Ewert R, Obst A, Mühle A, Halank M, Winkler J, Trümper B, Hoheisel G, Hoheisel A, Wiersbitzky M, Heine A,
Maiwald A, Gläser S, Stubbe B.

Respiration. 2021 Nov 19:1-14. doi: 10.1159/000519750. Online ahead of print.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is one of the most common chronic diseases associated with high mortality. Previous studies suggested a prognostic role for peak oxygen uptake (VO2peak) assessed during cardiopulmonary exercise testing (CPET) in patients with COPD. However, most of these studies had small sample sizes or short follow-up periods, and despite their relevance, CPET parameters are not included in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) tool for assessment of severity.
OBJECTIVES: We therefore aimed to assess the prognostic value of CPET parameters in a large cohort of outpatients with COPD.
METHODS: In this retrospective, multicentre cohort study, medical records of patients with COPD who underwent CPET during 2004-2017 were reviewed and demographics, smoking habits, GOLD grade and category, exacerbation frequency, dyspnoea score, lung function measurements, and CPET parameters were documented. Relationships with survival were evaluated using Kaplan-Meier analysis, Cox regression, and receiver operating characteristic (ROC) curves.
RESULTS: Of a total of 347 patients, 312 patients were included. Five-year and 10-year survival probability was 75% and 57%, respectively. VO2peak significantly predicted survival (hazard ratio: 0.886 [95% confidence interval: 0.830; 0.946]). The optimal VO2peak threshold for discrimination of 5-year survival was 14.6 mL/kg/min (area under ROC curve: 0.713). Five-year survival in patients with VO2peak <14.6 mL/kg/min versus ≥ 14.6 mL/kg/min was 60% versus 86% in GOLD categories A/B and 64% versus 90% in GOLD categories C/D.
CONCLUSIONS: We confirm that VO2peak is a highly significant predictor of survival in COPD patients and recommend the incorporation of VO2peak into the assessment of COPD severity.

Kaminsky LA, Arena R, Myers J, Peterman JE, Bonikowske AR, Harber MP, Medina Inojosa JR,
Lavie CJ, Squires RW.

Mayo Clin Proc. 2021 Nov 19:S0025-6196(21)00645-5. doi: 10.1016/j.mayocp.2021.08.020. Online ahead of print.

OBJECTIVE: To provide updated reference standards for cardiorespiratory fitness (CRF) for the United States derived from cardiopulmonary exercise (CPX) testing when using a treadmill or cycle ergometer.
PATIENTS AND METHODS: Thirty-four laboratories in the United States contributed data to the Fitness Registry and the Importance of Exercise National Database. Analysis included 22,379 tests (16,278 treadmill and 6101 cycle ergometer) conducted between January 1, 1968, through March 31, 2021, from apparently healthy adults (aged 20 to 89 years). Percentiles of peak oxygen consumption for men and women were determined for each decade from 20 through 89 years of age for treadmill and cycle exercise modes, as well as when defining maximal effort as respiratory exchange ratio (RER) greater than or equal to 1.0 or RER greater than or equal to 1.1.
RESULTS: For both men and women, the 50th percentile scores for each exercise mode decreased with age and were higher in men across all age groups and higher for treadmill compared with cycle CPX. The average rate of decline per decade over a 6-decade period was 13.5%, 4.0mLO2/kg/min for treadmill CPX and 16.4%, 4.3mLO2/kg/min for cycle CPX. Observationally, the mean peak oxygen consumption was similar whether using an RER criterion of greater than or equal to 1.0 or greater than or equal to 1.1 across the different test modes, ages, and for both sexes. The updated reference standards for treadmill CPX were 1.5 – 4.6 mL O2 × kg-1 × min-1 lower compared with the previous 2015 standards whereas the updated cycling standards were generally comparable to the original 2017 standards.
CONCLUSION: These updated cardiorespiratory fitness reference standards improve the representativeness of the US population compared with the original standards.

Mazaheri R; Schmied C; Niederseer D; Guazzi M;

Journal of clinical medicine [J Clin Med] 2021 Oct 29; Vol. 10 (21).
Date of Electronic Publication: 2021 Oct 29.

