Abstract
Purpose of Review
Cardiopulmonary exercise testing (CPET) informs the preoperative evaluation process by providing individualised risk profiles; guiding shared decision-making, comorbidity optimisation and preoperative exercise training; and informing perioperative patient management. This review summarises evidence on the role of CPET in preoperative evaluation and explores the role of novel and emerging CPET variables and alternative testing protocols that may improve the precision of preoperative evaluation in the future.
Recent Findings
CPET provides a wealth of physiological data, and to date, much of this is underutilised clinically. For example, impaired chronotropic responses during and after CPET are simple to measure and in recent studies are predictive of both cardiac and noncardiac morbidity following surgery but are rarely reported. Exercise interventions are increasingly being used preoperatively, and endurance time derived from a high intensity constant work rate test should be considered as the most sensitive method of evaluating the response to training. Further research is required to identify the clinically meaningful difference in endurance time. Measuring efficiency may have utility, but this requires exploration in prospective studies.
Summary
Further work is needed to define contemporaneous risk thresholds, to explore the role of other CPET variables in risk prediction, to better characterise CPET’s role in combination with other tools in multifactorial risk stratification and increasingly to evaluate CPET’s utility for preoperative exercise prescription in prehabilitation.
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Introduction
Cardiopulmonary exercise testing (CPET) provides a non-invasive, dynamic and integrative assessment of the cardiovascular, pulmonary and musculoskeletal systems’ response to physiological stress and provides an objective evaluation of cardiorespiratory fitness or functional capacity. CPET combines measurement of breath-by-breath expired gas with the simultaneous monitoring of heart rate (HR), blood pressure, oxygen saturations and electrocardiography (ECG). Over the last decade, CPET has increasingly been used in preoperative evaluation, and in the UK, a recent survey reported that approximately 30,000 tests are performed annually in surgical patients [1•, 2••]. With an increasingly frail and comorbid surgical population who may have limited life expectancy even in the absence of their surgical disease, the risks and benefits of surgery may be difficult to evaluate. CPET as an objective measure of functional capacity has been used to predict perioperative risk [3], to contribute to shared decision-making and consent [2], to triage to perioperative critical care-enhanced environments [4, 5], to diagnose and evaluate the severity of comorbidities and increasingly to direct preoperative exercise training programmes as an element of prehabilitation [6•, 7].
Exercise Capacity, Ventilatory Equivalents and Surgical Outcome
The perioperative CPET literature focuses on incremental exercise testing to the limit of tolerance (symptom limited ramp or incremental exercise test) using cycle ergometry, and three main indices of cardiorespiratory fitness and cardiorespiratory function are reported in relation to surgical outcome. These are:
- 1.
Peak oxygen uptake (\( \dot{\mathrm{V}} \)O2 peak), defined as the highest \( \dot{\mathrm{V}} \)O2 attained on a rapid incremental test expressed in ml.kg−1.min−1 or ml.min−1 absolute.
- 2.
Anaerobic threshold (AT), a submaximal index of exercise capacity defined as the oxygen uptake (\( \dot{\mathrm{V}} \)O2) above which there is a metabolic transition to increased glycolysis and lactate begins to rise with an associated metabolic acidosis, expressed in ml.kg−1.min−1 or ml.min−1 absolute.
- 3.
The ventilatory equivalent for carbon dioxide (\( \dot{\mathrm{V}} \)E/\( \dot{\mathrm{V}} \)CO2) defined as the ratio of minute ventilation to carbon dioxide production usually reported at the AT.
