Clin Res Cardiol (2013) 102:51–61 DOI 10.1007/s00392-012-0495-4
ORIGINAL PAPER
Step climbing capacity in patients with pulmonary hypertension Benjamin Daniel Fox • David Langleben • Andrew Hirsch • Kim Boutet • Avi Shimony
Received: 19 February 2012 / Accepted: 24 July 2012 / Published online: 9 August 2012 Ó Springer-Verlag 2012
Abstract Background Patients with pulmonary hypertension (PH) typically have exercise intolerance and limitation in climbing steps. Objectives To explore the exercise physiology of step climbing in PH patients, on a laboratory-based step test. Methods We built a step oximetry system from an ‘aerobics’ step equipped with pressure sensors and pulse oximeter linked to a computer. Subjects mounted and dismounted from the step until their maximal exercise capacity or 200 steps was achieved. Step-count, SpO2 and heart rate were monitored throughout exercise and recovery. We derived indices of exercise performance,
B. D. Fox (&) D. Langleben A. Hirsch K. Boutet A. Shimony Center for Pulmonary Vascular Disease and Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Room E-222, 3755 Cote Sainte Catherine, Montreal, QC H3T 1E2, Canada e-mail:
[email protected] D. Langleben e-mail:
[email protected] A. Hirsch e-mail:
[email protected] K. Boutet e-mail:
[email protected] A. Shimony e-mail:
[email protected] B. D. Fox Pulmonary Institute, Rabin Medical Center, Tel Aviv University, Petach Tikva, Israel K. Boutet Hoˆpital du Sacre´-Coeur de Montre´al, Universite´ de Montre´al, Montre´al, QC, Canada
desaturation and heart rate. A 6-min walk test and serum NT-proBrain Natriuretic Peptide (BNP) level were measured. Lung function tests and hemodynamic parameters were extracted from the medical record. Results Eighty-six subjects [52 pulmonary arterial hypertension (PAH), 14 chronic thromboembolic PH (CTEPH), 20 controls] were recruited. Exercise performance (climbing time, height gained, velocity, energy expenditure, work-rate and climbing index) on the step test was significantly worse with PH and/or worsening WHO functional class (ANOVA, p \ 0.001). There was a good correlation between exercise performance on the step and 6-min walking distance–climb index (r = -0.77, p \ 0.0001). The saturation deviation (mean of SpO2 values \95 %) on the step test correlated with diffusion capacity of the lung (q = -0.49, p = 0.001). No correlations were found between the step test indices and other lung function tests, hemodynamic parameters or NT-proBNP levels. Conclusions Patients with PAH/CTEPH have significant limitation in step climbing ability that correlates with functional class and 6-min walking distance. This is a significant impediment to their daily activities. Keywords Exercise pathophysiology Exercise testing Monitoring Oxygen desaturation Pulmonary arterial hypertension Pulmonary hypertension
Introduction Pulmonary hypertension (PH) has many causes and may lead to progressive right heart failure and death [1]. Patients with pulmonary arterial hypertension (PAH) almost invariably have exercise intolerance, and improvement in exercise capacity with therapy has been a
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mandatory outcome in clinical trials to date [2]. Stepclimbing imposes significant stress on the cardio-pulmonary system therefore difficulty in performing this task is common amongst patients with cardio-pulmonary disease. Step-climbing may reflect maximal exercise capacity better than a walking test [3, 4]. It is also a ubiquitous and necessary form of exercise for daily living and maintaining quality of life. The effect of PH on step-climbing ability has not previously been evaluated. In published literature, step-climbing protocols have varied between studies in terms of step height, total height climbed (usually limited by the height of the hospital building), the factor determining end-of-test (height, time) and the endpoint evaluated (height gained, climbing time, velocity, power etc.) [3–10]. Step climbing performance correlates well with the gold standard peak oxygen uptake (VO2), both in height- and time-limited tests. Step testing is also highly reproducible across different protocols [5, 6, 11]. Most studies have been performed on lung resection candidates or patients with chronic lung diseases. In this study, we evaluated a standardized step-climbing test with conventional tests of cardiopulmonary function.
