Übersicht über die Entwicklung der invasiven Spiroergometrie (iCPET)

Zusammenfassung

Die Standardmethode zur Messung der pulmonalen Hämodynamik ist der Rechtsherzkatheter (RHK) unter Ruhebedingungen, welcher international standardisiert ist. In den letzten Jahren wurden Bemühungen unternommen, auch die methodischen Aspekte des RHK unter Belastung zu vereinheitlichen und die somit gewonnenen Daten hinsichtlich ihrer prognostischen Aussagekraft zu definieren. Die Spiroergometrie als eine nichtinvasive Methode kann zusätzliche Aspekte der Pathophysiologie unter Belastung darstellen, und beide Methoden werden zunehmend kombiniert (als sog. invasive Spiroergometrie, iCPET) und ermöglichen eine sehr differenzierte Analyse der Belastungsreaktion.

In dieser Übersicht werden die bisherigen Erfahrungen mit der invasiven Spiroergometrie dargestellt und insbesondere methodische Details erläutert.

Die bisherigen Daten zur invasiven Spiroergometrie zeigen, dass diese komplexe Untersuchung besonders bei der Differenzierung der zugrundeliegenden Ursachen einer unklaren Dyspnoe hilfreich ist. Es zeichnet sich ab, dass über die Kombination aus hämodynamischen sowie ventilatorischen und gasanalytischen Daten schon frühe Formen einer kardialen bzw. pulmonalvaskulären Störung zu detektieren sind. Durch die zunehmende Validierung gewonnener Parameter aus der iCPET sind zukünftig Grenzwerte zur Unterscheidung normaler vs. pathologischer Belastungsreaktionen zu erwarten, die genauer als durch die alleinige Anwendung der jeweiligen Methoden möglich werden.

Abstract

Right heart catheterization (RHC) is the internationally standardized reference method for measuring pulmonary hemodynamics under resting conditions. In recent years, increasing efforts have been made to establish the reliable assessment of exercise hemodynamics as well, in order to obtain additional diagnostic and prognostic data. Furthermore, cardiopulmonary exercise testing (CPET), as the most comprehensive non-invasive exercise test, is increasingly performed in combination with RHC providing detailed pathophysiological insights into the exercise response, so-called invasive cardiopulmonary exercise testing (iCPET).

In this review, the accumulated experience with iCPET is presented and methodological details are discussed. This complex examination is especially helpful in differentiating the underlying causes of unexplained dyspnea. In particular, early forms of cardiac or pulmonary vascular dysfunction can be detected by integrated analysis of hemodynamic as well as ventilatory and gas exchange data. It is expected that with increasing validation of iCPET parameters, a more reliable differentiation of normal from pathological stress reactions will be possible.

Publication History

Article published online:
29 November 2021

• Literatur

• 1 Kovacs G, Herve P, Barbera JA. et al. An official European Respiratory Society statement: pulmonary haemodynamics during exercise. Eur Respir J 2017; 50: 1700578
• 2 Meyer FJ, Borst MM, Buschmann HC. et al. Belastungsuntersuchungen in der Pneumologie – Empfehlungen der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e. V. Pneumologie 2018; 72: 687-731
• 3 Cournand A, Ranges HA. Catheterization of the right auricle in man. Proc Soc Exper Biol Med 1941; 46: 462
• 4 Cournand A, Bing RJ, Dexter L. et al. Report of Committee on Cardiac Catheterization and Angiocardiography of the American Heart Association. Circulation 1953; 7: 769-73
• 5 Hickham JB, Cargill WH, Golden A. Cardiovascular reaction to emotional stimuli. Effect on the cardiac output, arteriovenous oxygen difference, arterial pressure, and peripheral resistance. J Clin Invest 1948; 27: 290-298
• 6 McMichael J, Johnston EA. Postural changes in cardiac output and respiration in man. Quart J exp Physiol 1937; 27: 55-72
• 7 Stead EA, Warren JV, Merrill AJ. et al. The cardiac output in male subjects as measured by the technique of right atrial catherization. Normal values with observations on effect on anxiety and tilting. J Clin Invest 1945; 24: 326-331
