capacity must be a priority in the management of elderly patients with cardiovascular disease. The assessment tools should have clinical applicability, be practical and efficient, since the maximal effort test is not always available. Besides, the prevalence of orthopedic and neurologic diseases has increased with population aging, which can make it difficult to perform exercise tests that require maximal effort.3

In light of this, 6MWT will become more and more present in the clinical practice, which makes it important to establish which variables may have affect its results, as well as intervention and prevention strategies for HF patients, aiming a better functionality and quality of life. Studies on factors associated with the 6MWT in patients with HP using multivariate analysis are scarce, especially in the Brazilian population, thus supporting the relevance of the present study.

This study aimed to identify determinants of the 6MWT in patients with chronic HF patients with NYHA classes I-III.

This was a cross-sectional study with 81 patients with chronic HF seen at the HF outpatient clinic of a referral hospital in Goiania, Goias, Brazil. Sample size was calculated using the GPower^® software, using a significance level of 5%, power of 0.90, effect size of 0.59 (calculated from the determination coefficient - R²) and number of predicting variables. A minimum of 79 patients with HF would be needed.

Inclusion criteria were: patients of both sexes aged ≥ 18 years old, with clinical diagnosis of HF, left ventricular ejection fraction (LVEF) < 50%, NYHA functional class I-III, not receiving optimized treatment, and clinically stability for at least one month. Patients with acute myocardial infarction in the last month, unstable angina, stroke, musculoskeletal disorders, understanding impairment that would make it difficult to perform the tests, neoplasms or diagnosis of pulmonary diseases, pregnant women, patients using medications or ergogenic aids were excluded from the study.

Mean age of participants was 56.7 ± 12.4 years; 58% were younger than 60 years, 65.4% were male (Table 1).

Table 2 describes emotional, quality of life, and physical functional characteristics, Borg scale and 6MWD.

6MWD was shorter in female participants with functional class II and III and in those with mMRC 2, 3 and 4. Although physically active subjects tended to walk a longer distance in the test, it was not statistically significant compared with the others (p = 007) (Table 3).

6MWD showed a moderate, significative correlation with age (r = -0.27; p = 0.01), MIP (r = 0.42; p < 0.01), MEP (r = 0.36; p < 0.01), HGS (r = 0.38, p < 0.01), Borg scale (-0.22, p = 0.04), Charlson index (r = -0.25; p = 0.02) and mMRC (r = -0.42, p < 0.01).

Following the association tests and exclusion of variables by collinearity, the variables were selected in descending order of importance in the stepwise variable selection. Thereby, the following variables were included in the final model for the (dependent variable) 6MWD: mMRC (p < 0.01); sex (p < 0.01), age (p < 0.01) and FVC (p = 0.01). These variables explained 37% of the variance in the 6MWD in the study population (Table 4).

In the hierarchical model, we found that clinical and physical functional variables were the ones with the best predictive value in the 6MWT (40% and 33%, respectively) (Table 5).

Our findings suggested four potential variables with predictive value for a shorter 6MWD: female sex, older age, lower FVC and higher mMRC, which simultaneously explained 37% of the variance for the 6MWD. Additional five variables showed bivariate correlation with the 6MWD - MIP, MEP, HGS, Borg scale, and Charlson index.

Previous studies have reported several predictive variables of the 6MWD, including age, sex, weight, BMI, LVEF, anxiety, depression, quality of life, etiology of HF, functional class (NYHA), N-terminal (NT)-pro hormone BNP (NT-proBNP), glomerular filtration rate, resting HR and maximal power in the maximal effort test.18^-24

Female sex was a predictor of shorter 6MWD in a study conducted with 571 HF patients and 668 patients without HF.19 Similar findings were reported in other studies on patients with HF.18^,22 On the other hand, Bajraktari et al.,23 did not report any difference in the 6MWD between men and women. This result may be explained by the younger age and better cardiac function (indicated by higher LVEF) in female subjects than in men in their study.23

With respect to age, previous studies have reported findings similar to ours. Age was found to be an independent predictive factor of the 6MWD in a study conducted in Poland,20 including 243 men with HF, and in two studies from the United Kingdom21^,22 on HF patients aged from 71 to 80.5 years.

Frankenstein et al.,19 evaluated 1,035 patients with HF, mean age of 54.9 years, and found a bivariate correlation between age and 6MWD (r = -0.32, p < 0.01), although no significant correlation was found in the multivariate analysis. In the study by Adel et al.,18 involving 40 HF patients (mean age of 55.6 years; 72.5% male), age was not associated with 6MWD. According to the authors, the small sample size contributed to these results.

Increasing age is a contributing factor to a shorter 6MWD.25 In young adults, peak VO₂ decreases by 8-10% per decade, which is exacerbated with increasing age, leading to cardiovascular and pulmonary dysfunction. Besides, other factors that may negatively affect functional capacity decreases with age, such as psychological components and neuromuscular function (e.g. sarcopenia, and decrease in muscle strength, flexibility, balance and cognition).3

The effect of sex on 6MWD may be attributed to differences in biological and structural features between men and women, including higher muscle strength, muscle mass, and height in men than in women.26

In studies conducted in the United Kingdom21 and in the Netherlands,24 pulmonary function was not a predictive variable of the 6MWD. The Dutch study showed only an association of FEV1, the FEV1/FVC ratio and total lung capacity with the distance covered by HF patients in the 6MWT. Agrawal et al.,27 correlated the 6MWD with spirometric parameters in 130 patients with chronic obstructive pulmonary disease (COPD) with characteristics similar to our study regarding age (mean of 55.6 years) and sex (58.4% male) and found a correlation of the distance covered with FEV1 and FVC.

