We found a significant correlation between the tests. However, many patients with poor questionnaire scores or shuttle walks had satisfactory CPET results. Hence, the ability of either simple test to determine risk in a heterogeneous surgical population is poor. CPET provides an objective measurement of cardiopulmonary fitness; however, evidence for this information improving patient outcome is limited and requires further research.

Copyright form disclosures:Dr. Ackland received support for travel from Baxter healthcare (talk on beta-blockers 2010); has a patent through UCL Business (patent filed related to assessment of autonomic function -patent application 1414161.8); and received support for article research from the BRITISH HEART FOUNDATION, Wellcome Trust, and Research Councils UK (RCUK). His institution received grant support from the Academy Medical Sciences/Health Foundation Clinician Scientist Award (GLA) (GLA and AVG are supported by the British Heart Foundation Programme Grant. Part of this work was undertaken at UCLH/UCL who received a proportion of funding from the UK Department of Health's NIHR Biomedical Research Centres funding scheme). Dr. Toner's institution has a patent through UCL Business (patent filed related to assessment of autonomic function -patent application 1414161.8). Dr. Whittle has a patent through UCL Business (patent filed related to assessment of autonomic function -patent application 1414161.8). Dr. Machhada received support for article research from the Research Councils UK (RCUK). Dr. Dyson served as a board member for Magnus Oxygen, consulted for Magnus Oxygen; is employed by Magnus Life Science/University College London, has a patent related to Magnus Oxygen and not the current manuscript, and has shares in Magnus Oxygen. Dr. Struthers' institution received grant support from the BJA/RCOA Project grant. Dr. Minto's institution received grant support from BJA/RCOA Project grant. Dr. Shah received support for article research from the BRITISH HEART FOUNDATION. His institution received grant support from King's College London BHF Centre of Excellence. Dr. Gourine received support for article research from the NIH, Research Councils UK (RCUK), and the British Heart Foundation. His institution received grant support from the Wellcome Trust Senior Research Fellow and British Heart Foundation Programme Grant. The remaining authors have disclosed that they do not have any potential conflicts of interest. Objectives: Molecular mechanisms linking autonomic dysfunction with poorer clinical outcomes in critical illness remain unclear. We hypothesized that baroreflex dysfunction alone is sufficient to cause cardiac impairment through neurohormonal activation of (NADPH oxidase-dependent) oxidative stress resulting in increased expression of G-protein coupled receptor kinase (GRK)-2, a key negative regulator of cardiac function. Europe PMC Funders GroupDesign: Laboratory/clinical investigations.Setting: University laboratory/medical centers.Subjects: Adult rats; wild-type/NAPDH oxidase subunit-2 (NOX-2) deficient mice; elective surgical patients.Interventions: Cardiac performance was assessed by transthoracic echocardiography following experimental baroreflex dysfunction (BD, sino-aortic denervation) in rats and mice. Immunoblots assessed GPCR recycling proteins expression in rodent cardiomyocytes and patient mononuclear leukocytes. In surgical patients, heart rate recovery after cardio-pulmonary exercise...

Liver transplantation (LT) is a lifesaving treatment. Because of the shortage of donor organs, some patients will not survive long enough to receive a transplant. The identification of LT candidates at increased risk of short-term mortality without transplantation may affect listing decisions. Functional capacity, determined with cardiopulmonary exercise testing (CPET), is a measure of cardiorespiratory reserve and predicts perioperative outcomes. This study examined the association between functional capacity and short-term survival before LT and the potential for CPET to predict 90-day mortality without transplantation. A total of 176 patients who were assessed for nonacute LT underwent CPET. Ninety days after the assessment, 10 of the 164 patients who had not undergone transplantation were deceased (mortality rate 5 6.1%). According to a comparison of survivors and nonsurvivors, the Model for End-Stage Liver Disease score, UK Model for End-Stage Liver Disease (UKELD) score, age, anaerobic threshold, and peak oxygen uptake (VO 2 ) were significant univariate predictors of 90-day mortality without transplantation, but only the UKELD score and peak VO 2 retained significance in a multivariate analysis. The mean peak VO 2 was significantly lower for nonsurvivors versus survivors (15.2 6 3.3 versus 21.2 6 5.3 mL/minute/kg, P < 0.001). According to a receiver operating characteristic (ROC) curve analysis, peak VO 2 performed well as a diagnostic test (area under the ROC curve 5 0.84, 95% confidence interval 5 0.76-0.92, sensitivity 5 0.90, specificity 5 0.74, P < 0.001). The optimal cutoff value for predicting mortality was 17.6 mL/minute/kg. The positive predictive value of a peak VO 2 17.6 mL/minute/kg for 90-day mortality was greatest for patients with high UKELD scores: 38% of the patients with a UKELD score 57 and a peak VO 2 17.6 mL/minute/kg died, whereas only 6% of the patients with a UKELD score 57 and a peak VO 2 > 17.6 mL/minute/kg died (P 5 0.03). In conclusion, patients assessed for LT with an impaired functional capacity have poorer short-term survival; this is particularly true for individuals with worse liver disease severity.

Explanatory mechanisms for the association between poor exercise capacity and infections following surgery are underexplored. We hypothesized that aerobic fitness—assessed by cardiopulmonary exercise testing (CPET)—would be associated with circulating inflammatory markers, as quantified by the neutrophil-lymphocyte ratio (NLR) and monocyte subsets. The association between cardiopulmonary reserve and inflammation was tested by multivariable regression analysis with covariates including anaerobic threshold (AT) and malignancy. In a first cohort of 240 colorectal patients, AT was identified as the sole factor associated with higher NLR (P = 0.03) and absolute and relative lymphopenia (P = 0.01). Preoperative leukocyte subsets and monocyte CD14+ expression (downregulated by endotoxin and indicative of chronic inflammation) were also assessed in two further cohorts of age-matched elective gastrointestinal and orthopaedic surgical patients. Monocyte CD14+ expression was lower in gastrointestinal patients (n = 43) compared to age-matched orthopaedic patients (n = 31). The circulating CD14+CD16− monocyte subset was reduced in patients with low cardiopulmonary reserve. Poor exercise capacity in patients without a diagnosis of heart failure is independently associated with markers of inflammation. These observations suggest that preoperative inflammation associated with impaired cardiorespiratory performance may contribute to the pathophysiology of postoperative outcome.

No abstract