Although still underutilized, cardiopulmonary exercise testing (CPET) allows the most accurate and reproducible measurement of cardiorespiratory fitness and performance in athletes. It provides functional physiologic indices which are key variables in the assessment of athletes in different disciplines. CPET is valuable in clinical and physiological investigation of individuals with loss of performance or minor symptoms that might indicate subclinical cardiovascular, pulmonary or musculoskeletal disorders. Highly trained athletes have improved CPET values, so having just normal values may hide a medical disorder. In the present review, applications of CPET in athletes with special attention on physiological parameters such as VO ₂ max, ventilatory thresholds, oxygen pulse, and ventilatory equivalent for oxygen and exercise economy in the assessment of athletic performance are discussed. The role of CPET in the evaluation of possible latent diseases and overtraining syndrome, as well as CPET-based exercise prescription, are outlined.

Tous-Espelosin M; Ruiz de Azua S; Iriarte-Yoller N; Sanchez PM; Elizagarate E; Sampedro A;

International journal of environmental research and public health [Int J Environ Res Public Health] 2021 Oct 29; Vol. 18 (21). Date of Electronic Publication: 2021 Oct 29.

Cardiorespiratory fitness (CRF) can be direct or estimated from different field tests. The Modified Shuttle Walk Test (MSWT) is suitable for all levels of function, allowing a peak response to be elicited. Therefore, we aimed (1) to validate the equation presented in the original study by Singh et al. for evaluating the relationship between MSWT with peak oxygen uptake (VO _2peak ) in adults with schizophrenia (SZ), (2) to develop a new equation for the MSWT to predict VO _2peak , and (3) to validate the new equation. Participants (N = 144, 41.3 ± 10.2 years old) with SZ performed a direct measurement of VO _2peak through a cardiopulmonary exercise test and the MSWT. A new equation incorporating resting heart rate, body mass index, and distance from MSWT (R ² = 0.617; adjusted R ² = 0.60; p < 0.001) performs better than the Singh et al. equation (R ² = 0.57; adjusted R ² = 0.57; p < 0.001) to estimate VO _2peak for the studied population. The posteriori cross-validation method confirmed the model’s stability (R ² = 0.617 vs. 0.626). The findings of the current study support the validity of the new regression equation incorporating resting heart rate, body mass index, and distance from MSWT to predict VO _2peak for assessment of CRF in people with SZ.

Pritchard A; Burns P; Correia J; Jamieson P; Moxon P; Purvis J; Thomas M; Tighe H;

BMJ open respiratory research [BMJ Open Respir Res] 2021 Nov; Vol. 8 (1).

Cardiopulmonary exercise testing (CPET) has become an invaluable tool in healthcare, improving the diagnosis of disease and the quality, efficacy, assessment and safety of treatment across a range of pathologies. CPET’s superior ability to measure the global exercise response of the respiratory, cardiovascular and skeletal muscle systems simultaneously in a time and cost-efficient manner has led to the application of CPET in a range of settings from diagnosis of disease to preoperative assessment.
The Association for Respiratory Technology and Physiology Statement on Cardiopulmonary Exercise Testing 2021 provides the practitioner and scientist with an outstanding resource to support and enhance practice, from equipment to testing to leadership, helping them deliver a quality assured service for the benefit of all patient groups.

Petek BJ; Churchill TW; Sawalla Guseh J; Loomer G; Gustus SK; Lewis GD; Weiner RB; Baggish AL; Wasfy MM;

Physiological reports [Physiol Rep] 2021 Nov; Vol. 9 (21), pp. e15105.

Cardiopulmonary exercise testing (CPET) guidelines recommend analysis of the oxygen (O ₂ ) pulse for a late exercise plateau in evaluation for obstructive coronary artery disease (OCAD). However, whether this O ₂ pulse trajectory is within the range of normal has been debated, and the diagnostic performance of the O ₂ pulse for OCAD in physically fit individuals, in whomV˙O2may be more likely to plateau, has not been evaluated. Using prospectively collected data from a sports cardiology program, patients were identified who were free of other cardiac disease and underwent clinically-indicated CPET within 90 days of invasive or computed tomography coronary angiography. The diagnostic performance of quantitative O ₂ pulse metrics (late exercise slope, proportional change in slope during late exercise) and qualitative assessment for O ₂ pulse plateau to predict OCAD was assessed. Among 104 patients (age:56 ± 12 years, 30% female, peakV˙O2119 ± 34% predicted), the diagnostic performance for OCAD (n = 24,23%) was poor for both quantitative and qualitative metrics reflecting an O ₂ pulse plateau (late exercise slope: AUC = 0.55, sensitivity = 68%, specificity = 41%; proportional change in slope: AUC = 0.55, sensitivity = 91%, specificity = 18%; visual plateau/decline: AUC = 0.51, sensitivity = 33%, specificity = 67%). When O ₂ pulse parameters were added to the electrocardiogram, the change in AUC was minimal (-0.01 to +0.02, p ≥ 0.05). Those patients without OCAD with a plateau or decline in O ₂ pulse were fitter than those with linear augmentation (peakV˙O2133 ± 31% vs. 114 ± 36% predicted, p < 0.05) and had a longer exercise ramp time (9.5 ± 3.2 vs. 8.0 ± 2.5 min, p < 0.05). Overall, a plateau in O ₂ pulse was not a useful predictor of OCAD in a physically fit population, indicating that the O ₂ pulse should be integrated with other CPET parameters and may reflect a physiologic limitation of stroke volume and/or O ₂ extraction during intense exercise.

