Bhatia R; Phoenix Children’s Hospital, Phoenix, Arizona, USA.

Indian pediatrics [Indian Pediatr] 2024 Oct 22.
Date of Electronic Publication: 2024 Oct 22.

Cardiopulmonary exercise testing (CPET) is a noninvasive test that provides a comprehensive assessment of the integrative exercise responses by measuring parameters calculated on a breath-by-breath basis. It can provide insight into the fitness level, cause of exercise limitation, and safe parameters for exercise prescription in children 6 years and older. Common indications for CPET include undiagnosed exercise-induced dyspnea, exercise intolerance in pediatric chronic conditions and for monitoring response after therapy/intervention. It can be utilized to assess the overall fitness, pre-operative risk, and prognosis in chronic conditions. CPET is accessible and dependable in pediatrics, yet challenges like a lack of standardized protocols are noted. With continued development and technological advancements in CPET, there is potential for revolutionizing pediatric diagnostic health care.

Alves ES; University Centre for Rural Health (UCRH) School of Health Sciences University of Sydney, Lismore, New South Wales, Australia.;
Bellet RN; Sharma P; Balmain BN; Aitken C; Doering T;Orola L; Green A; Paim T; , O’Connor F; Morris NR;

Rehabilitation research and practice [Rehabil Res Pract] 2024 Sep 30; Vol. 2024, pp. 1317817.
Date of Electronic Publication: 2024 Sep 30 (Print Publication: 2024).

Purpose: To compare physiological responses during a treadmill cardiopulmonary exercise test (CPX), 6-minute walk test (6MWT), and timed up and go test (TUGT) in individuals referred for unexplained breathlessness and symptom limited treadmill exercise testing.
Methods: Heart rate (HR), oxygen consumption (V̇O ₂ ), carbon dioxide production (V̇CO ₂ ), respiratory exchange ratio (RER), minute ventilation (V̇ _E ), systolic blood pressure (SBP), and rating of perceived exertion (RPE) were recorded throughout each test.
Results: Each test demonstrated a significant increase ( p < 0.01) in the cardiopulmonary (V̇O ₂ , V̇CO ₂ and V̇ _E , RPE, SBP, and HR) and perceptual (RPE) responses from rest to end exercise. The increase in cardiopulmonary and perceptual responses was greatest for the CPX with significantly smaller responses demonstrated during the 6MWT ( p < 0.01) and even smaller responses for the TUGT ( p < 0.01 vs CPX and 6MWT).
Conclusion: Not surprisingly, the treadmill CPX results is the greatest physiological response in our group. Despite being of short duration, the TUGT results in an increased physiological response.

Collins SÉ; Division of Pulmonary Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada;
Kirby M; Smith BM;Tan W; Bourbeau J; Thompson S; van Diepen S; Jensen D; Stanojevic S; Stickland M

Chest [Chest] 2024 Oct 03.
Date of Electronic Publication: 2024 Oct 03.

Background: Although it is generally accepted that aerobic exercise training does not change lung structure or function, some work suggests that greater pulmonary vascular structure and function is associated with higher exercise capacity (VO2peak).
Research Question: Is there a cross-sectional association between the pulmonary vasculature and VO2peak? We hypothesized that those with higher computed tomography (CT) blood vessel volumes, and pulmonary diffusing capacity for carbon monoxide (D _L CO) would have higher VO2peak, independent of airflow limitation.
Study Design and Methods: Participants from the CanCOLD study were categorized as: never-smokers with normal spirometry (n=263); ever-smokers with normal spirometry (n=407); and chronic obstructive pulmonary disease (COPD): individuals with spirometric airflow obstruction (n=334). Total vessel volume (TVV), the volume for all vessels with a cross-sectional area ≤5 mm ² (BV5), and between 5-10 mm ² (BV5-10) were generated from CT scans and used as indices of pulmonary vascular structure. D _L CO was used as an index of pulmonary microvascular function. VO2peak was evaluated via incremental cardiopulmonary exercise testing.
Results: General linear regression models revealed that even after controlling for FEV ₁ , emphysema severity and body morphology, D _L CO, TVV, BV5 and BV5-10, were independently associated with VO2peak. Interaction effects were observed between COPD and TVV, BV5, and BV5-10 indicating a weaker association between pulmonary vascular volumes and VO2peak in COPD.
Interpretation: Our results suggest that pulmonary vascular structure and D _L CO is independently associated with VO2peak, regardless of severity of airflow limitation and emphysema, suggesting that these associations are not limited to COPD.

