Impact of Heart Failure Clinic on Six-Minute Walk Test

Fundamentos: O teste de caminhada de seis minutos (TC6M) é de fácil aplicação e baixo custo, utilizado para avaliar objetivamente o grau de limitação funcional e prognóstico da insuficiência cardíaca (IC). Objetivo: Avaliar os TC6M de indivíduos com IC recém-diagnosticada, realizados na consulta admissional e após seis meses, analisando a diferença mínima importante (Minimal important difference MID) entre os dois testes. Métodos: Estudo tipo coorte histórico. O primeiro TC6M foi avaliado em pacientes com IC sistólica referenciados à Clínica de IC entre julho de 2012 e outubro de 2014 e o segundo TC6M após seis meses. O grupo que atingiu a distância MID no segundo teste foi comparado com o que não a atingiu. Delta-distância e necessidade de hospitalizações foram avaliados conforme adesão ao tratamento, classe funcional (CF) da New York Heart Association na primeira consulta e grau de disfunção ventricular esquerda. Resultados: A diferença de distância percorrida entre os TC6M foi 48,79 m na população estudada, e distância MID calculada de 49 m. Trinta pacientes (58,8%) apresentaram delta-distância menor que a MID, com média de idade maior que o outro grupo (p=0,01). A média do delta-distância foi significativamente maior nos pacientes aderentes ao tratamento e nos que estavam em CF III na primeira consulta. Conclusão: Houve aumento geral da distância média percorrida do primeiro para o segundo TC6M nos pacientes com IC, porém menos da metade dos pacientes obteve incremento significativo.


Introduction
HF is a complex clinical syndrome with multisystem involvement, characterized by the inability of the heart to generate output 1 .Its main clinical manifestation is a decreased tolerance to physical exertion 2,3 .It represents a major public health problem due to the large number of cases and high cost of treatment and admissions 4 .
Patients following treatment using the drug triad recommended at target doses obtain improvement in symptoms with consequent decrease in physical limitations and increased survival 4 .In addition, programs that involve specialized follow-up by a multidisciplinary team showed greater adherence to treatment, better education and more knowledge about the disease and greater inclusion of family members in the reality of patients, hence favoring the optimization of treatment 5 .
Tests that evaluate the degree of limitation are directly related to the prognosis of the disease 6 .The six-minute walk test (6MWT) measures the total distance covered, so it is a simple, easy to use and inexpensive, since it does not require sophisticated equipment [7][8][9][10] .It also has good availability, reproducibility and better patient acceptance.Added to the fact that it is a simple tool to assess physical ability and a good predictor of survival in patients with HF [11][12][13] makes it a cost effective test for patient follow-up in specialized clinic.
So far, studies on the 6MWT in HF patients have been targeted at correlating the distance covered with clinical variables or at the prognostic value, adopting outcomes such as mortality and hospital admissions.For this purpose, patients are stratified into groups according to cutoffs of distance covered such as, for example, <300 m and >300 m [14][15][16][17][18][19] .
The minimal important difference -MID is the smallest difference between the two measurements, meaning a clinically relevant change rather than a minimal change in the patient's symptoms 20 .Since few studies have defined which difference between the two tests would be considered clinically important for the patients, this study aimed to evaluate the 6MWT of patients with newly diagnosed HF performed on the admission visit and after six months, assessing the MID distance between the two tests in this population.

