Characterization of Pulmonary Arterial Hypertension Patients Walking More Than 450 m in 6 Min at Diagnosis

doi:10.1378/chest.09-2060

Chest

Volume 137, Issue 6, June 2010, Pages 1297-1303

https://doi.org/10.1378/chest.09-2060 Get rights and content

Background

At diagnosis of pulmonary arterial hypertension (PAH), some patients are considered to have a “near-normal” 6-min walk distance (6MWD) (ie, > 450 m). Because they are generally excluded from randomized controlled trials, little is known about these patients.

Methods

We analyzed the baseline characteristics and treatment responses of 49 consecutive patients with a 6MWD > 450 m at the time of newly diagnosed PAH. Data from this cohort were then compared with data from hemodynamically matched patients with a 6MWD ≤ 450 m.

Results

Patients with a 6MWD > 450 m were either in World Health Organization (WHO) functional class (FC) II (n = 23) or III (n = 26) at baseline. Compared with patients in FC II, those in FC III had more severe hemodynamic impairment (ie, a lower cardiac index and higher pulmonary vascular pressures and resistance) but similar 6MWD. At first evaluation after initiation of PAH-specific treatment (3–6 months), FC improved (FC I-II: n = 38; FC III: n = 11, P < .005) and cardiac index increased. However, 6MWD remained unchanged. Compared with matched patients with a 6MWD ≤ 450 m (n = 98), individuals with a 6MWD > 450 m were approximately 9 years younger (P = .0006) and had a lower BMI (P = .0009).

Conclusions

Anthropometric characteristics such as younger age and lower BMI may explain higher 6MWD in some PAH patients. In the cohort of patients with a 6MWD > 450 m, hemodynamic indices and WHO FC were more sensitive than 6MWD in detecting changes secondary to PAH-specific treatments.

Section snippets

Patients

All patients (those with a 6MWD > 450 m at the time of PAH diagnosis, and the matched patients with a 6MWD ≤ 450 m) were selected retrospectively from 295 consecutive patients with idiopathic, familial, or anorexigen-associated PAH referred to our center between January 1995 and March 2006. All clinical characteristics at diagnosis and follow-up were stored in the Registry of the French Network of Pulmonary Hypertension. This registry was set up in agreement with French legislation (Commission

Baseline Characteristics

Of 295 consecutive patients with idiopathic, familial, or anorexigen-associated PAH referred to our center between January 1995 and March 2006, we identified 49 patients (17%) with a 6MWD > 450 m at the time of PAH diagnosis. The baseline characteristics of these 49 patients are shown in Table 1. There were 23 patients in WHO FC II and 26 in FC III. The gender, age, height, weight, and 6MWD of patients in FC II were similar to those of patients in FC III (Table 2). However, patients in WHO FC

Discussion

The main results of the current study are that (1) some PAH patients with severe hemodynamic impairment may have a 6MWD > 450 m at the time of PAH diagnosis; (2) younger age, greater height, and lower BMI may explain higher 6MWD in these patients; and (3) use of PAH therapies is associated with improvements in hemodynamic parameters and WHO FC without concomitant improvement of 6MWD in patients with a baseline 6MWD > 450 m.

The 6MWT is a submaximal exercise test that is easy to perform, safe,

Conclusions

In summary, the present study indicates that patients with idiopathic, familial, or anorexigen-associated PAH with a baseline 6MWD that is considered near normal (ie, > 450 m) may nonetheless have severe hemodynamic impairment. Comparisons with matched patients with a 6MWD < 450 m indicate that younger age and lower BMI may at least partially explain higher 6MWDs. These patients may show improvements in WHO FC and hemodynamic parameters on treatment; however, 6MWD is unlikely to increase

Acknowledgments

Author contributions: Dr Degano: contributed to the design of the study, data collection, analysis and interpretation, and manuscript preparation.

Dr Sitbon: contributed to the design of the study, data collection, and analysis and interpretation.

Dr Savale: contributed to the design of the study and data analysis and interpretation.

Dr Garcia: contributed to the design of the study and data analysis and interpretation.