Impairments in \( \dot{\mathrm{V}} \)O2 peak [8, 9], AT [10, 11] and \( \dot{\mathrm{V}} \)E/\( \dot{\mathrm{V}} \)CO2 [12,13,14] (and thus reduced physiological reserve) are associated with an increased risk of postoperative morbidity and mortality following major noncardiac surgery [3, 15]. \( \dot{\mathrm{V}} \)O2 peak is interpreted as the maximal exercise capacity limited by oxygen delivery to the tissues. In reality it reflects the patient’s “best effort” on that day but is not necessarily a physiologically limited endpoint as it may be affected by the patient’s volition. \( \dot{\mathrm{V}} \)O2 peak can only be assumed to reflect the patient’s physiological limits if \( \dot{\mathrm{V}} \)O2 plateaus as the limit of tolerance is approached (defined as \( \dot{\mathrm{V}} \)O2 max). Surrogate endpoints that are used in healthy subjects to determine whether the effort was maximal in the absence of a plateau in \( \dot{\mathrm{V}} \)O2 are problematic in a clinical population where drugs which affect the chronotropic response are common (e.g. beta blockade). Likewise using the generation of a significant metabolic acidosis (Respiratory exchange ratio (RER) > 1.15 at peak exercise) as an index of maximal effort may be invalid in a patient with limiting respiratory disease. Thus \( \dot{\mathrm{V}} \)O2 peak, although easy to determine, may be affected by factors other than functional capacity or fitness. Despite these limitations however, it has been consistently linked to clinical outcomes after surgery and in cardiac disease [15]. The anaerobic threshold is an index of sustainable exercise capacity, marking a metabolic transition during incremental exercise from predominantly oxidative phosphorylation to an increasing proportion of glycolysis which is ultimately unsustainable. The AT cannot be influenced by volition, but identification is more complex, and consequently inter-rater reliability is less than for \( \dot{\mathrm{V}}{\mathrm{O}}_2 \) peak [16]. Furthermore, AT cannot be reliably identified in approximately 5% of cases (particularly in the presence of chronic lung disease) [17]. The ventilatory equivalent for carbon dioxide (\( \dot{\mathrm{V}} \)E/\( \dot{\mathrm{V}}{\mathrm{CO}}_2 \)) is an index of gas exchange efficiency. In the perioperative literature, predominantly the \( \dot{\mathrm{V}} \)E/\( \dot{\mathrm{V}} \)CO2 at the AT is reported. However in the absence of a discernible AT, the minimum recorded value or the gradient of the \( \dot{\mathrm{V}} \)E/\( \dot{\mathrm{V}} \)CO2 slope is approximately equivalent and can be used instead [17]. Thus an index of \( \dot{\mathrm{V}} \)E/\( \dot{\mathrm{V}} \)CO2 should be obtained in all incremental exercise tests. \( \dot{\mathrm{V}} \)E/\( \dot{\mathrm{V}} \)CO2 is a measure of gas exchange efficiency rather than exercise capacity per se and reflects both ventilation-perfusion matching and physiological dead space. It is elevated and has prognostic value in heart failure (HF) and chronic obstructive pulmonary disease (COPD), pulmonary hypertension and other respiratory disease. In the perioperative setting, it has been reported as predicting postoperative complications (particularly cardiopulmonary complications) [12, 13] and long-term mortality [14].
CPET as a part of preoperative evaluation in non-cardiothoracic surgery was first proposed in the early 1990s by Older and colleagues [18••] who observed an association between reduced AT and worsened postoperative outcomes following major intra-cavity surgery. Specifically an AT <11 ml.kg−1.min−1 was associated with a higher incidence of postoperative mortality. Prior to this, \( \dot{\mathrm{V}} \)O2 peak had been used in thoracic surgery to identify high-risk patients for lung resection surgery [8]. Subsequently, observational studies have supported the use of CPET for preoperative risk evaluation across a variety of surgical specialties including colorectal [19, 20], intra-abdominal [12, 18], vascular [13, 21], urological [22, 23], bariatric [24], thoracic [8, 9], oesophageal [25, 26] and hepatobiliary [10, 27] (including liver transplant surgery [10, 28]). Table 1 summarises the major cohort studies and risk thresholds, and the reader is referred to a number of recent review articles in this area for an exhaustive list of relevant studies [2, 29•]. In the vast majority of cohorts, exercise capacity expressed as either \( \dot{\mathrm{V}} \)O2 peak or AT is associated with postoperative morbidity and mortality. Of note unlike many other risk prediction tools for noncardiac surgery which focus on cardiac risk specifically, CPET predicts all-cause morbidity including respiratory complications and sepsis which in most case series are more prevalent than cardiac complications [11, 30].
