Pierantonio Laveneziana, Marcello Di Paolo  and Paolo Palange

Eur Respir Rev 2021; 30: 200187 [https://doi.org/10.1183/16000617.0187-2020].

ABSTRACT Cardiopulmonary exercise testing (CPET) has long been used as diagnostic tool for cardiac
diseases. During recent years CPET has been proven to be additionally useful for 1) distinguishing
between normal and abnormal responses to exercise; 2) determining peak oxygen uptake and level of
disability; 3) identifying factors contributing to dyspnoea and exercise limitation; 4) differentiating between
ventilatory (respiratory mechanics and pulmonary gas exchange), cardiovascular, metabolic and peripheral
muscle causes of exercise intolerance; 5) identifying anomalies of ventilatory (respiratory mechanics and
pulmonary gas exchange), cardiovascular and metabolic systems, as well as peripheral muscle
and psychological disorders; 6) screening for coexistent ischaemic heart disease, peripheral vascular disease
and arterial hypoxaemia; 7) assisting in planning individualised exercise training; 8) generating prognostic
information; and 9) objectively evaluating the impact of therapeutic interventions.
As such, CPET is an essential part of patients’ clinical assessment. This article belongs to the special
series on the “Ventilatory efficiency and its clinical prognostic value in cardiorespiratory disorders”,
addressed to clinicians, physiologists and researchers, and aims at encouraging them to get acquainted
with CPET in order to help and orient the clinical decision concerning individual patients.
Introduction

Legendre A; Moatemri F; Kovalska O; Balice-Pasquinelli M; Blanchard JC; Lamar-Tanguy A; Ledru F; Cristofini P;
Iliou MC;

International journal of cardiology [Int J Cardiol] 2021 Feb 08. Date of Electronic Publication: 2021 Feb 08.

Background: Exercise training (ET) increases exercise tolerance, improves quality of life and likely the prognosis in heart failure patients with reduced ejection fraction (HFrEF). However, some patients do not improve, whereas exercise training response is still poorly understood. Measurement of cardiac output during cardiopulmonary exercise test might allow ET response assessment according to the different steps of oxygen transport.
Methods: Fifty-three patients with HFrEF (24 with ischemic cardiomyopathy (ICM) and 29 with dilated cardiomyopathy (DCM) had an aerobic ET. Before and after ET program, peak oxygen consumption (VO _2peak ) and cardiac output using thoracic impedancemetry were measured. Oxygen convection (QO _2peak ) and diffusion (DO ₂ ) were calculated using Fick’s principle and Fick’s simplified law. Patients were considered as responders if the gain was superior to 10%.
Results: We found 55% VO _2peak responders, 62% QO _2peak responders and 56% DO ₂ responders. Four patients did not have any response. None baseline predictive factor for VO _2peak response was found. QO _2peak response was related to exercise stroke volume (r = 0.84), cardiac power (r = 0.83) and systemic vascular resistance (SVR _peak ) (r = -0.42) responses. Cardiac power response was higher in patients with ICM than in those with DCM (p < 0.05). Predictors of QO2 _peak response were low baseline exercise stroke volume and ICM etiology. Predictors of DO ₂ response were higher baseline blood creatinine and prolonged training.
Conclusion: The analysis of the response to training in patients with HFrEF according to the different steps of oxygen transport revealed different phenotypes on VO _2peak responses, namely responses in either oxygen convection and/or diffusion.

Yang SH; Yang MC; Wu YK; Wu CW; Hsieh PC; Kuo CY; Tzeng IS; Lan CC;

International journal of chronic obstructive pulmonary disease [Int J Chron Obstruct Pulmon Dis] 2021 Feb 10; Vol. 16, pp. 245-256. Date of Electronic Publication: 2021 Feb 10 (Print Publication: 2021).

