Exercise Pulmonary Hypertension: What You Need to Know
- Exercise pulmonary hypertension (PH) can be defined as a pulmonary artery pressure (PAP) / cardiac output (CO) slope of >3 mmHg/L/min.1,2 Indexing of PAP to CO is preferred to a single absolute cutoff point for exercise PAP to account for variable increases in flow with exercise.3 The definition of exercise PH as the presence of a resting mean PAP <25 mmHg and mean PAP >30 mmHg during exercise with total pulmonary resistance >3 Wood units was abandoned during the 4th World Symposium on Pulmonary Hypertension in 2008.4 The question of whether exercise PH should be reintroduced into the definition of PH was revisited at the 6th World Symposium on Pulmonary Hypertension; however, it was determined that too many uncertainties exist to establish a threshold for exercise PH as a pathologic condition.5
- Although exercise PH may identify patients with early pulmonary arterial hypertension (PAH), more research is needed prior to the re-inclusion of exercise PH in the guidelines. Pulmonary microvascular reserve leads to normal resting pulmonary hemodynamics until late in disease progression when ≥50% of the microcirculation has been lost, hence the impetus to diagnose pulmonary vascular disease earlier and exercise provocation as a means to do so.6 However, PAP variability with exercise related to normal aging,3 high CO states (elite athletes), and the challenges of discriminating exercise PH due to left heart disease from pulmonary vascular disease remain.7 Although adding total peripheral resistance has improved the discriminatory power of exercise PH, more research is needed prior to the re-inclusion of exercise PH as a standardized way to identify early PAH and development of a mutually agreeable definition for exercise PH that distinguishes it from PH due to left heart disease.5,7
- Patients with high PAP/CO slope had worse cardiovascular event-free survival compared with normal PAP/CO slope among patients undergoing evaluation of dyspnea.8 High PAP/CO slope was independently associated with a >twofold increased risk of cardiovascular hospitalization or death after adjustment for potential clinical confounders. High PAP/CO slope remained independently associated with cardiovascular hospitalization or death even after additional adjustment for baseline resting PAP. Further exercise PH has been associated with worse functional capacity and abnormal right ventricular contractile reserve.8
- Exercise right heart catheterization (RHC) is prognostically significant in patients with established Group 1 risk factors (e.g., scleroderma), in patients with multifactorial dyspnea (e.g., interstitial lung disease and PAH), and in patients with PH due to left heart disease, including valvular disease (e.g., aortic stenosis and mitral regurgitation).9-13
- Pulmonary capillary wedge pressures (PCWPs) of 15 mmHg at rest, 20 mmHg with upright exercise, or 25 mmHg with supine exercise have typically been used to discriminate precapillary (lower values) from postcapillary (higher values) PH. Recent evidence suggests that evaluating PCWP with respect to the increase in CO may be of value, with PCWP/CO slope >2 mmHg/L/ min identifying patients at greater risk of adverse cardiac outcomes.14
- Current cutoffs for PH (mean PAP >20 mmHg) and postcapillary PH (PCWP >15 mmHg) are applicable only in the supine position.5 Specific pressure cutoffs for mean PAP and PCWP are sensitive to body position. When a patient is brought from supine to upright position, there is a commensurate drop in mean PAP, PCWP, and CO due to the effects of gravity and reducing preload. Pulmonary vascular resistance seems unaffected by body position because changes in upstream and downstream pressure and CO are similarly affected by gravity.15
- Exercise RHC can be performed with upright or supine exercise and with or without cardiopulmonary exercise testing (the "gold standard") to assess aerobic capacity (peak V˙O2).16 If exercise RHC is performed with cardiopulmonary exercise testing, this is called invasive cardiopulmonary exercise testing.
- Exercise catheterization without a metabolic cart using thermodilution CO rather than direct Fick CO (calculated from measured V˙O2) is not recommended because this technique underestimates pulmonary blood flow at peak exercise.17 Indirect (or estimated/calculated) Fick is not accurate with exercise.
- Typically during supine invasive cardiopulmonary exercise testing, hemodynamics are obtained at rest, then repeated after patient places their feet in the mounted bike (because this may cause a fluid bolus to the heart and change resting hemodynamics), and then repeated at 0 watt and serially with incremental resistance (10 watt or 20 watt protocols depending on the patients baseline activity tolerance). Although supine invasive cardiopulmonary exercise testing allows easier assessment by fluoroscopy and less dynamic movement by the patient, this setup is not ideal in the significantly obese patient where abdominal fat may decrease lung expansion or in patients with parenchymal lung disease.
