conducting-maximal-submaximal-endurance-exercise-testing-to-measure

Conducting Maximal and Submaximal Endurance Exercise Testing to Measure Physiological and Biological Responses to Acute Exercise in Humans

Regular physical activity has a positive effect on human health, but the mechanisms controlling these effects remain unclear. The physiologic and biologic ...

Mayo Clinic

Patients with pulmonary arterial hypertension (PAH) and heart failure (HF) display many abnormalities in respiratory gas exchange. These abnormalities are accentuated with exercise and track with disease severity. However, use of gas exchange measures in day-to-day clinical practice is limited by several issues, including the large number of variables available and difficulty in data interpretation. Moreover, maximal exercise testing has limitations in clinical populations due to their complexity, patient anxiety and variability in protocols and cost. Therefore, a multivariable gas exchange index (MVI) that integrates key gas exchange variables obtained during submaximal exercise into a severity score that ranges from normal to severe-very-severe is proposed. To demonstrate the usefulness of this index, we applied this to 2 groups (PAH, n = 42 and HF, n = 47) as well as to age matched healthy controls (n = 25). We demonstrate that this score tracks WHO classification and right ventricular systolic pressure in PAH (r = 0.53 and 0.73, P ≤ 0.01) and NYHA and cardiac index in HF (r = 0.49 and 0.74, P ≤ 0.01). This index demonstrates a stronger relationship than any single gas exchange variable alone. In conclusion, MVI obtained from light, submaximal exercise gas exchange is a useful approach to simplify data interpretation in PAH and HF populations.

A multivariable index for grading exercise gas exchange severity in patients with pulmonary arterial hypertension and heart failure.

We determined whether a non-invasive gas exchange based estimate of pulmonary vascular (PV) capacitance [PVCAP = stroke volume (SV) × pulmonary arterial pressure (Ppa)] (GXCAP) tracked the PV response to exercise in heart-failure (HF) patients. Pulmonary wedge pressure (Ppw), Ppa, PV resistance (PVR), and gas exchange were measured simultaneously during cycle exercise in 42 HF patients undergoing right-heart catheterization. During exercise, PETCO2 and VE/VCO2 were related to each other (r = -0.93, P < 0.01) and similarly related to mean Ppa (mPpa) (r = -0.39 and 0.36; P < 0.05); PETCO2 was subsequently used as a metric of mPpa. Oxygen pulse (O2 pulse) tracked the SV response to exercise (r = 0.91, P < 0.01). Thus, GXCAP was calculated as O2 pulse × PETCO2. During exercise, invasively determined PVCAP and non-invasive GXCAP were related (r = 0.86, P < 0.01), and GXCAP correlated with mPpa and PVR (r = -0.46 and -0.54; P < 0.01). In conclusion, noninvasive gas exchange measures may represent a simple way to track the PV response to exercise in HF. 

Use of noninvasive gas exchange to track pulmonary vascular responses to exercise in heart failure.

Cardiac resynchronization therapy (CRT) has been an important treatment for heart failure. However, it is controversial as to whether an individualized approach to altering AV and VV timing intervals would improve outcomes. Changes in respiratory patterns and gas exchange are dynamic and may be influenced by timing delays. Light exercise enhances the heart and lung interactions. Thus, in this study we investigated changes in non-invasive gas exchange by altering AV and VV timing intervals during light exercise.

Effects of atrioventricular and interventricular delays on gas exchange during exercise in patients with heart failure.

It is unclear how dynamic changes in pulmonary-capillary blood volume (Vc), alveolar lung volume (derived from end-inspiratory lung volume, EILV) and interstitial fluid (ratio of alveolar capillary membrane conductance and pulmonary capillary blood volume, Dm/Vc) influence lung impedance (Z(T)). The purpose of this study was to investigate if positional change and exercise result in increased EILV, Vc and/or lung interstitial fluid, and if Z(T) tracks these variables.

Influence of lung volume, fluid and capillary recruitment during positional changes and exercise on thoracic impedance in heart failure.