Introduction: Chronic obstructive pulmonary disease (COPD) is a progressive disease with deteriorating cardiopulmonary function that decreases the health-related quality of life (HRQL) and exercise capacity. Patients with COPD often have cardiovascular and muscular problems that hinder oxygen uptake by peripheral tissues, resulting in poor oxygen consumption efficiency. It is important to develop new physiological parameters to evaluate oxygen consumption efficiency during activities and to evaluate its association with exercise capacity and HRQL. Work efficiency (WE) measures oxygen consumption efficiency during exercise. We hypothesize that patients with poor WE should have exercise intolerance and poor HRQL. Therefore, we aimed to evaluate the association between WE and exercise capacity, HRQL and other cardiopulmonary parameters.
Patients and Methods: Seventy-eight patients with COPD were evaluated with spirometry, cardiopulmonary exercise testing, and assessment of dyspnea score and HRQL (using the St. George’s Respiratory Questionnaire [SGRQ]). Cardiopulmonary exercise testing was performed using a cycle ergometer with an incremental protocol and exhaled breath analysis to assess oxygen consumption. WE was defined as the relationship between oxygen consumption and workload.
Results: There were 31 patients with normal WE (group I) and 47 patients (group II) with poor WE. Patients with poor WE had lower exercise capacity (maximal oxygen consumption, group I vs II as 1050±53 vs 845 ±34 mL/min, p=0.0011), poorer HRQL (SGRQ score 41.1±3.0 vs 55±2.2, p=0.0002), higher exertional dyspnea score (5.1±0.2 vs 6.1±0.2, p= 0.0034) and early anaerobic metabolism during exercise (anaerobic threshold, 672±27 vs 583 ±18 mL/min, p=0.0052).
Conclusion: WE is associated with exercise capacity and HRQL. Here, patients with poor WE also had exercise intolerance, poorer HRQL, and more exertional dyspnea.

Chuda A; Banach M; Maciejewski M; Bielecka-Dabrowa A;

Irish journal of medical science [Ir J Med Sci] 2021 Feb 17. Date of Electronic Publication: 2021 Feb 17.

Heart failure (HF) is the only cardiovascular disease with an ever increasing incidence. HF, through reduced functional capacity, frequent exacerbations of disease, and repeated hospitalizations, results in poorer quality of life, decreased work productivity, and significantly increased costs of the public health system. The main challenge in the treatment of HF is the availability of reliable prognostic models that would allow patients and doctors to develop realistic expectations about the prognosis and to choose the appropriate therapy and monitoring method. At this moment, there is a lack of universal parameters or scales on the basis of which we could easily capture the moment of deterioration of HF patients’ condition. Hence, it is crucial to identify such factors which at the same time will be widely available, cheap, and easy to use. We can find many studies showing different predictors of unfavorable outcome in HF patients: thorough assessment with echocardiography imaging, exercise testing (e.g., 6-min walk test, cardiopulmonary exercise testing), and biomarkers (e.g., N-terminal pro-brain type natriuretic peptide, high-sensitivity troponin T, galectin-3, high-sensitivity C-reactive protein). Some of them are very promising, but more research is needed to create a specific panel on the basis of which we will be able to assess HF patients. At this moment despite identification of many markers of adverse outcomes, clinical decision-making in HF is still predominantly based on a few basic parameters, such as the presence of HF symptoms (NYHA class), left ventricular ejection fraction, and QRS complex duration and morphology.

Smith E; Thomas M; Calik-Kutukcu E; Torres-Sánchez I; Granados-Santiago M; Quijano-Campos JC; Sylvester K; Burtin C; Sajnic A; DBrandt J; Cruz J;

ERJ open research [ERJ Open Res] 2021 Feb 08; Vol. 7 (1). Date of Electronic Publication: 2021 Feb 08 (Print Publication: 2021).

