Abstract
Heart failure (HF) is a complex syndrome characterized by myocardial dysfunction, derangement of multiple organ systems and poor outcome. Out of several markers of severity, abnormalities in exercise ventilation (VE) offer relevant insights into the pathophysiology of dyspnea, lung gas exchange, and control of ventilation and are now recognized as meaningful indicators of disease severity and prognosis. Ventilation inefficiency, identified as an increased slope of VE vs carbon dioxide production (VCO2) recognizes as major determinants an increased waste ventilation due to enhanced dead space, early occurrence of lactic acidosis, and an abnormal chemoreflex and/or metaboreflex activity. In some cases of HF, especially associated with advanced hemodynamic and neural deregulation, an exercise oscillatory ventilatory (EOV) pattern may occur. According to an increasing number of studies, EOV identifies the 15–30 % of higher-risk HF patients requiring aggressive treatment and provides an even more robust prediction of outcome compared to VE/VCO2 slope. Overall, a refined prevalence definition and more comprehensive use of these markers in a clinical environment and in future interventional trials seem challenging for the years to come.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: • Of importance
Weber KT, Janicki JS. Cardiopulmonary exercise testing for evaluation of chronic cardiac failure. Am J Cardiol. 1985;55(2):22A–31A.
Tumminello G, Lancellotti P, Lempereur M, D'Orio V, Pierard LA. Determinants of pulmonary artery hypertension at rest and during exercise in patients with heart failure. Eur Heart J. 2007;28(5):569–74.
Guazzi M, Adams V, Conraads V, Halle M, Mezzani A, Vanhees L, et al. EACPR/AHA Scientific Statement. Clinical recommendations for cardiopulmonary exercise testing data assessment in specific patient populations. Circulation. 2012;126(18):2261–74.
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(2):245–69. Interesting review that comprehensively analyzes pathophysiology and prognostic relevance of an impaired ventilatory efficiency during exercise.
Guazzi M. Treating exercise oscillatory ventilation in heart failure: the detail that may matter. Eur Respir J. 2012;40(5):1075–7.
Chua TP, Clark AL, Amadi AA, Coats AJS. Relation between chemosensitivity and the ventilatory response to exercise in chronic heart failure. J Am Coll Cardiol. 1996;27(3):650–7.
Robbins M, Francis G, Pashkow FJ, Snader CE, Hoercher K, Young JB, et al. Ventilatory and heart rate responses to exercise - Better predictors of heart failure mortality than peak oxygen consumption. Circulation. 1999;100(24):2411–7.
Ponikowski P, Francis DP, Piepoli MF, Davies LC, Chua TP, Davos CH, et al. Enhanced ventilatory response to exercise in patients with chronic heart failure and preserved exercise tolerance - Marker of abnormal cardiorespiratory reflex control and predictor of poor prognosis. Circulation. 2001;103(7):967–72.
Guazzi M, Reina G, Tumminello G, Guazzi MD. Exercise ventilation inefficiency and cardiovascular mortality in heart failure: the critical independent prognostic value of the arterial CO2 partial pressure. Eur Heart J. 2005;26(5):472–80.
Arena R, Myers J, Abella J, Peberdy MA, Bensimhon D, Chase P, et al. Development of a ventilatory classification system in patients with heart failure. Circulation. 2007;115(18):2410–7. Landmark study proposing a new objective classification of dyspnea sensation and prognosis in chronic heart failure by stratifying according to different categories of VE/VCO2 slope response.
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(10):1883–90.
Maeder MT, Thompson BR, Htun N, Kaye DM. Hemodynamic determinants of the abnormal cardiopulmonary exercise response in heart failure with preserved left ventricular ejection fraction. J Card Fail. 2012;18(9):702–10.
Wasserman K, Zhang YY, Gitt A, Belardinelli R, Koike A, Lubarsky L, et al. Lung function and exercise gas exchange in chronic heart failure. Circulation. 1997;96(7):2221–7.
Gitt AK, Wasserman K, Kilkowski C, Kleemann T, Kilkowski A, Bangert M, et al. Exercise anaerobic threshold and Ventilatory efficiency identify heart failure patients for high risk of early death. Circulation. 2002;106(24):3079–84.