Methods The study protocol was approved by the Jewish General Hospital Research Ethics Committee (reference 10-082). All subjects gave written informed consent. Patient selection Patients were recruited over a 5-month period during their routine clinic visit in the PH center. All patients with PAH or chronic thromboembolic PH (CTEPH), aged 18 years or more were eligible. Exclusion criteria were significant neuro-musculo-skeletal impairment or failure to record a reliable SpO2 signal. Healthy staff members acted as controls. A small number of patients who were evaluated in the clinic and found to have normal cardiopulmonary physiology, including cardiac catheterization were included in the control group. Patient testing and data collection After giving consent, a venous blood sample was drawn for NT-pro Brain Natriuretic Peptide (NT-proBNP) level. All patients performed a step oximetry test and a 6-min walk (6-MW) test in random order, with a 15–30-min rest period between each test. The two tests were supervised by different staff members unaware of the patient’s performance on the other test. The unencouraged 6-MW test was performed in accordance with the American Thoracic Society
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guidelines [12]. Data from the 6-MW were distance, preand post-walk SpO2 and the patient’s self-perceived dyspnea at the end of the test on the modified 10-point Borg score. We extracted data on lung function tests, echocardiography and right heart catheterization (RHC) from the medical record. Hemodynamic data from RHC or echocardiography were only extracted if they were obtained within 12 weeks of the study session, with no change in the patient’s clinical condition and medical therapy. Step oximetry test: patient monitoring/data collection The step oximetry device was built by the investigators from a 17-cm high ‘aerobics’ step, adapted with pressure sensors that transmit a signal to the computer when the subject mounted the step with both feet. A pulse oximeter (Radical 7, Massimo, Irvine, CA) outputted heart rate (HR) and SpO2 data to the computer. Integration of time, step count, HR and SpO2 were performed by a computer program. Before the step test, the subject read a standard written instruction, stating that they should climb for as long as possible and as fast as possible until their selfperceived limit was reached. A brief demonstration of stepping was performed by the study physician. During the step test, the subject mounted and dismounted from the step with both feet until he/she reached their self-perceived maximal exertion or an arbitrary limit of 200 steps (34-m vertical climb). Other than a verbal confirmation that the subject was climbing correctly, the test was performed unencouraged. Subjects were not aware of the 200 steps limit and were not allowed to view the computer monitor during the test. At the end of the step test, the subject rested on a chair while monitoring of HR/SpO2 continued until recovery (HR within 5 % of baseline and SpO2 with 2 % of baseline value). Subjects scored their self-perceived dyspnea at step-test completion on the 10-point Borg Scale. If a subject stopped climbing before 200 steps, the reason for stopping the test was recorded. Post-processing of the data was performed by a computer algorithm developed by the investigators. Exercise performance indices were: total height gained, climbing time, mean vertical climbing velocity, total work against gravity (energy) and work rate. We also derived the ‘Climb Index’ from velocity and height gained. From the HR data, we calculated the percent use predicted heart rate reserve (HRR = 220-age), and the slope of heart rate recovery regression line. Oxygenation parameters were defined as: maximum absolute drop in SpO2 from baseline value (desaturation), desaturation area (the integration of time with SpO2 values below 95 %) and the mean deviation of SpO2 below 95 % (saturation deviation). In patients with [2 % absolute desaturation, we calculated the time to
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recovery of SpO2 to within 2 % of baseline values (resaturation time). Data analysis The primary outcomes of interest were the effects of diagnosis or WHO functional class on exercise performance indices, oxygenation indices and heart rate. In addition, the correlation between exercise performance indices and 6-min walk was a primary outcome of interest. Secondary exploratory endpoints were the correlation between oxygenation indices and exercise capacity or diffusion capacity of the lung (DLCO), and correlations between exercise performance indices and NT-proBNP levels, resting hemodynamics from RHC or echocardiography: estimated right ventricular systolic pressure, right ventricular myocardial performance (Tei) index (RV-MPI), right ventricular tissue Doppler velocity (RV-TDV) and estimated cardiac output (eCO). Categorical data were summarized and analyzed using the Chi-squared test. Continuous data were summarized as mean [95 % confidence intervals (CI)] or median [interquartile range (IQR)]
Table 1 Demographic information on subjects
depending on the type and distribution of the data. Parameters with significant right skew were log transformed, analyzed and mean/CI reported in their original units after an anti-log transformation [13]. Differences between groups in non-normally distributed data were assessed by the Kruskal–Wallis test. Normally distributed data was analyzed for between-group differences with oneway ANOVA, followed where appropriate by a post-hoc Tukey’s exact test. The correlation between parameters of interest was by linear regression or Spearman’s rho, as appropriate. Given the large number of possible comparisons, we applied the Holm–Bonferroni correction and reported the uncorrected p values that remained significant after correction [14]. All tests were two-tailed and the predetermined level of significance was p \ 0.05.