This article provides an overview of outstanding sessions that were (co)organised by the Allied Respiratory Professionals Assembly during the European Respiratory Society International Congress 2020, which this year assumed a virtual format. The content of the sessions was mainly targeted at allied respiratory professionals, including respiratory function technologists and scientists, physiotherapists, and nurses. Short take-home messages related to spirometry and exercise testing are provided, highlighting the importance of quality control. The need for quality improvement in sleep interventions is underlined as it may enhance patient outcomes and the working capacity of healthcare services. The promising role of digital health in chronic disease management is discussed, with emphasis on the value of end-user participation in the development of these technologies. Evidence on the effectiveness of airway clearance techniques in chronic respiratory conditions is provided along with the rationale for its use and challenges to be addressed in future research. The importance of assessing, preventing and reversing frailty in respiratory patients is discussed, with a clear focus on exercise-based interventions. Research on the impact of disease-specific fear and anxiety on patient outcomes draws attention to the need for early assessment and intervention. Finally, advances in nursing care related to treatment adherence, self-management and patients’ perspectives in asthma and chronic obstructive pulmonary disease are provided, highlighting the need for patient engagement and shared decision making. This highlights article provides readers with valuable insight into the latest scientific data and emerging areas affecting clinical practice of allied respiratory professionals.

van Wijk L; van der Snee L; Buis CI; Hentzen JEKR; Haveman ME; Klaase JM;

Perioperative medicine (London, England) [Perioper Med (Lond)] 2021 Feb 17; Vol. 10 (1), pp. 5. Date of Electronic Publication: 2021 Feb 17.

Introduction: Despite improvements in perioperative care, major abdominal surgery continues to be associated with significant perioperative morbidity. Accurate preoperative risk stratification and optimisation (prehabilitation) are necessary to reduce perioperative morbidity. This study evaluated the screening and assessment of modifiable risk factors amendable for prehabilitation interventions and measured the patient compliance rate with recommended interventions.
Method: Between May 2019 and January 2020, patients referred to our hospital for HPB surgery were screened and assessed on six modifiable preoperative risk factors. The risk factors and screening tools used, with cutoff values, included (i) low physical fitness (a 6-min walk test < 82% of patient’s calculated norm and/or patient’s activity level not meeting the global recommendations on physical activity for health). Patients who were unfit based on the screening were assessed with a cardiopulmonary exercise test (anaerobic threshold ≤ 11 mL/kg/min); (ii) malnutrition (patient-generated subjective global assessment ≥ 4); (iii) iron-deficiency anaemia (haemoglobin < 12 g/dL for women, < 13 g/dL for men and transferrin saturation ≤ 20%); (iv) frailty (Groningen frailty indicator/Robinson frailty score ≥ 4); (v) substance use (smoking and alcohol use of > 5 units per week) and (vi) low psychological resilience (Hospital Anxiety and Depression Scale ≥ 8). Patients had a consultation with the surgeon on the same day as their screening. High-risk patients were referred for necessary interventions.
Results: One hundred consecutive patients were screened at our prehabilitation outpatient clinic. The prevalence of high-risk patients per risk factor was 64% for low physical fitness, 42% for malnutrition, 32% for anaemia (in 47% due to iron deficiency), 22% for frailty, 12% for smoking, 18% for alcohol use and 21% for low psychological resilience. Of the 77 patients who were eventually scheduled for surgery, 53 (68.8%) needed at least one intervention, of whom 28 (52.8%) complied with 100% of the necessary interventions. The median (IQR) number of interventions needed in the 77 patients was 1.0 (0-2).
Conclusion: It is feasible to screen and assess all patients referred for HPB cancer surgery for six modifiable risk factors. Most of the patients had at least one risk factor that could be optimised. However, compliance with the suggested interventions remains challenging.

Knuiman P; Straw S; Gierula J; Koshy A; Roberts LD; Witte KK; Ferguson C; Bowen TS;

ESC heart failure [ESC Heart Fail] 2021 Feb 20. Date of Electronic Publication: 2021 Feb 20.

