Correlation of the New York Heart Association Classification and the 6‐Minute Walk Distance: A Systematic Review

ABSTRACT

Background

Functional status assessment is the cornerstone of heart failure management and trials. The New York Heart Association (NYHA) classification and 6‐minute walk distance (6MWD) are commonly used tools; however, the correlation between them is not well understood.

Hypothesis

We hypothesised that the relationship between the NYHA classification and 6MWD might vary across studies.

Methods

A systematic literature search was performed to identify all studies reporting both NYHA class and 6MWD. Two reviewers independently assessed study eligibility and extracted data. Thirty‐seven studies involving 5678 patients were included.

Results

There was significant heterogeneity across studies in 6MWD within all NYHA classes: I (n = 16, Q = 934.2; P < 0.001), II (n = 25, Q = 1658.3; P < 0.001), III (n = 30, Q = 1020.1; P < 0.001), and IV (n = 6, Q = 335.5; P < 0.001). There was no significant difference in average 6MWD between NYHA I and II (420 m vs 393 m; P = 0.416). There was a significant difference in average 6MWD between NYHA II and III (393 m vs 321 m; P = 0.014) and III and IV (321 m vs 224 m; P = 0.027). This remained significant after adjusting for region of study, age, and sex.

Conclusions

Although there is an inverse correlation between NYHA II–IV and 6MWD, there is significant heterogeneity across studies in 6MWD within each NYHA class and overlap in 6MWD between NYHA I and II. The NYHA classification performs well in more symptomatic patients (NYHA III/IV) but less so in asymptomatic/mildly symptomatic patients (NYHA I/II). Nonetheless, the NYHA classification is an easily applied first‐line tool in everyday clinical practice, but its potential subjectivity should be considered when performing comparisons across studies.

Introduction

The New York Heart Association (NYHA) classification system was first developed in 1928 and has since undergone several revisions.1 The ease of application of this classification based on patients' reported symptoms has resulted in widespread use in many heart failure (HF) studies2, 3 and international guidelines.4, 5 The NYHA classification is often used as inclusion or exclusion criteria for therapy as well as for prognostication and assessment of outcomes.2, 3, 4, 5 Contrary to its extensive use, the actual objectivity of the NYHA is unclear. The NYHA classification is based on patient and physician assessment of cardiac symptoms including dyspnea, angina, and fatigue at different levels of physical activity, and its reliability and validity have been widely debated.6, 7, 8

Studies have evaluated the usefulness and reliability of more objective measures of HF severity, such as cardiopulmonary exercise testing (CPET) and bicycle and treadmill testing.9 Although CPET is regarded as the gold standard for assessment of aerobic functional capacity,10 there are significant financial and logistical costs involved. A viable alternative is the 6‐minute walk distance (6MWD), where the distance ambulated on a level surface within 6 minutes is used as a simple and inexpensive yet objective grading of HF severity and prognosis.11, 12, 13 Many studies have shown the objectivity and added prognostic value of the 6MWD in predicting outcomes.11, 12, 13

To date, there has not been any comprehensive literature review on the correlation between NYHA class and 6MWD. We aimed to assess the correlation between NYHA class and 6MWD by conducting a systematic review of all studies reporting both NYHA class and 6MWD.

Methods

Literature Search Strategy

A comprehensive search of the MEDLINE, Embase, and Cochrane Library databases was performed from January 1980 to Decemebr 2013 by 2 independent reviewers. The search terms used included “heart failure,” “congestive cardiac failure,” “New York Heart Association,” “six minute walk test,” and “six minute walk distance.” In addition, the references of the included studies and the bibliographies of review articles were searched for additional articles. There was no language restriction. The investigation conformed with the principles outlined in the Declaration of Helsinki. Because the study was based on review of existing literature with no active participation from study subjects, no approval from an ethics committee was required locally.