• 8 McMichael J, Sharpey-Schafer EP. Cardiac output in man by a direct Fick method: Effects of Posture, Venous Pressure Change, Atropine, And Adrenaline. Br Heart J 1944; 6: 33-40
• 9 Cournand A, Ranges HA, Riley RL. Comparison of results of the normal ballistocardiogram and a direct Fick method in measuring the cardiac output in man. J Clin Invest 1942; 21: 287-294
• 10 Werkö L, Berseus S, Lagerlöf HA. Comparison of the direct Fick and the Grollman methods for determination of the cardiac output in man. J Clin Invest 1949; 28: 516-520
• 11 Fick A. Über die Messungen des Blutquantums in den Herzventrikeln. Sitzungsberichte der Phys.-Med. Gesellschaft. Würzburg: 1870: XVI-XVII
• 12 Grollman A, Friedman B, Clark G. et al. Studies in congestive heart failure. XXIIII. A critical study of methods for determining the cardiac output in patients with cardiac disease. J Clin Invest 1933; 12: 751-766
• 13 Stewart GN. The pulmonary circulation time, the quantity of blood in the lungs and the output of the heart. Am J Physiol 1921; 58: 20-44
• 14 Hamilton WF, Moore JW, Kinsman JM. et al. Studies on the circulation IV. Further analysis of the injection method, and the changes in hemodynamics under physiological and pathological conditions. Am J Physiol 1932; 99: 534-551
• 15 Moore JW, Kinsman JM, Hamilton WF. et al. Studies on the circulation. II. Cardiac outut determination, comparison of the injection method with the direct Fick procedure. Am J Physiol 1929; 89: 331-339
• 16 Fegler G. Measurement of cardiac output in anaesthetized animals by a thermodilution method. Quarterly Journal of Experimental Physiology 1954; 39: 153-164
• 17 Nadeau S, Noble WH. Limitations of cardiac output measurements by thermodilution. Can Anaesth Soc J 1986; 33: 780-784
• 18 Nishikawa T, Dohi S. Errors in the measurement of cardiac output by thermodilution. Can J Anaesth 1993; 40: 142-153
• 19 Monnet X, Teboul JL. Transpulmonary thermodilution: advantages and limits. Crit Care 2017; 21: 147
• 20 Astrand PO, Ryhming IJ. A nomogram for calculation of aerobic capacity (physical fitness) from pulse rate during sub-maximal work. Appl Physiol 1954; 7: 218-221
• 21 LaFarge CG, Miettinen OS. The estimation of oxygen consumption. Cardiovasc Res 1970; 4: 23-30
• 22 Bergstra A, van Dijk RB, Hillege HL. et al. Assumed oxygen consumption based on calculation from dye dilution cardiac output: an improved formula. Eur Heart J 1995; 16: 698-703
• 23 Narang N, Thibodeau JT, Levine BD. et al. Inaccuracy of estimated resting oxygen uptake in the clinical setting. Circulation 2014; 129: 203-210
• 24 Kresoja KP, Faragli A, Abawi D. et al. Thermodilution vs estimated Fick cardiac output measurement in an elderly cohort of patients: A single-centre experience. PLoS One 2019; 14: e0226561
• 25 Wolf A, Pollman MJ, Trindade PT. et al. Use of assumed versus measured oxygen consumption for the determination of cardiac consumption using the Fick principle. Cathet Cardiovasc Diagn 1998; 43: 372-380
• 26 Fakler U, Pauli C, Hennig M. et al. Assumed oxygen consumption frequently results in large errors in the determination of cardiac output. J Thorac Cardiovasc Surg 2005; 130: 272-276
• 27 Swan HJ, Ganz W, Forrester J. et al. Catheterization of the heart in man with use of a flow-directed balloon-tipped catheter. N Engl J Med 1970; 283: 447-451
• 28 Einschwemmkatheter. Technik, Auswertung und praktische Konsequenzen. Buchwalsky R. Hrsg. Beiträge zur Kardiologie. Bd. 29. 3. vollst. überarb Aufl. Erlangen: Perimed Verl.-Ges; 1992
• 29 Rosenkranz S, Preston IR. Right heart catheterisation: best practice and pitfalls in pulmonary hypertension. Eur Respir Rev 2015; 24: 642-652
• 30 Primary Pulmonary Hypertension. Report on a WHO meeting. Hatano S, Strasser T. Geneva: WHO; 1975
• 31 Kovacs G, Olschewski A, Berghold A. et al. Pulmonary vascular resistances during exercise in normal subjects: a systematic review. Eur Respir J 2012; 39: 319-328
• 32 Kovacs G, Berghold A, Scheidl S. et al. Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J 2009; 34: 888-894