Aims: Heart failure with reduced ejection fraction (HFrEF) induces skeletal muscle mitochondrial abnormalities that contribute to exercise limitation; however, specific mitochondrial therapeutic targets remain poorly established. This study quantified the relationship and contribution of distinct mitochondrial respiratory states to prognostic whole-body measures of exercise limitation in HFrEF.
Methods and Results: Male patients with HFrEF (n = 22) were prospectively enrolled and underwent ramp-incremental cycle ergometry cardiopulmonary exercise testing to determine exercise variables including peak pulmonary oxygen uptake (V̇O _2peak ), lactate threshold (V̇O _2LT ), the ventilatory equivalent for carbon dioxide (V̇ _E /V̇CO _2LT ), peak circulatory power (CircP _peak ), and peak oxygen pulse. Pectoralis major was biopsied for assessment of in situ mitochondrial respiration. All mitochondrial states including complexes I, II, and IV and electron transport system (ETS) capacity correlated with V̇O _2peak (r = 0.40-0.64; P < 0.05), V̇O _2LT (r = 0.52-0.72; P < 0.05), and CircP _peak (r = 0.42-0.60; P < 0.05). Multiple regression analysis revealed that combining age, haemoglobin, and left ventricular ejection fraction with ETS capacity could explain 52% of the variability in V̇O _2peak and 80% of the variability in V̇O _2LT , respectively, with ETS capacity (P = 0.04) and complex I (P = 0.01) the only significant contributors in the model.
Conclusions: Mitochondrial respiratory states from skeletal muscle biopsies of patients with HFrEF were independently correlated to established non-invasive prognostic cycle ergometry cardiopulmonary exercise testing indices including V̇O _2peak , V̇O _2LT , and CircP _peak . When combined with baseline patient characteristics, over 50% of the variability in V̇O _2peak could be explained by the mitochondrial ETS capacity. These data provide optimized mitochondrial targets that may attenuate exercise limitations in HFrEF.

T. Takken, C.F. Mylius, D. Paap, W. Broeders, H.J. Hulzebos, M. Van Brussel & B.C. Bongers

Expert Review of Cardiovascular Therapy,
DOI: 10.1080/14779072.2019.1627874
https://doi.org/10.1080/14779072.2019.1627874

Introduction: Reference values for cardiopulmonary exercise testing (CPET) parameters provide the
comparative basis for answering important questions concerning the normalcy of exercise responses in
patients, and significantly impacts the clinical decision-making process.
Areas covered: The aim of this study was to provide an updated systematic review of the literature on
reference values for CPET parameters in healthy subjects across the life span.
A systematic search in MEDLINE, Embase, and PEDro databases were performed for articles describing
reference values for CPET published between March 2014 and February 2019.
Expert opinion: Compared to the review published in 2014, more data have been published in the last
five years compared to the 35 years before. However, there is still a lot of progress to be made. Quality
can be further improved by performing a power analysis, a good quality assurance of equipment and
methodologies, and by validating the developed reference equation in an independent (sub)sample.
Methodological quality of future studies can be further improved by measuring and reporting the level
of physical activity, by reporting values for different racial groups within a cohort as well as by the
exclusion of smokers in the sample studied. Normal reference ranges should be well defined in
consensus statements.

Papp D; Takken T;

December 2014. Expert Review of Cardiovascular Therapy 12(12):1439-53

Reference values (RV) for cardiopulmonary exercise testing (CPET) provide the comparative basis for answering important questions concerning the normality of exercise response in patients and significantly impacts the clinical decision-making process. The aim of this study is to systematically review the literature on RV for CPET in healthy adults. A secondary aim is to make appropriate recommendations for the practical use of RV for CPET. Systematic searches of MEDLINE, EMBASE and PEDro databases up to March 2014 were performed. In the last 30 years, 35 studies with CPET RV were published. There is no single set of ideal RV; characteristics of each population are too diverse to pool the data in a single equation. Therefore, each exercise laboratory must select appropriate sets of RV that best reflect the characteristics of the population/patient tested, and equipment and methodology utilized.