Prognostic Value of Cardiopulmonary Exercise Test in Elderly Women with Heart Failure and Reduced or Preserved Ejection Fraction

Angela Beatrice Scardovi, Renata De Maria, Alessandro Ferraironi, Marco Renzi, Franco Turi, Marina Parolini, Tiziana Di Giacomo, Roberto Ricci

Cardiology Department, S. Spirito Hospital, Rome, Italy.
CNR Clinical Physiology Institute, Cardio Thoracic and Vascular Department, Niguarda Hospital, Milan, Italy.

DOI: 10.4236/wjcd.2014.47043                

Abstract

The prognostic role of cardiopulmonary exercise test (CPET) in elderly women with chronic heart failure (HF) has not yet been clarified. We assessed the incremental value of CPET variables for risk stratification in female HF patients with preserved or reduced left ventricular ejection fraction (LVEF). We prospectively followed up 131 female HF outpatients aged 72 [interquartile range 62 - 77] years after a symptom limited CPET. 34% had ischemic heart disease and 14% permanent atrial fibrillation, 24% were in NYHA class III. LVEF was 50% [interquartile range 36 - 62], peak oxygen consumption was 11.3 [interquartile range 9.2 - 13.5] ml/kg/min; the slope of the regression line relating ventilation to CO₂ output was 33.9 [interquartile range 30.3 - 44.9]; 40% of patients showed exercise oscillatory breathing during CPET. During a median follow-up of 18 months [interquartile range 8 - 54], overall 39 patients (29.7%) met the combined end-point of cardiovascular mortality or HF admission using a time-to-first event approach. Moderate to severe mitral regurgitation, slope, exercise oscillatory breathing were independently associated to cardiovascular mortality or HF admission. When CPET ventilatory variables were added to clinical and echocardiographic parameters, prediction of the combined point improved significantly (AUC 0.755 (95% CI 0.662 to 0.832) vs 0.634 (95% CI 0.536 to 0.725), p = 0.016). In conclusion, among elderly female HF patients the CPET derived parameters EOB and VE/VCO₂ slope emerged as strong prognostic markers, with additive predictive value to clinical and echocardiographic parameters in patients with both reduced and preserved LVEF.

Keywords

Women, Heart Failure, Cardiopulmonary Exercise Test, Ventilatory Inefficiency

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Hsich, E.M. and Piña, I.L. (2009) Heart Failure in Women: A Need for Prospective Data. Journal of the American College of Cardiology, 54, 491-498. http://dx.doi.org/10.1016/j.jacc.2009.02.066
[2]	Levy, D., Kenchaiah, S., Larson, M.G., Benjamin, E.J., Kupka, M.J., Ho, K.K., Murabito, J.M. and Vasan, R.S. (2002) Long-Term Trends in the Incidence of and Survival with Heart Failure. The New England Journal of Medicine, 347, 1397-1402. http://dx.doi.org/10.1056/NEJMoa020265
[3]	Martinez-Selles, M., Doughty, R.N., Poppe, K., Whalley, G.A., Earle, N., Tribouilloy, C., McMurray, J.J., Swedberg, K., Køber, L., Berry, C., Squire, I. and Meta-Analysis Global Group In Chronic Heart Failure (MAGGIC) (2012) Gender and Survival in Patients with Heart Failure: Interactions with Diabetes and Aetiology. Results from the MAGGIC Individual Patient Meta-Analysis. European Journal of Heart Failure, 14, 473-479. http://dx.doi.org/10.1093/eurjhf/hfs026
[4]	Vaartjes, I., Hoes, A.W., Reitsma, J.B., et al. (2010) Age- and Gender-Specific Risk of Death after First Hospitalization for Heart Failure. BMC Public Health, 10, 637. http://dx.doi.org/10.1186/1471-2458-10-637
[5]	Koelling, T.M., Chen, R.S., Lubwama, R.N., L’Italien, G.J. and Eagle, K.A. (2004) The Expanding National Burden of Heart Failure in the United States: The Influence of Heart Failure in Women. American Heart Journal, 147, 74-78. http://dx.doi.org/10.1016/j.ahj.2003.07.021
[6]	Deswal, A. and Bozkurt, B. (2006) Comparison of Morbidity in Women versus Men with Heart Failure and Preserved Ejection Fraction. American Journal of Cardiology, 97, 1228-1231. http://dx.doi.org/10.1016/j.amjcard.2005.11.042
[7]	ESC (2012) Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. European Heart Journal, 33, 1787-1847. http://dx.doi.org/10.1093/eurheartj/ehs104
[8]	Mezzani, A., Agostoni, P., Cohen-Solal, A., Corrà, U., Jegier, A., Kouidi, E., Mazic, S., Meurin, P., Piepoli, M., Simon, A., Laethem, C.V. and Vanhees, L. (2009) Standards for the Use of Cardiopulmonary Exercise Testing for the Functional Evaluation of Cardiac Patients. European Journal of Cardiovascular Prevention & Rehabilitation, 6, 249-267. http://dx.doi.org/10.1097/HJR.0b013e32832914c8
[9]	Arena, R., Myers, J., Aslam, S.S., Varughese, E.B. and Peberdy, M.A. (2003) Technical Considerations Related to the Minute Ventilation/Carbon Dioxide Output Slope in Patients with Heart Failure. Chest, 124, 720-727. http://dx.doi.org/10.1378/chest.124.2.720
[10]	Leite, J.J., Mansur, A.J., de Freitas, H.F., Chizola, P.R., Bocchi, E.A., Terra-Filho, M., Neder, J.A. and Lorenzi-Filho, G. (2003) Periodic Breathing during Incremental Exercise Predicts Mortality in Patients with Chronic Heart Failure Evaluated for Cardiac Transplantation. Journal of the American College of Cardiology, 41, 2175-2178. http://dx.doi.org/10.1016/S0735-1097(03)00460-1
[11]	Cheitlin, M.D., Armstrong, W.F., Aurigemma, G.P., Beller, G.A., Bierman, F.Z., Davis, J.L., Douglas, P.S., Faxon, D.P., Gillam, L.D., Kimball, T.R., Kussmaul, W.G., Pearlman, A.S., Philbrick, J.T., Rakowski, H., Thys, D.M., Antman, E.M., Smith Jr., S.C., Alpert, J.S., Gregoratos, G., Anderson, J.L., Hiratzka, L.F., Faxon, D.P., Hunt, S.A., Fuster, V., Jacobs, A.K., Gibbons, R.J., Russell, R.O., ACC, AHA and ASE (2003) Guideline Update for the Clinical Application of Echocardiography A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASE Committee to Update the 1997 Guidelines for the Clinical Application of Echocardiography). Journal of the American Society of Echocardiography, 16, 1091-1110.
[12]	Nagueh, S.F., Appleton, C.P., Gillebert, T.C., Marino, P.N., Oh, J.K., Smiseth, O.A., Waggoner, A.D., Flachskampf, F.A., Pellikka, P.A. and Evangelisa, A. (2009) Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography. European Journal of Echocardiography, 10, 165-193. http://dx.doi.org/10.1093/ejechocard/jep007
[13]	Schoenfeld, D.A. (1983) Sample-Size Formula for the Proportional-Hazards Regression Model. Biometrics, 39, 499-503. http://dx.doi.org/10.2307/2531021
[14]	DeLong, E.R., DeLong, D.M. and Clarke-Pearson, D.L. (1988) Comparing the Areas under Two or More Correlated Receiver Operating Characteristic Curves: A Nonparametric Approach. Biometrics, 44, 837-845. http://dx.doi.org/10.2307/2531595
[15]	Senni, M., Parrella, P., De Maria, R., Cottini, C., Böhm, M., Ponikowski, P., Filippatos, G., Tribouilloy, C., Di Lenarda, A., Oliva, F., Pulignano, G., Cicoira, M., Nodari, S., Porcu, M., Cioffi, G., Gabrielli, D., Parodi, O., Ferrazzi, P. and Gavazzi, A. (2013) Predicting Heart Failure Outcome from Cardiac and Comorbid Conditions: The 3C-HF Score. International Journal of Cardiology, 163, 206-211. http://dx.doi.org/10.1016/j.ijcard.2011.10.071
[16]	Wang, T.J., Larson, M.G., Levy, D., Vasan, R.S., Leip, E.P., Wolf, P.A., D’Agostino, R.B., Murabito, J.M., Kannel, W.B. and Benjamin, E.J. (2003) Temporal Relations of Atrial Fibrillation and Congestive Heart Failure and Their Joint Influence on Mortality: The Framingham Heart Study. Circulation, 107, 2920-2925. http://dx.doi.org/10.1161/01.CIR.0000072767.89944.6E
[17]	Mountantonakis, S.E., Grau-Sepulveda, M.V., Bhatt, D.L., Hernandez, A.F., Peterson, E.D. and Fonarow, G.C. (2012) Presence of Atrial Fibrillation Is Independently Associated with Adverse Outcomes in Patients Hospitalized with Heart Failure: An Analysis of Get with the Guidelines-Heart Failure. Circulation: Heart Failure, 5, 191-201. http://dx.doi.org/10.1161/CIRCHEARTFAILURE.111.965681
[18]	Chamberlain, A.M., Redfield, M.M., Alonso, A., Weston, S.A. and Roger, V.L. (2011) Atrial Fibrillation and Mortality in Heart Failure: A Community Study. Circulation: Heart Failure, 4, 740-746. http://dx.doi.org/10.1161/CIRCHEARTFAILURE.111.962688
[19]	Mamas, M.A., Caldwell, J.C., Chako, S., Garratt, C.J., Fath-Ordoubadi, F. and Neyses, L. (2009) A Meta-Analysis of the Prognostic Significance of Atrial Fibrillation in Chronic Heart Failure. European Journal of Heart Failure, 11, 676-683. http://dx.doi.org/10.1093/eurjhf/hfp085
[20]	Linssen, G.C., Rienstra, M., Jaarsma, T., Voors, A.A., van Gelder, I.C., Hillege, H.L. and van Veldhuisen, D.J. (2011) Clinical and Prognostic Effects of Atrial Fibrillation in Heart Failure Patients with Reduced and Preserved Left Ventricular Ejection Fraction. European Journal of Heart Failure, 13, 1111-1120. http://dx.doi.org/10.1093/eurjhf/hfr066
[21]	Rossi, A., Dini, F.L., Faggiano, P., Agricola, E., Cicoira, M., Frattini, S., Simioniuc, A., Gullace, M., Ghio, S., Enriquez-Sarano, M. and Temporelli, P.L. (2011) Independent Prognostic Value of Functional Mitral Regurgitation in Patients with Heart Failure. A Quantitative Analysis of 1256 Patients with Ischaemic and Non-Ischaemic Dilated Cardiomyopathy. Heart, 97, 1675-1680. http://dx.doi.org/10.1136/hrt.2011.225789
[22]	Lund, L.H. and Mancini, D.M. (2008) Peak VO2 in Elderly Patients with Heart Failure. International Journal of Cardiology, 125, 166-171. http://dx.doi.org/10.1016/j.ijcard.2007.10.004
[23]	Scardovi, A.B., Coletta, C., De Maria, R., Perna, S., Aspromonte, N., Feola, M., Rosso, G., Greggi, M. and Ceci, V. (2007) The Cardiopulmonary Exercise Test Is Safe and Reliable in Elderly Patients with Chronic Heart Failure. Journal of Cardiovascular Medicine (Hagerstown), 8, 608-612. http://dx.doi.org/10.2459/01.JCM.0000281698.53983.4e
[24]	Elmariah, S., Goldberg, L.R., Allen, M.T. and Kao, A. (2006) Effects of Gender on Peak Oxygen Consumption and the Timing of Cardiac Transplantation. Journal of the American College of Cardiology, 47, 2237-2242. http://dx.doi.org/10.1016/j.jacc.2005.11.089
[25]	Corrà, U., Mezzani, A., Giordano, A., Pistono, M., Gnemmi, M., Caruso, R. and Giannuzzi, P. (2013) Peak Oxygen Consumption and Prognosis in Heart Failure: 14 mL/kg/min Is Not a “Gender-Neutral” Reference. International Journal of Cardiology, 167, 157-161. http://dx.doi.org/10.1016/j.ijcard.2011.12.055
[26]	Guazzi, M., Arena, R. and Myers, J. (2006) Comparison of the Prognostic Value of Cardiopulmonary Exercise Testing between Male and Female Patients with Heart Failure. International Journal of Cardiology, 113, 395-400. http://dx.doi.org/10.1016/j.ijcard.2005.11.105
[27]	Scardovi, A.B., De Maria, R., Ferraironi, A., Gatto, L., Celestini, A., Forte, S., Parolini, M., Sciarretta, S., Ricci, R. and Guazzi, M. (2012) A Case for Assessment of Oscillatory Breathing during Cardiopulmonary Exercise Test in Risk Stratification of Elderly Patients with Chronic Heart Failure. International Journal of Cardiology, 155, 115-119. http://dx.doi.org/10.1016/j.ijcard.2011.02.033
[28]	Guazzi, M., Arena, R., Ascione, A., Piepoli, M. and Guazzi, M.D. (2007) Exercise Oscillatory Breathing and Increased Ventilation to Carbon Dioxide Production Slope in Heart Failure: An Unfavorable Combination with High Prognostic Value. American Heart Journal, 153, 859-867. http://dx.doi.org/10.1016/j.ahj.2007.02.034
[29]	Arena, R., Myers, J., Abella, J., Peberdy, M.A., Bensimhon, D., Chase, P. and Guazzi, M. (2007) Development of a Ventilatory Classification System in Patients with Heart Failure. Circulation, 115, 2410-2417. http://dx.doi.org/10.1161/CIRCULATIONAHA.107.686576
[30]	Corrà, U., Pistono, M., Mezzani, A., Braghiroli, A., Giordano, A., Lanfranchi, P., Bosimini, E., Gnemmi, M. and Giannuzzi, P. (2006) Sleep and Exertional Periodic Breathing in Chronic Heart Failure: Prognostic Importance and Inter-dependence. Circulation, 113, 44-50. http://dx.doi.org/10.1161/CIRCULATIONAHA.105.543173
[31]	Guazzi, M., Myers, J., Peberdy, M.A., Bensimhon, D., Chase, P. and Arena, R. (2008) Exercise Oscillatory Breathing in Diastolic Heart Failure: Prevalence and Prognostic Insights. European Heart Journal, 29, 2751-2759. http://dx.doi.org/10.1093/eurheartj/ehn437
[32]	O’Connor, C.M., Whellan, D.J., Lee, K.L., Keteyian, S.J., Cooper, L.S., Ellis, S.J., Leifer, E.S., Kraus, W.E., Kitzman, D.W., Blumenthal, J.A., Rendall, D.S., Miller, N.H., Fleg, J.L., Schulman, K.A., McKelvie, R.S., Zannad, F. and Piña, I.L. (2009) Efficacy and Safety of Exercise Training in Patients with Chronic Heart Failure: HF-ACTION Randomized Controlled Trial. JAMA, 301, 1439-1450. http://dx.doi.org/10.1001/jama.2009.454