• 33 Naeije R, Chesler N. Pulmonary circulation at exercise. Compr Physiol 2012; 2: 711-741
• 34 Reeves JT, Dempsey JA, Grover RF. Pulmonary circulation during exercise. Weir EK, Reeves JT. eds. Pulmonary vascular physiology and pathophysiology. Lung Biology in Health and Disease, Vol. 38. Basel: Dekker Inc; 1989
• 35 Badesch DB, Champion HC, Sanchez MA. et al. Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol 2009; 54: S55-S66
• 36 Said SI, Banerjee CM. Venous admixture to the pulmonary circulation in human subjects breathing 100 per cent oxygen. J Clin Invest 1963; 42: 507-515
• 37 Kroidl RF, Schwarz S, Lehnigk B. Historical aspects on CPET (cardio pulmonary exercise testing). Pneumologie 2007; 61: 291-294
• 38 Weber KT, Kinasewitz GT, Janicki JS. et al. Oxygen utilization and ventilation during exercise in patients with chronic cardiac failure. Circulation 1982; 65: 1213-1223
• 39 Weber KT, Wilson JR, Janicki JS. et al. Exercise testing in the evaluation of the patient with chronic cardiac failure. Am Rev Respir Dis 1984; 129; S60-S62
• 40 Fagard R, Bulpitt C, Lijnen P. et al. Response of the systemic and pulmonary circulation to converting-enzyme inhibition (captopril) at rest and during exercise in hypertensive patients. Circulation 1982; 65: 33-39
• 41 Nery LE, Wasserman K, Andrews JD. et al. Ventilatory and gas exchange kinetics during exercise in chronic airways obstruction. J Appl Physiol Respir Environ Exerc Physiol 1982; 53: 1594-1602
• 42 Whipp BJ, Ward SA, Lamarra N. et al. Parameters of ventilatory and gas exchange dynamics during exercise. J Appl Physiol Respir Environ Exerc Physiol 1982; 52: 1506-1513
• 43 Sietsema KE, Cooper DM, Perloff JK. et al. Dynamics of oxygen uptake during exercise in adults with cyanotic congenital heart disease. Circulation 1986; 73: 1137-1144
• 44 Sietsema KE. Oxygen uptake kinetics in response to exercise in patients with pulmonary vascular disease. Am Rev Respir Dis 1992; 145: 1052-1057
• 45 Takaki H, Sunagawa K, Sugimachi M. et al. Percutaneous transvenous mitral commissurotomy immediately restores quick response of VO2 to mild exercise despite insignificant increases in peak VO2. Heart Vessels 1995; 10: 323-327
• 46 Keller CA, Ohar J, Ruppel G. et al. Right ventricular function in patients with severe COPD evaluated for lung transplantation. Lung Transplant Group. Chest 1995; 107: 1510-1516
• 47 Roger N, Barberà JA, Roca J. et al. Nitric oxide inhalation during exercise in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997; 156: 800-806
• 48 Kubo K, Ge RL, Koizumi T. et al. Pulmonary artery remodeling modifies pulmonary hypertension during exercise in severe emphysema. Respir Physiol 2000; 120: 71-79
• 49 Butler J, Schrijen F, Henriquez A. et al. Cause of the raised wedge pressure on exercise in chronic obstructive pulmonary disease. Am Rev Respir Dis 1988; 138: 350-354
• 50 Oswald-Mammosser M, Kessler R, Massard G. et al. Effect of lung volume reduction surgery on gas exchange and pulmonary hemodynamics at rest and during exercise. Am J Respir Crit Care Med 1998; 158: 1020-1025
• 51 Schrijen F, Ravez P, Candina-Villar R. et al. Cardiovascular changes during isometric and dynamic exercise in chronic lung disease. Eur J Respir Dis 1987; 70: 199-204
• 52 van Riel A, Systrom DM, Oliveira RKF. et al. Hemodynamic and metabolic characteristics associated with development of a right ventricular outflow tract pressure gradient during upright exercise. PlosOne 2017; 12: e0179053
• 53 Szlachcic J, Massie BM, Kramer BL. et al. Correlates and prognostic implication of exercise capacity in chronic congestive heart failure. Am J Cardiol 1985; 55: 1037-1042
• 54 Christensen CC, Ryg MS, Edvardsen A. et al. Relationship between exercise desaturation and pulmonary haemodynamics in COPD patients. Eur Respir J 2004; 24: 580-586
• 55 Griffin BP, Shah PK, Ferguson J. et al. Incremental prognostic value of exercise hemodynamic variables in chronic congestive heart failure secondary to coronary artery disease or to dilated cardiomyopathy. Am J Cardiol 1991; 67: 848-853