Dr O'Callaghan: contributed to the design of the study, data collection, and

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Factors contributing to exercise capacity in chronic thromboembolic pulmonary hypertension with near-normal hemodynamics
2021, Journal of Heart and Lung Transplantation
Citation Excerpt :
However, the 6MWD is influenced by many factors, including gender, age, height, weight, comorbidities, oxygen supplementation, corridor length used for testing, learning effect, and motivation.26,27 The limitation of 6MWD was decreased sensitivity in patients with milder symptoms who walked a longer distance (> 450m) at baseline and decreased adequacy in patients who were still under treatment.28 In general, 6MWD has been shown to be closely associated with hemodynamic parameters at baseline.21,29
Despite improved survival for patients with chronic thromboembolic pulmonary hypertension (CTEPH) due to progressive medical and interventional treatment, impaired exercise capacity remains common due to poorly understood mechanisms. We aimed to clarify the exercise capacity of CTEPH patients with near-normal pulmonary hemodynamics and evaluate its determinants among the hemodynamic, peripheral (e.g., oxygen use by the peripheral tissues), and muscular (e.g., skeletal muscle strength) factors.
Three hundred and twenty-nine patients with CTEPH (mean age, 63 ± 12 years; men/women, 73/256) with a near-normal mean pulmonary artery pressure (≤30 mm Hg) at rest were enrolled. We assessed exercise capacity by peak oxygen consumption (peak VO₂) using cardiopulmonary exercise testing with a right heart catheter. We also measured the 6-minute walk distance (6MWD) and quadriceps muscle strength.
The mean pulmonary artery pressure was 19 ± 4 mmHg and mean cardiac output was 4.8 ± 1.5 L/min at rest. The mean 6MWD was 444 ± 101 m, while the mean peak VO₂ was 14.4 ± 3.9 mL/min/kg. A multivariate model that predicted 6MWD included quadriceps strength (β = 0.45, p < 0.001) and peak arterial venous oxygen difference (β = 0.29, p < 0.001). In contrast, the peak VO₂ was best correlated with mPAP-CO slope (β = -0.30, p < 0.001), followed by quadriceps strength and peak arterial venous oxygen difference.
The 6MWD performance may be significantly influenced by peripheral oxygen use and muscular factors, while peak VO₂ is influenced by hemodynamic and peripheral factors in CTEPH patients with near-normal hemodynamics.
Balloon Pulmonary Angioplasty for the Treatment of Nonoperable Chronic Thromboembolic Pulmonary Hypertension: Single-Center Experience with Low Initial Complication Rate
2019, Journal of Vascular and Interventional Radiology
To evaluate the safety and efficacy of balloon pulmonary angioplasty (BPA) for nonoperable chronic thromboembolic pulmonary hypertension (CTEPH) patients during the initial experience of a single center.
A total of 18 CTEPH patients (5 with residual pulmonary hypertension after pulmonary endarterectomy) were treated with BPA during the period 2014–2018 and were retrospectively reviewed. Mean age was 61 ± 19 years; 55% were female; mean pulmonary artery pressure was 44 ± 12 mmHg; cardiac output was 4.3 ± 1.0 l/min; and pulmonary vascular resistance was 8.4 ± 3.6 WU. Patients were evaluated by New York Heart Association functional class, 6-minute walk distance, N-terminal pro b-type natriuretic peptide, echocardiography, right heart catheterization, and before and after completions of BPA.
A total of 91 procedures were performed, with a median number of 4 BPA sessions per patient (range, 2–8). There were no deaths or major complications requiring extracorporeal support or (non)invasive ventilation. The most common complication was self-limiting hemoptysis (3%). According to Society of Interventional Radiology classification, 4 mild, 4 moderate, and 1 severe adverse events were noted. Invasive hemodynamics significantly improved, with a cardiac index increase of 15% (P = .0333), decrease of mean pulmonary artery pressure of 30% (P = .0013), and decrease of pulmonary vascular resistance of 45% (P = .0048). Stroke volume index (P = .0171) and pulmonary arterial compliance (P = .0004) were also significantly enhanced.
BPA significantly improves cardiopulmonary hemodynamics with an acceptable safety profile. Further studies assessing the long-term efficacy of BPA are required.
Incremental shuttle walk test distance and autonomic dysfunction predict survival in pulmonary arterial hypertension
2017, Journal of Heart and Lung Transplantation
Citation Excerpt :
At the present time, 2 exercise tests are used in patients with PAH: 6MWT, which is not recommended, and cardiopulmonary exercise testing (CPET), which is an incremental maximal test. Because of the submaximal nature of the 6MWT, it loses its ability to reflect maximal oxygen aerobic capacity9–12 and pulmonary hemodynamic severity11,12 in patients with milder disease. Furthermore, changes in hemodynamic parameters may not be reflected by alteration in 6MWT distance.12–15
