Shifting Paradigms: Exercise Testing as a Metric of Long-Term Success in Surgery for Ebstein Anomaly.

Effects of left ventricular assist device on cardiopulmonary exercise performance.

In patients with systolic heart failure, the ability of cardiopulmonary exercise testing (CPX) variables to reflect pathophysiology is well established. The relationship between CPX and pathophysiology has, however, not been thoroughly investigated in patients with nonobstructive hypertrophic cardiomyopathy (NHCM). The objective of this study was to assess the ability of CPX variables to reflect resting hemodynamics in patients with nonobstructive hypertrophic cardiomyopathy NHCM. We performed CPX and right heart catheterization on 83 subjects with NHCM (51 male/32 female, mean age = 38 +/- 10 yr, NYHA I-III mean = 1.7). Peak oxygen consumption ( O2) and minute ventilation/carbon dioxide ratio (V E/VCO2) at peak exercise were compared to resting hemodynamics including pulmonary artery systolic, diastolic and mean pressures (PASP, PADP and MPAP), and pulmonary capillary wedge pressure (PCWP). Elevations in PCWP (> or = 15 mm Hg), PASP (> or =30 and > or = 40 mm Hg), PADP (> 15 mm Hg) and MPAP (> or = 20 mm Hg) were detected in 22, 33, 10, and 23% of subjects, respectively. Peak V E/VCO2 (positive correlation) and peak VO2 (negative correlation) correlated modestly with all pressure measurements (r = 0.33-0.51, P < 0.01 for all measurements). By receiver operating curve analysis, a V E/VCO2 >35.5 exhibited the best diagnostic accuracy with a curve areas of 0.81 for PAP > or = 30 mm Hg (sensitivity/specificity = 86%/67%), 0.87 for PAP > or = 40 mm Hg (77%/100%), 0.86 for MPAP > 20 mm Hg (83%/79%), and 0.84 for PCWP > or = 15 mm Hg (80%/76%). CPX can accurately identify abnormal resting hemodynamics in patients with NHCM. Further testing of this modality in other forms of diastolic dysfunction may be warranted.

The influence of aerobic fitness status on ventilatory efficiency in patients with coronary artery disease

Background: In cardiopulmonary exercise testing (CPET), oxygen uptake (V’O2) is calculated using the product of minute ventilation (V’E) and the difference between inspiratory and expiratory O2 concentrations (ΔFO2). However, little is known about the response of ΔFO2 to pulmonary rehabilitation (PR). The aim of the present study was (1) to investigate whether PR increases peak V’O2, based on whether ΔFO2 or V’E at peak exercise increase after PR, and (2) to investigate whether an improvement in ΔFO2 correlates with an improvement in ventilatory efficiency. Methods: A total of 38 patients with severe and very severe COPD, whose PR responses were evaluated by CPET, were retrospectively analyzed. Results: After PR, peak V’O2 was increased in 14 patients. The difference in ΔFO2 at peak exercise following PR correlated with the difference in peak V’O2 (r = 0.4884, p = 0.0019), the difference in V’E/V’CO2-nadir (r = −0.7057, p < 0.0001), and the difference in V’E–V’CO2 slope (r = −0.4578, p = 0.0039), but it did not correlate with the difference in peak V’E. Conclusions: The increased O2 extraction following PR correlated with improved exercise tolerance and ventilatory efficiency. In advanced COPD patients, a new strategy for improving O2 extraction ability might be effective in those in whom ventilatory ability can be only minimally increased.

This pilot study aimed to evaluate if peak VO2 and ventilatory efficiency in combination would improve preoperative risk stratification beyond only relying on peak VO2 . This was a single-center retrospective cohort study including all patients who underwent cardiopulmonary exercise testing (CPET) as part of preoperative risk evaluation before major upper abdominal surgery during years 2008-2021. The primary outcome was any major cardiopulmonary complication during hospitalization. Forty-nine patients had a preoperative CPET before decision to pursue to surgery (cancer in esophagus [n = 18], stomach [6], pancreas [16], or liver [9]). Twenty-five were selected for operation. Patients who suffered any major cardiopulmonary complication had lower ventilatory efficiency (i.e., higher VE/VCO2 slope, 37.3 vs. 29.7, p = 0.031) compared to those without complications. In patients with a low aerobic capacity (i.e., peak VO2 < 20 mL/kg/min) and a VE/VCO2 slope ≥ 39, 80% developed a major cardiopulmonary complication. In this pilot study of patients with preoperative CPET before major upper abdominal surgery, patients who experienced a major cardiopulmonary complication had significantly lower ventilatory efficiency compared to those who did not. A low aerobic capacity in combination with low ventilatory efficiency was associated with a very high risk (80%) of having a major cardiopulmonary complication.