Agostoni P, Corra U, Cattadori G, Veglia F, Battaia E, La Gioia R, et al. Prognostic value of indeterminable anaerobic threshold in heart failure. Circ Heart Fail. 2013;6(5):977–87.
Agostoni P, Emdin M, Corra U, Veglia F, Magri D, Tedesco CC, et al. Permanent atrial fibrillation affects exercise capacity in chronic heart failure patients. Eur Heart J. 2008;29(19):2367–72.
Guazzi M. Letter by Guazzi regarding article "Sleep and exertional periodic breathing in chronic heart failure: prognostic importance and interdependence". Circulation. 2006;114(3):e53. author reply e4.
Ingle L, Goode K, Carroll S, Sloan R, Boyes C, Cleland JG, et al. Prognostic value of the VE/VCO2 slope calculated from different time intervals in patients with suspected heart failure. Int J Cardiol. 2007;118(3):350–5.
Arena R, Humphrey R, Peberdy MA. Prognostic ability of VE/VCO2 slope calculations using different exercise test time intervals in subjects with heart failure. Eur J Cardiovasc Prev Rehabil : Off J Eur Soc Cardiol Work Groups Epidemiol Prev Card Rehabil Exerc Physiol. 2003;10(6):463–8.
Myers J, Salleh A, Buchanan N, Smith D, Neutel J, Bowes E, et al. Ventilatory mechanisms of exercise intolerance in chronic heart-failure. Am Heart J. 1992;124(3):710–9.
Reindl I, Wernecke KD, Opitz C, Wensel R, Konig D, Dengler T, et al. Impaired ventilatory efficiency in chronic heart failure: possible role of pulmonary vasoconstriction. Am Heart J. 1998;136(5):778–85.
Lewis GD, Shah RV, Pappagianopolas PP, Systrom DM, Semigran MJ. Determinants of ventilatory efficiency in heart failure: the role of right ventricular performance and pulmonary vascular tone. Circ Heart Fail. 2008;1(4):227–33.
Wada O, Asanoi H, Miyagi K, Ishizaka S, Kameyama T, Seto H, et al. Importance of abnormal lung perfusion in excessive exercise ventilation in chronic heart-failure. Am Heart J. 1993;125(3):790–8.
Wensel R, Georgiadou P, Francis DP, Bayne S, Scott AC, Genth-Zotz S, et al. Differential contribution of dead space ventilation and low arterial pCO(2) to exercise hyperpnea in patients with chronic heart-failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 2004;93(3):318–23.
Lewis GD, Murphy RM, Shah RV, Pappagianopoulos PP, Malhotra R, Bloch KD, et al. Pulmonary vascular response patterns during exercise in left ventricular systolic dysfunction predict exercise capacity and outcomes. Circ Heart Fail. 2011;4(3):276–85.
Guazzi M, Cahalin LP, Arena R. Cardiopulmonary exercise testing as a diagnostic tool for the detection of left-sided pulmonary hypertension in heart failure. J Card Fail. 2013;19(7):461–7.
Guazzi M, Reina G, Tumminello G, Guazzi MD. Alveolar-capillary membrane conductance is the best pulmonary function correlate of exercise ventilation efficiency in heart failure patients. Eur J Heart Fail. 2005;7(6):1017–22.
Wilson JR, Ferraro N, Weber KT. Respiratory gas analysis during exercise as a noninvasive measure of lactate concentration in chronic congestive heart failure. Am J Cardiol. 1983;51(10):1639–43.
Hachamovitch R, Brown HV, Rubin SA. Respiratory and circulatory analysis of CO2 output during exercise in chronic heart failure. Circulation. 1991;84(2):605–12.
Perego GB, Marenzi GC, Guazzi M, Sganzerla P, Assanelli E, Palermo P, et al. Contribution of PO2, P50, and Hb to changes in arteriovenous O2 content during exercise in heart failure. J Appl Physiol. 1996;80(2):623–31.
Ponikowski PP, Chua TP, Francis DP, Capucci A, Coats AJS, Piepoli MF. Muscle ergoreceptor overactivity reflects deterioration in clinical status and cardiorespiratory reflex control in chronic heart failure. Circulation. 2001;104(19):2324–30.
