Gulsin GS, Henson J, Brady EM, Sargeant JA, Wilmot EG, Athithan L, Htike ZZ, Marsh AM, Biglands JD, Kellman P, Khunti K, Webb D, Davies MJ, Yates T, McCann GP

Diabetes Care. 2020 Sep;43(9):2248-2256. doi: 10.2337/dc20-0706. Epub 2020 Jul 17.

OBJECTIVE: To assess the relationship between subclinical cardiac dysfunction and aerobic exercise capacity (peak VO2) in adults with type 2 diabetes (T2D), a group at high risk of developing heart failure.
RESEARCH DESIGN AND METHODS: Cross-sectional study. We prospectively enrolled a multiethnic cohort of asymptomatic adults with T2D and no history, signs, or symptoms of cardiovascular disease. Age-, sex-, and ethnicity-matched control subjects were recruited for comparison. Participants underwent bioanthropometric profiling, cardiopulmonary exercise testing, and cardiovascular magnetic resonance with adenosine stress perfusion imaging. Multivariable linear regression analysis was undertaken to identify independent associations between measures of cardiovascular structure and function and peak VO2.
RESULTS: A total of 247 adults with T2D (aged 51.8 ± 11.9 years, 55% males, 37% black or south Asian ethnicity, HbA1c 7.4 ± 1.1% [57 ± 12 mmol/mol], and duration of diabetes 61 [32-120] months) and 78 control subjects were included. Subjects with T2D had increased concentric left ventricular remodeling, reduced myocardial perfusion reserve (MPR), and markedly lower aerobic exercise capacity (peak VO2 18.0 ± 6.6 vs. 27.8 ± 9.0 mL/kg/min; P < 0.001) compared with control subjects. In a multivariable linear regression model containing age, sex, ethnicity, smoking status, and systolic blood pressure, only MPR (β = 0.822; P = 0.006) and left ventricular diastolic filling pressure (E/e’) (β = -0.388; P = 0.001) were independently associated with peak VO2 in subjects with T2D. CONCLUSIONS: In a multiethnic cohort of asymptomatic people with T2D, MPR and diastolic function are key determinants of aerobic exercise capacity, independent of age, sex, ethnicity, smoking status, or blood pressure.

Sebastian T; Barco S; Kreuzpointner R; Konstantinides S; Kucher N;

Thrombosis research [Thromb Res] 2021 Apr 08. Date of Electronic Publication: 2021 Apr 08.

Background: It is unclear whether cardiopulmonary exercise intolerance in patients with chronic obstruction of the inferior vena cava (IVC) is reversible following endovascular IVC reconstruction.
Methods: In 17 patients (mean age 45 ± 15 years, 71% men) with post-thrombotic syndrome due to IVC obstruction and preserved left ventricular ejection fraction (mean 58 ± 3%), we performed cardiopulmonary exercise testing before and 3 months after IVC reconstruction (mean 4.1 ± 1.5 implanted stents). The median time from latest episode of deep vein thrombosis to intervention was 150 (interquartile range 102-820) days.
Results: At baseline, 12 (71%) patients reported New York Heart Association (NYHA) class II or III symptoms, 76% did not achieve >85% of predicted oxygen uptake at peak exercise (mean 61.8 ± 13.7%). After IVC reconstruction, the following changes were observed at anaerobic threshold: work rate increased by 14.6 W, 95%CI (-0.7; 30.0), oxygen uptake increased by 1.8 ml/kg, 95%CI (0.3; 3.3). Oxygen pulse increased by 1.95 ml per beat, 95%CI (1.12; 2.78), corresponding to a mean relative increase of 22.5%, 95%CI (12.4; 32.7) (p < 0.001). The following changes were observed at peak exercise: work rate increased by 48.1 W, 95%CI (27.8; 68.4), oxygen uptake increased by 6.4 ml/kg, 95%CI (3.8; 9.1). Oxygen pulse increased by 2.68 ml per beat, 95%CI (1.60; 3.76), corresponding to a mean relative increase of 29.4%, 95%CI (17.7; 41.2) (p < 0.001). At follow-up, 5 (29%) patients remained in NYHA class II.
Conclusions: In patients with chronic IVC obstruction, cardiopulmonary exercise intolerance as a result of impaired cardiac filling is at least partially reversible following endovascular IVC reconstruction.