Chandan N; Institute for Cardio-Metabolic Medicine, University Hospital Coventry, Coventry, United Kingdom.;
Matthews V; He H; Lachlan T; Lim VG; Joshi S; Hee SW; Noufaily A; Parkes E; Patel S;Andronis L;Shakespeare J; Eftekhari H; Ali A; McGregor G; Osman F

PloS one [PLoS One] 2024 Oct 03; Vol. 19 (10), pp. e0310951.
Date of Electronic Publication: 2024 Oct 03 (Print Publication: 2024).

Background: Atrial fibrillation (AF) is associated with significant morbidity/mortality. AF-ablation is an increasingly used treatment. Currently, first-time AF-ablation success is 40-80% at 1-year, depending on individual factors. There is growing evidence for improved outcomes through management of AF risk-factors/comorbidities via patient education/exercise-rehabilitation. There are no studies assessing combined prehabilitation/rehabilitation in this cohort. The aim of this randomised controlled trial is to assess efficacy of comprehensive prehabilitation/rehabilitation and combining supervised exercise-training with AF risk-factor modification/education compared with standard care in people undergoing first-time AF ablation.
Methods: This single-centre pragmatic randomised controlled trial will recruit 106 adults with paroxysmal/persistent AF listed for first-time AF-ablation. Participants will be randomised 1:1 to cardiac prehabilitation/rehabilitation/education (CREED AF) intervention or standard care. Both groups will undergo AF-ablation at 8-weeks post-randomisation as per usual care. The CREED AF intervention will involve 6-weeks of prehabilitation (before AF-ablation) followed by 6-weeks rehabilitation (after AF-ablation) consisting of risk factor education/modification and supervised exercise training. Standard care will include a single 30-minute session of risk-factor education. Outcomes will be measured at baseline, 10-weeks and 12-months post AF-ablation, by researchers blinded to treatment allocation. The primary outcome is cardiorespiratory-fitness (peak oxygen uptake, VO2peak) assessed using cardiopulmonary exercise testing (CPET) at 10-weeks post-ablation. Secondary outcomes include health-related quality of life, AF recurrence/burden assessed by 7-day Holter-monitor, requirement for repeat AF-ablation, study defined major adverse cardiovascular events, and cost-effectiveness (incremental cost per quality-adjusted life year (QALY)).
Conclusions: This study will assess clinical-efficacy/cost-effectiveness of comprehensive prehabilitation/rehabilitation/patient-education for people undergoing first time AF-ablation. Results will inform clinical care and design of future multi-centre clinical trials.

Gass R; Hospital de Clínicas de Porto Alegre (HCPA), Brasil.
Plachi F; Silva FOB; Nolasco T; Tonetto MS; Goelzer LS; Muller PT; Knorst MM; Neder JA; Berton DC;

Respiratory physiology & neurobiology [Respir Physiol Neurobiol] 2024 Oct 08, pp. 104359.
Date of Electronic Publication: 2024 Oct 08.