Results Demographic data are presented in Table 1. There were no significant baseline differences in sex (p = 0.06) or age (p = 0.08) between the groups. Patients with CTEPH had
Controls (n = 20)
PAH (n = 52)
CTEPH (n = 14)
Age (years)
46 ± 12
48 ± 18
57 ± 15
Sex (M/F)
11; 9
12; 40
6; 8
Body mass index (kg/m2)**
24.3 ± 2.3
25 ± 5.2
WHO Class (I; II; III)***
19; 1; 0
Subdiagnosis
29.7 ± 8.1 ,
à
, à
3; 31; 18
2; 11; 1
Idiopathic 31
Inoperable 4
CTD 12
Pre-TE 7
Congenital 3
Post-TE, residual PH 3
Others 5 PAH medication
Continuous data shown as mean ± SD Significant difference between groups (*p \ 0.05; **p \ 0.01; ***p \ 0.001)
Post hoc tests: difference from normals, àdifference between PAH and CTEPH groups CCB calcium channel blocker, CTD connective tissue disease, CTEPH chronic thromboembolic pulmonary hypertension, ERA endothelin receptor antagonist, NYHA New York Heart Association, PAH pulmonary arterial hypertension, PDE5-I phosphoesterase 5 inhibitor, TE thrombo-endarterectomy
None
6
9
Prostanoids
17
2
PDE5-I
17
2
ERA
23
1
CCB
3
0
Monotherapy
30
5
Combination therapy
16
0
Lung function tests FVC (% predicted)
86 ± 22
88 ± 21
88 ± 13
FEV1 (% predicted)
94 ± 17
83 ± 19
83 ± 13
TLC (% predicted)
93 ± 15
95 ± 13
92 ± 16
DLCO (% predicted)
76 ± 27
69 ± 22
78 ± 13
7±5 60 ± 16
9±4 50 ± 11
Resting right heart catheter RAP (mmHg) MPAP (mmHg) CO (l/min)
4.9 ± 1.6
4.0 ± 1.5
PVR (wood units)
12.0 ± 6.4
12.2 ± 7.9
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higher body mass index than the other groups. Patients with PH were mostly in WHO functional class III, whereas the controls were almost exclusively in class I. Most (89 %) of the PAH patients were studied whilst on chronic vasodilator therapy. Forty-two percent of the CTEPH patients were receiving treatment. Levels of NT-proBNP were similar across both patient groups.
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Analysis of exercise performance indices: correlation with 6-MW All the step oximetry exercise performance indices (height gained, climbing time, velocity, energy, work rate, climb index) had positive linear correlation with 6-MW distance, after applying the Holm–Bonferroni correction (Fig. 1).