Exposure to hypoxia is associated with cognitive impairment, mediated by cerebral deoxygenation. This can be problematic for individuals who perform mental tasks at high altitude. Eight healthy men completed two experimental trials consisting of 5h of exposure to normobaric hypoxia (12.5% O2). In one of the experimental trials (Hypoxia) subjects remained resting in a seated position the entire 5h; in the other experimental trial (Hypoxia and Exercise) subjects rested 2h, cycled for 1h at constant wattage (workload equivalent to 50% of altitude adjusted VO2max), then rested the last 2h. Cerebral oxygenation was measured continuously via near-infrared spectroscopy and cognitive performance was assessed by Trail Making Test A and B. Cerebral oxygenation and cognitive performance both were impaired during exposure to hypoxia. In the Hypoxia and Exercise trial, subjects experienced further declinations in cerebral oxygenation without concomitant decreases in cognitive function. These data demonstrate that cognitive function declines during exposure to normobaric hypoxia and this decline is not exacerbated by low intensity exercise. 

Low intensity exercise does not impact cognitive function during exposure to normobaric hypoxia.

Cardiac resynchronization therapy (CRT) is an accepted intervention for chronic heart failure (HF), although approximately 30% of patients are non-responders. The purpose of this study was to determine whether exercise respiratory gas exchange obtained before CRT implantation predicts early response to CRT.

Ventilatory gas exchange and early response to cardiac resynchronization therapy.

In heart failure (HF), pulmonary hypertension (PH) is initially associated with a rise in the left ventricular filling pressure. PH is defined by pulmonary hemodynamic measurements including pulmonary capillary wedge pressure, mean pulmonary arterial pressure and pulmonary vascular resistance. Eventually, PH in HF may become more of a reactive process. Although the mechanism of the reactive PH development is not clearly understood, vascular dysfunction induced by remodeling, vasoactive substances and genetic variation appear to contribute significantly to this form of PH. Noninvasive cardiopulmonary exercise testing has been extensively utilized to assess disease severity in HF patients. It provides integrated information that is dependent on cardiopulmonary hemodynamics, lung mechanics, breathing pattern and strategy. In this review, we will discuss the mechanisms of PH development in HF and how noninvasive gas exchange measures obtained with submaximal exercise are influenced by PH in this population. 

Pulmonary Hypertension and Cardiopulmonary Exercise in Heart Failure.

Aging is associated with a fall in maximal aerobic capacity as well as with a decline in lean body mass. The purpose of the study was to investigate the influence of aging on the relationship between aerobic capacity and lean body mass in subjects that chronically train both their upper and lower bodies. Eleven older rowers (58±5 yrs) and 11 younger rowers (27±4 yrs) participated in the study. Prior to the VO2max testing, subjects underwent a dual energy X-ray absorptiometry scan to estimate total lean body mass. Subsequently, VO2max was quantified during a maximal exercise test on a rowing ergometer as well as a semi-recumbent cycle ergometer. The test protocol included a pre-exercise stage followed by incremental exercise until VO2max was reached. The order of exercise modes was randomized and there was a wash-out period between the two tests. Oxygen uptake was obtained via a breath-by-breath metabolic cart (Vmax™ Encore, San Diego, CA). Rowing VO2max was higher than cycling VO2max in both groups (p<0.05). Older subjects had less of an increase in VO2max from cycling to rowing (p<0.05). There was a significant relationship between muscle mass and VO2max for both groups (p<0.05). After correcting for muscle mass, the difference in cycling VO2max between groups disappeared (p>0.05), however, older subjects still demonstrated a lower rowing VO2max relative to younger subjects (p<0.05). Muscle mass is associated with the VO2max obtained, however, it appears that VO2max in older subjects may be less influenced by muscle mass than in younger subjects. 

The Effect of Aging on Relationships between Lean Body Mass and VO2max in Rowers.

Cardiac output (CO) assessment as a basic hemodynamic parameter has been of interest in exercise physiology, cardiology, and anesthesiology. Noninvasive techniques available are technically challenging, and thus difficult to use outside of a clinical or laboratory setting. We propose a novel method of noninvasive CO assessment using a single, upper-arm cuff. The method uses the arterial pressure pulse wave signal acquired from the brachial artery during 20-s intervals of suprasystolic occlusion. This method was evaluated in a cohort of 12 healthy individuals (age, 27.7 ± 5.4 yr, 50% men) and compared with an established method for noninvasive CO assessment, the open-circuit acetylene method (OpCirc) at rest, and during low- to moderate-intensity exercise. CO increased from rest to exercise (rest, 7.4 ± 0.8 vs. 7.2 ± 0.8; low, 9.8 ± 1.8 vs. 9.9 ± 2.0; moderate, 14.1 ± 2.8 vs. 14.8 ± 3.2 l/min) as assessed by the cuff-occlusion and OpCirc techniques, respectively. The average error of experimental technique compared with OpCirc was -0.25 ± 1.02 l/min, Pearson's correlation coefficient of 0.96 (rest + exercise), and 0.21 ± 0.42 l/min with Pearson's correlation coefficient of 0.87 (rest only). Bland-Altman analysis demonstrated good agreement between methods (within 95% boundaries); the reproducibility coefficient (RPC) = 0.84 l/min with R = 0.75 at rest and RPC = 2 l/min with R = 0.92 at rest and during exercise, respectively. In comparison with an established method to quantify CO, the cuff-occlusion method provides similar measures at rest and with light to moderate exercise. Thus, we believe this method has the potential to be used as a new, noninvasive method for assessing CO during exercise.