To ensure effective monitoring of pulmonary arterial hypertension (PAH), a simple, reliable assessment of exercise capacity applicable over a range of disease severity is needed. The aim of this study was to assess the ability of the incremental shuttle walk test (ISWT) to correlate with disease severity, measure sensitivity to change, and predict survival in PAH.
We enrolled 418 treatment-naïve patients with PAH with baseline ISWT within 3 months of cardiac catheterization. Clinical validity and prognostic value of ISWT distance were assessed at baseline and 1 year.
ISWT distance was found to correlate at baseline with World Health Organization functional class, Borg score, and hemodynamics without a ceiling effect (all p < 0.001). Walking distance at baseline and after treatment predicted survival; the area under the receiver operating characteristic curve for ability of ISWT distance to predict mortality was 0.655 (95% confidence interval 0.553–0.757; p = 0.004) at baseline and 0.737 (95% confidence interval 0.643–0.827; p < 0.001) at 1 year after initiation of treatment. Change in ISWT distance also predicted survival (p = 0.04). Heart rate (HR) and systolic blood pressure (SBP) parameters reflecting autonomic response to exercise (highest HR, change in HR, HR recovery at 1 minute >18 beats/min, highest SBP, change in SBP, and 3-minute SBP ratio) were significant predictors of survival (all p < 0.05).
In patients with PAH, the ISWT is simple to perform, allows assessment of maximal exercise capacity, is sensitive to treatment effect, predicts outcome, and has no ceiling effect. Also, measures of autonomic function made post-exercise predict survival in PAH.
Utility of right ventricular Tei-index for assessing disease severity and determining response to treatment in patients with pulmonary arterial hypertension
2014, Journal of Cardiology
Citation Excerpt :
A possible cause of this discrepancy is that the number of cases in our study was small, and the majority of patients had preserved exercise capacity (6MWD >450 m, 71% of the PAH group). Degano et al. have reported that 6MWD was less sensitive than hemodynamic variables and symptoms in detecting changes secondary to PAH-specific therapy in a cohort study of 49 patients with 6MWD > 450 m, which may point to a ceiling effect [27]. Further studies on patients with poor exercise capacity and symptoms will be required to define whether changes in RV Tei-index are related to changes in exercise capacity and symptoms.
We sought to evaluate the potential utility of echocardiography-derived morphological and functional right ventricular (RV) variables for assessing disease severity of pulmonary arterial hypertension (PAH) and determining the changes in the patient's hemodynamics in the clinical course.
This study consisted of 24 normal controls (the control group) and 24 patients with PAH at rest or with exercise (the PAH group) who underwent echocardiography, right heart catheterization, plasma brain natriuretic peptide (BNP) measurement, and six-minute walk distance (6MWD) test. The PAH group had poorer RV echocardiographic variables than the control group. RV Tei-index was more strongly correlated with 6MWD, BNP, cardiac index, mean pulmonary arterial pressure, and pulmonary vascular resistance (PVR) than other RV echocardiography-derived variables including RV end-diastolic areas, RV fractional area change, and tricuspid annular plane systolic excursion. In 16 of the 24 patients who successfully underwent repeated examination during follow up (13.3 ± 4.9 months; range, 5–24 months), PVR decreased from 486 ± 380 dyne s cm⁻⁵ to 346 ± 252 dyne s cm⁻⁵, and RV Tei-index decreased from 0.55 ± 0.30 to 0.42 ± 0.17, and the changes in RV Tei-index were correlated with the concomitant changes in PVR during the clinical course of PAH (r = 0.706, p = 0.002). Tricuspid annular plane systolic excursion and RV fractional area change did not change during the follow up.
Quantitative echocardiography revealed that the measurement of RV Tei-index is of great clinical utility for predicting disease severity of PAH and determining the changes in the patient's hemodynamics in the clinical course.
Clinical and functional assessment in COPD: From case finding to follow-up
2014, Presse Medicale
Une spirométrie avec test de bronchodilatation est indispensable pour pouvoir porter un diagnostic de bronchopneumopathie chronique obstructive (BPCO).
On considère actuellement qu’il faut restreindre les indications de détection de BPCO aux personnes ayant des symptômes (toux et/ou expectoration chronique) et un facteur de risque (tabagisme, exposition professionnelle).