Excess exercise ventilation (high ventilation (V̇ _E )/carbon dioxide output (V̇CO ₂ )) contributes significantly to dyspnea and exercise intolerance since the earlier stages of chronic obstructive pulmonary disease (COPD). A selective pulmonary vasodilator (inhaled nitric oxide) has shown to increase exercise tolerance secondary to lower V̇ _E /V̇CO ₂ and dyspnea in patients with early COPD. We aimed to assess whether a clinically more practical option – oral sildenafil – would be associated with similar beneficial effects. In a randomized, placebo-controlled study, twenty-four patients with mild-to-moderate COPD completed, on different days, two incremental cardiopulmonary exercise tests (CPET) one hour after sildenafil or placebo. Eleven healthy participants performed a CPET in a non-interventional visit for comparative purposes with patients when receiving placebo. Patients (FEV ₁ = 69.4 ± 13.5% predicted) showed higher ventilatory demands (V̇ _E /V̇CO ₂ ), worse pulmonary gas exchange, and higher dyspnea during exercise compared to controls (FEV ₁ = 98.3 ±11.6% predicted). Contrary to our expectations, however, sildenafil (50mg; N= 15) did not change exertional V̇ _E /V̇CO ₂ , dead space/tidal volume ratio, operating lung volumes, dyspnea, or exercise tolerance compared to placebo (P>0.05). Due to the lack of significant beneficial effects, nine additional patients were trialed with a higher dose (100mg). Similarly, active intervention was not associated with positive physiological or sensory effects. In conclusion, acute oral sildenafil (50 or 100mg) failed to improve gas exchange efficiency or excess exercise ventilation in patients with predominantly moderate COPD. The current study does not endorse a therapeutic role for sildenafil to mitigate exertional dyspnea in this specific patient subpopulation.

Gerçek M; Clinic for General and Interventional Cardiology/Angiology,  Bad Oeynhausen, Germany.
Goncharov A; Gerçek M; Mörsdorf M; Kirchner J; Rudolph F; Rudolph TK;Rudolph V; Friedrichs KP; Dumitrescu D;

Clinical research in cardiology : official journal of the German Cardiac Society [Clin Res Cardiol] 2024 Oct 09.
Date of Electronic Publication: 2024 Oct 09.

Background: Transcatheter tricuspid valve intervention (TTVI) has shown promising results with persistent reduction of tricuspid regurgitation (TR) and improvements in functional class and quality of life (QOL).
Objectives: To analyze the impact of TTVI on maximal and submaximal exercise capacity (SEC).
Methods: Constant work-rate exercise-time (CWRET) testing reflects SEC, which is more likely to be relevant for daily life activities and provides more differentiated physiological insight into the nature of exercise intolerance. Thus, 30 patients undergoing TTVI (21 direct annuloplasty and 9 edge-to-edge repair) received cardiopulmonary exercise testing (CPET) and CWRET (at 75% of maximum work rate in the initial CPET) before and 3 months after TTVI.
Results: Patients’ age was 80.5 [74.8-82.3] years and 53.3% were female. TR reduction ≥ 2 grades was achieved in 93.3% (TR grade ≤ moderate in 83.3%). Echocardiography revealed improved right ventricular (RV) characteristics with decreased RV basal diameter (47.0 mm [43.0-54.3] vs. 41.5 mm [36.8-48.0]; p < 0.001) and decreased inferior caval vein diameter. CWRET testing showed a significantly improved SEC (246.5 s [153.8-416.8] vs. 338.5 s [238.8-611.8] p = 0.001). Maximum oxygen uptake showed a positive trend without statistically significant differences (9.9 ml/min/kg [8.6-12.4] vs. 11.7 ml/min/kg [9.7-13.3]; p = 0.31). In contrast to the six-minute-walking distance (6MWD), SEC correlated moderately with effective regurgitation orifice area reduction (r = 0.385; p = 0.036), increased cardiac output (r = 0.378; p = 0.039), and improved QOL (r = 387; p = 0.035).
Conclusion: Improvements in exercise capacity after TTVI mainly occur in the submaximal rather than in the maximal exercise range and correlate with hemodynamic effects and QOL. This may have a methodological impact on assessment of exercise capacity in these patients.

Arvanitaki A; National Pulmonary Hypertension Service, Royal Brompton Hospital, London, UK.;
Diller GP; Gatzoulis MA; McCabe C; Price LC

European respiratory review : an official journal of the European Respiratory Society [Eur Respir Rev] 2024 Oct 09; Vol. 33 (174).
Date of Electronic Publication: 2024 Oct 09 (Print Publication: 2024).