Fig. 1 Correlation between 6-min walk distance and step oximetry exercise performance indices. Solid line regression line, dashed lines 95 % confidence interval
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The best fit of points around the regression line was observed with Climb Index (r = -0.77, 95 % CI [0.65, 0.85], r2 = 0.59, p \ 0.0001), followed by Height Gained (r = 0.63, p \ 0.0001) and velocity (r = 0.61, 95 % CI [0.44, 0.74], r2 = 0.37, p \ 0.0001), energy (r = 0.54, 95 %CI [0.35, 0.69], r2 = 0.29, p \ 0.00001) and work rate (r = 0.51, 95 %CI [0.31, 0.66], r2 = 0.26, p \ 0.0001). Analysis of exercise performance indices according to diagnosis/WHO functional class When analyzed according to diagnosis, there was a clear pattern of between-group differences. In almost all parameters generated by the step oximetry system, control subjects performed better than the PH patients (Table 2; Fig. 2). There was also a clear stratified and statistically significant decrease in all climbing parameters with worsening WHO functional class (Table 3; Fig. 3). Due to the possibility of interaction between WHO functional class, age and diagnosis on exercise performance, we performed a multi-variate analysis with Climb Index as the dependent
variable and the above parameters as explanatory. Model simplification was by step-wise deletion of factors until only significant factors remained. After simplification, WHO functional class was found to be a more significant factor (p \ 0.000001) than the presence of PH (p = 0.007) on Climb Index. There was no interaction between the two factors. In a subgroup analysis of only PAH/CTEPH, we analyzed the exercise performance indices according to presence or absence of a pulmonary vasodilator drug. No effect of drug was observed in all the exercise performance indices after applying the Holm–Bonferroni correction. Heart rate parameters during exercise In all patient and WHO groups, there were no significant differences in baseline HR (Tables 2, 3). At peak exercise, subjects utilized between 76 and 84 % of their predicted heart rate reserve during the step test with no significant differences between the diagnostic groups. Patients in WHO class III achieved lower peak HR than those in WHO I and II. The slope of the HR recovery line did not differ significantly between groups.
Table 2 Step oximetry and exercise capacity parameters by diagnosis of subject Normals (n = 25)
PAH (n = 52)
CTEPH (n = 14)
Climb time (s)***
365 [313, 426]
148 [126, 172]
227 [148, 348]à
Height climbed (m)***
30.4 [27.0, 33.7]
11.3 [9.1, 13.5]
Step climbing parameters
Climbing velocity (m/min)*** Energy (kJ)***
4.76 [4.40, 5.12] 20.0 [16.8, 24.0]
17.0 [11.2, 22.8]
3.87 [3.64, 4.10]
3.71 [3.21, 4.19] 10.9 [7.6, 15.7] ,
5.8 [4.8, 7.1]
à
, à
Work (W)***
56 [52, 60]
42 [38, 45]
52 [41, 61]
Climb index***
4.90 [4.69, 5.10]
3.59 [3.40, 3.78]
3.91 [3.54, 4.28] ,
Borg score
3 (2, 4)
3 (3, 4)
3 (3, 4) 90 [81, 97]
Cardiac parameters Baseline HR (bpm)
à
83 [77, 89]
85 [82, 89]
Maximum HR (% predicted)
0.79 [0.74, 0.84]
0.76 [0.73, 0.79]
0.81 [0.78, 0.85]
HR recovery slope (bpm/min)
-20.2 [-14.8, -27]
-16.7 [-13.9, -20.2]
-16.8 [-12.0, -23.3]
Baseline SpO2*
97 [96, 98]
94 [92, 95]
94 [93, 95]
Desaturation %***
1.1 [0.5, 2.9]
3.2 [2.3, 5.2]
Oxygenation parameters
Saturation deviation***
0.18 [0, -0.25]
6.8 [5.0, 10.1] ,
2.86 [1.4, 3.6]
à
5.00 [2.36, 7.11] ,
à , à
Desaturation area***
4.3 [0.8, 13.7]
214 [109, 420]
1,071 [573, 2,001]
Resaturation time (s)*
5.7 [0.9, 19.4]
27 [17, 43]
29 [13, 60]
Distance (m)*
545 [428, 663]
425 [398, 452]
458 [417, 500]
Desaturation %*
0.2 [-0.7, 2.8]
1.8 [0.9, 4.0]
4.6 [2.3, 9.1]
6-Minute walk
Borg score NT-proBNP (pg/ml)
3.5 (2.25, 5.5)
3 (2, 4)
3 (2, 3.75)
–
384 [251, 586]
428 [206,886]
Data given as mean [95 % confidence intervals] or median (interquartile range) Significant difference between groups (*p \ 0.05; **p \ 0.01; ***p \ 0.001) Post hoc tests: difference from normals, àdifference between PAH and CTEPH groups
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Fig. 2 Effect of Diagnosis on step oximetry exercise performance indices. PAH pulmonary arterial hypertension, CTEPH chronic thromboembolic pulmonary hypertension