L’utilisation du débit expiratoire de pointe, même couplée à des données cliniques, ne permet de détecter que les formes les plus sévères.
Un avis spécialisé est souvent indispensable pour porter un diagnostic de BPCO chez un patient ayant un trouble ventilatoire obstructif non réversible, évaluer la sévérité (notamment par la mesure pléthysmographique des volumes pulmonaires et de l’hématose) et définir un parcours de soins.
Dans le cadre du suivi, l’évaluation des symptômes, la spirométrie et la mesure des capacités d’exercice permettent de guider les interventions thérapeutiques, parmi lesquelles les traitements médicamenteux et la réhabilitation.
A spirometry with bronchodilator test is needed for the diagnosis of COPD.
It is recommended to detect COPD only in subjects with symptoms (dyspnoea and/or chronic cough and/or chronic sputum production) and a history of exposure to risk factors for the disease (tobacco smoking and/or occupational exposure).
Measurement of peak expiratory flow to detect COPD, although simpler than conventional spirometry, allows only detection of the most severe cases of COPD.
Specialist referral is often useful in the diagnosis of COPD, to establish the presence of incompletely reversible airflow obstruction, assess severity (using clinical questionnaires, plethysmography, exercise testing and arterial blood gases when indicated) and define future management.
The level of FEV1 is associated with individualized assessment of symptoms and evaluation of exacerbation risk in the management strategy of stable COPD.
Baseline body mass index does not significantly affect outcomes after pulmonary thromboendarterectomy
2014, Annals of Thoracic Surgery
Citation Excerpt :
This obesity-related dyspnea may prompt earlier evaluation and eventually lead to earlier diagnosis of CTEPH compared with patients having a normal or low BMI. Additionally, among patients with pulmonary arterial hypertension, those with near normal functional ability as measured by a 6-minute walk distance of more than 450 m had significantly lower BMI than the more impaired patients [12]. A similar association between functional ability and baseline BMI may be present in CTEPH, and may delay diagnosis of nonobese patients.
Obesity is a common comorbidity of patients with chronic thromboembolic pulmonary hypertension referred for pulmonary thromboendarterectomy, yet the effect of obesity on pulmonary thromboendarterectomy outcomes has not been well described.
We conducted a retrospective cohort study in which 476 consecutive operations over a 3.5-year period were examined to determine the effects of obesity on outcomes. Patients were grouped into four categories based on body mass index (BMI): less than 22 kg/m², 22 to 30 kg/m², 30 to 40 kg/m², and more than 40 kg/m².
There were important differences in baseline pulmonary hemodynamics, with obese patients having significantly lower pulmonary vascular resistances than nonobese patients. All patients achieved a significant reduction in pulmonary vascular resistance, although the improvement was greatest in the lower BMI groups. The overall in-hospital mortality was 0.8%, and there were no differences in risk among BMI groups. Among the BMI groups, there were no differences in incidence of postoperative complications, including atrial fibrillation (overall 24.8%), reperfusion lung injury (overall 23.1%), and surgical site infection (overall 4.4%) or in median lengths of stay (including ventilator days, intensive care unit days, and postoperative length of stay).
Pulmonary thromboendarterectomy outcomes have continued to improve, and this surgery can safely be completed in obese patients, previously deemed to be at high risk for poor outcomes.

View all citing articles on Scopus

For editorial comment see page 1258

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Chest

ORIGINAL RESEARCHPULMONARY ARTERIAL HYPERTENSIONCharacterization of Pulmonary Arterial Hypertension Patients Walking More Than 450 m in 6 Min at Diagnosis

Background

Methods

Results

Conclusions

Section snippets

Patients

Baseline Characteristics

Discussion

Conclusions

Acknowledgments

J Am Coll Cardiol

Vascul Pharmacol

J Am Coll Cardiol

Clin Chest Med

Chest

Respir Med

Chest

Lancet

Eur Heart J

Guidelines for the diagnosis and treatment of pulmonary hypertension

Eur Respir J

Treatment of pulmonary arterial hypertension

N Engl J Med

Surrogate and combined end points in pulmonary arterial hypertension

Proc Am Thorac Soc

Clinical correlates and prognostic significance of six-minute walk test in patients with primary pulmonary hypertension. Comparison with cardiopulmonary exercise testing

Am J Respir Crit Care Med

ORIGINAL RESEARCH
PULMONARY ARTERIAL HYPERTENSION
Characterization of Pulmonary Arterial Hypertension Patients Walking More Than 450 m in 6 Min at Diagnosis