• 56 Mancini D, Goldsmith R, Levin H. et al. Comparison of exercise performance in patients with chronic severe heart failure versus left ventricular assist devices. Circulation 1998; 98: 1178-1183
• 57 Kitzman DW, Higginbotham MB, Cobb FR. et al. Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: failure of the Frank-Starling mechanism. J Am Coll Cardiol 1991; 17: 1065-1072
• 58 Butler J, Chomsky DB, Wilson JR. Pulmonary hypertension and exercise intolerance in patients with heart failure. J Am Coll Cardiol 1999; 34: 1802-1806
• 59 Hasuda T, Okano Y, Yoshioka T. et al. Pulmonary pressure-flow relation as a determinant factor of exercise capacity and symptoms in patients with regurgitant valvular heart disease. Int J Cardiol 2005; 99: 403-407
• 60 Minatoguchi S, Ito H, Asano K. et al. Simultaneous evaluation of left- and right-sided heart pumping function during dynamic leg exercise in patients with mild chronic congestive heart failure, with special reference to afterload and plasma noradrenaline. Heart Vessels 1997; 12: 34-42
• 61 Franciosa JA, Leddy CL, Wilen M. et al. Relation between hemodynamic and ventilatory responses in determining exercise capacity in severe congestive heart failure. Am J Cardiol 1984; 53: 127-134
• 62 Pozzoli M, Capomolla S, Sanarico M. et al. Doppler evaluations of left ventricular diastolic filling and pulmonary wedge pressure provide similar prognostic information in patients with systolic dysfunction after myocardial infarction. Am Heart J 1995; 129: 716-725
• 63 Roul G, Moulichon ME, Bareiss P. et al. Prognostic factors of chronic heart failure in NYHA class II or III: value of invasive exercise haemodynamic data. Eur Heart J 1995; 16: 1387-1398
• 64 Lipkin D, Canepa-Anson R, Stephens MR. et al. Factors determining symptoms in heart failure: comparison of fast and slow exercise tests. Br Heart J 1986 55: 439-445
• 65 Reddy HK, Weber KT, Janicki JS. et al. Hemodynamic, ventilatory and metabolic effects of light isometric exercise in patients with chronic heart failure. J Am Coll Cardiol 1988; 12: 353-358
• 66 Sullivan MJ, Knight JD, Higginbotham MB. et al. Relation between central and peripheral hemodynamics during exercise in patients with chronic heart failure. Muscle blood flow is reduced with maintenance of arterial perfusion pressure. Circulation 1989; 80: 769-781
• 67 Manier G, Castaing Y. Contribution of multiple inert gas elimination technique to pulmonary medicine – 4. Gas exchange abnormalities in pulmonary vascular and cardiac disease. Thorax 1994; 49: 1169-1174
• 68 Dantzker DR, DʼAlonzo GE, Bower JS. et al. Pulmonary gas exchange during exercise in patients with chronic obliterative pulmonary hypertension. Am Rev Respir Dis 1984; 130: 412-416
• 69 Dantzker DR, Bower JS. Pulmonary vascular tone improves VA/Q matching in obliterative pulmonary hypertension. Appl Physiol 1981; 511: 607-613
• 70 Otulana B, Higenbottam T. The role of physiological deadspace and shunt in the gas exchange of patients with pulmonary hypertension: a study of exercise and prostacyclin infusion. Eur Respir J 1988; 1: 732-737
• 71 Fletcher EC, Luckett RA, Miller T. et al. Exercise hemodynamics and gas exchange in patients with chronic obstruction pulmonary disease, sleep desaturation, and a daytime PaO2 above 60 mmHg. Am Rev Respir Dis 1989; 140: 1237-1245
• 72 Taylor BJ, Smetana MR, Frantz RP. et al. Submaximal Exercise Pulmonary Gas Exchange in Left Heart Disease Patients With Different Forms of Pulmonary Hypertension. J Card Fail 2015; 21: 647-655
• 73 Ho JE, Zern EK, Lau ES. et al. Exercise Pulmonary Hypertension Predicts Clinical Outcomes in Patients With Dyspnea on Effort. J Am Coll Cardiol 2020; 75: 17-26
• 74 Sullivan MJ, Higginbotham MB, Cobb FR. Increased exercise ventilation in patients with chronic heart failure: intact ventilatory control despite hemodynamic and pulmonary abnormalities. Circulation 1988; 77: 552-559
