Heart rate slopes during 6-min walk test in pulmonary arterial hypertension, other lung diseases, and healthy controls

Adriano R Tonelli, Xiao-Feng Wang, Laith Alkukhun, Qi Zhang, Raed A Dweik, Omar A Minai, Adriano R Tonelli, Xiao-Feng Wang, Laith Alkukhun, Qi Zhang, Raed A Dweik, Omar A Minai

Abstract

Six-minute walk test (6MWT) continues to be a useful tool to determine the functional capacity in patients with vascular and other lung diseases; nevertheless, it has a limited ability to predict prognosis in this context. We tested whether the heart rate (HR) acceleration and decay slopes during the 6-m walk test are different in patients with pulmonary arterial hypertension (PAH), other lung diseases, and healthy controls. In addition, we assessed whether the HR slopes are associated with clinical worsening. Using a portable, signal-morphology-based, impedance cardiograph (PhysioFlow Enduro, Paris, France) with real-time wireless monitoring via a Bluetooth USB adapter we determined beat-by-beat HR. We included 50 subjects in this pilot study, 20 with PAH (all on PAH-specific treatment), 17 with other lung diseases (obstructive [n = 12, 71%] or restrictive lung diseases [5, 29%]), and 13 healthy controls. The beat-by-beat HR curves were significantly different among all three groups of subjects either during the activity or recovery of the 6MWT. HR curves were less steep in PAH than the other two groups (P < 0.001). HR acceleration rates were slower in patients with PAH or other lung diseases with progression of their disease (P < 0.001). In conclusion, the acceleration and decay slopes during 6MWT are different among patients with PAH, other lung diseases, and healthy controls. The HR slopes during 6MWT were steeper in patients without clinical worsening.

Keywords: 6‐min walk test; Chronic obstructive pulmonary disease; heart rate; pulmonary hypertension; restrictive lung disease.

© 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Figures

Figure 1.
Figure 1.
HR recordings during the activity and recovery phase of the 6‐min walk test (6MWT). Two patients in each group are presented. X‐axis shows the time in seconds and the Y‐axis the percentage change in HR. PAH, pulmonary arterial hypertension; OLD, other lung diseases.
Figure 2.
Figure 2.
Nonlinear mixed model curves during the activity phase of the 6‐min walk test (6MWT). X‐axis shows the time in seconds and the Y‐axis shows the percentage change in HR from baseline. PAH, pulmonary arterial hypertension.
Figure 3.
Figure 3.
Nonlinear mixed model curves during the recovery phase of the 6‐min walk test (6MWT). X‐axis shows the time in seconds and the Y‐axis shows the percentage change in HR from the end of the walking phase. PAH, pulmonary arterial hypertension.
Figure 4.
Figure 4.
Nonlinear mixed model curves during the activity phase of the 6‐min walk test (6MWT), contrasting patients with and without clinical worsening. X‐axis shows the time in seconds and the Y‐axis shows the percentage change in HR from baseline. PAH, pulmonary arterial hypertension.
Figure 5.
Figure 5.
Nonlinear mixed model curves during the recovery phase of the 6‐min walk test (6MWT), contrasting patients with and without clinical worsening. X‐axis shows the time in seconds and the Y‐axis shows the percentage change in HR from the end of the walking phase. PAH, pulmonary arterial hypertension.