Scott AC, Wensel R, Davos CH, Georgiadou P, Kemp M, Hooper J, et al. Skeletal muscle reflex in heart failure patients - Role of hydrogen. Circulation. 2003;107(2):300–6.
Tomita T, Takaki H, Hara Y, Sakamaki F, Satoh T, Takagi S, et al. Attenuation of hypercapnic carbon dioxide chemosensitivity after postinfarction exercise training: possible contribution to the improvement in exercise hyperventilation. Heart. 2003;89(4):404–10.
Ciarka A, Cuylits N, Vachiery JL, Lamotte M, Degaute JP, Naeije R, et al. Increased peripheral chemoreceptors sensitivity and exercise ventilation in heart transplant recipients. Circulation. 2006;113(2):252–7.
Piepoli M, Clark AL, Volterrani M, Adamopoulos S, Sleight P, Coats AJS. Contribution of muscle afferents to the hemodynamic, autonomic, and ventilatory responses to exercise in patients with chronic heart failure - Effects of physical training. Circulation. 1996;93(5):940–52.
Rosen SD, Murphy K, Leff AP, Cunningham V, Wise RJS, Adams L, et al. Is central nervous system processing altered in patients with heart failure? Eur Heart J. 2004;25(11):952–62.
O'Donnell CP, Tankersley CG, Polotsky VP, Schwartz AR, Smith PL. Leptin, obesity, and respiratory function. Respir Physiol. 2000;119(2-3):163–70.
Mancini DM, Eisen H, Kussmaul W, Mull R, Edmunds Jr LH, Wilson JR. Value of peak exercise oxygen consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure. Circulation. 1991;83(3):778–86.
Forman DE, Guazzi M, Myers J, Chase P, Bensimhon D, Cahalin LP, et al. Ventilatory power: a novel index that enhances prognostic assessment of patients with heart failure. Circ Heart Fail. 2012;5(5):621–6.
Ferreira AM, Tabet JY, Frankenstein L, Metra M, Mendes M, Zugck C, et al. Ventilatory efficiency and the selection of patients for heart transplantation. Circ Heart Fail. 2010;3(3):378–86.
Wessler BS, Kramer DG, Kelly JL, Trikalinos TA, Kent DM, Konstam MA, et al. Drug and device effects on peak oxygen consumption, 6-minute walk distance, and natriuretic peptides as predictors of therapeutic effects on mortality in patients with heart failure and reduced ejection fraction. Circ Heart Fail. 2011;4(5):578–88.
Guazzi M, Tumminello G, Di Marco F, Fiorentini C, Guazzi MD. The effects of phosphodiesterase-5 inhibition with sildenafil on pulmonary hemodynamics and diffusion capacity, exercise ventilatory efficiency, and oxygen uptake kinetics in chronic heart failure. J Am Coll Cardiol. 2004;44:2339–48. First demonstration that acute PDE5 inhibition with sildenafil acutely improves gas diffusion and exercise VE/VCO2 slope.
Agostoni P, Guazzi M, Bussotti M, De Vita S, Palermo P. Carvedilol reduces the inappropriate increase of ventilation during exercise in heart failure patients. Chest. 2002;122(6):2062–7.
Guazzi M, Agostoni PG. Monitoring gas exchange during a constant work rate exercise in patients with left ventricular dysfunction treated with carvedilol. Am J Cardiol. 2000;85(5):660.
Butland RJ, Pang JA, Geddes DM. The selectivity of the beta-adrenoceptor for ventilation in man. Br J Clin Pharmacol. 1982;14(5):707–11.
Clark AL, Cleland JG. Beta-blockers, exercise, and ventilation in chronic heart failure. J Card Fail. 2005;11(5):340–2.
Lewis GD, Shah R, Shahzad K, Camuso JM, Pappagianopoulos PP, Hung J, et al. Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension. Circulation. 2007;116(14):1555–62.
Guazzi M, Vicenzi M, Arena R, Guazzi MD. PDE5 inhibition with sildenafil improves left ventricular diastolic function, cardiac geometry, and clinical status in patients with stable systolic heart failure: results of a 1-year, prospective, randomized, placebo-controlled study. Circ Heart Fail. 2011;4(1):8–17.