Cafiero G; Passi F; Calo’ Carducci FI; Gentili F; Giordano U;  Perri C;   Hashem Said M; Turchetta A;

Italian journal of pediatrics [Ital J Pediatr] 2021 Nov 06; Vol. 47 (1), pp. 221.
Date of Electronic Publication: 2021 Nov 06.

Background: With the gradual resumption of sports activities after the lock-down period for coronavirus pandemic, a new problem is emerging: Allow all athletes to be able to return to compete after SARS-CoV-2 infection in total safety. Several protocols have been proposed for healed athletes but all of them have been formulated for the adult population. The aim of the present study is to evaluate the adequacy of Italian practical recommendations for return-to-paly, in order to exclude cardiorespiratory complications due to COVID-19 in children and adolescents.
Methods: Between April 2020 and January 2021 the Italian Sports Medical Federation formulated cardiorespiratory protocols to be applied to athletes recovered from SARS-CoV-2 infection. The protocols take into account the severity of the infection. Protocols include lung function tests, cardiopulmonary exercise test, echocardiographic evaluation, blood chemistry tests.
Results: From September 2020 to February 2021, 45 children and adolescents (aged from 9 to 18 years; male = 26) with previous SARS-CoV-2 infection were evaluated according to the protocols in force for adult. 55.5% of the subjects (N = 25) reported an asymptomatic infection; 44.5% reported a mild symptomatic infection. Results of lung function test have exceeded the limit of 80% of the theoretical value in all patients. The cardiorespiratory capacity of all patients was within normal limits (average value of maximal oxigen uptake 41 ml/kg/min). No arrhythmic events or reduction in the ejection fraction were highlighted.
Conclusion: The data obtained showed that, in the pediatric population, mild coronavirus infection does not cause cardiorespiratory complications in the short and medium term. Return to play after Coronavirus infection seems to be safe but it will be necessary to continue with the data analysis in order to modulate and optimize the protocols especially in the pediatric field.

Apostolo A; Vignati C; Della Rocca M; de Martino F; Berna G; Campodonico J; Contini M; Muratori M; Palermo P; Mapelli M; Alimento M; Pezzuto B; Agostoni P;

Journal of cardiac failure [J Card Fail] 2021 Nov 08.
Date of Electronic Publication: 2021 Nov 08.

Background: In advanced heart failure (HF), Levosimendan increases peak oxygen uptake (peakVO ₂ ). We investigated whether peakVO ₂ increase is linked to cardiovascular, respiratory or muscular performance changes.
Methods and Results: Twenty patients hospitalized for advanced HF underwent, before and shortly after Levosimendan infusion, two different cardiopulmonary exercise tests (CPET): a) a personalized ramp protocol with repeated arterial blood gas analysis and standard spirometry including alveolar-capillary gas diffusion measurements at rest and at peak exercise, and b) a step incremental workload CPET with continuous near-infrared spectroscopy analysis and cardiac output (CO) assessment by bioelectrical impedance analysis. Levosimendan significantly reduced natriuretic peptides, improved peakVO ₂ (11.3 [IQR 10.1-12.8] to 12.6 [10.2-14.4] ml/Kg/min, p<0.01) and reduced VE/VCO ₂ slope (47.7±10.7 to 43.4±8.1, p<0.01). In parallel, spirometry showed only a minor increase in forced expiratory volume, while peak exercise dead space ventilation was unchanged. However, during exercise, a smaller edema formation was observed after Levosimendan infusion, as inferable from the changes in diffusion components, i.e. membrane diffusion and capillary volume. The end-tidal pressure of CO ₂ (PetCO ₂ ) during the isocapnic buffering period increased after Levosimendan (from 28±3 mmHg to 31±2 mmHg, p<0.01). During exercise, CO increased in parallel with VO ₂ . After Levosimendan, total and oxygenated tissue hemoglobin, but not deoxygenated hemoglobin, increased in all exercise phases.
Conclusion: In advanced HF, Levosimendan increases peakVO ₂ , reduces the formation of exercise-induced lung edema, increases ventilation efficiency due to a reduction of reflex hyperventilation, and increases CO and muscular oxygen delivery and extraction.