References

    1. ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. 2002. ATS statement: guidelines for the six‐minute walk test. Am. J. Respir. Crit. Care Med.; 166:111-117.
    1. Arai Y., Saul J. P., Albrecht P., Hartley L. H., Lilly L. S., Cohen R. J. 1989. Modulation of cardiac autonomic activity during and immediately after exercise. Am. J. Physiol.; 256:H132-H141.
    1. Badesch D. B., Tapson V. F., McGoon M. D., Brundage B. H., Rubin L. J., Wigley F. M. 2000. Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial. Ann. Intern. Med.; 132:425-434.
    1. Batal O., Khatib O. F., Dweik R. A., Hammel J. P., McCarthy K., Minai O. A. 2012. Comparison of baseline predictors of prognosis in pulmonary arterial hypertension in patients surviving </=2 years and those surviving >/=5 years after baseline right‐sided cardiac catheterization. Am. J. Cardiol.; 109:1514-1520.
    1. Benza R. L., Gomberg‐Maitland M., Miller D. P., Frost A., Frantz R. P., Foreman A. J. 2012. The REVEAL Registry risk score calculator in patients newly diagnosed with pulmonary arterial hypertension. Chest; 141:354-362.
    1. Chaitman B. R. 2003. Abnormal heart rate responses to exercise predict increased long‐term mortality regardless of coronary disease extent: the question is why? J. Am. Coll. Cardiol.; 42:839-841.
    1. Ciarka A., Doan V., Velez‐Roa S., Naeije R., van de Borne P. 2010. Prognostic significance of sympathetic nervous system activation in pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med.; 181:1269-1275.
    1. Colucci W. S., Ribeiro J. P., Rocco M. B., Quigg R. J., Creager M. A., Marsh J. D. 1989. Impaired chronotropic response to exercise in patients with congestive heart failure. Role of postsynaptic beta‐adrenergic desensitization. Circulation; 80:314-323.
    1. Dimopoulos S., Anastasiou‐Nana M., Katsaros F., Papazachou O., Tzanis G., Gerovasili V. 2009. Impairment of autonomic nervous system activity in patients with pulmonary arterial hypertension: a case control study. J. Card. Fail.; 15:882-889.
    1. Enright P. L., Sherrill D. L. 1998. Reference equations for the six‐minute walk in healthy adults. Am. J. Respir. Crit. Care Med.; 158:1384-1387.
    1. Galie N., Ghofrani H. A., Torbicki A., Barst R. J., Rubin L. J., Badesch D. 2005. Sildenafil citrate therapy for pulmonary arterial hypertension. N. Engl. J. Med.; 353:2148-2157.
    1. Galie N., Olschewski H., Oudiz R. J., Torres F., Frost A., Ghofrani H. A. 2008. Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double‐blind, placebo‐controlled, multicenter, efficacy (ARIES) study 1 and 2. Circulation; 117:3010-3019.
    1. Galie N., Brundage B. H., Ghofrani H. A., Oudiz R. J., Simonneau G., Safdar Z. 2009. Tadalafil therapy for pulmonary arterial hypertension. Circulation; 119:2894-2903.
    1. Gupta M., Bansal V., Chhabra S. K. 2013. Abnormal heart rate recovery and chronotropic incompetence on exercise in chronic obstructive pulmonary disease. Chron. Respir. Dis.; 10:117-126.
    1. Hijmering M. L., Stroes E. S., Olijhoek J., Hutten B. A., Blankestijn P. J., Rabelink T. J. 2002. Sympathetic activation markedly reduces endothelium‐dependent, flow‐mediated vasodilation. J. Am. Coll. Cardiol.; 39:683-688.
    1. Huang P. H., Leu H. B., Chen J. W., Wu T. C., Lu T. M., Ding Y. A. 2006. Comparison of endothelial vasodilator function, inflammatory markers, and N‐terminal pro‐brain natriuretic peptide in patients with or without chronotropic incompetence to exercise test. Heart; 92:609-614.
    1. Humbert M., Sitbon O., Yaici A., Montani D., O'Callaghan D. S., Jais X. 2010. Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension. Eur. Respir. J.; 36:549-555.
    1. Imai K., Sato H., Hori M., Kusuoka H., Ozaki H., Yokoyama H. 1994. Vagally mediated heart rate recovery after exercise is accelerated in athletes but blunted in patients with chronic heart failure. J. Am. Coll. Cardiol.; 24:1529-1535.
    1. Kannankeril P. J., Le F. K., Kadish A. H., Goldberger J. J. 2004. Parasympathetic effects on heart rate recovery after exercise. J. Investig. Med.; 52:394-401.
    1. Lacasse M., Maltais F., Poirier P., Lacasse Y., Marquis K., Jobin J. 2005. Post‐exercise heart rate recovery and mortality in chronic obstructive pulmonary disease. Respir. Med.; 99:877-886.
    1. Lauer M. S., Okin P. M., Larson M. G., Evans J. C., Levy D. 1996. Impaired heart rate response to graded exercise. Prognostic implications of chronotropic incompetence in the Framingham Heart Study. Circulation; 93:1520-1526.
    1. Lauer M. S., Francis G. S., Okin P. M., Pashkow F. J., Snader C. E., Marwick T. H. 1999. Impaired chronotropic response to exercise stress testing as a predictor of mortality. JAMA; 281:524-529.