Guazzi M, Samaja M, Arena R, Vicenzi M, Guazzi MD. Long-term use of sildenafil in the therapeutic management of heart failure. J Am Coll Cardiol. 2007;50:2136–44.
Wong AK, Symon R, AlZadjali MA, Ang DS, Ogston S, Choy A, et al. The effect of metformin on insulin resistance and exercise parameters in patients with heart failure. Eur J Heart Fail. 2012;14(11):1303–10.
Jaussaud J, Blanc P, Derval N, Bordachar P, Courregelongue M, Roudaut R, et al. Ventilatory response and peak circulatory power: new functional markers of response after cardiac resynchronization therapy. Arch Cardiovasc Dis. 2010;103(3):184–91.
Guazzi M, Reina G, Tumminello G, Guazzi MD. Improvement of alveolar-capillary membrane diffusing capacity with exercise training in chronic heart failure. J Appl Physiol. 2004;97(5):1866–73.
Arzt M, Schulz M, Wensel R, Montalvan S, Blumberg FC, Riegger GAJ, et al. Nocturnal continuous positive airway pressure improves ventilatory efficiency during exercise in patients with chronic heart failure. Chest. 2005;127(3):794–802.
Naughton MT, Liu PP, Benard DC, Goldstein RS, Bradley TD. Treatment of congestive-heart-failure and cheyne-stokes respiration during sleep by continuous positive airway pressure. Am J Respir Crit Care Med. 1995;151(1):92–7.
Naughton MT, Benard DC, Liu PP, Rutherford R, Rankin F, Bradley TD. Effects of nasal CPAP on sympathetic activity in patients with heart failure and central sleep apnea. Am J Respir Crit Care Med. 1995;152(2):473–9.
Belardinelli R, Georgiou D, Purcaro A. Low dose dobutamine echocardiography predicts improvement in functional capacity after exercise training in patients with ischemic cardiomyopathy: prognostic implication. J Am Coll Cardiol. 1998;31(5):1027–34.
Davey P, Meyer T, Coats A, Adamopoulos S, Casadei B, Conway J, et al. Ventilation in chronic heart-failure - effects of physical-trainig. Br Heart J. 1992;68(5):473–7.
Adamopoulos S, Coats AJS, Brunotte F, Arnolda L, Meyer T, Thompson CH, et al. Physical-training improves skeletal-muscle metabolism in patients with chronic heart-failure. J Am Coll Cardiol. 1993;21(5):1101–6.
Piepoli MF, Ponikowski PP, Volterrani M, Francis D, Coats AJ. Aetiology and pathophysiological implications of oscillatory ventilation at rest and during exercise in chronic heart failure. Do Cheyne and Stokes have an important message for modern-day patients with heart failure? Eur Heart J. 1999;20(13):946–53.
Corra U, Pistono M, Mezzani A, Braghiroli A, Giordano A, Lanfranchi P, et al. Sleep and exertional periodic breathing in chronic heart failure - Prognostic importance and interdependence. Circulation. 2006;113(1):44–50.
Sun XG, Hansen JE, Beshai JF, Wasserman K. Oscillatory breathing and exercise gas exchange abnormalities prognosticate early mortality and morbidity in heart failure. J Am Coll Cardiol. 2010;55(17):1814–23.
Guazzi M, Myers J, Peberdy MA, Bensimhon D, Chase P, Arena R. Exercise oscillatory breathing in diastolic heart failure: prevalence and prognostic insights. Eur Heart J. 2008;29(22):2751–9.
Guazzi M, Boracchi P, Labate V, Arena R, Reina G. Exercise oscillatory breathing and NT-proBNP levels in stable heart failure provide the strongest prediction of cardiac outcome when combining biomarkers with cardiopulmonary exercise testing. J Card Fail. 2012;18(4):313–20.
Kremser CB, O'Toole MF, Leff AR. Oscillatory hyperventilation in severe congestive heart failure secondary to idiopathic dilated cardiomyopathy or to ischemic cardiomyopathy. Am J Cardiol. 1987;59(8):900–5.