• 75 Mohsenifar Z, Tashkin DP, Levy SE. et al. Lack of sensitivity of measurements of Vd/Vt at rest and during exercise in detection of hemodynamically significant pulmonary vascular abnormalities in collagen vascular disease. Am Rev Respir Dis 1981; 123: 508-512
• 76 Mohsenifar Z, Tashkin DP, Wolfe JD. et al. Abnormal responses of wasted ventilation fraction (VD/VT) during exercise in patients with pulmonary vascular abnormalities. Respiration 1983; 44: 44-49
• 77 Reaside DA, Smith A, Brown A. et al. Pulmonary artery pressure measurement during exercise testing in patients with suspected pulmonary hypertension. Eur Respir J 2000; 16: 282-287
• 78 Borlaug BA, Reddy YN. Determinants and Correlates of Exercise Capacity in Heart Failure. JACC Heart Fail 2015; 3: 815-817
• 79 Borlaug BA, Melenovsky V, Koepp KE. Inhaled Sodium Nitrite Improves Rest and Exercise Hemodynamics in Heart Failure With Preserved Ejection Fraction. Circ Res 2016; 119: 880-886
• 80 Metra M, Dei Cas L, Panina G. et al. Exercise hyperventilation chronic congestive heart failure, and its relation to functional capacity and hemodynamics. Am J Cardiol 1992; 70: 622-628
• 81 Degani-Costa LH, Levarge B, Digumarthy SR. et al. Pulmonary vascular response patterns during exercise in interstitial lung disease. Eur Respir J 2015; 46: 738-749
• 82 Miki K, Maekura R, Hiraga T. et al. The degree of exercise hypoxemia reflects pulmonary artery pressure during early exercise in chronic obstructive pulmonary disease patients. Clin Physiol Funct Imaging 2008; 28: 64-69
• 83 Singh I, Oliveira RKF, Heerdt P. et al. Dynamic right ventricular function response to incremental exercise in pulmonary hypertension. Pulm Circ 2020; 10: 1-8
• 84 Lewis GD, Shah RV, Pappagianopolas PP. et al. Determinants of ventilatory efficiency in heart failure: the role of right ventricular performance and pulmonary vascular tone. Circ Heart Fail 2008; 1: 227-233
• 85 Lewis GD, Murphy RM, Shah RV. et al. Pulmonary vascular response patterns during exercise in left ventricular systolic dysfunction predict exercise capacity and outcomes. Circ Heart Fail 2011; 4: 276-285
• 86 Metra M, Faggiano P, D'Aloia A. et al. 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
• 87 Mancini D, Katz S, Donchez L. et al. Coupling of hemodynamic measurements with oxygen consumption during exercise does not improve risk stratification in patients with heart failure. Circulation 1996; 94: 2492-2496
• 88 Agostoni P, Dumitrescu D. How to perform and report a cardiopulmonary exercise test in patients with chronic heart failure. Int J Cardiol 2019; 288: 107-113
• 89 Riley MS, Pórszász J, Engelen MP. et al. Gas exchange responses to continuous incremental cycle ergometry exercise in primary pulmonary hypertension in humans. Eur J Appl Physiol 2000; 83: 63-70
• 90 Sun X-G, Hansen JE, Stringer WW. et al. Carbon dioxide pressure-concentration relationship in arterial and mixed venous blood during exercise. J Appl Physiol 2001; 90: 1798-1810
• 91 Sun XG, Hansen JE, Oudiz RJ. et al. Gas exchange detection of exercise-induced right-to-left shunt in patients with primary pulmonary hypertension. Circulation 2002; 105: 54-60
• 92 Murphy RM, Shah RV, Malhotra R. et al. Exercise oscillatory ventilation in systolic heart failure: an indicator of impaired hemodynamic response to exercise. Circulation 2011; 124: 1442-1451
• 93 Santos M, Opotowsky AR, Shah AM. et al. Central cardiac limit to aerobic capacity in patients with exertional pulmonary venous hypertension: implications for heart failure with preserved ejection fraction. Circ Heart Fail 2015; 8: 278-285
• 94 Tolle JJ, Waxman AB, Van Horn TL. et al. Exercise-induced pulmonary arterial hypertension. Circulation 2008; 118: 2183-2189
• 95 Bhatti YJ, Rice AJ, Kempny A. et al. Early histological changes of pulmonary arterial hypertension disclosed by invasive cardiopulmonary exercise testing. Pulm Circul 2019; 9: 2045894019845615
• 96 Houstis NE, Eisman AS, Pappagianopoulos PP. et al. Exercise Intolerance in Heart Failure With Preserved Ejection Fraction: Diagnosing and Ranking Its Causes Using Personalized O₂ Pathway Analysis. Circulation 2018; 137: 148-161
