© 2002 European Society of Cardiology
Prognostic value of 6-minute walk corridor test in patients with mild to moderate heart failure: comparison with other methods of functional evaluation
U.O. Clinica Medica e Cardiologia, Università di Firenze Florence, Italy
* Corresponding author. U.O. Clinica Medica e Cardiologia, Università di Firenze, Viale Morgagni 85, 50134 Florence, Italy. Tel.: +39-55-4277518; fax: +39-55-4277518. E-mail address: c.rostagno{at}katamail.com
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Abstract |
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 Top Abstract 1. Introduction2. Material and methods3. Results4. Comparison using different...5. DiscussionReferences |
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Aim: The study was designed to evaluate the prognostic value of the 6-min walk test (6MWT) in patients with mild to moderate congestive heart failure (CHF).
Methods and results: Two hundred and fourteen patients (119 men and 95 women, mean age 64 years) were followed for a mean period of 34 months to assess event-free survival (death, heart transplantation). Sixty-six patients (34%) died (63 cardiovascular causes, 2 cancer and 1 stroke) and five patients underwent heart transplantation. For patients who walked <300 m during the 6MWT, survival was 62% compared with 82% in patients who walked 300–450 m or>450 m. With univariate analysis, NYHA class was the strongest predictor of death. LVEF (P<0.0001), aetiology of heart failure (P<0.001), LV filling pattern (P=0.002) and 6MWT distance (P<0.01) were all significantly related to survival. No significant relationship was found between survival, peak oxygen consumption or anaerobic threshold. Multivariate analysis using the Cox-stepwise regression model showed that LV fractional shortening (P<0.009) and 6MWT distance (P<0.0005) were the strongest prognostic markers.
Conclusion: A 6MWT distance of <300 m is a simple and useful prognostic marker of subsequent cardiac death in unselected patients with mild to moderate CHF.
Key Words: Heart failure • Prognosis • Functional evaluation
Received April 26, 2001; Revised March 11, 2002; Accepted May 29, 2002
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1. Introduction |
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TopAbstract1. Introduction2. Material and methods3. Results4. Comparison using different...5. DiscussionReferences |
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Prognosis in patients with heart failure is strictly related to functional capacity [1,2]. The assessment of peak oxygen consumption (pVO2) during cardiopulmonary exercise testing is used extensively to evaluate cardiovascular performance. Several studies have supported its value as an independent prognostic index of survival in patients with heart failure [3,4]. A pVO2<10–12 ml/kg/min is considered a reliable indicator for heart transplantation [5,6]. However, cardiopulmonary exercise testing is both expensive and time consuming. In addition, approximately 30% of patients with heart failure may be unable to perform a maximal symptom limited exercise test or to tolerate the tight mask used for breath-by-breath gas analysis. The 6-min walk test (6MWT) has been suggested as a simple, safe and inexpensive alternative to cardiopulmonary exercise testing [7]. Direct comparison of the two methods however has not shown a close relationship suggesting that they may not give the same information [8,9]. The prognostic usefulness of the 6MWT was first reported by Bittner et al. [10] for patients in the SOLVD study. Mortality at mean 242 days of follow-up was significantly higher in patients with a lower 6MWT performance level (10.23% in patients who walked less than 300 m, compared to 2.99% in patients who walked more than 300 m, P<0.01). The prognostic value of 6MWT distance was subsequently confirmed by other authors both in patients with severe heart failure undergoing evaluation for heart transplantation [11,12] and in patients with moderate (NYHA class II–III) systolic heart failure [13]. The accuracy of the 6MWT in predicting mortality in advanced heart failure has been questioned by Aaronson et al. [14] and more recently by Lucas et al. [15].
The aim of the present study was to prospectively evaluate the prognostic value of the 6MWT in unselected patients with mild to moderate congestive heart failure (CHF) and to compare it to other indices of cardiovascular function, in particular to pVO2.