Driver S; Reynolds M; Brown K; Vingren JL; Hill DW; Bennett M; Gilliland T; McShan E; Callender L; Reynolds E; Borunda N;Mosolf J; Cates C; Jones A;

British journal of sports medicine [Br J Sports Med] 2021 Apr 13. Date of Electronic Publication: 2021 Apr 13.

Objectives: To (1) determine if wearing a cloth face mask significantly affected exercise performance and associated physiological responses, and (2) describe perceptual measures of effort and participants’ experiences while wearing a face mask during a maximal treadmill test.
Methods: Randomised controlled trial of healthy adults aged 18-29 years. Participants completed two (with and without a cloth face mask) maximal cardiopulmonary exercise tests (CPETs) on a treadmill following the Bruce protocol. Blood pressure, heart rate, oxygen saturation, exertion and shortness of breath were measured. Descriptive data and physical activity history were collected pretrial; perceptions of wearing face masks and experiential data were gathered immediately following the masked trial.
Results: The final sample included 31 adults (age=23.2±3.1 years; 14 women/17 men). Data indicated that wearing a cloth face mask led to a significant reduction in exercise time (-01:39±01:19 min/sec, p<0.001), maximal oxygen consumption (VO ₂ max) (-818±552 mL/min, p<0.001), minute ventilation (-45.2±20.3 L/min), maximal heart rate (-8.4±17.0 beats per minute, p<0.01) and increased dyspnoea (1.7±2.9, p<0.001). Our data also suggest that differences in SpO ₂ and rating of perceived exertion existed between the different stages of the CPET as participant’s exercise intensity increased. No significant differences were found between conditions after the 7-minute recovery period.
Conclusion: Cloth face masks led to a 14% reduction in exercise time and 29% decrease in VO ₂ max, attributed to perceived discomfort associated with mask-wearing. Compared with no mask, participants reported feeling increasingly short of breath and claustrophobic at higher exercise intensities while wearing a cloth face mask. Coaches, trainers and athletes should consider modifying the frequency, intensity, time and type of exercise when wearing a cloth face mask.

Watson M; Ionescu MF; Sylvester K; Fuld J;

European respiratory review : an official journal of the European Respiratory Society [Eur Respir Rev] 2021 Apr 13; Vol. 30 (160). Date of Electronic Publication: 2021 Apr 13 (Print Publication: 2021).

Dysfunctional breathing refers to a multi-dimensional condition that is characterised by pathological changes in an individual’s breathing. These changes lead to a feeling of breathlessness and include alterations in the biomechanical, psychological and physiological aspects of breathing. This makes dysfunctional breathing a hard condition to diagnose, given the diversity of aspects that contribute to the feeling of breathlessness. The disorder can debilitate individuals without any health problems, but may also be present in those with underlying cardiopulmonary co-morbidities. The ventilatory equivalent for CO ₂ ( V _{eqCO 2} ) is a physiological parameter that can be measured using cardiopulmonary exercise testing. This review will explore how this single measurement can be used to aid the diagnosis of dysfunctional breathing. A background discussion about dysfunctional breathing will allow readers to comprehend its multidimensional aspects. This will then allow readers to understand how V _{eqCO 2} can be used in the wider diagnosis of dysfunctional breathing. Whilst V _{eqCO 2} cannot be used as a singular parameter in the diagnosis of dysfunctional breathing, this review supports its use within a broader algorithm to detect physiological abnormalities in patients with dysfunctional breathing. This will allow for more individuals to be accurately diagnosed and appropriately managed.

Ward SA;

European respiratory review : an official journal of the European Respiratory Society [Eur Respir Rev] 2021 Apr 13; Vol. 30 (160). Date of Electronic Publication: 2021 Apr 13 (Print Publication: 2021).