More recent studies have focused on the use of \( \dot{\mathrm{V}} \)E/\( \dot{\mathrm{V}} \)CO2 to predict complications after lung resection surgery [31], where it may have greater predictive precision than \( \dot{\mathrm{V}} \)O2 peak and in the prediction of long-term mortality postoperatively [14]. The CPET literature is, however, limited by the fact that the majority of reports are retrospective and single centre, although recently multicentre cohorts have been reported [32,33,34, 35••]. The predictive precision of CPET varies in reported case cohorts, and it is notable that it tends to be greater in blinded cohorts than unblinded cohorts which may reflect confounding by indication [2]. The thresholds for identifying a high-risk group also differ in different surgical cohorts and surgical procedures which probably reflect variation in the physiological stress induced by the procedure (e.g. open oesophagectomy vs laparoscopic colorectal surgery). Overall there has been a tendency for the exercise capacity thresholds at which risk increases to decrease over time [11], (e.g. the AT reported risk thresholds falling from 11 to 9–10 ml.kg−1.min−1 in some types of surgery) possibly because of evolution in surgical techniques (e.g. laparoscopic surgery) and improvements in perioperative care. There is a need for ongoing multicentre, prospective cohort data to define contemporaneous risk thresholds. Of note, the recent large prospective and blinded Measurement of Exercise Tolerance before Surgery (METS) study compared the prognostic accuracy of a variety of methods of assessing preoperative functional capacity (including subjective clinical assessment). CPET was found to be the only test predictive of in-hospital moderate or severe complications [35]. The Duke Activity Status Index (DASI) questionnaire (a physical activity questionnaire designed for cardiac patients) and beta natriuretic protein (BNP) were better at predicting myocardial infarction (MI) and myocardial injury and mortality at 1 year. This cohort study aimed to evaluate a high-risk surgical population but the overall mortality was only 0.4% (a low risk population). This may reflect a “healthy bias” effect which is common in exercise studies generally, whereby the study participants are fitter than the population mean. The average \( \dot{\mathrm{V}} \)O2 peak at 19.2 ml.kg−1.min−1 in the study is higher than in unselected retrospective cohort studies. The design of future studies should take this effect into account when predicting event rates to ensure the study is adequately powered [36]. Of note new arrhythmias or myocardial ischaemia were detected in 27 cases during CPET in the METS study leading to unblinding of clinicians and a significant change in management for the patients. These changes included delaying the surgical procedure for investigation such as angiography, referring to other medical specialists for optimisation and changing the previously planned surgical procedure. This illustrates CPET’s potential role in the detection and optimisation of both known and previously undiagnosed comorbidity even in a low risk population.
Novel and Emerging CPET Variables for Preoperative Evaluation
Oxygen Pulse
There is physiological rationale and emerging evidence to support the utility of several other CPET variables in perioperative risk prediction. The oxygen pulse provides an indirect assessment of dynamic stroke volume and oxygen extraction under stress. Oxygen pulse is defined as the ratio of oxygen consumption to HR (\( \dot{\mathrm{V}} \)O2/HR) and is the volume of oxygen ejected with each cardiac contraction. As can be derived from the Fick equation, [(\( \dot{\mathrm{V}} \)O2 =\( \dot{\mathrm{Q}} \) (SV x HR) x (CaO2 – CvO2)], where \( \dot{\mathrm{Q}} \) is cardiac output, SV is stroke volume and CaO2 – CvO2 is the difference between arterial and venous oxygen content (O2 extraction), it equates to the product of stroke volume and the arterial oxygen extraction. However, a note of caution should be raised. Despite the \( \dot{\mathrm{V}} \)O2/HR being widely reported and interpreted clinically as a surrogate marker of exercise SV, whether this relationship holds true during incremental ramp exercise remains to be fully elucidated and thus \( \dot{\mathrm{V}} \)O2/HR should not be interpreted as a definitive indicator of cardiac disease in isolation. The profile of the oxygen pulse is abnormal (flattened) in the presence of exercise induced ischaemia [37], significant aortic stenosis or a dynamic impairment in ventricular function [38]. The peak oxygen pulse is reduced in cardiac failure but also impacted by other factors independently of changes in SV such as general deconditioning/training status, medications (e.g. beta blockers), pulmonary arterial hypertension, anaemia and in lung disease (particularly in cases where exercise induced desaturation occurs). Recent work found an association between a reduced oxygen pulse (< 90% of population-predicted normal values) and lower preoperative arterial pulse pressure (≤ 53 mmHg), the latter being associated with excess morbidity in a cohort of high-risk surgical patients [39]. The prognostic implication of peak oxygen pulse requires further evaluation in multifactorial models along with other possible indicators of increased cardiac risk such as increased preoperative BNP.
