Category Archives: Publications

Poor anaerobic threshold and VO 2 max recorded during cardiopulmonary exercise testing (CPET) prior to cytoreductive surgery in advanced (stage 3/4) ovarian cancer (AOC) is associated with suboptimal cytoreduction but does not preclude maximum effort cytoreduction.

Element K; Asher V; Bali A; Abdul S; Gomez D; Tou S; Curtis R; Low J; Phillips A;

Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology [J Obstet Gynaecol] 2021 May 02, pp. 1-7. Date of Electronic Publication: 2021 May 02.

This study assessed Cardiopulmonary Exercise Testing (CPET) in predicting oncological outcomes, post-operative recovery and complications in advanced ovarian cancer (AOC) cytoreductive surgery. We reviewed all patients who had CPET prior to AOC cytoreductive surgery with evidence of upper abdominal disease on preoperative imaging at the University Hospitals of Derby and Burton (UHDB) between August 2016 and July 2019. Patients were stratified by AT and maximum VO 2 levels. 43 patients were identified. AT showed no relationship with major complications. 100% of patients in the AT ≥11 group received R0 ( n  = 21, 91.30%), or R1 ( n  = 2, 8.70%) cytoreduction, whereas in the AT <11 group, only 75.00% achieved and R0 or R1 resection ( p  = .02). Surgical complexity was higher in the AT ≥11 group ( p  = .001) and the VO 2 ≥15 group ( p  = .0006). No other correlations were seen between AT or VO 2 max and complications or readmissions. No difference in overall survival was seen if R0 resection was achieved.IMPACT STATEMENT
What is already known on this subject? CPET testing allows pre-operative assessment of functional capacity to generate variables that can be used as a risk-stratification tool for major surgery. Whilst CPET testing has been shown to predict morbidity in non-gynaecological surgery, it remains unproven in cytoreductive surgery for ovarian cancer surgery despite being increasingly utilised.
What do the results of study add? Our data suggest that CPET testing does not predict complication rates or survival in AOC. Patients with poor CPET performance are more likely to receive suboptimal cytoreductive outcomes from surgery.
What are the implications of these findings for clinical practice and/or further research? CPET results should not be used to discount patients from cytoreductive surgery further research should address the interplay with nutrition, haematological markers, neoadjuvant chemotherapy and CPET performance.

A randomized placebo-control trial of the acute effects of oxygen supplementation on exercise hemodynamics, autonomic modulation, and brain oxygenation in patients with pulmonary hypertension.

Boutou AK; Dipla K; Zafeiridis A; Markopoulou A; Papadopoulos S; Kritikou S; Panagiotidou E; Stanopoulos I;
Pitsiou G;

Respiratory physiology & neurobiology [Respir Physiol Neurobiol] 2021 May 03, pp. 103677. Date of Electronic Publication: 2021 May 03.

Background: The integrative physiological effects of O 2 treatment on patients with pulmonary hypertension (PH) during exercise, have not been fully investigated. We simultaneously evaluated, for the first time, the effect of oxygen supplementation on hemodynamic responses, autonomic modulation, tissue oxygenation, and exercise performance in patients with pulmonary arterial hypertension (PAH)/Chronic Thromboembolic PH(CTEPH).
Material-Methods: In this randomized, cross-over, placebo-controlled trial, stable outpatients with PAH/CTEPH underwent maximal cardiopulmonary exercise testing, followed by two submaximal trials, during which they received supplementary oxygen (O 2 ) or medical-air. Continuous, non-invasive hemodynamics were monitored via photophlythesmography. Cerebral and quadriceps muscle oxygenation were recorded via near-infrared spectroscopy. Autonomic function was assessed by heart rate variability; root mean square of successive differences (RMSSD) and standard-deviation-Poincare-plot (SD1) were used as indices of parasympathetic output. Baroreceptor sensitivity (BRS) was assessed throughout the protocols.
Results: Nine patients (51.4 ± 9.4 years) were included. With O 2 -supplementation patients exercised for longer (p = 0.01), maintained higher cerebral oxygenated hemoglobin (O 2 Hb;p = 0.02) levels, exhibited an amelioration in cortical deoxygenation (HHb;p = 0.02), and had higher average cardiac output (CO) during exercise (p < 0.05), compared to medical air; with no differences in muscle oxygenation. With O 2 -supplementation patients exhibited higher BRS and sample-entropy throughout the protocol (p < 0.05) vs. medical air, and improved the blunted RMSSD, SD1 responses during exercise (p = 0.024).
Conclusion: We show that O 2 administration improves BRS and autonomic function during submaximal exercise in PAH/CTEPH, without significantly affecting muscle oxygenation. The improved autonomic function, along with enhancements in cardiovascular function and cerebral oxygenation, probably contributes to increased exercise tolerance with O 2 -supplementation in PH patients.

