Chagas disease, a major cause of heart failure (HF) in Latin America, affects approximately eight million people ¹ and represents a significant public health and socio-economic problem in these countries. ² Chagas heart disease (CHD) is associated with worse prognosis ³ and symptoms such as fatigue and dyspnea, which contribute to a progressive reduction in functional capacity (FC), ⁴ , ⁵ reflecting a negative impact on the perception of health-related quality-of-life (HRQoL) in these individuals. ⁶

The FC can be assessed by laboratory stress tests with direct or estimated measurements of maximal oxygen consumption (VO _{2 max}) and field tests by the distance walked. ⁷ The cardiopulmonary exercise test (CPET), the gold standard in the analysis of FC in HF, is expensive and not well-tolerated by some patients. ⁸ , ⁹ On the other hand, field tests are simple, easy to administer, inexpensive and more tolerated by patients. ⁸

Among field tests, the 6-min walk test (6MWT), widely used in cardiac ¹⁰ and chagasic patients, ¹¹ , ¹² , ¹³ has shown moderate correlation between FC evaluated by distance walked with VO _2max. ¹⁴ One of the factors cited for the moderate correlation between these measures is the methodological differences between the tests. Although in 6MWT load is self-controlled and the patient determines their walking pace, ¹⁵ the CPET has standardized load increments protocols. ¹⁶

In an attempt to minimize these methodological discrepancies, an alternative proposal for the field tests has been used the incremental shuttle walk test (ISWT), which has more similar procedures to those of maximum stress tests. ¹⁷ It is also a symptom-limited test and load (speed) has stages with standardized increments. ¹⁸ Previous studies have shown better correlation between the distance walked by the ISWT with peak oxygen uptake (VO _2peak) in heart disease; ¹⁹ , ²⁰ although, its value and significance in CHD patients remains to be established.

On the other hand, in recent decades, there has been increased interest in the assessment of HRQoL and patient′s perception about the impact of the disease and the benefits of treatment. ²¹ The assessment of HRQoL in CHD is a complex process by the interrelation of biological, historical, political and socio-economic factors with a strong labor impact and stigmatizing character. Despite growing interest in HRQoL assessment and the importance of it in CHD patients, very few studies exist in research databases involving HRQoL profiles of the CHD group. ²² , ²³ , ²⁴

This study aims to verify the applicability of ISWT in evaluate FC in CHD patients by correlating the distance walked with VO2peak by CPET and the relationship of these measures with HRQoL questionnaires.

Study design

This cross-sectional study was conducted at the Chagas disease outpatient clinic and the Cardiology Service of the Hospital of the Federal University of Minas Gerais, Brazil, a tertiary Chagas disease referral center. The research was carried out in accordance with the declaration of Helsinki (2000) and was approved by the Ethics Committee of the Federal University of Minas Gerais. All the patients gave their written informed consent before participating in the study.

Criteria for inclusion were the presence of two or more positive serological tests for Trypanosoma cruzi; to be in stable clinical condition (no acute exacerbation of heart disease in the last 3 months), both sexes, age between 30 and 60 years. Criteria for exclusion were: Having participated in the last 6 months of any program of regular physical activity for at least 30 min on most days of the week; presence of heart disease for any other cause, use of a cardiac pacemaker; presence of hypertension Stage II or III, depending on the classification of Joint National Committee VII ²⁵ and presence of lung, pleural or renal disease, musculoskeletal limitations, diabetes mellitus or any other condition that affects the ability to perform functional tests.

The previously selected subjects underwent clinical evaluation, echocardiography, CPET, 6MWT, ISWT and HRQoL questionnaires short-form health survey (SF-36) and Minnesota Living with Heart Failure Questionnaire (MLHFQ).

Each test was conducted by one researcher. Stress tests were performed with an interval of 1 week between them and at the same time of day to avoid circadian changes.

Echocardiogram

Images were acquired using Philips HDI 5000-ATL echo machine (Bothell, Washington, USA). The echocardiography techniques and calculations of different cardiac dimension and volumes were performed according to the recommendations of the American Society of Echocardiography. ²⁶ Left ventricular ejection fraction (LVEF) was calculated according to the modified Simpson′s rule.

CPET

The CPET was carried out in an air-conditioned laboratory on a treadmill with the metabolic analysis system Ergo PC Elite Micromed-Brasilia/DF. The gas analyzer was expired MetaLyzer ^®3B Cortex-Leipzig, Germany, 1998. The CPX was conducted from ramp protocol, treadmill Centurion 200 of Micromed Biotechnology Ltda. Oxygen consumption (VO ₂) was measured breath-by-breath and is considered as the biggest value of VO ₂obtained in the test (VO _2peak).