Inclusion and Exclusion Criteria

Only studies that provided the average 6MWD and its distribution for each individual class of NYHA were included. Studies that did not report the number of patients in each class, or where there were <5 patients in each class, were excluded. Studies that reported average 6MWD for combined NYHA classes (eg, combined class I–II) were also excluded. Figure 1 describes the study selection process.

Figure 1.

Flowchart of study selection. Abbreviations: 6MWD, 6‐minute walk distance; NYHA, New York Heart Association.

Data Extraction and Study Characteristics

Two reviewers (F.Y.L., L.L.T.) independently assessed the eligibility of the studies and performed data extraction on a prespecified data‐collection form. Discrepancies were resolved by consensus and consultation with a third investigator (J.Y.). Study characteristics collected included the date and type of study; region of study; number, age, and sex of study population; and average 6MWD and its distribution per NYHA class.

Statistical Analysis

For the pooled mean of the 6MWD, we used a random‐effects model based on the DerSimonian and Laird method. 14, 15 Random‐effect models methodology was selected as it was anticipated that systematic differences between studies (heterogeneity) would be likely. A Q statistic and corresponding P value was calculated using χ² test to quantify the heterogeneity among combined results. Inconsistency was calculated using an I² index to determine the impact of heterogeneity.

For each of the 4 NYHA classes, a separate meta‐analysis was performed to estimate the pooled mean of the 6MWD. Forest plots were produced to illustrate mean of 6MWD and its 95% confidence interval (CI). The studies are ordered by the size of the study, from the largest to smallest. In studies where median and interquartile range (IQR) of 6MWD were reported instead of mean and SD, estimation of the mean using IQR was determined within each of the NYHA classes. In these imputations, we assumed the distribution of 6MWD was similar to the normal distribution as the estimated average of 6MWD was close to the reported median.

To identify the association between 6MWD and NYHA, we further undertook study‐level meta‐regression analysis to assess the effects of NYHA, controlling for region, age, and sex (% of male sex). In this analysis, we compared the mean of the 6MWD for one class of NYHA to the next (adjacent) class, such as I vs II, II vs III, and III vs IV. Average age of each NYHA class was used as a continuous variable. Due to small numbers in the subgroups, region was categorized to 3 groups (North America, Europe, Others) in the meta‐regression analysis. The predicted 6MWD with multiple linear model of NYHA class, region, age, and sex was shown in the scatter plot. Stata software version 13 (StataCorp, Ltd., College Station, TX) was used for all analyses.

Results

Out of 321 studies, 35 studies involving 5422 patients met the study criteria and were included. Ten (29%) studies were from North America, 20 (57%) were from Europe, and 5 (14%) were from other regions (eg, South America, Asia). Table 1 describes the characteristics of the included studies. Sixteen studies reported data on NYHA class I, 24 on NYHA class II, 29 on NYHA class III, and 7 on NYHA class IV.

Table 1.