Oxygen Uptake Efficiency Slope
The oxygen uptake efficiency slope (OUES) was first proposed as a potentially useful measure of cardiorespiratory reserve by Baba and colleagues [40•]. OUES is derived from the relationship between \( \dot{\mathrm{V}} \)O2 (ml.min−1) and logarithmically transformed minute ventilation (\( \dot{\mathrm{V}} \)E, L.min−1) during incremental exercise and represents the effectiveness of \( \dot{\mathrm{V}} \)O2 that is related to both metabolic acidosis and pulmonary dead space. In common with the measurement of AT, one benefit of the OUES is that it can be obtained from a submaximal test, and so it is not as dependent on patient volition as a \( \dot{\mathrm{V}} \)O2 measurement. It may also be useful in patients who are unable to perform a maximal exercise test as may be the case in morbid obesity [41] and those with poor mobility or joint problems. It is therefore possible to obtain useful data for the vast majority of patients. OUES shows excellent test retest reliability [42, 43] and is positively correlated with \( \dot{\mathrm{V}} \)O2 peak [44,45,46] and AT (r = 0.80, p < 0.001) [45]. In addition, OUES is a sensitive and specific predictor of clinically utilised AT risk thresholds (≤ 11 ml.kg−1.min−1), with an area under the curve (95% CI) of 0.876 (0.780–0.972, p < 0.001) [46]. This suggests that OUES may provide a valid measure of preoperative cardiorespiratory fitness and assist in discriminating those at higher risk of postoperative morbidity, particularly where an AT cannot be determined. In the preoperative setting, the OUES has been quantified in patients with lung cancer undergoing CPET prior to lung resection [45, 47], in elderly patients scheduled for major colorectal surgery [46] and in candidates for major intra-cavity surgery from mixed surgical specialties [48].
In 49 lung resection candidates, OUES was lower in those experiencing postoperative cardiopulmonary complications and showed a good ability to discriminate between those with and without postoperative complications [area under the receiver operating characteristic (AUROC) curve: 0.81] [47]. Furthermore, the OUES was associated with postoperative survival in 125 patients scheduled to undergo lung surgery (r = 0.69, p < 0.01) and correlated with \( \dot{\mathrm{V}} \)O2 peak (r = 0.69, p < 0.01) [45]. No sensitivity or specificity analysis or Kaplan-Meier survival estimates were reported in this study, however, which limits interpretation of the predictive precision of the OUES. Furthermore, not all studies have reported an association between OUES and outcomes, and in another cohort of 1725 patients undergoing major intra-cavity surgery, CPET-derived OUES was not predictive of 30-day, 1-year or 5-year mortality. Interestingly exercise capacity variables were also not predictive of mortality in this cohort [48]. Although encouraging, the data supporting the prognostic value of OUES is limited to date due to a lack of appropriately powered prospective studies and warrants further investigation. The OUES displays prognostic value in patients with HF [49,50,51] and coronary artery disease (CAD) [52, 53] and has been shown to be responsive to physical training in patients with CAD [54, 55].