Methods
Descriptive historical cohort study carried out through analysis of records of patient with systolic HF referred to HF Clinic (first or second visit) from July 2012 to October 2014 at Hospital Santa Casa de Misericórdia de Vitoria (HSMV), which provides healthcare service through the Brazilian Public Health System (SUS).
This study has been approved by the Research Ethics Committee of the institution under no.663 779.All patients signed an Informed Consent Form.
6MWT was performed routinely by the medical and academic staff in patients without contraindications at the admission visit and after six months.
The MID distance was determined using the one-SEM method (one standard error of measurement) 21,22 using the following formula: MID=DPx√(1-r), where SD is the standard deviation of the population and r is the intraclass correlation coefficient.
The group that reached the MID distance in the second test was compared to the group that did not reach it.The delta-distance and the need for hospitalizations in the period were evaluated according to adherence to treatment, New York Heart Association functional class (NYHA FC) at the first visit and the degree of left ventricular dysfunction assessed by echocardiography.
Inclusion criteria were patients newly admitted to the HF clinic (first or second visit) aged >18 and echocardiography with left ventricular ejection fraction (LVEF) <50% with or without prior follow-up in non-HF service centers.Patients with decompensated HF FC NYHA IV, limitation of physical activity due to factors other than stress and fatigue dyspnea, such as intermittent claudication, arthrosis and arthritis of the lower limbs, psychiatric illness preventing testing and any fever or infectious disease have been excluded from the study.
The distances covered in both 6MWT were assessed.In addition, the following data have been examined: sex, age, date of the first 6MWT and date of the last 6MWT.Regarding the HF, etiology, LVEF by Doppler echocardiography (Simpson's method), functional class on the testing dates, the number of admissions in the time interval between the tests, presence of cardiovascular risk factors (hypertension, dyslipidemia, diabetes, smoking or history of smoking and prior clinical conditions such as coronary angioplasty, coronary artery bypass grafting surgery and chronic renal failure) and atrial fibrillation on electrocardiography have been analyzed.
The lack of adherence to treatment was empirically assessed by assisting medical staff consisting of two cardiologists, according to the following criteria: patients who reported not regularly taking the prescribed medications and/or patients with low attendance at medical appointments at the HF clinic.Patients were encouraged to practice physical activities of moderate intensity on a regular basis, but in the absence of a full cardiac rehabilitation program at the HF clinic, this data was not measured in the study.The laboratory tests analyzed were serum creatinine and creatinine clearance calculated using the Cockroft-Gault formula, hemoglobin and serum sodium.On the dates of the tests, it was researched whether the patients were treated, with treatment adherence and at optimized doses with: oral anticoagulants, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, spironolactone, loop diuretics, digoxin, statin and acetylsalicylic acid.All of these data were filled out on the medical registry form routinely used in the clinic.
The statistical analysis was performed using the software application SPSS version 20.0 with Pearson's chi-square test, Fisher's test, Student's t test and ANOVA test.In this study, p<0.05 was considered statistically significant.

Results
Altogether, 74 patients newly referred to the HF clinic were recruited to participate in the study, but 23 were excluded: 11 patients failed to perform the second 6MWT, 8 of which because of death and 3 of which have abandoned treatment during follow-up at the clinic.The other 12 patients failed to undergo the first test: 4 of which were classified as NYHA FC IV and 8 of which had limited mobility and/or learning about the test during the first visits.
The 51 patients included in the study showed an average increase in the distance between the first and the second 6MWT of 48.79 m and the MID distance calculated for this sample was 49 m (SD=42; r=0.7696).The two tests were uneventful for all patients.In the population studied, only 6 (11.8%) patients had a decrease in the distance covered.Fourteen (27.5%) patients failed to demonstrate proper adherence, either by failure to follow the therapy and/or low attendance to the visits at the clinic.
Demographic data and clinical characteristics of the patients upon admission are presented in Table 1.As for the HF base etiology, a large percentage of the sample population had ischemic etiology, followed by alcoholism and hypertension.The sample was classified as for NYHA FC.Homogeneous distribution was observed in classes I, II and III.The drug classes used by patients during the admission visit to the HF clinic were analyzed as shown in Table 2.
The patients were divided as for NYHA FC and compared as for the distance covered (Table 5).It was found that the higher the functional class, the shorter the distance covered.There was a marked improvement for the most symptomatic cases, reflected on a bigger difference between the tests for patients with higher functional classes on the admission visit.
When classifying patients for LVEF (Table 6), a trend towards greater delta-distance was observed in patients with severe HF (LVEF <40%) compared to those with mild/moderate HF (LVEF ≥40%), although the difference was not statistically significant.
Adherence to treatment is analyzed in Table 7.The positive impact for those patients with good adherence to treatment is demonstrated by routine clinical assessment.These patients had a significantly higher delta-distance compared to those not adhering to treatment.The number of patients who experienced hospitalizations was relatively smaller in the group of greater adherence, but without statistical significance.
The overall results obtained by the sample population in the 6MWT performed at the admission visit and after six months are presented in Table 3, as well as the average number of visits per patient during the study period, adherence to the proposed treatment and the need for hospitalization for decompensated HF.