Desaturation during exercise and step oximetry oxygenation indices Control subjects had very low absolute desaturation (1.1 %, 95 %CI [0.5, 2.9]), saturation deviation (0.18, 95 %CI [0.0, 0.25]) and very small desaturation areas (4.3, 95 %CI [0.8, 13.7]) during step oximetry (Table 2). In the
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patient subgroups, the largest and most prolonged desaturations during step climbing occurred in the CTEPH patients, followed by the PAH patients. We correlated the step oximetry oxygenation indices with DLCO. There was significant negative correlation between DLCO and saturation deviation (q = -0.49, p = 0.001) and desaturation area (q = -0.44, p = 0.004) but not with absolute
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Table 3 Step oximetry and exercise capacity parameters by WHO functional class WHO I (n = 25)
WHO II (n = 44)
WHO III (n = 22)
414 [370, 459]
216 [169, 264]
150 [101, 201]
Step climbing parameters Climb time (s)***
Height climbed (m)***
31.2 [27.8, 34.9]
11.3 [9.5, 13.4]
Climbing velocity (m/min)***
4.70 [4.35, 5.05]
3.9 [3.64, 4.15]
7.2 [5.7, 9.2] ,
3.40 [3.01, 3.84]
Energy (kJ)***
22.5 [20.1, 24.7]
9.8 [7.5, 12.3]
Work (W)***
54 [50, 59]
47 [42, 51]
à
5.9 [3.9, 7.9] 39 [33, 45]
Climb index***
4.99 [4.84, 5.14]
3.81 [3.63, 3.98]
3.25 [2.95, 3.54] ,
Borg score
3 (3, 3)
3 (3, 4)
4 (3, 5.25)
à
Cardiac parameters Baseline HR (bpm)
84 [78, 90]
87 [83, 91]
86 [80, 91]
Maximum HR (% predicted)** HR recovery slope (bpm/min)
0.79 [0.75, 0.84] -19 [-14, -26]
0.80 [0.76, 0.82] -17.7 [-15.0, -20.9]
0.72 [0.67, 0.77] , à -15 [-10.4, -22]
98 [97, 98]
95 [94, 96]
92 [89, 95] ,
Oxygenation parameters Baseline SpO2
à
Desaturation %
2.8 [2.1, 4.7]
4.77 [3.72, 7.04]
3.55 [2.22, 6.43]
Saturation deviation***
0.2 [0.11, 1.32]
2.2 [1.53, 4.05]
2.27 [0.37, 3.50]
Desaturation area***
8 [2, 22]
258 [121, 550]
Resaturation time (s)
11.5 [4.4, 29.0]
28.9 [18.3, 46.1]
588 [495, 682]
460 [441, 480] ,
269 [96, 752] 25.2 [11.9, 53.2]
6-Minute walk Distance (m)
à
361 [318, 405] ,
Desaturation %
4.3 [0.8, -7]
5.4 [2.3, 5.75]
Borg score**
1 (0, 2)
2 (1, 3)
4 (3, 5)
132 [46, 376]
288 [196, 423]
773 [374, 1,597]
NT-proBNP (pg/ml)
à
4.95 [2.65, 5.45]
Data given as Mean [95 % confidence intervals] or median (interquartile range) Significant difference between groups (*p \ 0.05; **p \ 0.01; ***p \ 0.001) Post hoc tests: difference from NYHA I, àdifference between NYHA II and NYHA III groups
desaturation (q = -0.27, p = 0.08) (Fig. 4). Similarly absolute desaturation during 6-MW did not correlate with DLCO. We performed a multi-variate analysis of the effects of age, body mass index, DLCO, diagnosis, presence of drug therapy and functional class on desaturation area. After model simplification, only diagnosis (of CTEPH) was found to be significantly associated with higher desaturation areas. Correlation with pulmonary hemodynamics, NT-proBNP and lung function Fifteen patients (13 PAH, 2 CTEPH) had a RHC and 44 (34 PAH, 10 CTEPH) had an echocardiogram within 12 weeks of the step test without any intervening change in clinical condition or medical treatment. In all the RHC parameters (right atrial pressure, mean pulmonary artery pressure, cardiac output and pulmonary vascular resistance), we did not demonstrate any significant correlations with step oximetry exercise performance indices or 6-MWD (p [ 0.05 in all comparisons). With all the echocardiographic parameters and NT-proBNP data, there were no
significant correlations after applying the Holm–Bonferroni correction. Lung function tests (FEV1, FVC, TLC and DLCO) had poor correlation with step oximetry and 6-MW exercise performance parameters. Subjective data In the PH cohort, the commonest reasons for stopping the test were: leg discomfort (42 %), dyspnea (36 %) and climbing 200 steps (19 %). Borg scores on the step test were significantly different between groups and between different functional classes (p \ 0.001). Sicker patients had higher scores than healthier ones (Table 3). Borg scores were higher in patients stopping due to dyspnea (median 4.0, IQR 3.0, 5.0) than those stopping for other reasons (median 3.0, IQR 3.0, 4.0) Wilcoxon test p = 0.03. To compare the relative difficulty of performing the step test versus the 6-min walk test on a per-subject basis, we did a Bland–Altman analysis (Fig. 5) and a Wilcoxon pairedsamples test. Relative to 6-MW, Borg scores during step climbing were 0.8 higher 95 %CI [-2.29, 3.88], p \ 0.0001.