Pulmonary hypertension (PH) is highly prevalent in patients with interstitial lung disease (ILD) and is associated with increased morbidity and mortality. Widely available noninvasive screening tools are warranted to identify patients at risk for PH, especially severe PH, that could be managed at expert centres. This review summarises current evidence on noninvasive diagnostic modalities and prediction models for the timely detection of PH in patients with ILD. It critically evaluates these approaches and discusses future perspectives in the field. A comprehensive literature search was carried out in PubMed and Scopus, identifying 39 articles that fulfilled inclusion criteria. There is currently no single noninvasive test capable of accurately detecting and diagnosing PH in ILD patients. Estimated right ventricular pressure (RVSP) on Doppler echocardiography remains the single most predictive factor of PH, with other indirect echocardiographic markers increasing its diagnostic accuracy. However, RVSP can be difficult to estimate in patients due to suboptimal views from extensive lung disease. The majority of existing composite scores, including variables obtained from chest computed tomography, pulmonary function tests and cardiopulmonary exercise tests, were derived from retrospective studies, whilst lacking validation in external cohorts. Only two available scores, one based on a stepwise echocardiographic approach and the other on functional parameters, predicted the presence of PH with sufficient accuracy and used a validation cohort. Although several methodological limitations prohibit their generalisability, their use may help physicians to detect PH earlier. Further research on the potential of artificial intelligence may guide a more tailored approach, for timely PH diagnosis.
Competing Interests: Conflict of interest: A. Arvanitaki, M.A. Gatzoulis and C. McCabe declare no conflicts of interest relevant to this work. ​G.P. Diller has received honoraria and travel grants from Janssen Global. L.C. Price has received consultancy fees from Janssen and educational support and conference support from Janssen and Ferrer. S.J. Wort has received consultancy fees from Janssen, Acceleron, MSD, Ferrer and Bayer, honoraria from Janssen, Acceleron, MSD, Ferrer and Bayer, as well as travel and research grants from Janssen and Ferrer.

VanAken G; Department of Internal Medicine University of Michigan Ann Arbor Michigan USA.
Wieczorek D; Rubick D; Jabri A; Franco-Palacios D; Grafton G; Kelly B; Osinbowale O; Ahsan ST; Awdish R; Aronow HD; Shore S; Aggarwal V

Pulmonary circulation [Pulm Circ] 2024 Oct 10; Vol. 14 (4), pp. e12451.
Date of Electronic Publication: 2024 Oct 10 (Print Publication: 2024).

Recent reports have revealed a substantial morbidity burden associated with “post-PE syndrome” (PPES). Cardiopulmonary exercise testing (CPET) has shown promise in better characterizing these patients. In this systematic review and pooled analysis, we aim to use CPET data from PE survivors to understand PPES better. A literature search was conducted in PubMed, EMBASE, and Cochrane for studies reporting CPET results in post-PE patients without known pulmonary hypertension published before August 1, 2023. Studies were independently reviewed by two authors. CPET findings were subcategorized into (1) exercise capacity (percent predicted pVO ₂ and pVO ₂ ) and (2) ventilatory efficiency (VE/VCO ₂ slope and V _D /V _T ). We identified 14 studies ( n  = 804), 9 prospective observational studies, 4 prospective case-control studies, and 1 randomized trial. Pooled analysis demonstrated a weighted mean percent predicted pVO ₂ of 76.09 ± 20.21% ( n  = 184), with no difference between patients tested <6 months ( n  = 76, 81.69±26.06%) compared to ≥6 months post-acute PE ( n  = 88, 82.55 ± 21.47%; p  = 0.817). No difference was seen in pVO ₂ in those tested <6 months ( n  = 76, 1.67 ± 0.51 L/min) compared to ≥6 months post-acute PE occurrence ( n  = 144, 1.75 ± 0.57 L/min; p  = 0.306). The weighted mean VE/VCO ₂ slope was 32.72 ± 6.02 ( n  = 244), with a significant difference noted between those tested <6 months ( n  = 91, 36.52 ± 6.64) compared to ≥6 months post-acute PE ( n  = 191, 31.99 ± 5.7; p  < 0.001). In conclusion, this study, which was limited by small sample sizes and few multicenter studies, found no significant difference in exercise capacity between individuals tested <6 months versus ≥6 months after acute PE. However, ventilatory efficiency was significantly improved in patients undergoing CPET ≥ 6 months compared to those <6 months from the index PE.