In patients with heart failure, enhanced ventilatory response to exercise is associated with severe obstructive sleep apnea.

Bittencourt L; Javaheri S; Servantes DM; Pelissari Kravchychyn AC; Almeida DR; Tufik S;

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine [J Clin Sleep Med] 2021 May 05. Date of Electronic Publication: 2021 May 05.

Study Objectives: Patients with chronic heart failure (CHF) while undergoing exercise test, frequently exhibit elevated ratio of minute ventilation over CO₂ output (VE/VCO₂ slope). One of the factors contributing to this elevated slope is increased chemosensitivity to CO₂, as this slope significantly correlates with the slope of the ventilatory response to CO₂ rebreathing at rest. A previous study in patients with CHF and central sleep apnea (CSA) has shown the highest VE/VCO2 slope during exercise was associated with the most severe CSA. In the current study, we tested the hypothesis that in patients with CHF and obstructive sleep apnea (OSA), the highest VE/VCO₂ slope is also associated with most severe OSA. If correct, it implies that in CHF, augmented instability in the negative feedback system controlling breathing predisposes to both OSA and CSA.
Methods: This preliminary study involved 70 patients with stable CHF and spectrum of OSA severity who underwent full night polysomnography, echocardiography, and cardiopulmonary exercise testing. Peak oxygen consumption (VO₂ max) and VE/VCO₂ slope were calculated.
Results: There were significant positive correlations between apnea hypopnea index (AHI) and VE/VCO₂ slope (r= 0.359; p=0.002). In the regression model, involving relevant variable, age, body mass index, gender, VE/VCO₂ slope, VO₂, and left ventricular ejection fraction, AHI retained significance with VE/VCO₂.
Conclusions: In patients with CHF, the VE/VCO₂ slope obtained during exercise correlates significantly to the severity of OSA suggesting that an elevated CO₂ response should increase suspicion for presence of severe OSA, a treatable disorder that is potentially associated with excess mortality.

Correlation Between Heart Rate at Maximal Fat Oxidation and Aerobic Threshold in Healthy Adolescent Boys and Girls.

Meucci M; Nandagiri VKavirayuni VS; Whang A; Collier SR;

Pediatric exercise science [Pediatr Exerc Sci] 2021 May 06, pp. 1-5. Date of Electronic Publication: 2021 May 06.

Purpose: To investigate the association between the heart rate (HR) at maximal fat oxidation (MFO) and the HR at the aerobic threshold (AerT) in adolescent boys and girls, and to identify sex differences in the intensity that elicits MFO (Fatmax) as a percentage of HR peak (HRpeak).
Methods: Fifty-eight healthy adolescents participated in this study (29 boys and 29 girls). Participants performed a cardiopulmonary exercise test on a cycle ergometer. MFO was calculated using a stoichiometric equation, and the AerT was identified using gas exchange parameters.
Results: A strong correlation between HR at Fatmax and HR at AerT was found in both boys and girls (r = .96 and .94, respectively). Fatmax as a percentage of HRpeak occurred at 61.0% (4.9%) of HRpeak and 66.8% (6.9%) of HRpeak in adolescent boys and girls (P = .001, F = 13.6), respectively. MFO was higher in boys compared with girls (324 [150] and 240 [95] mg/min, respectively), and no sex differences were observed in the relative contribution of fat to energy expenditure at Fatmax.
Conclusions: HR at Fatmax and HR at AerT were highly correlated in adolescent boys and girls. Girls obtained Fatmax at a higher percentage of HRpeak than boys.