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Fig. 3 Effect of WHO functional class on step oximetry exercise performance indices. Circles controls, triangles pulmonary arterial hypertension, squares chronic thromboembolic pulmonary hypertension
Discussion This is the first study to explore step-climbing ability in a group of patients with PH. The main finding was a strong correlation between step-climbing exercise performance indices and 6-min walk, and also with presence of disease
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and WHO functional class. Whilst these findings are expected, this study represents the first attempt to quantify step-climbing limitation in PH patients. As far as we are aware, this is also the first study to demonstrate a clear relationship between the patient’s report of his/her own functional capacity and step climbing. Since functional
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Fig. 4 Correlation between DLCO and step oximetry oxygenation indices or desaturation during 6-min walk. Solid line regression line, dashed lines 95 % confidence interval
Fig. 5 Bland-Altman plot of 10-point Borg Scale reported after 6-min walk/step oximetry test. Mean Borg score of both tests is shown on the abscissa, and difference in Borg score (step test minus 6-min walk) on the ordinate. Solid line mean difference, dashed lines 95 % confidence intervals
class is accepted as an important prognostic factor in PH patients, our findings are clinically significant [1]. Measuring exercise capacity in PH patients has long been considered a worthy endpoint for clinical practice and clinical trials, since exercise capacity predicts prognosis
[1]. The cardiopulmonary exercise test (CPET) is the accepted gold-standard test of exercise capacity. CPET gives the most complete information about exercise capacity including maximal oxygen uptake (VO2) and the factors influencing or limiting exercise capacity. A complete CPET examination includes both aerobic and anaerobic phases of exercise. The CPET requires expertise to perform and interpret correctly, and significant expense of purchasing and maintaining the CPET device. CPET has been difficult to standardize across centers for use in clinical trials and has therefore not become the gold standard in this setting [15]. The 6-MW test, on the other hand requires only a long corridor and relatively straightforward training of staff and patients [12]. 6-MW is regarded as a submaximal test of exercise capacity, since the anaerobic threshold is not typically exceeded in during the test and the distance walked correlates reasonably well with peak oxygen uptake [15, 16]. The 6-MW has recently been criticized for lacking sensitivity in relatively well PH patients (walking [450 m), precisely because it is a submaximal test [17, 18]. The step-climbing test should be
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considered a complementary examination of exercise capacity rather than a replacement for other techniques. In this study, most PH patients stopped their step-test because of symptoms, with Borg scores that were significantly higher than those reached on 6-min walk. These patients presumably had performed a maximal exercise test. The majority of healthy controls and a minority of PH patients reached the arbitrary 200 step limit suggesting a submaximal effort in these subjects. It should be emphasized that 200 steps represents climbing 10 floors of a standard office building. In all subjects, the maximal heart rate was approximately 80 % of predicted. In control subjects, this probably represents a submaximal exertion. PH patients climbed significantly less than controls despite reaching similar peak HR, suggesting stroke volume limitation. Moreover, patients with PH have previously been shown to have autonomic dysfunction and chronotropic incompetence [19]. Of note, the patients in WHO class III had the lowest peak heart rates and worst oxygenation indices, suggesting multi-factorial limitation in step climbing [20–22]. We did not monitor patients with a metabolic cart or blood gases since we wanted to study a simple ’in-clinic’ exercise test. In a parallel experiment, general pulmonology patients were tested on the stepoximetry device with metabolic monitoring [23]. The patients achieved slightly higher VO2 on the step-climbing monitor compared to standard cycle-ergometry CPET [23]. We therefore conclude that the step-climbing test is a useful indicator of exercise capacity which (in sufficiently limited patients) can bring the patient to their maximal exercise capacity without the complexity of a full CPET. Of note, in patients walking over 450 m in the 6-MW in this study had a relatively wide range of exercise performance indices compared to 6-MW (Fig. 4), which could increase the chances of being able to detect significant change