Association of preoperative spirometry with cardiopulmonary fitness and postoperative outcomes in surgical patients: A multicentre prospective cohort study

Cardiopulmonary exercise testing (CPET) is a low risk, non-invasive investigation that allows accurate, dynamic assessment of cardiac and pulmonary performance during exercise. Pulmonary, cardiovascular, endocrine, neuropsychiatric, and skeletal muscle systems are all required to be functioning in a coordinated fashion in a stressed patient. Most pre-operative investigations assess one system when it is at rest (e.g. echocardiogram) [1]. By measuring dynamic gas exchange during graded exercise, CPET can identify potential deficiencies within these systems. These are often not adequately reflected in the indices of resting lung and cardiac function [2]. Traditional methods that assess maximum exercise capacity such as exercise time or maximum oxygen uptake are influenced by the patient’s motivation when performing a maximum exercise test or by non-cardiorespiratory symptoms [3]. These can lead to premature termination of the test. When performing graded exercise, the anaerobic threshold (AT) is an estimate of the onset of metabolic acidosis due to an oxygen supply: demand imbalance. Numerically, it is presented as the rate of oxygen consumption (VO2) at which acid starts to accumulate. This is seldom invasively measured but is usually taken as the time at which the patient starts to exhale increasing amounts of carbon dioxide (VeCO2) to compensate for a build up of lactic acid and resulting metabolic acidosis. It should always be expressed as a percentage of the maximum oxygen consumption (VO2 max) [4]. The AT occurs at about 50–60% of VO2 max in normal individuals but has a range of 30–80%. It is a well defined physiological point that can be measured in most patients. A low pre-operative AT has been shown to correlate with postoperative mortality [2]. Although there is no clear agreement on the best single predictor of outcome, thresholds of peak oxygen consumption (VO2 peak) of 15 ml O2.kg−1.min−1 and an oxygen consumption at the anaerobic threshold (AT) of 11 ml O2.kg−1.min−1 have been shown to discriminate between higher and lower risk patients in non-cardiac surgery [2]. This information has been used to optimise the use of critical care beds or to guide the choice of therapy. However, if the information is going to be used to recommend against radical but potentially life saving treatments because of the perceived risk, then we have got to be very confident in the accuracy of these data. Several factors could introduce error in AT measurement during the CPET. These include genuine alterations in level of fitness, the reliability of the CPET equipment and inter and intra-observer variations in interpretation of CPET results. Variation in protocols and changes in performance caused by a learning effect with repeated testing can also affect results. A learning effect is defined as an increased skill or improved performance caused by previous exposure to the exercise [5]. This is well documented with treadmill testing, although there is little evidence relating to cycle-based CPET in clinical populations [6]. The linking of VO2 max and AT raises the first problem with its use for preoperative risk assessment [7]. VO2 max is related to age and many patients over 80 years will have a predicted VO2 max of 20 ml.kg−1.min−1 or less. It is easy to see that they may have an AT of < 11 ml.kg−1.min−1 and still be ‘normal’. Similarly an AT of 11 ml.kg−1.min−1 in a 20 year-old male would be far more significant than the same result in an 80 year-old. Both of these numbers cannot carry the same degree of risk. Patient medication and specifically beta blockers often affect the results of a CPET. Many patients with impaired left ventricular function are heart rate dependent to increase oxygen delivery. This poses a difficult question for patients who have a low AT who are on beta blockers. Ischaemia may not be obvious during the test because of the blunted heart rate response to exercise. However, is it correct to continue beta blockers if under stress they are unable to adequately increase oxygen delivery? Looking at both the oxygen pulse and the continuous ECG may help to answer this question. The oxygen pulse is a non-invasive estimate of the stroke volume. It is a ratio of the VO2 to heart rate (HR) and is a reflection of the amount of oxygen extracted per heart beat. If the VO2 is largely dependent on cardiac output then if the heart rate is fixed but the VO2 continues to rise, then this must be mostly due to an increase in stroke volume [8]. Conversely if the HR is fixed and the VO2 remains low during exercise then the heart is not able to increase stroke volume and is rate dependent to meet any increase in oxygen demand. Part of the CPET test is a continuous12-lead ECG