• 97 Oliveira RKF, Waxman AB, Agrawal M. et al. Pulmonary haemodynamics during recovery from maximum incremental cycling exercise. Eur Respir J 2016; 48: 158-167
• 98 Malhotra R, Dhakal BP, Eisman AS. et al. Pulmonary Vascular Distensibility Predicts Pulmonary Hypertension Severity, Exercise Capacity, and Survival in Heart Failure. Circ Heart Fail 2016; 9: e003011
• 99 Biering-Sørensen T, Santos M, Rivero J. et al. Left ventricular deformation at rest predicts exercise-induced elevation in pulmonary artery wedge pressure in patients with unexplained dyspnoea. Eur J Heart Fail 2017; 19: 101-110
• 100 Walkey J, Ieong M, Alikhan M. et al. Cardiopulmonary exercise testing with right-heart catheterization in patients with systemic sclerosis. J Rheumatol 2010; 37: 1871-1877
• 101 Kovacs G, Maier R, Aberer E. et al. Borderline Pulmonary Arterial Pressure Is Associated with Decreased Exercise Capacity in Scleroderma. Am J Respir Crit Care Med 2009; 180: 881-886
• 102 Ninaber MK, Hamersma WBGJ, Schouffoer AA. et al. Detection of pulmonary vasculopathy by novel analysis of oxygen uptake in patients with systemic sclerosis: association with pulmonary arterial pressures. Clin Exp Rheumatol 2014; 32: S60-S67
• 103 Boerrigter BG, Bogaard HJ, Trip P. et al. Ventilatory and cardiocirculatory exercise profiles in COPD: the role of pulmonary hypertension. Chest 2012; 142: 1166-1174
• 104 Borrigter BG, Trip P, Bogaard HJ. et al. Right atrial pressure affects the interaction between lung mechanics and right ventricular function in spontaneously breathing COPD patients. PlosOne 2012; 7: 30208
• 105 Oldham WM, Lewis GD, Opotowsky AR. et al. Unexplained exertional dyspnea caused by low ventricular filling pressures: results from clinical invasive cardiopulmonary exercise testing. Pulm Circ 2016; 6: 55-62
• 106 Eleid MF, Bjarnason H, Frye RL. et al. Exercise right heart catheterization for inferior vena cava obstruction: confirming the hemodynamic significance of an anatomic lesion. Catheter Cardiovasc Interv 2014; 83: E105-E108
• 107 Eisman AS, Shah RV, Dhakal BP. et al. Pulmonary Capillary Wedge Pressure Patterns During Exercise Predict Exercise Capacity and Incident Heart Failure. Circ Heart Fail 2018; 11: e004750
• 108 Singh I, Rahaghi FN, Naeije R. et al. Dynamic right ventricular-pulmonary arterial uncoupling during maximum incremental exercise in exercise pulmonary hypertension and pulmonary arterial hypertension. Pulm Circul 2019; 9: 2045894019862435
• 109 Dhakal BP, Malhotra R, Murphy RM. et al. Mechanisms of exercise intolerance in heart failure with preserved ejection fraction: the role of abnormal peripheral oxygen extraction. Circ Heart Fail 2015; 8: 286-94
• 110 Nayor M, Xanthakis V, Tanguay M. et al. Clinical and Hemodynamic Associations and Prognostic Implications of Ventilatory Efficiency in Patients With Preserved Left Ventricular Systolic Function. Circ Heart Fail 2020; 13: e006729
• 111 Shah RV, Schoenike MW, Armengol de la Hoz MA. et al. Metabolic Cost of Exercise Initiation in Patients With Heart Failure With Preserved Ejection Fraction vs Community-Dwelling Adults. JAMA Cardiol 2021; 6: 653-660
• 112 Singh I, Oliveira RKF, Heerdt PM. et al. Sex-related Differences in Dynamic Right Ventricular-Pulmonary Vascular Coupling in Heart FailureWith Preserved Ejection Fraction. Chest 2021; 159: 2402-2416
• 113 Medoff BD, Oelberg DA, Kanarek DJ. et al. Breathing Reserve at the Lactate Threshold to Differentiate a Pulmonary Mechanical From Cardiovascular Limit to Exercise. Chest 1998; 113: 913-918
• 114 Markowitz DH, Systrom DM. Diagnosis of pulmonary vascular limit to exercise by cardiopulmonary exercise testing. J Heart Lung Transplant 2004; 23: 88-95
• 115 Yasunobu Y, Oudiz RJ, Sun X-G. et al. End-tidal PCO2 abnormality and exercise limitation in patients with primary pulmonary hypertension. Chest 2005; 127: 1637-1646
• 116 Maron BA, Cockrill BA, Waxman AB. et al. The invasive cardiopulmonary exercise test. Circulation 2013; 127: 1157-1164