Pulmonary function may be altered in HF, particularly when combined with cardiomegaly, a condition characterized by enlargement of the heart. In this case, enlarged heart compete for intrathoracic space, causing compression of the lungs and limiting their expansion.28 In a systematic review, Silva et al.,28 reported an association between cardiomegaly and reduced MIP, FVC and FEV1 in HF patients.

In the present study, FVC was an independent predictor of six-minute walk distance. We did not measure cardiothoracic index in the study group for the presence of cardiomegaly. However, HF was caused by Chagas disease in most patients, a condition frequently associated with cardiomegaly. Besides, other factors may be associated with changes in pulmonary function, such as respiratory muscle weakness, chronic pulmonary congestion and pleural effusion, which decrease pulmonary compliance and increase respiratory work.29 Our study group showed reduced MIP, which correlated with 6MWD. This, together with cardiomegaly, may have contributed to altered pulmonary function. Further explanation on the influence of pulmonary function on 6MWD in patients with HF is needed.

In the present study, mMRC was a predictor of 6MWD. Valadares et al.,29 reported a correlation of mMRC with the London Chest Activity of Daily Living (LCAD) (r = -0.68, p < 0.05), another instrument for assessment of ADLs, that showed a strong correlation with the 6MWT (r = -0.83, p < 0.05). Camargo et al.,30 found a moderate correlation between mMRC and 6MWD in 50 patients with COPD. Similar to our findings, 80% of the patients were classified as mMRC I and II, and the mean 6MWD was 435 m; nevertheless, in their study, mMRC was not a predictive factor in the multivariate analysis. Although mMRC has been rarely used in patients with HF, the instrument has been shown to be both easy to apply and easy to understand in patients with COPD. Thus, mMRC may be a fast, simple alternative tool to evaluate functional status in HF patients.

In hierarchical analysis, clinical and physical functional factors showed a greater impact on 6MWD; in contrast, sociodemographic and emotional factors showed little effect. These findings differ from previous studies showing that emotional factors, especially depression, were associated with poor functional capacity and shorter 6MWD.21^,22^,24 These discrepancies may be related to characteristics of the study population, including age, severity of HF, comorbidities such as COPD and asthma, as well as use of walking aids (not observed in our population).

This study had some limitations - the outcome measures accounted for less than half of the variance of the 6MWD, and other factors that contributed for 63% of the variance need further investigation. It is possible that physiological factors, including renal function and B-type natriuretic peptide (BNP), contribute to these differences. These factors have been frequently reported as predictive factors of the 6MWD and were not evaluated in our study. In addition, most of our patients were NYHA class I and II and in most of them had Chagas' heart disease. The possibility that the inclusion of patients with worse functional status could lead to different results cannot be ruled out.

Lack of homogeneity of the samples in the studies made it difficult to compare the results. Performance of the second 6MWT and the size of the hallway were not standardized among the studies either. In most studies, only one test was performed, and a hallway shorter than 30 meters was used in the tests. Repeated administration may influence the 6MWD, which is known as the learning effect.31 Also, the measurement of the HGS considered for analysis is not standardized; in this study, we decided to consider the mean of three measurements, rather than the highest measurement, since this is the most common method described in the literature.

Sex and age are expected to influence the 6MWD, regardless of the presence of HF.25 Nevertheless, both pulmonary function and dyspnea on ADLs are modifiable variables that may be altered in HF. In addition, we found a bivariate correlation of the 6MWD with Borg scale, Charlson comorbidity index, MIP, MEP and HGS. These findings indicate that a careful and systematic approach by a multidisciplinary team is crucial for better outcome and impact on functional capacity of HF patients.

Most patients had a sedentary lifestyle in our study. However, although active subjects covered a longer distance during the 6MWT, it was not statistically different (despite a trend) than that in sedentary subjects. Regular physical activity has well documented beneficial effects on peripheral muscle function, pulmonary function, exercise tolerance and quality of life, and hence is important in patients with HF.32^,33

Determinants of functional capacity are multifactorial, depending on demographic, socioeconomic, physiological, cultural and psychosocial factors.34^,35 Therefore, predictive factors may differ between cultural and sociodemographic profiles. Also, in the present study, most patients had Chagas' heart disease, as the study was conducted in an endemic region of Chagas disease in Brazil. This is different from the studies cited throughout this article.

Four variables were identified as determinants of a shorter 6MWD in patients with chronic HF - severe dyspnea on ADLs (mMRC), female sex, older age, and lower FVC. Other variables, not explored in the present study, explain 63% of the variance in the 6MWD, indicating the multidimensionality of functional capacity in chronic HF patients.