An 11-lead electrocardiographic monitoring was obtained at rest in the supine position and during exertion, continuously (Eletocardiografo/Elite-Micromed Biotecnologia Ltda). Blood pressure was measured by Tycos ^®sphygmomanometer and stethoscope Littmann ^®at rest and in the effort every 3 min.

6MWT

The 6MWT was guided by international guidelines. ⁷ , ²⁷ Patients were instructed about the right to interrupt the test in case of discomfort or other complications. Briefly, the subjects were instructed to walk as fast as possible without running in a corridor of 30 m. We used standardized words of encouragement every minute. Two tests were applied to each subject, with 15-min interval between them and the longest distance walked was considered for analysis.

ISWT

Tests were guided by the pioneering study by Singh et al. ¹⁸ and undertaken in a course of 10 m, identified by two cones located 0.5 m from the end of the path to avoid abrupt changes of direction. The speed reached by the patient was controlled by an audio signal in 12 levels of intensity. Patient should finish the course determined by the number of laps (10 m each) corresponding to each stage before the beep. The test was finished when patient completed the 12 levels of intensity or when he could not complete the distance target for each level within the time for 3 times.

HRQoL

HRQoL was assessed by the SF-36 and MLHFQ. The SF-36 is a generic questionnaire containing 36 items in 8 domains (physical functioning [PF], role physical [RP], bodily pain, general health [GH], vitality, social functioning [SF], role emotional and mental health [MH]), previously validated for Brazilian Portuguese by Ciconelli et al. ²⁸ Furthermore, the MLHFQ is a specific questionnaire for patients with HF. The questionnaire consists of 21 questions about functionality and disabilities related to HF and is also validated for Brazilian Portuguese language by Carvalho et al. ²⁹

Statistical analysis

The sample size calculation has been done to assess the correlation between VO _2peakby CPET and distance walked in ISWT. The coefficient of determination was based on a previous article, ¹⁹ where the correlation between VO _2peakand distance walked in ISWT was 0.51. Using G Power software, version 3.1.0 (Heinrich Heine. University, Dusseldorf, Germany) and considering an alpha error of 0.05, beta error of 0.10 (statistical power of 90%) and coefficient of determination of 30% (r = 0.5), there was obtained a sample of 30 patients.

Data were analyzed with Statistical Package for the Social Sciences version 17.0 (SPSS Inc., Chicago, IL, USA). The normal distribution of data was verified by Kolmogorov-Smirnov test. The descriptive analysis was shown as mean and standard deviation in data with normal distribution or median and interquartile range (MD/25-75%) in non-normal distribution. Pearson and Spearman correlation was carried out to evaluate correlations between distance walked in field tests and VO _2peakwhen appropriate. To compare the distance between field tests, was used the Wilcoxon signed rank test.

A receiver-operator curve was used to verify the accuracy of the ISWT in predicting a reduced VO _2peak(25 mL/kg/min or lower) and to identify the cut-off value with the best combination of sensitivity and specificity for that prediction. The value of 25 mL/kg/min was adopted in accordance with the classifications of American College of Sports Medicine ³⁰ for the age group of patients recruited into the study. The level of significance was α <5%.

Characteristics of the sample and correlation between stress tests

A total of 53 subjects with CHD were selected and 35 were considered as eligible for the study. Then, 28 subjects were excluded and nine of these had non-cardiac forms of Chagas disease, four were physically active, three had cardiac pacemaker, two were diabetic, two had orthopedic impairments (arthritis and sequelae of stroke), two were transplanted. Sample characteristics are summarized in Table 1.{Table 1}

The graphs of correlation are shown in Figure 1. The distance walked by ISWT was significantly correlated with VO _2peakobtained by CPET (r = 0.587; P < 0.001) Figure 1a and with distance walked by 6MWT (r = 0.484; P = 0.003) [Figure 1b]. We also found a significant correlation between the VO _2peakand the distance walked in 6MWT (r = 0.577, P < 0.001). There was no significant difference between the distance walked in both field tests (P = 0.694). Figure 1

(a) Correlations between peak oxygen uptake and distance walked in incremental shuttle walk test (ISWT); (b) Correlations between the distance walked in 6-min walk test and ISWT

Peak VO ₂directly measured by expired gas analysis is the best way to assess FC in patients with HF.