with real time ST segment analysis. In theory, if ischaemia is detected after the AT, then this is less concerning than if it occurs before the AT. This is especially important if the AT is low. Improving the ischaemia may improve the cardiac function and in so doing the AT. In patients on beta blockers with a low AT, CPET allows a safe assessment of their cardiac response during stress when beta blockers are stopped [8]. If the AT improves and little or no ischaemia is found, then this would seem a safer way forward. On the other hand if ischaemia is detected and the AT remains low, either the stress of the operation and recovery need to be modified or coronary perfusion will have to be improved. No studies are available to support the use of pre-operative CPET testing as a guide to selecting patients who would benefit from coronary revascularisation. However, if we believe that a low AT is a strong predictor of postoperative outcome and coronary ischaemia is the primary limiting factor to improving oxygen delivery in the patient, then intervention of some form seems logical. In practice some of these patients will have signs and symptoms that warrant intervention in their own right. Considering that at least 24 variables are measured during a CPET, it would seem unwise to place too much emphasis on only one of these variables. It is analogous to only assessing the ejection fraction on an echocardiogram and then trying to make a detailed assessment of cardiac function. The AT needs to be reported in the context of the other results so that a more accurate assessment can be made of not only prognosis but possible therapeutic interventions. A standardised reporting format for pre-operative patients would help to reduce error. We feel that at the very minimum the report should comment on: The patient’s cooperation and effort. The AT (absolute number and as a percentage of VO2max). Peak and predicted maximum VO2. Cardiac ischaemia; if it was detected, how it was measured and when it occurred. A summary of what the team feel the cardiorespiratory risk for the patient is and if they feel any intervention or change in medication would help. At present, no national standard exists for a pre-operative CPET test. Failure to contextualise a patient’s report or selective reporting of certain variables will dangerously bias the test result. If these tests are to be widely used then it is important that not only the clinicians doing the test but also the clinicians receiving the report have a detailed understanding of the data and its limitations. If you do not know what an oxygen pulse is, you are unlikely to ask for it. However, if it is given and interpreted then this is far more helpful. We also feel that it is wrong to separate the pre-operative CPET from the clinicians performing the anaesthetic. Ideally, this service should be run by a combination of anaesthetists involved with high risk cases and cardiologists. This allows an individual plan to be made to meet specific needs. If we do not put the time in before the operation we will put the time in afterwards dealing with the complications. Tests that measure multiple variables and that depend on both patient and technician for accurate results, have a strong possibility of error. Poor patient effort or preparation, incorrect machine calibration and sampling error or gas leak can all introduce significant error. These all occur before we attempt to interpret the test. The interpretation also has considerable scope for inter-observer variability. No degree of accurate interpretation will make up for a poor test and vice-versa. Centres that perform a higher number of tests are likely to have more reproducible results, and our local experience is that at least 30 trial runs are required before attempting to introduce a clinical service and this is with experienced cardiac physiologists running the tests. No discussion would be complete without discussing the cost of this test. CPET machines cost about £20 000 and service contracts about £3 000 per year. In addition to this, cardiac physiologist and consultant time needs to be considered. If a unit performs three tests per week then each test will cost approximately £150. The fewer tests that a unit performs, the more expensive each test is. If a unit only does 25 tests a year then each test costs approximately £440. It would seem logical to have pre operative CPET at larger hospitals and for smaller hospitals to refer patients to these centres [9]. This seems the best way of producing cost effective, reproducible results. In summary, AT is a useful tool if it is accurate and presented with supporting data. It is an expensive but safe test. However there are with many areas for potential error. It is important that clinicians know the limitations and pitfalls of the AT if they are going to use it to inform clinical decisions.