Coisne A; Aghezzaf S; Galli E; Mouton S; Richardson M; Dubois D; Delsart P; Domanski O; Bauters C; Charton M; L’Official G; Modine T; Vincentelli A; Juthier F; Lancellotti P; Donal E; Montaigne D;

European heart journal. Cardiovascular Imaging [Eur Heart J Cardiovasc Imaging] 2021 Nov 09.
Date of Electronic Publication: 2021 Nov 09.

Aims: To compare the clinical significance of exercise echocardiography (ExE) and cardiopulmonary exercise testing (CPX) in patients with ≥moderate primary mitral regurgitation (MR) and discrepancy between symptoms and MR severity.
Methods and Results: Patients consulting for ≥moderate discordant primary MR prospectively underwent low (25 W) ExE, peak ExE, and CPX within 2 months in Lille and Rennes University Hospital. Patients with Class I recommendation for surgical MR correction were excluded. Changes in MR severity, systolic pulmonary artery pressure (SPAP), left ventricular ejection fraction (LVEF), and tricuspid annular plane systolic excursion were evaluated during ExE. Patients were followed for major events (ME): cardiovascular death, acute heart failure, or mitral valve surgery. Among 128 patients included, 22 presented mild-to-moderate, 61 moderate-to-severe, and 45 severe MR. Unlike MR variation, SPAP and LVEF were successfully assessed during ExE in most patients. Forty-one patients (32%) displayed reduced aerobic capacity (peak VO2 < 80% of predicted value) with cardiac limitation in 28 (68%) and muscular or respiratory limitation in the 13 others (32%). ME occurred in 61 patients (47.7%) during a mean follow-up of 27 ± 21 months. Twenty-five Watts SPAP [hazard ratio (HR) (95% confidence interval, CI) = 1.03 (1.01-1.06), P = 0.003] and reduced aerobic capacity [HR (95% CI) = 1.74 (1.03-2.95), P = 0.04] were independently predictive of ME, even after adjustment for MR severity. The cut-off of 55 mmHg for 25 W SPAP showed the best accuracy to predict ME (area under the curve = 0.60, P = 0.05).
Conclusion: In patients with ≥moderate primary MR and discordant symptoms, 25 W exercise pulmonary hypertension, defined as an SPAP ≥55 mmHg, and poor aerobic capacity during CPX are independently associated with adverse events.

Peterman JE; Arena R; Myers J; Marzolini S; Ades PA; Savage PD; Lavie CJ; Kaminsky LA;

Journal of the American Heart Association [J Am Heart Assoc] 2021 Nov 16; Vol. 10 (22), pp. e022336.
Date of Electronic Publication: 2021 Nov 08.

Background The importance of cardiorespiratory fitness for stratifying risk and guiding clinical decisions in patients with cardiovascular disease is well-established. To optimize the clinical value of cardiorespiratory fitness, normative reference standards are essential. The purpose of this report is to extend previous cardiorespiratory fitness normative standards by providing updated cardiorespiratory fitness reference standards according to cardiovascular disease category and testing modality.
Methods and Results The analysis included 15 045 tests (8079 treadmill, 6966 cycle) from FRIEND (Fitness Registry and the Importance of Exercise National Database). Using data from tests conducted January 1, 1974, through March 1, 2021, percentiles of directly measured peak oxygen consumption (VO _2peak ) were determined for each decade from 30 through 89 years of age for men and women with a diagnosis of coronary artery bypass surgery, myocardial infarction, percutaneous coronary intervention, or heart failure. There were significant differences between sex and age groups for VO _2peak ( P <0.001). The mean VO _2peak was 23% higher for men compared with women and VO _2peak decreased by a mean of 7% per decade for both sexes. Among each decade, the mean VO _2peak from treadmill tests was 21% higher than the VO _2peak from cycle tests. Differences in VO _2peak were observed among the age groups in both sexes according to cardiovascular disease category.
Conclusions This report provides normative reference standards by cardiovascular disease category for both men and women performing cardiopulmonary exercise testing on a treadmill or cycle ergometer. These updated and enhanced reference standards can assist with patient risk stratification and guide clinical care.