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2. Material and methods |
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2.1. Patient characteristics
We studied 214 consecutive patients, aged
70 years, with CHF defined according to the clinical criteria used in the Framingham study [16], who were admitted to our institution between 1 January 1994 and 30 June 1995. One hundred and nineteen patients were male and 95 female. Ages ranged from 29 to 70 years (mean 57.3 years). Most of the patients (
65%) were referred from other hospitals or by general practitioners to undergo further clinical evaluation, which often included coronary angiography. The remaining 35% of patients were admitted through the Emergency Department of our hospital. At the time of the investigation all patients were in a clinically stable condition. The aetiology of heart failure for all patients is shown in Table 1. Diagnosis of coronary artery disease was based on clinical data and/or coronary angiography. Idiopathic dilated cardiomyopathy was diagnosed using standard echocardiographic criteria in patients without angiographic evidence of coronary artery disease (stenosis >50% of one or more coronary vessels). Patients with a normal left ventricular ejection fraction (>50%) were included in the study if clinical and/or radiological signs of heart failure were present or if the left ventricular filling pattern suggested impaired diastolic function. Patients with recent myocardial infarction (<3 months), unstable angina or primary lung disease were excluded from the study. Concomitant medication included digoxin (75%) and ACE-inhibitors (81%). Only 25% of patients were on beta-blockers. The dosage of diuretics, if used, was not changed in the 48 h preceding functional evaluation. The clinical characteristics of patients, subdivided according to their NYHA classification, are shown in Table 2.
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2.2. Study design
Following hospital admission, patients underwent a thorough physical examination and their history was recorded. The severity of symptoms was assessed using the New York Heart Association functional classification [17]. Within 3 days following hospital admission all patients underwent chest X-ray, echocardiographic evaluation and peak expiratory flow measurement. Cardiopulmonary stress testing and 6MWC test was performed on two consecutive days at the same time in the morning and in a randomly assigned sequence. Since the tests were part of the routine clinical examination, the patients signed the standard informed consent at hospital admission.
2.3. Cardiopulmonary exercise test
The cardiopulmonary exercise test was performed using an incremental treadmill stress test according to the modified Bruce's protocol [18]. During the test, arterial pressure and 12-lead electrocardiogram were monitored. Cardiopulmonary functional capacity was assessed by determining the anaerobic threshold and pVO2 by expired gas analysis (OXYCON ALFA-JAEGER, Wuertzburg, Germany). The pVO2 was defined as the highest oxygen consumption in the last minute of the exercise test. The results were only considered for statistical analysis in patients who reached anaerobic threshold, determined according to Wasserman [19].
2.4. 6-min walk corridor test
The walk test was performed in an indoor corridor 25 m long, according to the recommendations of Guyatt et al [7]. Patients were instructed to walk the corridor from one end to the other, as many times as possible, in the permitted time. The test was performed under the control of a physician who encouraged the patients using phrases like ‘You are doing well’ or ‘You are doing a good job’. At the end of the 6-min, the physician measured the total distance walked by the patient. On the basis of the distance walked, performance was grouped into three different levels (level I, >450 m, level II, 300–450 m, level III, <300 m). The reproducibility of the test was assessed in 50 patients by performing the test twice in the same day. In these patients the difference in distance walked between the two tests was less than 5% of the distance walked.
2.5. Other measurements
Echocardiographic examination was performed with the patient in the left side recumbent position, using a SIM 5000 echocardiograph (Esaote Biomedica, Florence, Italy) with monoplane probes (2.50 and 3.75 MHz). Measurements were made according to the recommendations of the American Society of Echocardiography [20].
The peak expiratory flow rate (PEFR) was measured using a flow-meter (Mini-Wright flow meter, Armstrong Industries Inc., Northbrook, IL). The test was performed with the patient in a sitting position in bed. The highest of three attempts was recorded. Cardiothoracic index was measured on a standard chest X-ray performed in the postero-anterior projection.
2.6. Statistical analysis
The results were expressed as the mean±standard deviation. Differences between groups were evaluated using Student's t-test. Correlation between different variables was evaluated with the standard regression coefficient analysis. Univariate analysis was performed using a 
2-test with Yates’ correction when necessary. Survival was analysed by the Kaplan–Meier method and survival curves were compared by the log–rank test. Cox proportional hazards model was used for multivariate survival analysis. A P-value of <0.05 was considered statistically significant.
