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 Table of Contents  
COMMENTARY
Year : 2023  |  Volume : 7  |  Issue : 1  |  Page : 52-54

Cardiopulmonary exercise testing in heart failure risk assessment and prognosis


1 Department of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland; Department of Medicine, Institute of Clinical Medicine, University of Eastern Finland, Kuopio; Department of Medicine, The Wellbeing Services County of Central Finland, Jyväskylä, Finland
2 Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK

Date of Submission02-Dec-2022
Date of Acceptance19-Jan-2023
Date of Web Publication13-Mar-2023

Correspondence Address:
prof. Jari A Laukkanen
Department of Medicine, Institute of Clinical Medicine, University of Eastern Finland, P. O. Box 1627, Kuopio 70211
Finland
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/hm.hm_57_22

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How to cite this article:
Laukkanen JA, Kunutsor SK. Cardiopulmonary exercise testing in heart failure risk assessment and prognosis. Heart Mind 2023;7:52-4

How to cite this URL:
Laukkanen JA, Kunutsor SK. Cardiopulmonary exercise testing in heart failure risk assessment and prognosis. Heart Mind [serial online] 2023 [cited 2023 Mar 23];7:52-4. Available from: http://www.heartmindjournal.org/text.asp?2023/7/1/52/371616

Cardiopulmonary exercise testing (CPET) is an examination that involves concomitant gas exchange assessment and provides an integrative and comprehensive assessment of physiologic responses to exercise and the most reliable data on cardiorespiratory fitness (CRF) levels.[1],[2] In contrast to the exercise electrocardiography (ECG) only approach, the direct noninvasive determination of respiratory gases analysis (oxygen uptake [VO2] and carbon dioxide [CO2] output) at rest and during exercise and recovery phases provide the most accurate information on the interaction of ventilation, gas exchange, and cardiovascular and musculoskeletal function.

Heart failure (HF) is a global public health threat which is associated with increased incidence of hospitalization and morbidity, and substantial mortality and economic costs, especially among the aging population.[3] The most common underlying causes of HF include coronary heart disease (CHD), valvular heart disease, and hypertension.[4],[5] Impaired exercise capacity is commonly seen in patients with HF. The degree of impairment in CRF may be similar between individuals with symptomatic HF with preserved or lowered left ventricular (LV) ejection fraction. Although peak VO2 is often the most commonly used CPET derivative to grade the severity of HF,[6] there are other noninvasive gas exchange parameters, which can be estimated at exercise onset, during low-level and submaximal exercise, and during recovery; these parameters can provide insights into cardiovascular capacity and provide incremental prognostic value when added to peak VO2.[7],[8],[9],[10] Abnormally delayed VO2 recovery to baseline resting levels following the incremental exercise phase (known as the postexercise VO2 recovery delay [VO2RD]) has been documented in HF patients compared with healthy individuals.[11],[12] It is a relatively novel, easily recognizable, and noninvasively derived metric that indicates impaired cardiac output augmentation during exercise and is a predictor of adverse outcomes in HF.[13],[14] It is a parameter that could potentially be used in both HF with reduced ejection fraction (HFrEF) and preserved ejection fraction; however, most studies on VO2RD in HF have mostly focused on the HFrEF patient population,[14] and there remains limited understanding of VO2 recovery patterns in HF and its subtypes. The existing evidence on VO2RD in HF is sparse and variable. In the current issue of the Heart and Mind journal, Charounipha Soydara et al., therefore, conducted a systematic review to explore VO2 RD patterns across the spectrum of LV function and degree of HF.[15]

Exercise testing has primarily been used as a noninvasive assessment tool for the diagnosis of CHD. False-positive exercise ECG findings with ST-segment assessment may, however, be observed in asymptomatic adults and patients with a low-pretest likelihood for CHD. It is, therefore, necessary that exercise ECG tests should be conducted in specific patient populations based on their pretest probability. Furthermore, there is insufficient evidence to recommend exercise ECG testing as a routine screening tool in asymptomatic populations.[16] This is reflected in the fact that guideline bodies do not recommend the diagnostic use of exercise testing in individuals with a very low pretest likelihood of CHD. Nevertheless, several studies have increased knowledge on the prognostic value of many exercise-related parameters, in addition to ECG only, and suggest that the clinical importance of exercise testing may have been underappreciated. CRF, a key parameter of cardiovascular and pulmonary system function during exercise testing, has been proposed as a crucial clinical measure and one of the strongest prognostic indicators ever to have been evaluated.[2],[17]