Perioperative risk assessment – focus on functional capacity.

Hanley C; Wijeysundera DN;

Current opinion in anaesthesiology [Curr Opin Anaesthesiol] 2021 Jun 01; Vol. 34 (3), pp. 309-316.

Purpose of Review: This review examines how functional capacity informs preoperative risk stratification, as well as strengths and limitations of options for estimating functional capacity.
Recent Findings: Functional capacity (or cardiopulmonary fitness) overlaps with other important characteristics, including muscular strength, balance, and frailty. Poor functional capacity is associated with postoperative morbidity, especially noncardiovascular complications. Both patient interviews and exercise tests are used to assess functional capacity. The usual approach of an unstructured patient interview does not predict outcomes. Structured interviews that incorporate validated questionnaires (Duke Activity Status Index) or standardized questions about physical activity (ability to climb stairs) do predict moderate-or-severe complications and cardiovascular complications. Among exercise tests, cardiopulmonary exercise testing (CPET) has shown the most consistent association with risks of complications. Other tests (6-min walk test, incremental shuttle walk test, stair climbing) might predict complications, but still require further high-quality evaluation.
Summary: A straightforward way to better assess functional capacity is a structured interview with validated questionnaires or standardized questions about physical activities. Functional capacity can also be assessed by exercise tests, with the strongest evidence supporting CPET. Although some simpler exercise tests have shown promise, more research remains needed to better define their role in preoperative evaluation.

The impact of plasma 25-hydroxyvitamin D on pulmonary function and exercise physiology in cystic fibrosis: a multicentre retrospective study.

Iniesta RR; Causer AJ; Arregui-Fresneda I; Connett G; Allenby MI; Daniels T; Carroll MP; Urquhart DS; Saynor ZL;

Journal of human nutrition and dietetics : the official journal of the British Dietetic Association [J Hum Nutr Diet] 2021 Apr 28. Date of Electronic Publication: 2021 Apr 28.

Background: 25-hydroxyvitamin D (25OHD) may exert immunomodulatory effects on respiratory health, which may translate to improvements in exercise physiology. Thus, we aimed to investigate whether plasma 25OHD is associated with lung function and aerobic fitness in people with cystic fibrosis (pwCF).
Methods: A multi-centre retrospective review of pwCF (>9 years old) attending the Royal Hospital for Sick Children (Edinburgh) or Wessex CF-Unit (Southampton) was performed between July 2017 to October 2019. Demographic and clinical data were collected. Plasma 25OHD measured closest in time to clinical cardiopulmonary exercise testing (CPET) and/or spirometry (forced expiratory volume FEV 1 % predicted) was recorded. Pancreatic insufficiency was diagnosed based on faecal elastase of <100 µg/g. We performed multiple-regression analysis with aerobic fitness outcomes [peak oxygen uptake (VO 2 peak)] and FEV 1 % predicted as primary outcomes.
Results: Ninety pwCF [mean±SD age: 19.1±8.6 years, 54 (60%) children, 48 (53%) males and 88 (98%) Caucasian] were included. 25OHD deficiency and insufficiency was 15 (17%) and 44 (49%) respectively. 25OHD deficiency and insufficiency was significantly associated with pancreatic insufficiency (χ2(4.8); p = 0.02). Plasma 25OHD was not significantly associated with FEV 1 % predicted [R 2 = 0.06; p= 0.42; 95%; CI (-0.09 – 0.19)] or VO 2peak [R 2 = 0.04; p= 0.07; 95% CI (-011 – 0.005)] in all pwCF. However, 25OHD was significantly associated with both FEV 1 % [R 2 = 0.15; p= 0.02; 95% CI (1.99 – 2.64)] and VO 2peak [R 2 = 0.13; p= 0.05; 95% CI (-0.26 – (-0.005)] in the paediatric cohort.
Conclusion: We showed that 25OHD is associated with improved lung function and aerobic fitness in children and adolescents with CF. Mechanistic and high-quality prospective studies including both lung function and aerobic fitness as primary outcomes are now warranted.