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3. Results |
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TopAbstract1. Introduction2. Material and methods3. Results4. Comparison using different...5. DiscussionReferences |
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Of the 214 patients studied, 199 were followed for an average period of 34 months, the remaining 15 patients were lost to follow-up (7%). 100 patients were followed as outpatients with regular monitoring every 6 months. The other 99 were contacted by phone and their health status was assessed using a questionnaire. At the end of follow-up 66 patients (34%) had died, (63 cardiovascular causes, two lung cancer and one following a stroke) and five patients had undergone heart transplantation.
3.1. Walk test
Event-free survival (death or heart transplantation) at 36 months was significantly lower (62%) in patients who walked less than 300 m, compared to those who had an intermediate (300–450 m) or high level (>450 m) of performance (82% in both groups).
The event free survival curve in patients who walked less than 300 m was significantly different from the curve for patients who walked >450 m (P=0.0126) and for those who walked 300–450 m (P=0.0119) (Fig. 1). Although the survival curves for the two higher performance levels were not significantly different, after 45 months of follow-up the two curves began to diverge (Fig. 1).
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3.2. Cardiopulmonary exercise test
In the subgroup of patients undergoing cardiopulmonary testing survival was not significantly different in patients stratified according to pVO2 (greater or less than 14 ml/kg/min).
3.3. Other variables
Event-free survival at 36 months was not significantly different in the three groups subdivided for age (20% for the younger group (<55 years) and 28% in the other two groups 56–65 years and over 65 years). Kaplan–Meier survival analysis did not show any significant differences among the three age groups, with only a trend for an higher mortality in older patients.
Three year survival was 55% in patients with idiopathic dilated cardiomyopathy, significantly lower than in patients with ischemic heart disease (75%) or other causes of heart failure (87%).
At the end of follow-up, survival was 91% for patients in NYHA class I and 83% for patients in NYHA class II, this difference was not statistically significant. Survival for patients in NYHA classes III and IV was less than 50% which was significantly different compared to both NYHA class I and NYHA class II (P<0.0001).
Patients with LV ejection fraction >50%, in which diastolic dysfunction was the main mechanism of heart failure, showed the better survival rate (85 and 75% at 3 and 5 years, respectively). Patients with EF between 30 and 50% had a 3 and 5 year survival of 78 and 55%, respectively. An ejection fraction <30% was associated with a mortality of 55% at 3 years and of 65% at 5 years.
A restrictive pattern of left ventricular filling (characterised by an E/A ratio >2) was associated with a significantly higher mortality compared to patients with a normal pattern of left ventricular filling.
Pulmonary hypertension (mean pulmonary artery pressure >30 mmHg) was related to a significantly lower survival (62% compared to 76% for patients with normal or slightly elevated pulmonary artery pressure).
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4. Comparison using different methods |
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TopAbstract1. Introduction2. Material and methods3. Results4. Comparison using different...5. DiscussionReferences |
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With univariate analysis, NYHA class showed the highest predictive value for survival. LV ejection fraction, LV end-diastolic diameter, LV fractional shortening and a restrictive pattern of LV diastolic filling were also statistically related to survival (Table 3). In addition, patients with dilated cardiomyopathy showed a higher mortality compared to patients with heart failure due to other aetiology.
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Among functional indices only the distance covered during 6MWT was statistically related to survival, we failed to find any statistically significant relationship between mortality and pVO2 or anaerobic threshold.
With multivariate analysis using Cox-stepwise regression model, LV fractional shortening and the distance covered during the 6MWT were the strongest prognostic indices (Table 4).
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5. Discussion |
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TopAbstract1. Introduction2. Material and methods3. Results4. Comparison using different...5. DiscussionReferences |
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Our results suggest that the distance covered during the 6MWT seems to be an independent predictor of survival in unselected patients with mild to moderate heart failure. In particular, mortality was significantly higher in the group of patients who covered less than 300 m during the test. The prognostic significance of low LV ejection fraction, high (III–IV) NYHA class, pulmonary hypertension and a restrictive pattern of left ventricular filling are in agreement with previous investigations [21–23]. In the subgroup of patients undergoing cardiopulmonary exercise testing, survival curves were not significantly different for patients who reached or did not reach a pVO2 of 14 ml/kg/min.