Genetic and environmental factors have a substantial influence on CRF; about half of the variation in CRF has been attributed to heritable factors,[18] with contributions from physical activity and exercise training.[19],[20] CRF is also determined by several other factors such as baseline health and fitness status and components of physical activity such as the type, frequency, duration, and intensity.[1],[21] The level of CRF is an indicator of a series of physiological exercise-related responses that include lung and vascular function, right ventricle and LV function, the ability of the arteries to effectively transport blood and oxygen from the heart to body muscles, the capacity of the muscle cells to utilize the oxygen and many important micronutrients, and the capability to activate most essential muscle fibers needed for high-level aerobic endurance exercise.[22] Maximal heart rate, LV stroke volume, vascular function, and arteriovenous oxygen difference during maximal aerobic exercise mainly determine levels of CRF. In addition, LV function is a key measure of HF and thus levels of CRF reflect LV function. Given that CRF is related to the integration of human body function during demanding physiological conditions, it can be utilized as a key CPET indicator of the risk for HF, reffecting exercise performance among patients with HF.

During a maximal CPET, parameters that can be measured during respiratory gas analysis include VO2peak, the oxygen pulse, ventilatory efficiency slope (VE/VCO2 slope), the ventilatory anaerobic threshold, the ventilatory equivalent for CO2 (VE/VCO2) slope, and the VO2 efficiency slope curve. However, the measurement of maximal exercise test-related variables in all kinds of HF patient populations is challenging, given the fact that the definitions of these parameters usually require a demanding exercise test to have been completed to the maximal or near maximal level. Investigators have consistently found that VO2RD was associated with abnormalities in cardiac structure and function that lead to circulatory delay.[15] VO2RD is suggested to be a specific CPET measure for cardiac function. As an easily derived noninvasive measure, VO2RD has the potential role of distinguishing between HF subtypes in a cardiology clinic and it could be used in the prognostication of HF. Although the concept of VO2RD is not entirely novel, it has not been yet adopted into usual CPET interpretation algorithms given the limited evidence available on its potential applications; the mechanistic pathways underlying VO2 recovery patterns in HF and its clinical implications need to be investigated further before being suggested for routine clinical use. The recent evidence suggests an incremental value of VO2RD in HF risk assessment, however, the value of these CPET parameters varies according to the patient population.[15] Exercise test results, including heart rate and blood pressure responses, are dependent on a number of factors, which include the test population, preexisting use of medications such as β-blockers and other implemented cardiovascular interventions. It is not well known if VO2RD is associated with LV ejection fraction or diastolic function (E/e'), indicating the performance of the LV relaxation phase at a high heart rate during exercise.

In addition to HF patient population risk assessment, CPET is considered the standard method for measuring aerobic fitness in patients with or without diagnosed cardiac disease. On the other hand, assessment of CRF using CPET protocols with the collection of detailed respiratory gases may be quite challenging in very large populations, with the comprehensive assessment of common cardiovascular risk factors, which are related to prognosis and need to be assessed. However, we have shown that CRF, assessed by submaximal exercise testing, is considered to be safe for asymptomatic populations and patients, and improves mortality risk prediction when added on top of conventional cardiovascular risk factors, particularly in participants at low pretest risk for CHD.[23] Within a contemporary adult population, we found that the association between CRF and mortality was strong, inverse, and independent, consistent with a graded response relationship.[23] Furthermore, our recent meta-analysis of 37 cohort studies assessing the association between CRF and mortality risk confirmed the relationship.[24] Our pooled analysis involving a total of 2.2 million men and women with an objective definition of CRF demonstrated that participants in the top third of CRF levels had a 45% reduced risk of all-cause mortality compared with those in the bottom third of CRF.[24] In dose-response analysis, a 1-metabolic equivalent higher level of CRF was linked to an 11% decrement in the risk of all-cause death.[24] There is overwhelming and robust evidence that supports the need for CRF to be included in risk assessment panels.

There is value in using exercise testing in clinical practice because it provides accurate information on the hemodynamic and ECG responses and aerobic fitness, which are the main measures of prognosis. Exercise testing can be used as an additional tool for diagnostics and assessing physiology when the resources and skills are available. Indeed, exercise testing, ideally with the combination of respiratory gas analyses during CPET, has a need in cardiology clinics and its use should be appreciated – even in the risk assessment of HF phenotypes. Peak VO2 is the key point of CPET in HF, with the availability of breath-by-breath gas exchange patterns at exercise onset, during exercise, and recovery phase. It may provide further insight into HF severity and etiologies of all possible exercise limitations. Thus, VO2RD, a noninvasive gas exchange metric following the completion of an incremental exercise test, can be considered a potentially useful parameter for HF risk assessment and enhance precise interpretation of CPET results.