Bowel cancer is the third most common cancer in the UK 1. Many of these patients will present for surgical treatment. The 2017 Annual Report of the National Bowel Cancer Audit describes data collected from over 30,000 patients diagnosed with bowel cancer between April 2015 and March 2016 in England and Wales 2. This national audit is commissioned by the Healthcare Quality Improvement Partnership (HQIP) and funded by NHS England and Wales. The audit is carried out by the Clinical Effectiveness Unit of the Royal College of Surgeons of England in partnership with the Association of Coloproctology of Great Britain and Ireland and NHS Digital. Sixty-three percent of these patients had undergone a major surgical resection 2. Centres in the UK are increasingly using pre-operative cardiopulmonary exercise testing (CPET) to risk stratify patients before major surgery. Within the same period, the National Bowel Cancer Audit conducted an organisational survey to determine the availability of on-site services including CPET for the objective evaluation of cardiopulmonary fitness and peri-operative risk at each NHS site 3. Cardiopulmonary exercise testing-derived metrics have the potential to predict morbidity and mortality after major abdominal surgery 4. It may also allow individualised risk assessment; inform shared decision making; identify requirement for postoperative critical care; and assesses and identifiy scope for optimisation of comorbidities and prehabilitation 5. The latest survey of CPET in the UK identified increasing utilisation with over 30,000 tests performed annually 6. National Bowel Cancer Audit data are publicly available online under the Open Government Licence via NHS Digital. We analysed the two latest datasets 2, 3 to determine if there were any differences between the clinical outcomes of patients who underwent surgery in centres with and without CPET. We compared 90-day mortality between hospitals that provided CPET and those that did not. Statistical analysis was conducted using MedCalc Statistical Software version 16.4.3 (MedCalc Software bvba, Ostend, Belgium; 2016). Patients were pooled for sites with and without CPET facilities. Relative risk (RR) was calculated for patients treated at sites with and without CPET. In centres that had onsite CPET facilities, 10,694/17,986 (59%) patients had major surgery. This was associated with an 18% reduction (RR 0.82, 95%CI 0.70–0.96, p = 0.0157) in 90-day mortality in centres that had CPET. There was no significant difference in disease severity (patients with distant metastases at the time of surgery) between centres with and without CPET (RR 0.99, 95%CI 0.90–1.09, p = 0.7947) or in the volume of patients in each centre on a curative major resection treatment pathway (RR 1.01, 95%CI 0.98–1.05, p = 0.53). Although there were more patients recorded as ASA status 1 in centres with CPET (RR 1.1, 95%CI 1.02–1.20, P = 0.0159), there was no difference in patients recorded as ASA physical status 2, 3 or 4/5 between centres with and without CPET (ASA 2 RR 0.97, 95%CI 0.95–1.0, p = 0.067; ASA 3 RR 0.96, 95%CI 0.91–1.01, p = 0.090; ASA 4/5 RR 0.87, 95%CI 0.73–1.04, p = 0.126). National Bowel Cancer Audit data are real-world data that are freely available for analysis and characterises routine clinical practice. Our analysis of this dataset suggests an association between better outcomes and centres that have CPET, which warrants further scrutiny. Exercise-oncology research is expanding and CPET-based prehabilitation has potential to improve outcomes after cancer surgery. Current data submission to the National Bowel cancer Audit includes patient-level CPET data and we would encourage the auditors to describe and refine further any correlation between CPET and outcomes after major colorectal cancer surgery in future reports.

ObjectiveWe aimed to evaluate whether or not using the slope of the increase in minute ventilation in relation to carbon dioxide (VE/VCo2-slope), with a cutoff value of 35, could improve risk stratification for major pulmonary complications or death following lobectomy in lung cancer patients at moderate risk (Vo2peak = 10-20 mL/kg/min). MethodsSingle center, retrospective analysis of 146 patients with lung cancer who underwent lobectomy and preoperative cardiopulmonary exercise testing in 2008-2020. The main outcome was any major pulmonary complication or death within 30 days of surgery. Patients were categorized based on their preoperative cardiopulmonary exercise testing as: low-risk group, peak oxygen uptake >20 mL/kg/min; low-moderate risk, peak oxygen uptake 10 to 20 mL/kg/min and VE/VCo2-slope <35; and moderate-high risk, peak oxygen uptake 10 to 20 mL/kg/min and VE/VCo2-slope ≥35. The frequency of complications between groups was compared using χ2 test. Logistic regression was used to calculate the odds ratio with 95% CI for the main outcome based on the cardiopulmonary exercise testing group. ResultsOverall, 25 patients (17%) experienced a major pulmonary complication or died (2 deaths). The frequency of complications differed between the cardiopulmonary exercise testing groups: 29%, 13%, and 8% in the moderate-high, low-moderate, and low-risk group, respectively (P = .023). Using the low-risk group as reference, the adjusted odds ratio for the low-moderate risk group was 3.44 (95% CI, 0.66-17.90), whereas the odds ratio for the moderate-high risk group was 8.87 (95% CI, 1.86-42.39). ConclusionsUsing the VE/VCo2-slope with a cutoff value of 35 improved risk stratification for major pulmonary complications following lobectomy in lung cancer patients with moderate risk based on a peak oxygen uptake of 10 to 20 mL/kg/min. This suggests that the VE/VCo2-slope can be used for preoperative risk evaluation in lung cancer lobectomy.