Noninvasive assessment of cardiac output by brachial occlusion-cuff technique: comparison with the open-circuit acetylene washin method.

Exercise immunology has become a growing field in the past 20 years, with an emphasis on understanding how different forms of exercise affect immune function. Mechanistic studies are beginning to shed light on how exercise may impair the development of cancer or be used to augment cancer treatment. The beneficial effects of exercise on the immune system may be exploited to improve patient responses to cancer immunotherapy.

A systems biology approach to investigating the influence of exercise and fitness on the composition of leukocytes in peripheral blood.

We developed a simplified automated algorithm to interpret noninvasive gas exchange in healthy subjects and patients with heart failure (HF, n = 12), pulmonary arterial hypertension (PAH, n = 11), chronic obstructive lung disease (OLD, n = 16), and restrictive lung disease (RLD, n = 12). They underwent spirometry and thereafter an incremental 3-minute step test where heart rate and SpO respiratory gas exchange were obtained. A custom-developed algorithm for each disease pathology was used to interpret outcomes. Each algorithm for HF, PAH, OLD, and RLD was capable of differentiating disease groups ( < .05) as well as healthy cohorts (n = 19,  < .05). In addition, this algorithm identified referral pathology and coexisting disease. Our primary finding was that the ranking algorithm worked well to identify the primary referral pathology; however, coexisting disease in many of these pathologies in some cases equally contributed to the cardiorespiratory abnormalities. Automated algorithms will help guide decision making and simplify a traditionally complex and often time-consuming process.

Algorithm for Predicting Disease Likelihood From a Submaximal Exercise Test.

Cardiopulmonary exercise testing (CPET) using a spectrum of different approaches demonstrates usefulness for objectively assessing patient disease severity in clinical and research settings. Still, an absence of trained specialists and/or improper data interpretation techniques can pose major limitations to the effective use of CPET for the clinical classification of patients. This study aimed to test an automated disease likelihood scoring algorithm system based on cardiopulmonary responses during a simplified step-test protocol. For patients with heart failure (HF), pulmonary hypertension (PAH), obstructive lung disease (OLD), or restrictive lung disease (RLD), we compared patient scores stratified into one of four "silos" generated from our novel algorithm system against patient evaluations provided by expert clinicians. Patients with HF (n = 12), PAH (n = 9), OLD (n = 16), or RLD (n = 10) performed baseline pulmonary function testing followed by submaximal step-testing. Breath-by-breath measures of ventilation and gas exchange, in addition to oxygen saturation and heart rate were collected continuously throughout testing. The algorithm demonstrated close alignment with patient assessments provided by clinical specialists: HF (r = 0.89, P < 0.01); PAH (r = 0.88, P < 0.01); OLD (r = 0.70, P < 0.01); and RLD (r = 0.88, P < 0.01). Furthermore, the algorithm was capable of differentiating major disease from other disease pathologies. Thus, in a clinically relevant manner, these data suggest this simplified automated disease algorithm scoring system used during step-testing to identify the likelihood that patients have HF, PAH, OLD, or RLD closely correlates with patient assessments conducted by trained clinicians.

Streamlining cardiopulmonary exercise testing for use as a screening and tracking tool in primary care.