However, the equipment is expensive and not available in many centers. Hence, the use of alternative tools for assessment of FC, in the context of Chagas disease, is extremely important, because endemic areas are generally poor and have few resources. Thus, the present study correlated the distance walked in ISWT with VO _2peakmeasured by the CPET, the gold standard in the assessment of FC and distance walked in 6MWT, the most widely used field test in patients with heart diseases.

This study is the first to demonstrate a significant correlation between the FC by distance walked in Incremental Shuttle Walk Test (ISWT) and direct measurement of VO _2peakin patients exclusively with CHD. In addition, we describe the accuracy of ISWT to predict a VO _2peak≤25 mL/kg/min and its relationship with HRQoL assessment tools in this population.

Studies evaluating the relationship between the distance walked in ISWT with VO _2peakfound a strong correlation between these measures. ⁹ , ¹⁹ , ²⁰ Lewis et al. ²⁰ observed in 25 patients with HF (53 ± 8 years, New York Heart Association [NYHA] II-III) a strong correlation between the distance walked in ISWT and VO _2peak(r = 0.730, P < 0.001). Similar results (r = 0.830, P < 0.001) were reported by Morales et al. ¹⁹ between the same measures applied to 46 patients with HF (53.0 ± 10.0 years, NYHA II-IV). Using a larger sample, Pulz et al. ⁹ also found a strong correlation between the distance walked in ISWT and the CPET VO _2peak(r = 0.79, P < 0.001).

Among field tests, Pulz et al. ⁹ studied 63 patients with HF (51.3 ± 10.2 years, 16 chagasic) and compared the responses in FC analyzed by the two field tests (6MWT and ISWT) and found a significant difference between them (P < 0.001), with greater distance walked during the 6MWT. In contrast, in our study, the distance walked in both testes was similar. This discrepancy may be due, at least, to the difference in samples studies. Although Pulz et al. ⁹ evaluated only patients with more compromised cardiac function (LVEF 24 ± 5.6%; NYHA II-IV), our sample was consisted, on average, by individuals with more preserved cardiac function.

Our results indicate that ISWT correlates with the direct measurement of VO ₂and 6MWT. Walking tests are less expensive and could be used in the early detection of changes in FC in poor and endemic areas and increase effectiveness in the prevention and treatment of heart disease. Studies with direct measurements of VO ₂during the walking tests should be explored to clarify the relationship of each of these tests with cardiac performance.

The present study also demonstrated a good sensibility and specificity of distance walked in ISWT to predict a VO _2peakof, at least, 25 mL/kg/min. This accuracy in the prediction can be useful in screening and risk stratification of patients with CHD.

Our study also evaluate the relationship of FC, assessed by the CPET and the ISWT, with HRQoL in these patients, since a major goal of treatment for HF is to maximize the functionality and independence of these individuals, reflecting better HRQoL. ³¹ Currently, there are two main ways of measuring HRQoL: Generic and specific instruments. As the two instruments provide different information, they can be used concomitantly.

By comparing the HRQoL generic questionnaire SF-36 and VO _2peakassessed by CPET of 27 patients (54.6 ± 9.2 years) with HF, Quittan et al. ³² found a significant correlation between VO _2peakand SF (r = 0.5, P = 0.01) and GH (r = 0.55, P = 0.007) domains of SF-36. However, Nogueira et al. ³³ showed a mild and no significant correlation between VO _2peakand all the domains of SF-36 in 46 patients with HF (52.26 ± 9.09 years) and the higher commitment in the physical aspect. The results in our study are similar and showed a correlation only between VO _2peakand PF domain of the SF-36, suggesting that functional limitation imposed by the disease is associated to the worsening of HRQoL.

The same study ³³ showed a negative correlation (r = -0.5, P < 0.05) between VO _2peakand the score obtained by MLHFQ specific questionnaire, remembering that higher scores in MLHFQ reflect worse HRQoL. In contrast, we found a no significant correlation between these variables, however, our sample consisted of patients with lower cardiac impairment and highest score of HRQoL assessed by MLHFQ compared to them (14 vs. 41.86, respectively).

In the present study, when HRQoL was compared to the distance walked in ISWT, we observed a negative correlation between the distance walked in ISWT and MLHFQ and positive correlation between the distance walked in ISWT and PF, RP and MH domains of the SF-36. No studies that verify the correlation between HRQoL and ISWT in patients with heart disease were found.

Considering the results obtained, we suggest that the ISWT, because it has good correlation with VO _2peakand better relationship with HRQoL instruments, can be used as an alternative test in the evaluation of FC by the distance walked in patients with CHD.

The present study not intended to be representative of all patients with CHD considering its pleomorphism. Thus, further studies with this approach should be conducted in different stages of this disease.