Exercise capacity should be determined in all patients undergoing lung resection for lung cancer surgery and cardiopulmonary exercise testing (CPET) remains the gold standard. The purpose of this study was to investigate associations between preoperative CPET and postoperative outcomes in patients undergoing lung resection surgery for lung cancer through a review of the existing literature. A search was conducted on PubMed, Scopus, Cochrane Library and CINAHL from inception until December 2022. Studies investigating associations between preoperative CPET and postoperative outcomes were included. Risk of bias was assessed using the QUIPS tool. A random effect model meta-analysis was performed. I2 > 40% indicated a high level of heterogeneity. Thirty-seven studies were included with 6450 patients. Twenty-eight studies had low risk of bias. [Formula: see text] peak is the oxygen consumption at peak exercise and serves as a marker of cardiopulmonary fitness. Higher estimates of [Formula: see text] peak, measured and as a percentagege of predicted, showed significant associations with a lower risk of mortality [MD: 3.66, 95% CI: 0.88; 6.43 and MD: 16.49, 95% CI: 6.92; 26.07] and fewer complications [MD: 2.06, 95% CI: 1.12; 3.00 and MD: 9.82, 95% CI: 5.88; 13.76]. Using a previously defined cutoff value of > 15mL/kg/min for [Formula: see text] peak, showed evidence of decreased odds of mortality [OR: 0.55, 95% CI: 0.28-0.81] and but not decreased odds of postoperative morbidity [OR: 0.82, 95% CI: 0.64-1.00]. There was no relationship between [Formula: see text] slope, which depicts ventilatory efficiency, with mortality [MD: -9.60, 95% CI: -27.74; 8.54] however, patients without postoperative complications had a lower preoperative [Formula: see text] [MD: -2.36, 95% CI: -3.01; -1.71]. Exercise load and anaerobic threshold did not correlate with morbidity or mortality. There was significant heterogeneity between studies. Estimates of cardiopulmonary fitness as evidenced by higher [Formula: see text] peak, measured and as a percentage of predicted, were associated with decreased morbidity and mortality. A cutoff value of [Formula: see text] peak > 15mL/kg/min was consistent with improved survival but not with fewer complications. Ventilatory efficiency was associated with decreased postoperative morbidity but not with improved survival. The heterogeneity in literature could be remedied with large scale, prospective, blinded, standardised research to improve preoperative risk stratification in patients with lung cancer scheduled for lung resection surgery.

Exercise Capacity and Ventilatory Efficiency in Patients With Pulmonary Embolism After Short Duration of Anticoagulation Therapy