Summary of Included Studies

Study	Country (Region)	Study Type	No. of Patients	Age, years, (SD/Range)	Male Sex, %	LVEF, %, SD (Range)	Data on NYHA Class(es)
Goode et al 20087	UK (Europe)	Case–control	1139	71 (64–77)	–	<40	I, II
Rostagno et al 200313	Italy (Europe)	Cohort	146	64 (10)	–	46	I, II
Alahdab et al 200918	US (North America)	Cohort	198	55.7 (12.9)	63.1	29 (40)	I, II, III, IV
Forman et al 201220	US (North America)	Cohort	2054	59 (51–68)	71.0	≤35	II, III
Zugck et al 200021	Germany (Europe)	Cohort	113	54 (12)	79.646	19	I, II, III
Radke et al 200524	US (North America)	Cohort	17	–	52.9	–	I
Gary et al 200425	US (North America)	RCT	32	–	0	55	II, III
Ingle et al 200826	UK (Europe)	Case–control	186	–	–	–	I, II
Boşnak Guçlu et al 201127	Turkey (Other)	Cohort	34	69 (10)	82	34 (8)	II, III
Karavidas et al 201028	Greece (Europe)	Case–control	18	62 (10)	77.8	<35	II
Jankowska et al 200829	Poland (Europe)	Cohort	10	70 (6)	90	30 (5)	II, III
Ates et al 201330	Turkey (Other)	Cohort	29	64 (7)	52	32 (3)	II
Keast et al 201331	Canada (North America)	RCT	27	62.5 (11.4)	81.5	27 (5)	III
Pepera et al 201232	UK (Europe)	Case–control	10	–	80	46	I
Zaidi et al 201333	US (North America)	Cohort	5	35.5 (25–42)	–	48 (9)	II
Jaski et al 201134	US (North America)	Cohort	39	60.5 (11.4)	87.2	22	III
Leszek et al 201035	Poland (Europe)	Cohort	34	61.5 (9.0)	61.8	57 (12)	II, III
Jehn et al 200936	Germany (Europe)	Cohort	50	60.9 (14.0)	76	39 (16)	I, II, III
Goscinska‐Bis et al 200837	Poland (Europe)	RCT	23	64.7 (7.0)	87.0	30 (3)	III
Miller et al 200738	US (North America)	Cohort	25	50.1 (13.1)	–	16 (6)	IV
Freimark et al 200739	Israel (Other)	Case–control	56	–	76.8	–	II
Román et al 200640	Spain (Europe)	Cohort	22	45.4 (19–77)	18.2	–	II
Torre‐Amione et al 200541	US (North America)	RCT	37	–	70	22	II
Ince et al 200442	Germany (Europe)	RCT	6	–	100	28 (9)	III
Guimãraes et al 200243	Brazil (South America)	Cohort	12	45 (12)	100	23 (7)	III
Lellamo et al 201044	Italy (Europe)	RCT	32	69 (8)	0	33 (6)	III
Rostagno et al 200045	Italy (Europe)	Cohort	140	45.4 (29–70)	–	35	I, II, III, IV
Rostagno et al 200046	Italy (Europe)	Cohort	33	57.3 (31–72)	–	38	I
Faggiano et al 199747	Italy (Europe)	Cohort	26	56 (11)	92	22 (6)	II, III, IV
Bagur et al 201148	Canada (North America)	Cohort	46	56 (8)	–	53 (15)	I, II, III
Tay et al 201149	UK (Europe)	Cohort	12	80 (10)	17	≥40	II, III
Jehn et al 201050	Switzerland (Europe)	Cohort	97	34 (13)	76	40 (18)	I, II, III
Vrtovec et al 201351	Slovenia (Europe)	RCT	40	61 (10)	85	26 (4)	III
Deuschle et al 201152	Germany (Europe)	Cohort	95	56 (25–80)	–	60 (22–77)	I, II, III, IV
Souza et al 200753	Brazil (South America)	Cohort	38	37 (2)	–	–	I, II, III, IV

Abbreviations: LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; RCT, randomized controlled trial; SD, standard deviation; UK, United Kingdom; US, United States.

Analysis Within Each New York Heart Association Class

An analysis of the reported 6MWD by NYHA classes showed a pooled estimate of 358 m (P < 0.0001; Q = 5580.1) and higher 6MWD associated with lower NYHA functional class (Table 2). There was significant heterogeneity between studies seen in each of NYHA classes (all P < 0.0001; Q = 934.2, 1657.6, 964.0, and 248.4 for NYHA classes I, II, III, and IV, respectively; Table 2 and Figure 2).

Table 2.

Heterogeneity Within Each NYHA Class

NYHA Class	No. of Studies	No. of Patients	Pooled Average 6MWD, m (95% CI)	I 2, %	Q	P Value
I	16	984	420 (379 to 462)	98.4	934.2	<0.0001
II	24	2769	393 (362 to 424)	98.6	1657.6	<0.0001
III	29	1530	325 (296 to 354)	97.1	964.0	<0.0001
IV	7	139	225 (115 to 336)	97.6	248.4	<0.0001
Overall	35	5422	358 (338 to 379)	98.7	5580.1	<0.0001

Abbreviations: 6MWD, 6‐minute walk distance; CI, confidence interval; NYHA, New York Heart Association.