Discussion
Although the 6MWT is widely used to obtain prognostic information in chronic HF, so far, few studies have defined which difference between the two tests would be considered clinically important for patients under treatment.The MID distance in this study after six months was 49 m, which is close to the value found in a recent systematic review of 13 studies carried out by Shoemaker et al. 23 , in which the average MID distance was 43 m with a variation of 20-151 m.
In Täger et al. 24 , the MID distance was calculated by the same method as in this study and the value found was 35 m in the six-month cohort and 37 m in the one-year cohort.By comparing the study by Täger et al. 24 to this one, it must be considered that the patients included were selected with maximum HF stability, hence virtually eliminating the clinical events in the first year of followup.Moreover, the high intraclass correlation coefficient found (0.88) indicates a high stability of the actions over time.In this study, patients were newly admitted at the HF clinic and, in most cases, they had been discharged less than one month before.The intraclass correlation coefficient found was lower (0.77), which may explain the fact that the value of the MID distance in this study was slightly higher.
Shoemaker et al. 25 suggest that a change in the distance covered of approximately 32 m would be clinically significant.It was also observed that the change in performance in 6MWD did not appear to be strongly linked to everyday activities.It is noteworthy that the follow-up period of only eight weeks was much smaller than the one in this study and a questionnaire was used to find out whether there was any change in daily activities.
The 6MWT is also used in randomized clinical trials in HF.In the review of Shoemaker et al. 23 , the average change in 6MWT distance in the intervention groups was 45.5 m.Additionally, the ROC curves are used to quantify the optimal delta-distance threshold to discriminate between exercise-based intervention and control group.When the goal is 100% specificity to ensure that the actual clinical change has occurred, the optimal threshold is 48 m.However, a cutoff point of about 45 m should be used to determine the significant clinical change, which is quite close to the one found in this study.
In patients with delta-distance smaller than the MID distance, old age and tendency to lower creatinine clearance levels were observed.Old age is a predictor of worse performance in the 6MWT, which corroborates the findings presented in this study 26,27 .Given the high prevalence of comorbidities in the elderly, it can be expected that these conditions limit the distance covered 20 .Spruit et al. 19 studied the prognostic value of 6MWT in elderly patients with HF and found that the fact that the distance covered is below the average of the cohort (40 m) did not significantly affect mortality and the number of hospital admissions.
NYHA FC at the admission visit was positively correlated with the delta-distance in both tests and negatively correlated with the distance covered in the first 6MWT.
By arriving more decompensated at the HF clinic, patients walk less and, with good adherence to treatment, they are capable of obtaining a greater increase in the distance covered in the second 6MWT.The need for hospitalizations was higher in patients with NYHA FC III, though with borderline statistical significance.The patients in NYHA FC I, i.e., less symptomatic and more stable, increased the delta-distance by only 20.6 m.This result was similar to that found by Ingle et al. 18 , which compared the delta-distance with self-reported change in symptoms, in which there was a negative correlation between the two.Patients who reported improvement of symptoms had a delta-distance of 54 m and those who presented a worse performance covered a distance 84 m shorter than the first.Furthermore, stable patients reported stability of 6MWT measurements and patients who reported no change in the symptoms presented a delta-distance of only 9 m.
Spertus et al. 17 found that the delta-distance between the two 6MWT after six weeks to achieve moderate improvement increased 55 m and, for moderate worsening, it decreased 90 m.It was also reported that the magnitude of change in the distance covered in the 6MWT significantly depended on subjective clinical change.In 320 patients with stable HF, the delta-distance was 4.6 m.
There was significant improvement in the delta-distance of patients who arrived at the clinic more uncompensated and symptomatic, i.e., higher NYHA FC with severe left ventricular (LV) dysfunction (LVEF <40%), although the latter was not statistically significant.Ingle et al. 28 reported that 6MWT is a prognostic marker for moderate to severe dysfunction, but it should not be used to stratify risk in patients with mild dysfunction.The need for hospital admissions was not different according to the degree of LV dysfunction.
The highest delta-distance was also seen in patients adhering to treatment.This shows that when the patient is under follow-up at the HF clinic and proper instructions are followed, such as adherence to drug therapy, dietary measures, change of lifestyle, physical activity program, among others, it is possible to achieve the benefits of cardiac remodeling and consequent improvement of symptoms and physical limitations 4 .All this can be demonstrated by a better performance in the 6MWT.The need for hospital admissions was not different according to adherence to treatment.
HF clinics play a well-known role with multidisciplinary healthcare provided to patients and are cited in the Brazilian 4 , American 29 and European 30 guidelines.They are able to improve clinical outcomes (reducing mortality and hospital admissions) with follow-up structured around the patient education, optimization of treatment, psychosocial support and better access to healthcare 30 .Furthermore, we found in this study an improvement of functional capacity in systolic HF.The HF Clinic actively looks for patients who may have abandoned or given up on the appointments, re-encouraging them to return and not to abandon their treatment.
Despite the significant results of the study, some limitations should be pointed out, such as little scientific data on the optimal time interval between the two 6MWT.Another limitation is the small sample, due to the clinic's limited capacity, as well as the follow-up time available to assess some outcomes, such as the need for hospitalizations.
Sample selection bias may also have occurred, since most patients come from the service itself and have often initiated treatment before admission to the clinic, even if for a short time.
Another major limiting factor is the characteristic of the sample.Since it is a population with low income, of elderly people and often with certain physical limitations due to symptoms, there is a negative interference in the follow-up at the HF clinic.These factors are reasons for dropout or contribute to an underoptimal attendance.In addition, physical activity practiced by the patients, its regularity and intensity, in follow-up during the study, was not measured, which can also be a source of bias.The method adopted to evaluate adherence to treatment is subjective and a scientifically validated a questionnaire could be useful for this purpose.