To explore the exercise characteristics of patients with idiopathic pulmonary arterial hypertension (IPAH). From November 2010 to September 2012 , 76 consecutive IPAH patients and 24 healthy controls from Fuwai Cardiovascular Hospital were enrolled to undergo cardiopulmonary exercise testing. The exercise parameters were compared. Correlations among peak oxygen consumption, anaerobic threshold, peak oxygen pulse, New York Heart Association (NYHA) class, N-terminal pro-brain natriuretic peptide (NT-proBNP), 6-minute walking distance (6 MWD) and cardiac index are analyzed in IPAH. There were 21 males and 55 females in IPAH and 8 males and 16 females in controls. Their mean ages were (31.5 ± 10.6) and (35.5 ± 6.4) years respectively. Significant differences (P = 0.000) existed between two groups in peak oxygen consumption ((12.7 ± 3.3) vs (25.6 ± 5.8) ml·min(-1)·kg(-1)), anaerobic threshold ((9.8 ± 2.5) vs (16.7 ± 3.9) ml·min(-1)·kg(-1)), peak oxygen pulse ((5.3 ± 1.6) vs (9.9 ± 2.5) ml/bpm) and ventilator efficiency (slope of minute ventilation in relation to CO2 produced) ((42.6 ± 2.0) vs (25.5 ± 3.5)). In IPAH, peak oxygen consumption was significantly correlated with NYHA class (r = -0.509, P = 0.000), 6 MWD (r = 0.443, P = 0.002) and NT-proBNP levels (r = -0.423, P = 0.011). And anaerobic threshold was significantly correlated with NYHA class (r = -0.362, P = 0.002), 6MWD (r = 0.343, P = 0.004) and NT-proBNP levels (r = -0.275, P = 0.017). Peak oxygen pulse and ventilator efficiency were both correlated well with total pulmonary vascular resistance. Partial correlation analysis demonstrated that there were significant correlations among peak oxygen consumption, anaerobic threshold, NYHA class, NT-proBNP levels and 6MWD after adjusting for age, gender and weight. Peak oxygen consumption and anaerobic threshold decrease ventilator efficiency in IPAH patients. Cardiopulmonary exercise testing is an invasive tool of assessing safely the function of IPAH patients.

Tricuspid valve regurgitation is an inherent part of Ebstein's anomaly, yet whether the severity of the regurgitation further impairs exercise capacity and contributes to long-term morbidity on top of the lesion severity per se is unknown. To evaluate for this potential effect, we included 30 patients with Ebstein's anomaly who did not undergo any form of surgical interventions and had a cardiopulmonary exercise test and echocardiographic studies in this retrospective analysis. Echocardiographic studies and cardiopulmonary exercise tests were critically reviewed for lesion severity grade, tricuspid regurgitation degree, and exercise parameters. Cardiac-related hospitalisations were recorded from computerised medical records and during clinic visits. Fourteen patients (47%) had moderate and 8 (27%) had severe regurgitation. Patients with ≥ moderate regurgitation exhibited significantly lower exercise capacity (median % predicted maximal oxygen consumption, 62 versus 79%, p = 0.03) and venilatory efficiency at exercise. When stratifying exercise results by regurgitation degree, a stepwise decrease in oxygen consumption and ventilatory efficiency with increasing regurgitation severity was observed, regardless of the anatomic lesion severity. During a median follow-up of 4.6 years, &gt; moderate tricuspid regurgitation was associated with significantly lower cumulative probability of freedom from cardiac hospitalisations. We report that among non-operated Ebstein's anomaly patients, greater tricuspid regurgitation severity was associated with worse exercise capacity and with overall higher probability of cardiac-related hospitalisations independent from the underlying lesion severity.

Gender Differences in Leptin and Ventilatory Control in Patients with Heart Failure

Preoperative cardiopulmonary exercise testing (CPET) provides an objective assessment of functional capability. In other intra-abdominal surgical specialties, CPET outcomes are predictive of operative morbidity. However, in ovarian cancer surgery, its predictive value remains unknown. In this study, we evaluated the association between CPET performance and surgical morbidity in ovarian cancer patients. Secondly, we assessed the association between CPET performance and other surgical outcomes (i.e., hospital stay, readmission and residual disease). This was a retrospective cohort study of patients undergoing primary surgery for ovarian cancer between 2020 and 2023. CPET performance included peak oxygen uptake (VO2 max), ventilatory efficiency (VE/VO2) and anaerobic threshold. Outcomes were operative morbidity and included intra- and postoperative complications (Clavien-Dindo), hospital stay, readmission within 30 days and residual disease. A total of 142 patients were included. A lower VO2 peak and a higher VE/VCO2 were both associated with the occurrence of postoperative complications, and a poorer anaerobic threshold was associated with more transfusions. VE/VCO2 remained significantly associated after multivariate analysis (p = 0.035). None of the CPET outcomes were associated with length of stay, readmission or residual disease. In conclusion, VE/VCO2 was significantly associated with an increased risk of all-cause postoperative complications in ovarian cancer patients undergoing primary surgery.