Haemodynamic Responses Measured during CPET
Haemodynamic indices such as resting HR, chronotropic response during incremental exercise and HR recovery are simple and routine measures recorded during CPET that may provide a useful indicator of autonomic nervous system activity. Both an impaired HR response to exercise (chronotropic incompetence, (CI)) [56,57,58] and attenuated recovery of HR post exercise (labelled HR recovery (HRR)) [59,60,61] are associated with cardiac and all-cause mortality. In addition, an elevated resting HR has been shown to be associated with an increased risk of multiple cardiovascular outcomes including CAD, sudden cardiac death, HF, atrial fibrillation, stroke, cardiovascular disease, as well as total cancer and all-cause mortality in a dose-response manner (apart from atrial fibrillation which showed a J-shaped relationship) [62].
These haemodynamic indices have also been investigated in the perioperative setting. In 15,000 patients undergoing noncardiac surgery, raised preoperative HR > 96 beats.min−1 was associated with postoperative myocardial injury after noncardiac surgery (MINS), MI and mortality within 30 days of surgery [63]. An elevated resting HR (> 87 beats.min−1) was also independently associated with impaired CPET-derived \( \dot{\mathrm{V}} \)O2 peak (≤ 14 ml.kg−1.min−1) and a delayed HRR (≤ 6 beats.min−1). In addition, a CPET-derived exaggerated HR (EHRR) increase (underpinned by raised sympathetic autonomic activity) during unloaded cycling (defined as ≥ 12 beats.min−1) was associated with an increased risk of exercise ischaemia on ECG (defined as > 1 mm ST depression in lead II) and inferior cardiorespiratory fitness (AT 10.6 versus 11.1 ml.kg−1.min−1, p = 0.008; \( \dot{\mathrm{V}} \)O2 peak 74% versus 78% of predicted, p = 0.05) and reduced cardiac performance (quantified by the oxygen pulse, being a surrogate marker of left ventricular stroke volume) 85% versus 95% predicted, p = 0.0001. This study also demonstrated a prolonged hospital stay in patients exhibiting an EHRR [64].
Impaired HRR after exercise is common with 40% occurrence being reported in the METS study [65]. Cardiac vagal dysfunction defined as a delayed HRR (where impaired HRR is defined as ≤ 12 beats.min−1 measured 1-min post cessation of preoperative CPET) is also associated with an increased risk of perioperative cardiac injury (defined by serum troponin concentration within 72 h of undergoing noncardiac surgery) [66]. In addition, cardiorespiratory fitness is reduced in patients exhibiting an impaired HRR (\( \dot{\mathrm{V}} \)O2 peak standard deviation [SD] 17.1 (5.6) versus 20.8 (6.5) ml.kg−1.min−1; AT 11.6 (3.4) versus 13.4 (4.4) ml.kg−1.min−1). Taken together these findings highlight that both resting and recovery haemodynamic responses that can be routinely obtained during CPET, but are rarely utilised clinically, can be used to identify a group of patients with impaired cardiopulmonary performance consistent with markers of subclinical cardiac failure prior to surgery and at increased risk of deleterious perioperative cardiac outcomes. This may allow more tailored perioperative management strategies to alleviate these risks as well as better inform the preoperative evaluation process in higher risk surgical candidates.