Conclusions
There was a general increase in the average distance covered from the first to the second 6MWT in patients with newly diagnosed HF.However, considering the MID distance, less than half of patients achieved a significant increase in the 6MWT conducted after six months compared to the admission visit.There was an association between old age and worse performance in the evolution between the two 6MWT.
This study shows a positive impact of the specialized clinic in the lives of individuals with HF.Analyzing the functional capability through the 6MWT, a significant improvement was observed of the delta-distance of patients adhering to treatment and patients in all functional classes included.The positive impact on performance in the 6MWT was higher in patients who arrived more uncompensated and symptomatic, i.e., in a higher NYHA FC, suggesting an even more significant benefit for those who are initially at an advanced stage of the disease.

Potential Conflicts of Interest
This study has no relevant conflicts of interest.

Sources of Funding
This study had no external funding sources.

Academic Association
This study is not associated with any graduate programs.

Table 1 Characteristics of the population studied Characteristics
SD -standard deviation

Table 2 Medications used by patients at the admission visit Medications at the first visit
ACEI -angiotensin-converting enzyme inhibitor; ARB -aldosterone receptor blocker

Table 3 Results of the six-minute walk tests and medical follow-up in the period of the study Results
SD -standard deviation

Table 4
distance was older.Although the glomerular filtration rate of patients represented by creatinine clearance has only a borderline statistical significance, it showed a tendency to impact the performance difference in the tests.The other factors showed no statistically significant difference between the groups.

Table 5 Distances covered in the 6MWT and hospitalizations in the period according to the functional class at the admission visit
6MWT -six-minute walk test; FC -functional class; SD -standard deviation