“Ventilatory efficiency” is widely used in cardiopulmonary exercise testing to make inferences regarding the normality (or otherwise) of the arterial CO ₂ tension ( P _{aCO 2} ) and physiological dead-space fraction of the breath ( V _D / V _T ) responses to rapid-incremental (or ramp) exercise. It is quantified as: 1) the slope of the linear region of the relationship between ventilation ( V ‘ _E ) and pulmonary CO ₂ output ( V ‘ _{CO 2} ); and/or 2) the ventilatory equivalent for CO ₂ at the lactate threshold ( V ‘ _E / V ‘ _{CO 2} [Formula: see text]) or its minimum value ( V ‘ _E / V ‘ _{CO 2} min), which occurs soon after [Formula: see text] but before respiratory compensation. Although these indices are normally numerically similar, they are not equally robust. That is, high values for V ‘ _E / V ‘ _{CO 2} [Formula: see text] and V ‘ _E / V ‘ _{CO 2} min provide a rigorous index of an elevated V _D / V _T when P _{aCO 2} is known (or can be assumed) to be regulated. In contrast, a high V ‘ _E – V ‘ _{CO 2} slope on its own does not, as account has also to be taken of the associated normally positive and small V ‘ _E intercept. Interpretation is complicated by factors such as: the extent to which P _{aCO 2} is actually regulated during rapid-incremental exercise (as is the case for steady-state moderate exercise); and whether V ‘ _E / V ‘ _{CO 2} [Formula: see text] or V ‘ _E / V ‘ _{CO 2} min provide accurate reflections of the true asymptotic value of V ‘ _E / V ‘ _{CO 2} , to which the V ‘ _E – V ‘ _{CO 2} slope approximates at very high work rates.

Emery MS

American College of Cardiology. April 13:2021

Cardiopulmonary exercise testing (CPET) has been a valuable tool in medicine and sports performance for decades. However, the intercept of the fields, particularly in consideration of the utility of CPET, is relatively new with the growth of sports cardiology. CPET in medicine is generally indicated in the evaluation of unexplained dyspnea and/or for stratification of patients for heart or lung transplants. In sports performance, CPET has been used to provide details and parameters for the athlete to improve training and human performance. With the promotion of CPET in sports cardiology, it is now not uncommon to see an athlete performing exercise testing in the same lab as those patients undergoing heart transplant evaluations. With some athletes capable of achieving maximal oxygen uptake (VO₂max) in excess of 60 ml/kg/min or greater than 140% of predicted, clinicians need to be aware of some fundamental differences in athletes that reflect normal physiology rather than a pathological response as would be encountered in patients with heart and lung disease.

Thomas M; Price OJ; Hull JH;

Current opinion in physiology [Curr Opin Physiol] 2021 Mar 26. Date of Electronic Publication: 2021 Mar 26.

In people recovering from COVID-19, there is concern regarding potential long-term pulmonary sequelae and associated impairment of functional capacity. Data published thus far indicate that spirometric indices appear to be generally well preserved, but that a defect in diffusing capacity (DLco) is a prevalent abnormality identified on follow-up lung function; present in 20-30% of those with mild to moderate disease and 60% in those with severe disease. Reductions in total lung capacity were commonly reported. Functional capacity is also often impaired, with data now starting to emerge detailing walk test and cardiopulmonary exercise test outcome at follow-up. In this review, we evaluate the published evidence in this area, to summarise the impact of COVID-19 infection on pulmonary function and relate this to the clinico-radiological findings and disease severity.

Neder JA; Phillips DB; Marillier M; Bernard AC; Berton DC; O’Donnell DE;

Frontiers in physiology [Front Physiol] 2021 Mar 18; Vol. 12, pp. 552000. Date of Electronic Publication: 2021 Mar 18 (Print Publication: 2021).

Several shortcomings on cardiopulmonary exercise testing (CPET) interpretation have shed a negative light on the test as a clinically useful tool. For instance, the reader should recognize patterns of dysfunction based on clusters of variables rather than relying on rigid interpretative algorithms. Correct display of key graphical data is of foremost relevance: prolixity and redundancy should be avoided. Submaximal dyspnea ratings should be plotted as a function of work rate (WR) and ventilatory demand. Increased work of breathing and/or obesity may normalize peak oxygen uptake (V̇O ₂ ) despite a low peak WR. Among the determinants of V̇O ₂ , only heart rate is measured during non-invasive CPET. It follows that in the absence of findings suggestive of severe impairment in O ₂ delivery, the boundaries between inactivity and early cardiovascular disease are blurred in individual subjects. A preserved breathing reserve should not be viewed as evidence that “the lungs” are not limiting the subject. In this context, measurements of dynamic inspiratory capacity are key to uncover abnormalities germane to exertional dyspnea. A low end-tidal partial pressure for carbon dioxide may indicate either increased “wasted” ventilation or alveolar hyperventilation; thus, direct measurements of arterial (or arterialized) PO ₂ might be warranted. Differentiating a chaotic breathing pattern from the normal breath-by-breath noise might be complex if the plotted data are not adequately smoothed. A sober recognition of these limitations, associated with an interpretation report free from technicalities and convoluted terminology, is crucial to enhance the credibility of CPET in the eyes of the practicing physician.