- Upright exercise is more physiologic and is associated with less lung volume loss but requires frequent change in patient position and is difficult for fluoroscopy positioning. If exercise is performed in the upright position, it is recommended to first obtain data in the supine position.
- Accurate transducer zeroing is essential at all positions. When the patient is in the supine position, the transducer is zeroed at half the anteroposterior dimension of the chest. Zeroing in the upright position can be done by placing the tip of the pulmonary artery catheter in the atrium by fluoroscopy. Then scissors are placed at the tip of the pulmonary artery catheter and a laser set at the scissors. Lastly, the transducer stopcock is placed at the laser.16 Invasive cardiopulmonary exercise testing requires significant training and education to maintain valid reproducible data.
- Accurate measurements of waveforms in obese patients and patients with obstructive lung disease is challenging, particularly during exercise related to exaggerated respiratory swings. Reporting of both end expiratory and mean of the respiratory cycle values is recommended. Traditionally, end-expiration at end-diastole wedge measurement at rest is used for patients with predominant left heart disease, and mean is used for patients with predominant intrinsic lung disease.18
- Naeije R, Vanderpool R, Dhakal BP, et al. Exercise-induced pulmonary hypertension: physiological basis and methodological concerns. Am J Respir Crit Care Med 2013;187:576-83.
- 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;4:276-85.
- Kovacs G, Herve P, Barbera JA, et al. An official European Respiratory Society statement: pulmonary haemodynamics during exercise. Eur Respir J 2017;50:1700578.
- Simonneau G, Robbins IM, Beghetti M, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2009;54:S43-54.
- Simonneau G, Montani D, Celermajer DS, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J 2019;53:1801913.
- Lau EM, Humbert M, Celermajer DS. Early detection of pulmonary arterial hypertension. Nat Rev Cardiol 2015;12:143-55.
- Herve P, Lau EM, Sitbon O, et al. Criteria for diagnosis of exercise pulmonary hypertension. Eur Respir J 2015;46:728-37.
- 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.
- Stamm A, Saxer S, Lichtblau M, et al. Exercise pulmonary haemodynamics predict outcome in patients with systemic sclerosis. Eur Respir J 2016;48:1658-67.
- Walkey AJ, Ieong M, Alikhan M, Farber HW. Cardiopulmonary exercise testing with right-heart catheterization in patients with systemic sclerosis. J Rheumatol 2010;37:1871-7.
- Naeije R, Saggar R, Badesch D, et al. Exercise-Induced Pulmonary Hypertension: Translating Pathophysiological Concepts Into Clinical Practice. Chest 2018;154:10-5.
- Lancellotti P, Magne J, Donal E, et al. Determinants and prognostic significance of exercise pulmonary hypertension in asymptomatic severe aortic stenosis. Circulation 2012;126:851-9.
- Kusunose K, Popović ZB, Motoki H, Marwick TH. Prognostic significance of exercise-induced right ventricular dysfunction in asymptomatic degenerative mitral regurgitation. Circ Cardiovasc Imaging 2013;6:167-76.
- 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.
- Forton K, Motoji Y, Deboeck G, Faoro V, Naeije R. Effects of body position on exercise capacity and pulmonary vascular pressure-flow relationships. J Appl Physiol (1985) 2016;121:1145-50.
- Rischard FP, Borlaug BA. Tools of the Trade: How Do You Perform and Interpret an Exercise Test? Adv Pulm Hypertens 2019;18:47-55.
- Hsu S, Brusca SB, Rhodes PS, Kolb TM, Mathai SC, Tedford RJ. Use of thermodilution cardiac output overestimates diagnoses of exercise-induced pulmonary hypertension. Pulm Circ 2017;7:253-5.
- Fukumoto Y. Pulmonary Hypertension due to Left Heart Disease. J Card Fail 2013;19:S124.
Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Valvular Heart Disease, Vascular Medicine, Pulmonary Hypertension, Exercise, Hypertension, Mitral Regurgitation
Keywords: Hypertension, Pulmonary, Pulmonary Wedge Pressure, Thermodilution, Risk Factors, Mitral Valve Insufficiency, Microcirculation, Pulmonary Artery, Supine Position, Diastole, Vascular Resistance, Exercise
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