Figure 2.

Distribution of 6MWD within NYHA, (A) class I, (B) class II, (C) class III, and (D) class IV. Abbreviations: 6MWD, 6‐minute walk distance; CI, confidence interval; NYHA, New York Heart Association.

Analysis Across New York Heart Association Classes

When adjacent classes of NYHA are compared, the smallest difference between 6MWD was seen in patients with class I and II (420 m vs 393 m) and the largest difference was in patients with classes III and IV (325 m vs 225 m). Meta‐regression analyses were used to assess the associations between 6MWD and NYHA functional class (Table 3). Significant difference between studies was present between class II and III (coefficient 67.4; 95% CI: 10.1 to 124.7, P = 0.022) and between class III and IV (coefficient 102.7; 95% CI: 13.0 to 192.4, P = 0.026). There was no significant difference between class I and II (coefficient 27.1; 95% CI: −39.8 to 93.9, P = 0.422). Adjusting for region, age, and sex did not change these associations. The estimated variance (τ²) between studies was reduced from 10 480 to 7239 when all these variables were combined in the model (Table 3, Figure 3).

Table 3.

Comparison of 6MWD by NYHA Class

	Coefficient (95% CI)	P Value	Coefficient (95% CI)a	P Valuea
NYHA I vs II	27.1 (−39.8 to 93.9)	0.422	49.8 (−9.1 to 108.8)	0.096
NYHA II vs III	67.4 (10.1 to 124.7)	0.022	70.5 (21.6 to 119.3)	0.005
NYHA III vs IV	102.7 (13.0 to 192.4)	0.026	105.0 (25.5 to 184.5)	0.010

Abbreviations: 6MWD, 6‐minute walk distance; CI, confidence interval; NYHA, New York Heart Association.

^aCorrected for region, age, and sex.

Figure 3.

Comparison of 6MWD by NYHA class. Abbreviations: 6MWD, 6‐minute walk distance; NYHA, New York Heart Association.

Discussion

This is the first study to systemically analyze the correlation between NYHA class and 6MWD. It demonstrates the subjectivity of the NYHA classification when compared with a more objective measure like the 6MWD, with the 6MWD in all NYHA classes showing significant heterogeneity across different studies. Despite this heterogeneity, worsening NYHA class status appears to correlate well with decreasing 6MWD between class II and III, and between class III and IV.

The basis of the NYHA classification stems from a patient's perceived and reported cardiac symptoms, as well the physician's assessment of these symptoms. This easy availability has resulted in its extensive use in numerous trials as well as guidelines. Some studies have shown the NYHA classification to be subjective. Surveys among physicians assessing NYHA class showed only about 54% to 56% concordance, giving a result little better than chance.6, 8 There was also no consistent method used to assess NYHA class with criteria ranging from self‐reported walking distance to difficulty climbing stairs.8 Self‐reported walking distance has been shown to neither correlate with formally measured exercise capacity nor have any prognostic relevance.8 Goode et al found significant difference in physician‐rated and patient‐rated NYHA class in a study of >1000 HF patients.7 Severo et al also found discrepant interobserver thresholds of NYHA classification.16