between tests compared to 6-MWD. An untested hypothesis is that step-climbing exercise performance indices may be useful in prognosticating, long-term monitoring and follow-up of patients with PH and could be used as a clinical trial endpoint. This would require a longterm multicenter study. At the present time, we also have no data available to give ’normal ranges’ for the various parameters over a large and varied population. Therefore at this time, the step-climbing test and device should be considered a research tool only. There was no correlation between the step test exercise performance indices and pulmonary function tests. This is consistent with previous studies where tests of static lung function typically are poor predictors of exercise capacity, including on a step test [5, 11]. There was also poor correlation between step oximetry exercise parameters and RHC/echo/NT-proBNP, although the dataset available was small and this finding should be interpreted with caution.
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Exercise-induced oxygen desaturation is well described in patients with pulmonary vascular disease [20]. In this study, we demonstrated significant correlation between oxygenation and DLCO and with diagnosis of CTEPH. The best correlations with DLCO were seen with derived measurements of SpO2 such as saturation deviation and desaturation area where the extent of desaturation is averaged over time or integrated with time, respectively. The simple calculation of absolute desaturation (baseline SpO2 - lowest SpO2) was less well correlated with DLCO, especially during the 6 minute walk. The stepclimbing test therefore gives the clinician some insight into the gas transfer capacity of the lung, which is not obtained from the 6-min walk test. Of note, patients with CTEPH had worse desaturation characteristics than PAH patients (Table 2). We were unable to explain this between-group difference by multivariate analysis and given the small sample size, it may simply represent a type-I statistical error. Although there are advantages to a stationary step-test as discussed above, there are important differences between the step test and a climbing test performed on a staircase. During normal step climbing, the subject performs work against gravity with each sequential upwards step. In our test, most of the anti-gravity work occurs when lifting the lower foot up onto the step. There is also a step-down phase in the step oximetry test, which is less energy consuming (eccentric muscle contraction) than continuing a sequential upward climb. The subject therefore has regular ‘rest’ during the test. Energy expenditure and work-rate in our step test are calculated only for the ascending work via classical physics equations. These differences in technique probably explain the relatively low work-rates reported by our technique, relative to those reported during hospital staircase-based climbing experiments [5]. One concern during any form of exercise testing in general (and for PH patients in particular) is that the subject could feel unwell or even collapse during the test, which could result in further injury if the patient is climbing a concrete staircase typical of a hospital building. The patient would also be difficult to reach with monitoring and resuscitation equipment. The step-oximetry test is laboratory-based, and involves continuous monitoring, and the maximum potential fall is 18 cm. We speculate that the step-oximetry test might be safer than a step test performed on a staircase. One potential limitation was the pooling of PH patients by diagnosis, irrespective of their medical treatment. Treatment with pulmonary vasodilators improves exercise capacity in patients with PAH and probably patients with CTEPH [1, 24]. However, mixing of treated and untreated patients did not change the conclusions of this study since step-climbing ability stratified cleanly with functional class rather than treatment. The purpose of the study was to
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compare different clinical tests of exercise capacity (WHO and 6-MWD) with the new test at a certain point-in-time. In this respect, having untreated patients actually increases the range of functional capacities ‘available’ to study. In summary, we provide the first quantitative study of step climbing in a cohort of patients with PAH/CTEPH and controls using a dedicated device. Patients with PH have severe limitation in step climbing. For a patient, ability to climb steps may be as important to maintaining their quality of life as the distance that they can walk in fixed time period. Evaluating patients’ step climbing ability compliments the conventional techniques and enriches our understanding of their limitations and the severity of their illness.
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