• 117 Berry NC, Manyoo A, Oldham WM. et al. Protocol for exercise hemodynamic assessment: performing an invasive cardiopulmonary exercise test in clinical practice. Pulm Circul 2015; 5: 610-618
• 118 Huang W, Resch S, Oliveira RKF. et al. Invasive cardiopulmonary exercise testing in the evaluation of unexplained dyspnea: Insights from a multidisciplinary dyspnea center. Eur J Prev Cardiol 2017; 24: 1190-1199
• 119 Lewis GD, Lachmann J, Camuso J. et al. Sildenafil improves exercise hemodynamics and oxygen uptake in patients with systolic heart failure. Circulation 2007; 115: 59-66
• 120 Arena R, Owens DS, Arevalo J. et al. Ventilatory efficiency and resting hemodynamics in hypertrophic cardiomyopathy. Med Sci Sports Exerc 2008; 40: 799-805
• 121 Caravita S, Faini A, Deboeck G. et al. Pulmonary hypertension and ventilation during exercise: Role of the pre-capillary component. J Heart Lung Transplant 2017; 36: 754-762
• 122 Dumitrescu D, Nagel C, Kovacs G. et al. Cardiopulmonary exercise testing for detecting pulmonary arterial hypertension in systemic sclerosis. Heart 2017; 103: 774-782
• 123 Wong YY, Raijmakers PG, Knaapen P. et al. Supine-exercise-induced oxygen supply to the right myocardium is attenuated in patients with severe idiopathic pulmonary arterial hypertension. Heart 2011; 97: 2069-2074
• 124 Blumberg F, Arzt M, Lange T. et al. Impact of right ventricular reserve on exercise capacity and survival in patients with pulmonary hypertension. Eur J Heart Fail 2013; 15: 771-775
• 125 Schwaiblmair M, Faul C, von Scheidt W. et al. Detection of exercise-induced pulmonary arterial hypertension by cardiopulmonary exercise testing. Clin Cardiol 2012; 35: 548-553
• 126 Reichenberger F, Voswinckel R, Schulz R. et al. Noninvasive detection of early pulmonary vascular dysfunction in scleroderma. Respir Med 2009; 2009: 1713-1718
• 127 Guth S, Wiedenroth CB, Rieth A. et al. Exercise right heart catheterisation before and after pulmonary endarterectomy in patients with chronic thromboembolic disease. Eur Respir J 2018; 52: 1800458
• 128 Ehlken N, Lichtblau M, Klose H. et al. Exercise training improves peak oxygen consumption and haemodynamics in patients with severe pulmonary arterial hypertension and inoperable chronic thrombo-embolic pulmonary hypertension: a prospective, randomized, controlled trial. Eur Heart J 2016; 37: 35-44
• 129 Skjorten I, Hilde JM, Melsom MN. et al. Exercise capacity in COPD patients with exercise-induced pulmonary hypertension. Int J Chron Obstruct Pulm Dis 2018; 13: 3599-3610
• 130 Correale M, Monaco I, Ferraretti A. et al. Ventilatory power, a cardiopulmonary exercise testing parameter for the prediction of pulmonary hypertension at right heart catheterization. Int J Cardiol Heart Vasc 2020; 28: 100513
• 131 Rosenkranz S, Lang IM, Blindt R. et al. Pulmonary hypertension associated with left heart disease: Updated Recommendations of the Cologne Consensus Conference 2018. Int J Cardiol 2018; 272S: 53-62
• 132 Guazzi M, Naeije R. Pulmonary Hypertension in Heart Failure: Pathophysiology, Pathobiology, and Emerging Clinical Perspectives. J Am Coll Cardiol 2017; 69: 1718-1734
• 133 Herve P, Lau EM, Sitbon O. et al. Criteria for diagnosis of exercise pulmonary hypertension. Eur Respir J 2015; 46: 728-737
• 134 Gerges C, Gerges M, Fesler P. et al. In-depth haemodynamic phenotyping of pulmonary hypertension due to left heart disease. Eur Respir J 2018; 51: 180067
• 135 Naeije R, Gerges M, Vachiery J-L. et al. Hemodynamic Phenotyping of Pulmonary Hypertension in Left Heart Failure. Circ Heart Fail 2017; 10: e004082
• 136 Vachiéry JL, Tedford RJ, Rosenkranz S. et al. Pulmonary hypertension due to left heart disease. Eur Respir J 2019; 53: 1801897
• 137 Guazzi M, Arena R, Halle M. et al. 2016 Focused Update: Clinical Recommendations for Cardiopulmonary Exercise Testing Data Assessment in Specific Patient Populations. Circulation 2016; 133: e694-e711
• 138 Pieske B, Tschöpe C, de Boer RA. et al. How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). Eur Heart J 2019; 40: 3297-3317