Background Exercise intolerance, obesity, and low hemoglobin (hemoglobin<13 and <12 g/dl, men/women, respectively) are common features of heart failure. Despite serving as potent contributors to metabolic dysfunction, the impact of obesity and low hemoglobin on exercise intolerance is unknown. This study tested the hypotheses, compared with non-obese (NO) heart failure with normal hemoglobin, (a) counterparts with low hemoglobin and obesity or non-obesity will demonstrate reduced peak exercise oxygen uptake; (b) obese with normal hemoglobin will demonstrate decreased peak exercise oxygen uptake; (c) compared across stratifications, obese with low hemoglobin will demonstrate the sharpest decrement in peak exercise oxygen uptake. Methods Adults with heart failure ( n = 315; left ventricular ejection fraction≤40%; 77% men) (Group 1: normal hemoglobin and non-obese, n = 137; Group 2: low hemoglobin and non-obese, n = 51; Group 3: normal hemoglobin+obesity, n = 89; Group 4, n = 38: low hemoglobin+obesity; body mass index = 26 ± 3, 26 ± 2, 34 ± 4, 34 ± 4 kg/m, respectively) completed treadmill cardiopulmonary exercise testing as part of routine clinical management. Peak exercise oxygen uptake was measured via standard metabolic system. Results There were no group-wise differences for heart failure class, gender, left ventricular ejection fraction, and resting cardiopulmonary function. Group 1 demonstrated increased peak exercise oxygen uptake versus Groups 2-4 (20 ± 6 versus 17 ± 6, 17 ± 5, 13 ± 4 ml/kg/min, respectively; all p < 0.001); whereas Group 4 peak exercise oxygen uptake was reduced versus all groups ( p < 0.001). Additionally, both body mass index (R = 0.10) and hemoglobin (R = 0.12) were significant predictors of peak exercise oxygen uptake in Group 1; which were relationships not mirrored for Groups 2-4. Conclusion These data suggest obesity together with low hemoglobin are potent contributors to impaired peak exercise oxygen uptake and, hence, oxidative metabolic capacity. In diverse populations of heart failure where obesity and/or low hemoglobin are present, it is important to consider these features together when interpreting peak exercise oxygen uptake and underlying exercise limitations.

Obesity and hemoglobin content impact peak oxygen uptake in human heart failure.

The lungs-and particularly the alveolar-capillary membrane-may be sensitive to continuous flow (CF) and pulmonary pressure alterations in heart failure (HF). We aimed to investigate long-term effects of CF pumps on respiratory function.

Article	Year
A multivariable index for grading exercise gas exchange severity in patients with pulmonary arterial hypertension and heart failure. Pulmonary medicine\| PubMed ID: 23346397	2012
Use of noninvasive gas exchange to track pulmonary vascular responses to exercise in heart failure. Clinical medicine insights. Circulatory, respiratory and pulmonary medicine\| PubMed ID: 24093002	2013
Effects of atrioventricular and interventricular delays on gas exchange during exercise in patients with heart failure. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation\| PubMed ID: 24594137	2014
Influence of lung volume, fluid and capillary recruitment during positional changes and exercise on thoracic impedance in heart failure. Respiratory physiology & neurobiology\| PubMed ID: 25128641	2014
Low intensity exercise does not impact cognitive function during exposure to normobaric hypoxia. Physiology & behavior\| PubMed ID: 26160408	2015
Ventilatory gas exchange and early response to cardiac resynchronization therapy. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation\| PubMed ID: 26163155	2015
Pulmonary Hypertension and Cardiopulmonary Exercise in Heart Failure. Pulse (Basel, Switzerland)\| PubMed ID: 26389080	2014
The Effect of Aging on Relationships between Lean Body Mass and VO2max in Rowers. PloS one\| PubMed ID: 27479009	2016
Noninvasive assessment of cardiac output by brachial occlusion-cuff technique: comparison with the open-circuit acetylene washin method. Journal of applied physiology (Bethesda, Md. : 1985)\| PubMed ID: 27765846	2016
A systems biology approach to investigating the influence of exercise and fitness on the composition of leukocytes in peripheral blood. Journal for immunotherapy of cancer\| PubMed ID: 28428879	2017
Algorithm for Predicting Disease Likelihood From a Submaximal Exercise Test. Clinical medicine insights. Circulatory, respiratory and pulmonary medicine\| PubMed ID: 28757799	2017
Streamlining cardiopulmonary exercise testing for use as a screening and tracking tool in primary care. Pulmonary circulation\| PubMed ID: 29693481	2018
Obesity and hemoglobin content impact peak oxygen uptake in human heart failure. European journal of preventive cardiology\| PubMed ID: 30247068	2018
Pulmonary function assessment post-left ventricular assist device implantation. ESC heart failure\| PubMed ID: 30311748	2018

Chul-ho Kim

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