 
  References Top

1.
Laukkanen JA, Kunutsor SK. There is still a role for exercise testing in prognostic cardiology. Int J Cardiol 2022;365:32-3.  Back to cited text no. 1
    
2.
Ross R, Blair SN, Arena R, Church TS, Després JP, Franklin BA, et al. Importance of assessing cardiorespiratory fitness in clinical practice: A case for fitness as a clinical vital sign: A scientific statement from the American heart association. Circulation 2016;134:e653-99.  Back to cited text no. 2
    
3.
Groenewegen A, Rutten FH, Mosterd A, Hoes AW. Epidemiology of heart failure. Eur J Heart Fail 2020;22:1342-56.  Back to cited text no. 3
    
4.
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McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021;42:3599-726.  Back to cited text no. 5
    
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Balady GJ, Arena R, Sietsema K, Myers J, Coke L, Fletcher GF, et al. Clinician's Guide to cardiopulmonary exercise testing in adults: A scientific statement from the American Heart Association. Circulation 2010;122:191-225.  Back to cited text no. 6
    
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Guazzi M, Dickstein K, Vicenzi M, Arena R. Six-minute walk test and cardiopulmonary exercise testing in patients with chronic heart failure: A comparative analysis on clinical and prognostic insights. Circ Heart Fail 2009;2:549-55.  Back to cited text no. 7
    
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Laukkanen JA, Kunutsor SK, Araújo CG, Savonen K. Cardiorespiratory optimal point during exercise testing is related to cardiovascular and all-cause mortality. Scand J Med Sci Sports 2021;31:1949-61.  Back to cited text no. 10
    
11.
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Nanas S, Nanas J, Kassiotis C, Nikolaou C, Tsagalou E, Sakellariou D, et al. Early recovery of oxygen kinetics after submaximal exercise test predicts functional capacity in patients with chronic heart failure. Eur J Heart Fail 2001;3:685-92.  Back to cited text no. 12
    
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Bailey CS, Wooster LT, Buswell M, Patel S, Pappagianopoulos PP, Bakken K, et al. Post-exercise oxygen uptake recovery delay: A novel index of impaired cardiac reserve capacity in heart failure. JACC Heart Fail 2018;6:329-39.  Back to cited text no. 13
    
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Fortin M, Turgeon PY, Nadreau É, Grégoire P, Maltais LG, Sénéchal M, et al. Prognostic value of oxygen kinetics during recovery from cardiopulmonary exercise testing in patients with chronic heart failure. Can J Cardiol 2015;31:1259-65.  Back to cited text no. 14
    
15.
Soydara C, Jurgens CY, Lewis GD. Postexercise oxygen uptake recovery delay among patients with heart failure: A systematic review. Heart Mind 2023;7:40-4.  Back to cited text no. 15
  [Full text]  
16.
Laukkanen JA, Mäkikallio TH, Rauramaa R, Kurl S. Asymptomatic ST-segment depression during exercise testing and the risk of sudden cardiac death in middle-aged men: A population-based follow-up study. Eur Heart J 2009;30:558-65.  Back to cited text no. 16
    
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Salokari E, Laukkanen JA, Lehtimaki T, Kurl S, Kunutsor S, Zaccardi F, et al. The Duke treadmill score with bicycle ergometer: Exercise capacity is the most important predictor of cardiovascular mortality. Eur J Prev Cardiol 2019;26:199-207.  Back to cited text no. 17
    
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Bouchard C. Genomic predictors of trainability. Exp Physiol 2012;97:347-52.  Back to cited text no. 18
    
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Church TS, Earnest CP, Skinner JS, Blair SN. Effects of different doses of physical activity on cardiorespiratory fitness among sedentary, overweight or obese postmenopausal women with elevated blood pressure: A randomized controlled trial. JAMA 2007;297:2081-91.  Back to cited text no. 19
    
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Duscha BD, Slentz CA, Johnson JL, Houmard JA, Bensimhon DR, Knetzger KJ, et al. Effects of exercise training amount and intensity on peak oxygen consumption in middle-age men and women at risk for cardiovascular disease. Chest 2005;128:2788-93.  Back to cited text no. 20
    
21.
Laukkanen JA, Laaksonen D, Lakka TA, Savonen K, Rauramaa R, Mäkikallio T, et al. Determinants of cardiorespiratory fitness in men aged 42 to 60 years with and without cardiovascular disease. Am J Cardiol 2009;103:1598-604.  Back to cited text no. 21
    
22.
Laukkanen JA, Laaksonen D, Lakka TA, Savonen K, Rauramaa R, Mäkikallio T, et al. Determinants of cardiorespiratory fitness in men aged 42 to 60 years with and without cardiovascular disease. Am J Cardiol 2009;103:1598-604.  Back to cited text no. 22
    
23.
Laukkanen JA, Kunutsor SK, Yates T, Willeit P, Kujala UM, Khan H, et al. Prognostic Relevance of cardiorespiratory fitness as assessed by submaximal exercise testing for all-cause mortality: A UK Biobank prospective study. Mayo Clin Proc 2020;95:867-78.  Back to cited text no. 23
    
24.
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