• 139 Rosenkranz S, Diller G-P, Dumitrescu D. et al. Hemodynamic Definition of Pulmonary Hypertension: Commentary on the Proposed Change by the 6th World Symposium on Pulmonary Hypertension. Dtsch Med Wochenschr 2019; 144: 1367-1372
• 140 Maron BA, Abman SH, Elliot CG. et al. Pulmonary Arterial Hypertension: Diagnosis, Treatment, and Novel Advances. Am J Respir Crit Care Med 2021; 203: 1472-1487
• 141 Balady GJ, Arena R, Sietsema K. et al. Clinicianʼs Guide to cardiopulmonary exercise testing in adults: a scientific statement from the American Heart Association. Circulation 2010; 122: 191-225
• 142 Neder JA, Berton DC, Nery LE. et al. A frame of reference for assessing the intensity of exertional dyspnoea during incremental cycle ergometry. Eur Respir J 2020; 56: 2000191
• 143 Borlaug BA, Nishimura RA, Sorajja P. et al. Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction. Circ Heart Fail 2010; 3: 588-595
• 144 Ewert R, Heine A, Müller-Heinrich A. et al. Exercise and fluid challenge during right heart catheterisation for evaluation of dyspnoea. Pulm Circ 2020; 10
• 145 Zeder K, Avian A, Bachmaier G. et al. Exercise Pulmonary Resistances Predict Long-Term Survival in Systemic Sclerosis. Chest 2021; 159: 781-790
• 146 Rusche W, Ince A, Alvarez F. et al. Cardiopulmonary Exercise Testing With Pulmonary Artery Catheterization Detects Early Pulmonary Vasculature Changes in Patients With Connective Tissue Diseases. J Clin Rheumatol 2002; 8: 247-250
• 147 Kovacs G, Maier R, Aberer E. et al. Assessment of pulmonary arterial pressure during exercise in collagen vascular disease: echocardiography vs right-sided heart catheterization. Chest 2010; 138: 270-278
• 148 Borst MM, Leschke M, König U. et al. Repetitive Hemodilution in Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension: Effects on Pulmonary Hemodynamics, Gas Exchange, and Exercise Capacity. Respiration 1999; 66: 225-232
• 149 Henriquez A, Schrijen F, Poincelot F. et al. Maximal oxygen consumption and pulmonary circulation in patients with chronic bronchitis. Eur J Clin Invest 1986; 16: 526-530
• 150 Agusti AG, Barberá JA, Roca J. et al. Hypoxic pulmonary vasoconstriction and gas exchange during exercise in chronic obstructive pulmonary disease. Chest 1990; 97: 268-275
• 151 Paitl CE, Nery LE, Romaldini H. et al. Effects of captopril on hemodynamics, gas exchange and exercise capacity in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease. Arq Bras Cardiol 1989; 52: 59-67
• 152 von Heindl W, Raber W, Bleyer R. et al. Ruhefunktionsdaten und Belastungsregulation bei Patienten mit Lungenfibrose. Atemw-Lungenkrkh 1986; 12: 1-8
• 153 Abudiab MM, Redfield MM, Melenovsky V. et al. Cardiac output response to exercise in relation to metabolic demand in heart failure with preserved ejection fraction. Eur J Heart Fail 2013; 15: 776-785
• 154 Roubin GS, Anderson SD, Shen WF. et al. Hemodynamic and metabolic basis of impaired exercise tolerance in patients with severe left ventricular dysfunction. J Am Coll Cardiol 1990; 15: 986-994
• 155 Linehan JH, Haworth ST, Nelin LD. et al. A simple distensible vessel model for interpreting pulmonary vascular pressure-flow curves. J Appl Physiol (1985) 1992; 73: 987-994
• 156 Held M, Kolb P, Grün M. et al. Functional Characterization of Patients with Chronic Thromboembolic Disease. Respiration 2016; 91: 503-509
• 157 Neder JA, Phillips DB, Marillier M. et al. Clinical Interpretation of Cardiopulmonary Exercise Testing: Current Pitfalls and Limitations. Front Physiol 2021; 12: 552000
• 158 Kovacs G, Herve P, Olschewski H. PEX-NET Clinical Research Collaboration. The pulmonary haemodynamics during exercise – research network (PEX-NET) ERS Clinical Research Collaboration: investigating the prognostic relevance of exercise haemodynamics. Eur Respir J 2019; 53: 1900458
• 159 Rieth AJ, Richter M, Tello K. et al. Exercise hemodynamics in heart failure patients with preserved and mid-range ejection fraction: key role of the right heart. Clin Res Cardiol 2021; [Online ahead of print]