Aune SK; Byrkjeland R;  Solheim S; Arnesen H; Trøseid M; Awoyemi A; Seljeflot I; Helseth R;

Diabetology & metabolic syndrome [Diabetol Metab Syndr] 2021 Apr 01; Vol. 13 (1), pp. 36. Date of Electronic Publication: 2021 Apr 01.

Aim: Gut leakage has been shown to associate with low-grade inflammation and lower cardiorespiratory fitness in diabetic subjects. We aimed to investigate whether gut leakage markers related to cardiorespiratory fitness in patients with both coronary artery disease and type 2 diabetes, and whether these were affected by long-term exercise training.
Methods: Patients with angiographically verified coronary artery disease and type 2 diabetes mellitus (n = 137) were randomized to either 12 months exercise intervention or conventional follow-up. A cardiopulmonary exercise test and fasting blood samples were obtained before and after intervention to assess VO ₂ peak and the biomarkers soluble CD14, lipopolysaccharide-binding protein and intestinal fatty-acid binding protein as markers of gut leakage.
Results: 114 patients completed the intervention satisfactory. VO ₂ peak correlated inversely to sCD14 (r = - 0.248, p = 0.004) at baseline. Dividing sCD14 into quartiles (Q), VO ₂ peak was significantly higher in Q1 vs. Q2-4 (p = 0.001), and patients in Q2-4 (sCD14 > 1300 ng/mL) had an OR of 2.9 (95% CI 1.2-7.0) of having VO ₂ peak below median (< 23.8 ml/kg/min) at baseline. There were no statistically significant differences in changes in gut leakage markers between the two randomized groups (all p > 0.05) after 12 months.
Conclusions: Cardiorespiratory fitness related inversely to sCD14, suggesting physical capacity to be associated with gut leakage in patients with CAD and T2DM. Long-term exercise training did not affect circulating gut leakage markers in our population. Trial registration NCT01232608,

Peterman JE; Whaley MH; Harber MP; Fleenor BS; Imboden MT; Myers J; Arena R; Kaminsky LA;

European journal of preventive cardiology [Eur J Prev Cardiol] 2021 Apr 10; Vol. 28 (2), pp. 142-148.

Aims: A recent scientific statement suggests clinicians should routinely assess cardiorespiratory fitness using at least non-exercise prediction equations. However, no study has comprehensively compared the many non-exercise cardiorespiratory fitness prediction equations to directly-measured cardiorespiratory fitness using data from a single cohort. Our purpose was to compare the accuracy of non-exercise prediction equations to directly-measured cardiorespiratory fitness and evaluate their ability to classify an individual’s cardiorespiratory fitness.
Methods: The sample included 2529 tests from apparently healthy adults (42% female, aged 45.4 ± 13.1 years (mean±standard deviation). Estimated cardiorespiratory fitness from 28 distinct non-exercise prediction equations was compared with directly-measured cardiorespiratory fitness, determined from a cardiopulmonary exercise test. Analysis included the Benjamini-Hochberg procedure to compare estimated cardiorespiratory fitness with directly-measured cardiorespiratory fitness, Pearson product moment correlations, standard error of estimate values, and the percentage of participants correctly placed into three fitness categories.
Results: All of the estimated cardiorespiratory fitness values from the equations were correlated to directly measured cardiorespiratory fitness (p < 0.001) although the R2 values ranged from 0.25-0.70 and the estimated cardiorespiratory fitness values from 27 out of 28 equations were statistically different compared with directly-measured cardiorespiratory fitness. The range of standard error of estimate values was 4.1-6.2 ml·kg-1·min-1. On average, only 52% of participants were correctly classified into the three fitness categories when using estimated cardiorespiratory fitness.
Conclusion: Differences exist between non-exercise prediction equations, which influences the accuracy of estimated cardiorespiratory fitness. The present analysis can assist researchers and clinicians with choosing a non-exercise prediction equation appropriate for epidemiological or population research. However, the error and misclassification associated with estimated cardiorespiratory fitness suggests future research is needed on the clinical utility of estimated cardiorespiratory fitness.