In contrast to previous investigations [24,25] we found a higher mortality in patients with dilated cardiomyopathy compared to patients with heart failure secondary to ischemic heart disease or other causes. This finding may be related to the referral practice at our institution, a tertiary centre with a diagnostic and interventional catheterization laboratory. Patients with dilated cardiomyopathy are referred for functional and hemodynamic evaluation, prior to inclusion on the list for heart transplantation. Therefore these patients may have a more severe degree of heart failure than patients with different aetiologies.
The prognostic predictive value of the 6MWT in patients with heart failure was first reported by Bittner et al. [10]. In this study, 898 patients with left ventricular dysfunction or radiological evidence of pulmonary congestion from the SOLVD investigation were followed up for a mean period of 242 days. Mortality was 10.23% in patients who walked less than 350 m compared to 2.99% (P<0.01) in patients who walked more than 450 m. Ejection fraction and the distance walked were independent predictors of mortality or hospitalisation.
Recently, Roul et al. [13] followed 121 patients with mild to moderate heart failure (NYHA class II–III) due to systolic dysfunction (average LVEF 29±13%) for a mean period of 18 months. Distance walked during the 6MWT was not significantly lower in patients who reached the combined end point of death or hospitalisation for heart failure, compared to the event-free group (410±26 m vs. 448±92 m). However, pVO2 was significantly higher in event free patients (18.5±4 ml/kg/min vs. 13.9±4 ml/kg/min, P<0.0001). In addition, patients who walked less than 300 m had an higher rate of combined events of death and hospitalisation. In this subgroup of patients there was a stronger correlation between pVO2 and distance covered during 6MWT (r=0.65) compared to the whole group (r=0.21) suggesting that in these patients performance during the 6MWT was closer to maximal exercise capacity.
The prognostic value of the 6MWT has also been studied in patients with severe heart failure (NYHA classes III–IV) referred for heart transplantation. Swedberg et al. [12] evaluated 359 patients in a multicentre trial of continuous epoprostenol administration. Patients walking a distance below the median, 210 m, had a 6-month mortality of 50 vs. 20% in patients who covered a longer distance. Cahalin et al. [13] studied 45 patients referred for heart transplantation evaluation. A 6MWT distance of <300 m predicted an increased likelihood of death or hospitalisation for inotropic or mechanical support within 6 months but failed to predict overall or event-free survival at a follow-up of 62 weeks.
The predictive value of 6MWT in patients with advanced heart failure was questioned by Aaronson et al. [14]. Although 6-min walk strata (<350 m, 350–450 m, >450 m) were significantly associated with pVO2 strata (< or >14 ml/kg/min; 2=29.5), pVO2 was predictive of survival whereas 6MWT was not.
More recently Lucas et al. [15] in a study of 321 patients with severe heart failure did not demonstrate a predictive value of 6MWT. pVO2 was the strongest predictor of mortality.
The results from our present investigation suggest that in a population of patients with heart failure referred to a tertiary centre, a 6MWT distance of <300 m allows us to identify a high risk subgroup with a 3-year event-free survival approaching 60%. In this subset of patients pVO2 at cardiopulmonary exercise test did not show any predictive value of event-free survival.
In conclusion the 6MWT may be a useful screening test in unselected patients with heart failure, while maximal exercise testing is a more reliable prognostic index in patients with severe heart failure referred for heart transplantation. Although 6MWT is simple and inexpensive, the test still remains largely under-utilised. More extensive use of the 6MWT, in particular in departments of Internal Medicine who are faced with many of the patients with chronic heart failure who are unsuitable for heart transplantation or left ventricular assist devices, could improve the functional and prognostic characterisation of patients and allow a better understanding of the clinical evolution of the disease.
5.1. Study limitations
In this investigation only 45% of patients performed cardiopulmonary exercise testing within 24 h of the 6MWT. Therefore comparison of the prognostic value of the two tests may have been influenced by the different characteristics of the groups under investigation (the whole group and the group who performed both cardiopulmonary exercise test and 6MWT). However, the clinical characteristics of the two groups were similar, although patients undergoing cardiopulmonary exercise testing were younger (mean age 59 vs. 64 years) and showed a more severe left ventricular impairment (lower average LV ejection fraction—35 vs. 40%—and larger LV end diastolic diameter—64 vs. 60 mm). Survival at 36 months was not significantly different, 34 vs. 32% in the two groups.
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