A recent planned secondary analysis of two prospective, multicentre, blinded observational studies (the METS and POM-HR study) also found that all-cause morbidity (defined using the Postoperative Morbidity Survey and Clavien-Dindo grading of postoperative complications) within 5 days of noncardiac surgery was more common in patients with impaired cardiac vagal function (HRR ≤ 12 beats.min−1 after preoperative CPET) than those with a normal HRR (OR: 1.29, 95% CI 1.06–1.58; p = 0.001) [67•]. Importantly, an impaired HRR was associated with specific domains of in-hospital morbidity including more frequent episodes of cardiovascular (OR: 1.39, 95% CI 1.15–1.69; p < 0.001), pulmonary (OR: 1.31, 95% CI 1.05–1.62; p = 0.02), infection (OR: 1.38, 95% CI 1.10–2.70; p = 0.006), renal (OR: 1.91, 95% CI 1.30–2.79; p = 0.02), neurological (OR: 1.73, 95% CI 1.11–2.70; p = 0.02) and pain morbidities (OR: 1.38, 95% CI 1.14–1.68; p = 0.001). This has important implications for patients in the immediate postoperative period but may also have longer survival consequences, given the previously reported observation that postoperative morbidity of any aetiology increases risk of death for up to 3 years after surgical intervention [68]. This data may therefore have utility in better informing collaborative/shared decision-making around the short-term and longer-term risks of surgery and thereby aid the preoperative evaluation and decision-making processes.
The chronotropic response to exercise can be defined as the ability to increase HR appropriately to match cardiac output to metabolic demands [69]. When the ability to augment HR is impaired, this is termed chronotropic incompetence (CI) [70]. CI during exercise is a predictor of major adverse cardiovascular events in patients with cardiovascular diseases [71,72,73] but may also be a phenotype that is associated with cardiovascular risk and impaired gas exchange (\( \dot{\mathrm{V}} \)O2 peak) in the general population [74]. Variation in cut-off values and methods used to define CI underpin the disparity in reported prevalence rates, but figures of between 25% and 75% have been reported in HF [75,76,77], patients with known or suspected CAD [78] and prior to high-risk noncardiac surgery [65]. Although related to preoperative biomarker indicators of subclinical HF (N-terminal pro-B-type natriuretic peptide [NT pro-BNP] > 300 pg ml−1) and more common in patients with impaired CPET-derived cardiorespiratory fitness \( \Big(\dot{\mathrm{V}} \)O2 peak ≤ 14 ml.kg−1 min−1) and gas exchange inefficiency (\( \dot{\mathrm{V}} \)E/\( \dot{\mathrm{V}} \)CO2 slope ≥ 34), preoperative chronotropic incompetence (defined as chronotropic index (CI) < 0.6, a surrogate marker of sympathetic dysfunction) was not associated with postoperative myocardial injury on day 3 or 1-year mortality. Whether this is the case for other markers of postoperative morbidity remains to be elucidated. The authors suggest that these findings add support to the notion that cardiac vagal dysfunction is the most important autonomic determinant of myocardial injury and perioperative outcomes [79, 80]. Such impairments can be quantified preoperatively through the use of CPET.
Alternative Testing Protocols: High Intensity Constant Work Rate Tests and Metabolic Efficiency
The traditional CPET protocol is the incremental-ramp exercise test whereby work rate is increased linearly, or quasi-linearly, until the patient reaches their limit of tolerance, ideally performing 8–12 min of ramped exercise [81]. Constant work rate tests may also have applications in the perioperative setting.
High Intensity Constant Work Rate Tests to Evaluate Exercise Interventions
Exercise programmes either as stand-alone interventions or as part of multimodal prehabilitation are increasingly used in the preoperative period. A test that is sensitive to changes in fitness is required to evaluate the efficacy of such interventions. A high intensity constant work rate test at 75%–80% of the maximal work rate achieved on an incremental exercise test is more sensitive to changes in fitness than \( \dot{\mathrm{V}} \)O2 peak and AT or the 6-min walk test [82]. The tolerance time or endurance time (tLIM) is the duration from the imposition of the work rate to the point of task failure expressed in seconds or minutes. The clinically meaningful difference for a prehabilitation exercise intervention is unknown, although it is of note that in the one prospective randomised controlled trial of prehabilitation to demonstrate a 50% reduction in postoperative complications, there was a 135% increase in the tLIM in the intervention group [6]. Interestingly, despite the 135% increase in tLIM, the 6-min walk test distance did not change, suggesting that it is not sensitive to clinically meaningful changes in fitness in this context.