In contrast, the 6MWD is a more objective test of a patient's functional capacity, requiring the patient to walk in a reproducible environment. The 6MWD has been shown in studies to have good prognostic value in the different subsets of HF patients. In a study of about 200 patients with mild to moderate HF, 6MWD was a strong predictor of mortality.13 Castel et al showed that in patients with moderate to severe HF receiving cardiac resynchronization therapy, 6MWD was found to be an independent predictor of mortality.17 Six‐minute walk distance also strongly predicted mortality and HF rehospitalisations in patients hospitalized for acute HF.18 However, the 6MWD is not without limitations. The test does not provide insight into the mechanisms of exercise limitation, and its results can be affected by a variety of factors unrelated to cardiopulmonary status, including age, sex, height, and weight. Some studies have shown that the change in 6MWD after the onset of therapy does not appear to predict outcomes in HF.19 Other than 6MWD, cardiopulmonary exercise testing has often been used as the gold standard for functional assessment,10 but this test requires appropriate equipment, trained staff, and logistical support and is relatively expensive. Several studies have shown the 6WMD to have similar utility and prognostic predictive value as CPET in patients with HF.20, 21 The appeal of the 6MWD stems from its reproducibilty, simplicity, and cost‐effectiveness. However, the limitations of this test, as mentioned above, have to be considered.

In this study, the variation between NYHA class and 6MWD was comprehensively analyzed in 2 distinct ways: within each NYHA class and between 2 adjacent NYHA classes. Comparing the different studies reporting 6MWD within each NYHA class, there was significant heterogeneity of 6MWD reported within all of the NYHA classes. Comparing the average 6MWD by NYHA class, there was no significant difference between class I and II, although there was a difference noted between class II vs III and class III vs IV. In this analysis, NYHA class appears useful for discriminating between mild and severe HF, but it may be more subjective in differentiating between mild and moderate HF. This has potential implications. Currently, various major guidelines, like the European4 and American guidelines22, 23 for device therapy (eg, implantable cardioverter‐defibrillator and cardiac resynchronization therapy), base their recommendations on the NYHA functional class. For example, implantable cardioverter‐defibrillator therapy is recommended as a class I indication for primary prevention in NYHA II/III patients with impaired ejection fraction (EF), but it is not recommended for those with poor functional status.22 Cardiac resynchronisation therapy is also recommended as a class I indication in suitable NYHA II/III and ambulatory NYHA IV patients, but not to those in NYHA I.4, 23 Differences in interpretation of NYHA class can result in a change in strength of indication for therapy from a class I recommendation to a lesser one. This conclusion appears mostly relevant for the group of patients who are asymptomatic/mildly symptomatic (NYHA I/II) and less so in more symptomatic HF patients (NYHA III/IV). Although NYHA classification is to some degree subjective, it is still an easily applied first‐line tool in everyday clinical practice to assess patients' functional limitation. Moreover, in more symptomatic patients (NYHA III/IV), the NYHA classification appears to be a well‐performing, accurate clinical tool to estimate these patients' functional limitation and guide therapy.

Study Limitations

Limitations of this study include the potential influence of other variables such as age, sex, comorbidities, and ethnicity on both NYHA class and 6MWD. Age and sex were corrected for in the analyses. For differences in ethnicity, an attempt to correct for this was made by considering the region of study. As data on comorbidities were not uniformly available in these reports, these could not be accounted for during the analysis. Differences between patients with reduced and preserved EF may exist. In the included studies that reported data on preserved EF,24, 25, 26 these were not higher than those with reduced EF. Ingle et al reported similar 6MWD between both groups of patients.26 Second, we would ideally have liked to compare both NYHA and 6MWD to cardiopulmonary exercise testing or clinical outcomes, but these were not available in all studies. Other limitations included lack of information on clinical significance of repeated measurements within each study.

Conclusion

Although there is an inverse correlation between NYHA class II to IV and 6MWD, there is significant heterogeneity across studies in reported 6MWD within each NYHA class and overlap in reported 6MWD between NYHA I and II. The NYHA classification appears to perform well in more symptomatic patients (NYHA III/IV) but less so in asymptomatic/mildly symptomatic patients (NYHA I/II). Nonetheless, the NYHA is an easily applied first‐line tool in everyday clinical practice, but its potential subjectivity should be considered when performing comparisons across studies.