    1. Lindstrom M. L., Bates D. M. 1990. Nonlinear mixed effects models for repeated measures data. Biometrics; 46:673-687.
    1. Macchia A., Marchioli R., Marfisi R., Scarano M., Levantesi G., Tavazzi L. 2007. A meta‐analysis of trials of pulmonary hypertension: a clinical condition looking for drugs and research methodology. Am. Heart J.; 153:1037-1047.
    1. Maddox T. M., Ross C., Ho P. M., Masoudi F. A., Magid D., Daugherty S. L. 2008. The prognostic importance of abnormal heart rate recovery and chronotropic response among exercise treadmill test patients. Am. Heart J.; 156:736-744.
    1. Mak S., Witte K. K., Al‐Hesayen A., Granton J. J., Parker J. D. 2012. Cardiac sympathetic activation in patients with pulmonary arterial hypertension. Am. J. Physiol. Regul. Integr. Comp. Physiol.; 302:R1153-R1157.
    1. McLaughlin V. V., Benza R. L., Rubin L. J., Channick R. N., Voswinckel R., Tapson V. F. 2010. Addition of inhaled treprostinil to oral therapy for pulmonary arterial hypertension: a randomized controlled clinical trial. J. Am. Coll. Cardiol.; 55:1915-1922.
    1. Minai O. A., Gudavalli R., Mummadi S., Liu X., McCarthy K., Dweik R. A. 2012. Heart rate recovery predicts clinical worsening in patients with pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med.; 185:400-408.
    1. Olschewski H., Simonneau G., Galie N., Higenbottam T., Naeije R., Rubin L. J. 2002. Inhaled iloprost for severe pulmonary hypertension. N. Engl. J. Med.; 347:322-329.
    1. Pierpont G. L., Adabag S., Yannopoulos D. 2013. Pathophysiology of exercise heart rate recovery: a comprehensive analysis. Ann. Noninvasive Electrocardiol.; 18:107-117.
    1. Provencher S., Chemla D., Herve P., Sitbon O., Humbert M., Simonneau G. 2006. Heart rate responses during the 6‐minute walk test in pulmonary arterial hypertension. Eur. Respir. J.; 27:114-120.
    1. Ramos R. P., Arakaki J. S., Barbosa P., Treptow E., Valois F. M., Ferreira E. V. 2012. Heart rate recovery in pulmonary arterial hypertension: relationship with exercise capacity and prognosis. Am. Heart J.; 163:580-588.
    1. Riley M. S., Porszasz J., Engelen M. P., Shapiro S. M., Brundage B. H., Wasserman K. 2000. Responses to constant work rate bicycle ergometry exercise in primary pulmonary hypertension: the effect of inhaled nitric oxide. J. Am. Coll. Cardiol.; 36:547-556.
    1. Rubin L. J., Badesch D. B., Barst R. J., Galie N., Black C. M., Keogh A. 2002. Bosentan therapy for pulmonary arterial hypertension. N. Engl. J. Med.; 346:896-903.
    1. Sakamaki F., Satoh T., Nagaya N., Kyotani S., Nakanishi N., Ishida Y. 1999. Abnormality of left ventricular sympathetic nervous function assessed by (123)I‐metaiodobenzylguanidine imaging in patients with COPD. Chest; 116:1575-1581.
    1. Savarese G., Paolillo S., Costanzo P., D'Amore C., Cecere M., Losco T. 2012. Do changes of 6‐minute walk distance predict clinical events in patients with pulmonary arterial hypertension?: a meta‐analysis of 22 randomized trials. J. Am. Coll. Cardiol.; 60:1192-1201.
    1. Savin W. M., Davidson D. M., Haskell W. L. 1982. Autonomic contribution to heart rate recovery from exercise in humans. J. Appl. Physiol. Respir. Environ. Exerc. Physiol.; 53:1572-1575.
    1. Simonneau G., Barst R. J., Galie N., Naeije R., Rich S., Bourge R. C. 2002. Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double‐blind, randomized, placebo‐controlled trial. Am. J. Respir. Crit. Care Med.; 165:800-804.
    1. Simonneau G., Rubin L. J., Galie N., Barst R. J., Fleming T. R., Frost A. E. 2008. Addition of sildenafil to long‐term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension: a randomized trial. Ann. Intern. Med.; 149:521-530.
    1. Stewart A. G., Waterhouse J. C., Howard P. 1991. Cardiovascular autonomic nerve function in patients with hypoxaemic chronic obstructive pulmonary disease. Eur. Respir. J.; 4:1207-1214.
    1. Tonelli A. R., Alnuaimat H., Li N., Carrie R., Mubarak K. K. 2011. Value of impedance cardiography in patients studied for pulmonary hypertension. Lung; 189:369-375.
    1. Tonelli A. R., Alkukhun L., Arelli V., Ramos J., Newman J., McCarthy K. 2013. Value of impedance cardiography during 6‐minute walk test in pulmonary hypertension. Clin. Transl. Sci.; 6:474-480.
    1. Volterrani M., Scalvini S., Mazzuero G., Lanfranchi P., Colombo R., Clark A. L. 1994. Decreased heart rate variability in patients with chronic obstructive pulmonary disease. Chest; 106:1432-1437.
    1. Wensel R., Jilek C., Dorr M., Francis D. P., Stadler H., Lange T. 2009. Impaired cardiac autonomic control relates to disease severity in pulmonary hypertension. Eur. Respir. J.; 34:895-901.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever