Cardiopulmonary and Noninvasive Hemodynamic Responses to Exercise Predict Outcomes in Heart Failure



      An impaired cardiac output response to exercise is a hallmark of chronic heart failure (HF). We determined the extent to which noninvasive estimates of cardiac hemodynamics during exercise in combination with cardiopulmonary exercise test (CPX) responses improved the estimation of risk for adverse events in patients with HF.

      Methods and Results

      CPX and impedance cardiography were performed in 639 consecutive patients (mean age 48 ± 14 years), evaluated for HF. Clinical, hemodynamic, and CPX variables were acquired at baseline and subjects were followed for a mean of 460 ± 332 days. Patients were followed for the composite outcome of cardiac-related death, hospitalization for worsening HF, cardiac transplantation, and left ventricular assist device implantation. Cox proportional hazards analyses including clinical, noninvasive hemodynamic, and CPX variables were performed to determine their association with the composite endpoint. There were 113 events. Among CPX variables, peak oxygen uptake (VO2) and the minute ventilation (VE)/carbon dioxide production (VCO2) slope were significant predictors of risk for adverse events (age-adjusted hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.05–1.11 for both; P < .001). Among hemodynamic variables, peak cardiac index was the strongest predictor of risk (HR 1.08, 95% CI 1.0–1.16; P = .01). In a multivariate analysis including CPX and noninvasively determined hemodynamic variables, the most powerful predictive model included the combination of peak VO2, peak cardiac index, and the VE/VCO2 slope, with each contributing significantly and independently to predicting risk; an abnormal response for all 3 yielded an HR of 5.1 (P < .001).


      These findings suggest that noninvasive indices of cardiac hemodynamics complement established CPX measures in quantifying risk in patients with HF.

      Key Words

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        • Pina I.L.
        • Apstein C.S.
        • Balady G.J.
        • Belardinelli R.
        • Chaitman B.R.
        • Duscha B.D.
        • et al.
        Exercise and heart failure; a statement from the American Heart Association Committee on Exercise, Rehabilitation, and Prevention.
        Circulation. 2003; 107: 1210-1225
        • Arena R.
        • Myers J.
        • Guazzi M.
        The clinical and research applications of aerobic capacity and ventilatory efficiency in heart failure: an evidence-based review.
        Heart Fail Rev. 2008; 13: 245-269
        • Ingle L.
        Theoretical rationale and practical recommendations for cardiopulmonary exercise testing in patients with chronic heart failure.
        Heart Fail Rev. 2007; 12: 12-22
        • Balady G.J.
        • Arena R.
        • Sietsema K.
        • Myers J.
        • Coke L.
        • Fletcher G.F.
        • et al.
        • American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee of the Council on Clinical Cardiology, Council on Epidemiology and Prevention, Council on Peripheral Vascular Disease, Interdisciplinary Council on Quality of Care and Outcomes Research
        Clinician’s guide to cardiopulmonary exercise testing in adults.
        Circulation. 2010; 122: 191-225
        • Cattadori G.
        • Salvioni E.
        • Gondoni E.
        • Agostoni P.
        Evaluation of noninvasive exercise cardiac output determination in chronic heart failure patients: a proposal of a new diagnostic and prognostic method.
        J Cardiovasc Med. 2011; 12: 19-27
        • Lang C.C.
        • Agostoni P.
        • Mancini D.M.
        Prognostic significance and measurement of exercise-derived hemodynamic variables in patient with heart failure.
        J Cardiac Fail. 2007; 13: 672-679
        • Lang C.C.
        • Karlin P.
        • Haythe J.
        • Lim T.K.
        • Mancini D.M.
        Peak cardiac power output, measured noninvasively, is a powerful predictor of outcome in chronic heart failure.
        Circ Heart Fail. 2009; 2: 33-38
        • Goda A.
        • Lang C.C.
        • Williams P.
        • Jones M.
        • Farr M.J.
        • Mancini D.M.
        Usefulness of noninvasive measurement of cardiac output during sub-maximal exercise to predict outcome in patient with chronic heart failure.
        Am J Cardiol. 2009; 104: 1556-1560
        • Rosenblum H.
        • Helmke S.
        • Williams P.
        • Teruya S.
        • Jones M.
        • Burkhoff D.
        • et al.
        Peak cardiac power measured noninvasively with a bioreactance technique is a predictor of adverse outcomes in patients with advanced heart failure.
        Congest Heart Fail. 2010; 16: 254-258
        • Williams S.G.
        • Jackson M.
        • Cooke G.A.
        • Barker D.
        • Patwala A.
        • Wright D.J.
        • et al.
        How do different indicators of cardiac pump function impact upon the long-term prognosis of patients with chronic heart failure?.
        Am Heart J. 2005; 150: 983.e1-983.e6
        • Hunt S.A.
        ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure).
        J Am Coll Cardiol. 2005; 46: e1-e82
        • Myers J.
        • Buchanan N.
        • Walsh D.
        • et al.
        Comparison of the ramp versus standard exercise protocols.
        J Am Coll Cardiol. 1991; 17: 1334-1342
        • Arena R.
        • Guazzi M.
        • Myers J.
        • Peberdy A.M.
        Prognostic characteristics of cardiopulmonary exercise testing in heart failure: comparing American and European models.
        Eur J Cardiovasc Prev Rehabil. 2005; 12: 562-567
        • Arena R.
        • Myers J.
        • Aslam S.
        • Varughese E.B.
        • Peberdy M.A.
        Technical considerations related to the minute ventilation/carbon dioxide output slope in patients with heart failure.
        Chest. 2003; 124: 720-727
        • Charloux A.
        • Lonsdorfer-Wolf E.
        • Richard R.
        • Lampert E.
        • Oswald-Mammosser M.
        • Mettauer B.
        • et al.
        A new impedance cardiograph device for the noninvasive evaluation of cardiac output at rest and during exercise; comparison with the “direct” Fick method.
        Eur J Appl Physiol. 2000; 82: 313-320
        • Lepretre P.M.
        • Koralsztein J.P.
        • Billat V.L.
        Effect of exercise intensity on relationship between VO2 and cardiac output.
        Med Sci Sports Exerc. 2004; 36: 1357-1363
        • Richard R.
        • Lonsdorfer-Wolf E.
        • Charloux A.
        • Doutreleau S.
        • Buchheit M.
        • Oswald-Mammosser M.
        • et al.
        Noninvasive cardiac output evaluation during a maximal progressive exercise test, using a new impedance cardiograph device.
        Eur J Appl Physiol. 2001; 85: 202-207
        • Tordi N.
        • Mourot L.
        • Matusheski B.
        • Hughson R.L.
        Measurements of cardiac output during constant exercises: comparison of two noninvasive techniques.
        Int J Sports Med. 2004; 25: 145-149
        • Myers J.
        • Gujja P.
        • Neelagaru S.
        • Burkhoff D.
        Cardiac output and cardiopulmonary responses to exercise in heart failure: application of a new bio-reactance device.
        J Cardiac Fail. 2007; 13: 629-636
        • Jakovljevic D.G.
        • Moore S.
        • Hallsworth K.
        • Fattakhova G.
        • Thoma C.
        • Trenell M.I.
        Comparison of cardiac output determined by bioimpedance and bioreactance methods at rest and during exercise.
        J Clin Monit Comput. 2012; 26: 63-68
        • Lang C.C.
        • Karlin P.
        • Haythe J.
        • Tsao L.
        • Mancini D.M.
        Ease of noninvasive measurement of cardiac output coupled with peak VO2 determination at rest and during exercise in patients with heart failure.
        Am J Cardiol. 2007; 99: 404-405
        • Mancini D.M.
        • Eisen H.
        • Kussmaul W.
        • Mull R.
        • Edmunds Jr., L.H.
        • Wilson J.R.
        Value of peak exercise oxygen consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure.
        Circulation. 1991; 83: 778-786
        • Wilson J.R.
        • Rayos G.
        • Yeoh T.
        • Gothard P.
        Dissociation between peak exercise consumption and hemodynamic dysfunction in potential heart transplant candidates.
        J Am Coll Cardiol. 1995; 26: 429-435
        • Chomsky D.B.
        • Lang C.C.
        • Rayos G.H.
        • Shyr Y.
        • Yeoh T.K.
        • Pierson R.N.
        • et al.
        Hemodynamic exercise testing: a valuable tool in the selection of cardiac transplantation candidates.
        Circulation. 1996; 94: 3176-3183
        • Metra M.
        • Faggiano P.
        • d’Aloia A.
        • Nodari S.
        • Gualeni A.
        • Raccagni D.
        • Dei Cas L.
        Use of cardiopulmonary exercise testing with hemodynamic monitoring in the prognostic assessment of ambulatory patients with chronic heart failure.
        J Am Coll Cardiol. 1999; 33: 943-950
        • Myers J.
        • Gullestad L.
        The role of exercise testing and gas-exchange measurement in the prognostic assessment of patients with heart failure.
        Current Opinion in Cardiology. 1998; 13: 145-155
        • Myers J.
        • Gullestad L.
        • Vagelos R.
        • Do D.
        • Bellin D.
        • Ross H.
        • Fowler M.
        Clinical, hemodynamic, and cardiopulmonary exercise test determinants of survival in patients referred for evaluation of heart failure.
        Ann Int Med. 1998; 29: 286-293
        • Methvin A.
        • Georgiopoulou V.V.
        • Kalogeropoulos A.P.
        • Malik A.
        • Anarado P.
        • Chowdhury M.
        • et al.
        Usefullness of cardiac index and peak exercise oxygen consumption for determining priority for cardiac transplantation.
        Am J Cardiol. 2010; 105: 1353-1355
        • Aaronson K.D.
        • Schwartz J.S.
        • Chen T.M.
        • Wong K.L.
        • Goin J.E.
        • Mancini D.M.
        Development and prospective validation of a clinical index to predict survival in ambulatory patients referred for cardiac transplant evaluation.
        Circulation. 1997; 95: 2660-2667
        • Mancini D.
        • Katz S.D.
        • Donchez L.
        • Aaronson K.
        Coupling of hemodynamic measurements with oxygen consumption during exercise does not improve risk stratification in patient with heart failure.
        Circulation. 1996; 94: 2492-2496
        • Cotter G.
        • Williams S.G.
        • Vered Z.
        • Tan L.B.
        Role of cardiac power in heart failure.
        Curr Opin Cardiol. 2003; 18: 215-222
        • Myers J.
        • Voodi L.
        • Froelicher V.F.
        A survey of exercise testing: methods, utilization, interpretation, and safety in the VAHCS.
        J Cardiopulm Rehabil. 2000; 20: 251-258
        • Myers J.
        • Arena R.
        • Dewey F.
        • Bensimhon D.
        • Abella J.
        • Hsu L.
        • et al.
        A cardiopulmonary exercise testing score for predicting outcomes in patients with heart failure.
        Am Heart J. 2008; 156: 1177-1183
        • Arena R.
        • Myers J.
        • Aslam S.S.
        • Varughese E.B.
        • Peberdy M.A.
        Peak VO2 and VE/VCO2 slope in patients with heart failure: a prognostic comparison.
        Am Heart J. 2004; 147: 354-360
        • Guazzi M.
        • Myers J.
        • Arena R.
        Cardiopulmonary exercise testing in the clinical and prognostic assessment of diastolic heart failure.
        J Am Coll Cardiol. 2005; 46: 1883-1890
        • Bard R.L.
        • Gillespie B.W.
        • Clarke N.S.
        • Egan T.G.
        • Nicklas J.M.
        Determining the best ventilatory efficiency measure to predict mortality in patients with heart failure.
        J Heart Lung Transpl. 2006; 25: 589-595
        • Robbins M.
        • Francis G.
        • Pashkow F.J.
        • et al.
        Ventilatory and heart rate responses to exercise: better predictors of heart failure mortality than peak oxygen consumption.
        Circulation. 1999; : 2411-2417
        • Corra U.
        • Mezzani A.
        • Bosimini E.
        • Scapellato F.
        • Imparato A.
        • Giannuzzi P.
        Ventilatory response to exercise improves risk stratification in patients with chronic heart failure and intermediate functional capacity.
        Am Heart J. 2002; 143: 418-426
        • Williams S.G.
        • Cooke G.A.
        • Wright D.J.
        • et al.
        Peak cardiac power output: a powerful prognostic indicator in chronic heart failure.
        Eur Heart J. 2001; 22: 1496-1503
        • Roul G.
        • Moulichon M.E.
        • Bareiss P.
        • et al.
        Prognostic factors of chronic heart failure in NYHA class II or II: value of invasive exercise hemodynamic data.
        Eur Heart J. 1995; 16: 1387-1398
        • Tabet J.Y.
        • Metra M.
        • Nodari S.
        • et al.
        Comparison of the prognostic value of the peak VO2, the peak circulatory power and the VE/VCO2 slope in chronic heart failure patients on betablockers.
        J Am Coll Cardiol. 2005; 45: 134A
        • Mancini D.
        • LeJemtel T.
        • Aaronson K.
        Peak VO2: a simple yet enduring standard.
        Circulation. 2000; 101: 1080-1082
        • Cohen-Solal A.
        • Tabet J.Y.
        • Logeart D.
        • Bourgoin P.
        • Tokmakova M.
        • Dahan M.
        A noninvasively determined surrogate of cardiac power (“circulatory power”) at peak exercise is a powerful prognostic factor in chronic heart failure.
        Eur Heart J. 2002; 23: 806-814