Low Intensity Constant Work Rate Tests to Evaluate Metabolic Efficiency
CPET measures the ability of the integrated respiratory-circulatory-metabolic unit to meet the increasing O2 demands of exercise. Surgery, like exercise, places significant metabolic stress on the body and requires effective O2 delivery to the tissues and efficient O2 utilisation to aid recovery in the pro-inflammatory and hypermetabolic postoperative period [83]. Metabolic efficiency reflects the ratio of work generated to the total metabolic energy cost [84] and provides an index of how effectively an individual can convert chemical energy into mechanical power. The oxygen cost of any given work is reduced in an individual with enhanced metabolic efficiency. This may potentially translate into a greater physiological reserve for sustainable aerobic oxidative phosphorylation before supplemental anaerobic energy pathways are required to contribute to overall energy production.
The most commonly used measure of metabolic efficiency is gross efficiency, the product of (work accomplished/energy expended) × 100. Energy expenditure can be calculated from the steady-state \( \dot{\mathrm{V}} \)O2 and the respiratory exchange ratio (RER) measured during a sub-anaerobic threshold constant work rate test [83] and from this metabolic efficiency can be determined. Pedalling cadence must be standardised as it influences efficiency, and a test duration of at least 6 min is required to ensure that steady-state \( \dot{\mathrm{V}} \)O2 and \( \dot{\mathrm{V}} \)CO2 are achieved. Skeletal muscle efficiency reflects mitochondrial function and efficiency [85, 86]. Mitochondrial dysfunction and mitochondrial coupling inefficiency have been directly implicated in the reduced exercise efficiency observed with age [87, 88], greater fatigability in older subjects [89], sarcopenia and cancer cachexia, type 2 diabetes [85], impairments in aerobic capacity [90],all conditions commonly observed in a surgical population. Skeletal muscle efficiency has not been reported in surgical patients to date; however, it provides a potential opportunity for targeted intervention to improve exercise performance given that it is at least in part determined by mitochondrial function. Exercise training induces changes in mitochondrial volume, density and enzyme activity [91, 92,93, 94], and there is a suggestion that mitochondrial coupling efficiency may be improved with dietary nitrate supplementation although this is controversial [95,96,97].
Conclusion
In summary, CPET informs the preoperative evaluation process by providing individualised risk profiles; guiding shared decision-making, comorbidity optimisation and preoperative exercise training; and informing perioperative patient management. \( \dot{\mathrm{V}} \)O2 peak, AT and \( \dot{\mathrm{V}} \)E/\( \dot{\mathrm{V}} \)CO2 at AT have been the CPET variables routinely used for risk prediction, and the literature supports an association between exercise capacity and surgical outcome. Future risk prediction studies should prospectively evaluate CPET variables in combination with other known predictors of outcome such as BNP, renal function and albumin in prospective cohorts. CPET can both quantify exercise capacity and identify the cause of exercise intolerance, which provides an opportunity for targeted optimisation of known and newly identified comorbidities in the preoperative period (e.g. rate control in atrial fibrillation). Although CPET provides a wealth of physiological data, to date much of this is underutilised clinically. For example, impaired chronotropic responses during and after CPET are simple to measure and in recent studies are predictive of both cardiac and noncardiac morbidity following surgery but are rarely reported. Exercise interventions are increasingly being used preoperatively, and tLIM derived from a high intensity constant work rate test should be considered as the most sensitive method of evaluating the response to training. Further research is required to identify the clinically meaningful difference in tLIM. Measuring efficiency may have utility, but this requires exploration in prospective studies.
References
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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James Otto performed routine CPET as part of a patient's standard clinical care whose data was included in the POM-HR study. James Otto also performed CPET on patients at University College London Hospital who were enrolled into the METS study.
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Otto, J.M., Levett, D.Z.H. & Grocott, M.P.W. Cardiopulmonary Exercise Testing for Preoperative Evaluation: What Does the Future Hold?. Curr Anesthesiol Rep 10, 1–11 (2020). https://doi.org/10.1007/s40140-020-00373-x
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DOI: https://doi.org/10.1007/s40140-020-00373-x