Aerobic reserve capacity in multiple sclerosis-Preliminary evidence.

Feasel CD; Sandroff BM; Motl RW;

Acta neurologica Scandinavica [Acta Neurol Scand] 2021 Apr 29. Date of Electronic Publication: 2021 Apr 29.

Objectives: Aerobic reserve capacity reflects the available energy for performing everyday life tasks, and it has been studied in older adult populations. This preliminary study examined proof of concept and measurement of aerobic reserve capacity in multiple sclerosis (MS).
Materials & Methods: Twenty-one fully ambulatory people with MS performed a maximal, cardiopulmonary exercise test (CPET). We calculated aerobic reserve capacity based on the difference between peak aerobic power (VO 2peak ) and first stage oxygen consumption (VO 2 ). Participants completed assessments for disability (Expanded Disability Status Scale, EDSS), cognition (Symbol Digit Modalities Test, SDMT), mood (Beck Depression Inventory, BDI), walking endurance (six-minute walk distance, 6MWD), walking speed (Timed Twenty-Foot Walk, T25FW), impact of MS (Multiple Sclerosis Impact Scale, MSIS-29), and anthropometric measurements (height and weight).
Results: Aerobic reserve capacity was 9.3 ± 3.7 ml/kg/min. Aerobic reserve capacity was positively associated with VO 2peak (ρ = .67, p < .01), time to exhaustion (ρ = .63, p < .01), and SDMT (ρ = .51, p < .05). Aerobic reserve capacity was negatively associated with BMI (ρ = -.62, p < .01) and RHR (ρ = -0.47, p < .05).
Conclusion: We provide preliminary evidence that aerobic reserve capacity is a feasible outcome derived from maximal CPET (eg, modified Balke protocol) in MS. Aerobic reserve capacity was associated with clinically relevant outcomes and could become an important outcome for rehabilitation in future research.

Effect of pulmonary hypertension on exercise tolerance in patients with COPD: a prognostic systematic review and meta-analysis.

Torres-Castro R; Gimeno-Santos E; Vilaró J; Roqué-Figuls M; Moisés J; Vasconcello-Castillo L; Orizaga T; Barberà JA; Blanco I;

European respiratory review : an official journal of the European Respiratory Society [Eur Respir Rev] 2021 Apr 29; Vol. 30 (160). Date of Electronic Publication: 2021 Apr 29 (Print Publication: 2021).

Background: Pulmonary hypertension (PH) is a frequent complication in patients with COPD.
Objective: To determine if, in patients with COPD, the presence of PH decreases exercise tolerance.
Methods: We included studies that analysed exercise tolerance using a cardiopulmonary exercise test (CPET) in patients with COPD with PH (COPD-PH) and without PH (COPD-nonPH). Two independent reviewers analysed the studies, extracted the data and assessed the quality of the evidence.
Results: Of the 4915 articles initially identified, seven reported 257 patients with COPD-PH and 404 patients with COPD-nonPH. The COPD-PH group showed differences in peak oxygen consumption ( VO 2peak ), -3.09 mL·kg -1 ·min -1 (95% CI -4.74 to -1.43, p=0.0003); maximum workload (W max ), -20.5 W (95% CI -34.4 to -6.5, p=0.004); and oxygen pulse (O 2 pulse), -1.24 mL·beat -1 (95% CI -2.40 to -0.09, p=0.03), in comparison to the group with COPD-nonPH. If we excluded studies with lung transplant candidates, the sensitivity analyses showed even bigger differences: VO 2 , -4.26 mL·min -1 ·kg -1 (95% CI -5.50 to -3.02 mL·kg -1 ·min -1 , p<0.00001); W max , -26.6 W (95% CI -32.1 to -21.1 W, p<0.00001); and O 2 pulse, -2.04 mL·beat -1 (95% CI -2.92 to -1.15 mL·beat -1 , p<0.0001).
Conclusion: Exercise tolerance was significantly lower in patients with COPD-PH than in patients with COPD-nonPH, particularly in nontransplant candidates.