Ribeiro JP, Knutzen A, Rocco MB, Hartley LH, Colucci WS. Periodic breathing during exercise in severe heart failure. Reversal with milrinone or cardiac transplantation. Chest. 1987;92(3):555–6.
Bendov I, Sietsema KE, Casaburi R, Wasserman K. Evidence that circulatory oscillations accompany ventilatory oscillations during exercise in patients with heart-failure. Am Rev Respir Dis. 1992;145(4):776–81.
Leite JJ, Mansur AJ, de Freitas HFG, Chizola PR, Bocchi EA, Terra M, et al. Periodic breathing during incremental exercise predicts mortality in patients with chronic heart failure evaluated for cardiac transplantation. J Am Coll Cardiol. 2003;41(12):2175–81.
Corra U, Giordano A, Bosimini E, Mezzani A, Piepoli M, Coats AJ, et al. Oscillatory ventilation during exercise in patients with chronic heart failure: clinical correlates and prognostic implications. Chest. 2002;121(5):1572–80.
Guazzi M, Raimondo R, Vicenzi M, Arena R, Proserpio C, Sarzi Braga S, et al. Exercise oscillatory ventilation may predict sudden cardiac death in heart failure patients. J Am Coll Cardiol. 2007;50(4):299–308. Unique study that addresses the potential of CPX-derived variables to predict cardiac sudden death and identification of EOV as the only variable capable to discriminate it.
Yajima T, Koike A, Sugimoto K, Miyahara Y, Marumo F, Hiroe M. Mechanism of periodic breathing in patients with cardiovascular disease. Chest. 1994;106(1):142–6.
Ponikowski P, Anker SD, Chua TP, Francis D, Banasiak W, Poole-Wilson PA, et al. Oscillatory breathing patterns during wakefulness in patients with chronic heart failure - Clinical implications and role of augmented peripheral chemosensitivity. Circulation. 1999;100(24):2418–24.
Murphy RM, Shah RV, Malhotra R, Pappagianopoulos PP, Hough SS, Systrom DM, et al. Exercise oscillatory ventilation in systolic heart failure: an indicator of impaired hemodynamic response to exercise. Circulation. 2011;124(13):1442–51.
Olson TP, Frantz RP, Snyder EM, O'Malley KA, Beck KC, Johnson BD. Effects of acute changes in pulmonary wedge pressure on periodic breathing at rest in heart failure patients. Am Heart J. 2007;153(1):104. e1-7.
Guazzi M, Arena R, Ascione A, Piepoli M, Guazzi MD. Gruppo Studio Fisiologia dE. Exercise oscillatory breathing and increased ventilation to carbon dioxide production slope in heart failure: an unfavorable combination with high prognostic value. Am Heart J. 2007;153(5):859–67.
Cahalin LP, Chase P, Arena R, Myers J, Bensimhon D, Peberdy MA, et al. A meta-analysis of the prognostic significance of cardiopulmonary exercise testing in patients with heart failure. Heart Fail Rev. 2013;18(1):79–94.
Zurek M, Corra U, Piepoli MF, Binder RK, Saner H, Schmid JP. Exercise training reverses exertional oscillatory ventilation in heart failure patients. Eur Respir J Off J Eur Soc Clin Respir Physiol. 2012;40(5):1238–44. Remarkable demonstration that beneficial effects of aerobic exercise training extend to EOV modulation and reversal.
Guazzi M, Vicenzi M, Arena R. Phosphodiesterase 5 inhibition with sildenafil reverses exercise oscillatory breathing in chronic heart failure: a long-term cardiopulmonary exercise testing placebo-controlled study. Eur J Heart Fail. 2012;14(1):82–90.
Compliance with Ethics Guidelines
ᅟ
Conflict of Interest
Marco Guazzi declares that he has no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Guazzi, M. Abnormalities in Cardiopulmonary Exercise Testing Ventilatory Parameters in Heart Failure: Pathophysiology and Clinical Usefulness. Curr Heart Fail Rep 11, 80–87 (2014). https://doi.org/10.1007/s11897-013-0183-3
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11897-013-0183-3