All-cause mortality predicted by peak oxygen uptake differs depending on spirometry pattern in patients with heart failure and reduced ejection fraction.

Van Iterson EH; Cho L; Tonelli A; Finet JE; Laffin LJ;

ESC heart failure [ESC Heart Fail] 2021 May 01. Date of Electronic Publication: 2021 May 01.

Aims: In patients with heart failure and reduced ejection fraction (HFrEF), it remains unclear how exacerbated impairments in peak exercise oxygen uptake (V̇O 2peak ) caused by coexistent obstructive or restrictive ventilatory defects affect mortality risk. We evaluated in patients with HFrEF, whether demonstrating either an obstructive or restrictive-patterned ventilatory defect on spirometry affects V̇O 2peak to yield all-cause mortality risk predicted by V̇O 2peak that is spirometry pattern specific.
Methods and Results: We retrospectively analysed resting spirometry and treadmill cardiopulmonary exercise testing data of patients with HFrEF (left ventricular ejection fraction ≤ 40%). The study sample (N = 329) was grouped by spirometry pattern: normal [Group 1: N = 101; forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) ≥ 0.70; FVC ≥ 80% predicted], restrictive without airflow obstruction (Group 2: N = 104; FEV 1 /FVC ≥ 0.70; FVC < 80% predicted), or obstructive (Group 3: N = 124; FEV 1 /FVC < 0.70). Patients were followed up to 1 year for the endpoint of all-cause mortality. V̇O 2peak was higher in Group 1 versus Groups 2 and 3 (13.4 ± 4.0 vs. 12.1 ± 3.7 and 12.2 ± 3.3 mL/kg/min, respectively; P = 0.014). Over the 1 year follow-up, n = 9, n = 16, and n = 12 deaths occurred in Groups 1-3, respectively, with corresponding crude survival rates of 88%, 81%, and 92%, respectively (log-rank; P = 0.352). V̇O 2peak was associated with all-cause mortality (crude hazard ratio = 0.77; P < 0.001). In multivariate analyses, a significant V̇O 2peak -by-spirometry group interaction yielded 1.99 (95% confidence interval, 1.14-3.46) and 2.43 (95% confidence interval, 1.44-4.11) higher mortality risk associated with V̇O 2peak in Group 2 versus Groups 1 and 3, respectively.
Conclusions: Demonstrating a restrictive pattern on spirometry yields the severest mortality risk associated with V̇O 2peak . Using spirometry to screen patients with HFrEF for ventilatory defects has a potential role in improving risk stratification based on V̇O 2peak .

Cardiopulmonary Exercise Testing in the Coronavirus Disease – 2019 Era: Safety and Protocol Considerations.

Duscha BD; Johnson JL; Bennett WC; Ball KN; Mae Fos LB; Reaves MA; Kraus WE

Current sports medicine reports [Curr Sports Med Rep] 2021 May 01; Vol. 20 (5), pp. 259-265.

Abstract: Cardiopulmonary exercise testing (CPX) is a valuable tool in both clinical practice and research settings. Therefore, it is advantageous for human performance laboratories to continue operating during the coronavirus disease 2019 (COVID-19) pandemic. All institutions should adhere to general COVID-19 guidelines provided by the Centers for Disease Control. Because of the testing environment, CPX laboratories must consider additional precautionary safety measures. This article provides recommendations for modifying the CPX protocol to ensure safety for all stakeholders during the pandemic. These modifications are universal across all populations, types of institutions and testing modalities. Preliminary measures include careful review of federal, local, and institutional mandates. The description outlines how to evaluate a testing environment and alter workflow. Guidelines are provided on what specific personal protective equipment should be acquired; as well as necessary actions before, during, and after the CPX test. These precautions will limit the possibility of both clients and staff from contracting or spreading the disease while maintaining testing volume in the laboratory.