Radtke T; Department of Paediatric Respiratory and Sleep Medicine, Edinburgh, United Kingdom.
Urquhart DS; Braun J; Barry PJ; Waller I; Petch N; Mei-Zahav M;
Kramer MR; Hua-Huy T; Dinh-Xuan AT; Innes JA; McArthur S; Sovtic A;
Gojsina B; Verges S; de Maat T; Morrison L; Wood J; Crute S; Williams CA;
Tomlinson OW; Bar-Yoseph R; Hebestreit A; Quon BS; Kwong E; Saynor ZL;
Causer AJ; Stephenson AL; Schneiderman JE; Shaw M; Dwyer T; Stevens D;
Remus N; Douvry B; Foster K; Benden C; Ratjen F; Hebestreit H

Annals of the American Thoracic Society. 21(3):411-420, 2024 Mar. VI 1

Rationale: Cardiopulmonary exercise testing (CPET) provides prognostic
information in cystic fibrosis (CF); however, its prognostic value for
patients with advanced CF lung disease is unknown. Objectives: To
determine the prognostic value of CPET on the risk of death or lung
transplant (LTX) within 2 years.
Methods: We retrospectively collected data from 20 CF centers in Asia, Australia, Europe, and North America on
patients with a forced expiratory volume in 1 second (FEV1) 40% predicted
who performed a cycle ergometer CPET between January 2008 and December
2017. Time to death/LTX was analyzed using mixed Cox proportional hazards
regression. Conditional inference trees were modeled to identify subgroups
with increased risk of death/LTX. Results: In total, 174 patients (FEV1,
30.9% +/- 5.8% predicted) were included. Forty-four patients (25.5%) died
or underwent LTX. Cox regression analysis adjusted for age, sex, and FEV1
revealed percentage predicted peak oxygen uptake ([Formula: see
text]o2peak) and peak work rate (Wpeak) as significant predictors of
death/LTX: adjusted hazard ratios per each additional 10% predicted were
0.60 (95% confidence interval, 0.43-0.90; P = 0.008) and 0.60 (0.48-0.82;
P < 0.001). Tree-structured regression models, including a set of 11
prognostic factors for survival, identified Wpeak to be most strongly
associated with 2-year risk of death/LTX. Probability of death/LTX was
45.2% for those with a Wpeak 49.2% predicted versus 10.9% for those with
a Wpeak > 49.2% predicted (P < 0.001).
Conclusions: CPET provides prognostic information in advanced CF lung disease, and Wpeak appears to
be a promising marker for LTX referral and candidate selection.

Ittermann T; Clinical-Epidemiological Research, University Medicine Greifswald, Germany
Kaczmarek S; Obst A; Konemann R; Bahls M; Dorr M; Stubbe B; Heine A; Habedank D; Ewert R;

Scientific Reports. 14(1):5394, 2024 03 05. VI 1

Recently, the parameter internal work (IW) has been introduced as change
in oxygen uptake (VO2) between resting and unloading workload in
cardiopulmonary exercise testing (CPET). The proportional IW (PIW) was
defined as IW divided by VO2 at peak exercise. A second option is to
calculate the PIW based on the workload [PIW (Watt)] by considering the
aerobic efficiency. The aim of our study was to investigate whether IW and
PIW differ between patients with and without pulmonary hypertension and
healthy controls. Our study population consisted of 580 patients and 354
healthy controls derived from the Study of Health in Pomerania. The PIW
was slightly lower in patients (14.2%) than in healthy controls (14.9%; p
= 0.030), but the PIW (Watt) was higher in patients (18.0%) than in the
healthy controls (15.9%; p = 0.001). Such a difference was also observed,
when considering only the submaximal workload up to the VAT (19.8% in
patients and 15.1% in healthy controls; p < 0.001). Since the PIW (Watt)
values were higher in patients with pulmonary hypertension, this marker
may serve as a useful CPET parameter in clinical practice. In contrast to
most of the currently used CPET parameters, the PIW does not require a
maximal workload for the patient. Further studies are needed to validate
the prognostic significance of the PIW.

Kristenson K; Linköping University, Linköping, Sweden.
Hylander J; Boros M; Hedman K;

Journal of thoracic disease [J Thorac Dis] 2024 Jan 30; Vol. 16 (1), pp. 123-132.
Date of Electronic Publication: 2024 Jan 24.

Background: Cardiopulmonary exercise testing (CPET) enables measurement of the slope of the increase in minute ventilation in relation to carbon dioxide elimination during exercise (the VE/VCO ₂ slope). Several studies have shown that the VE/VCO ₂ slope is a strong marker for postoperative complications and mortality. However, current thresholds for adverse outcomes are generated from historical data in heart failure patients.
Methods: This was a retrospective analysis of 158 patients with lung cancer who underwent lobectomy or pneumonectomy during 2008-2020. The main outcome was major pulmonary complications (MPC) or death ≤30 days of cancer surgery. Patients were first categorized using two different single threshold approaches; the traditional threshold of 35 and the highest Youden value from the receiver operating curve (ROC) analysis. Secondly, patients were categorized into three risk groups using two thresholds. These two thresholds were determined in an ROC analysis, where the VE/VCO ₂ slope values generating either a 90% sensitivity (lower threshold) or a 90% specificity (upper threshold) for the main outcome were chosen. The frequency of complications was compared using Chi ² . The overall model quality was evaluated by an area under the curve (AUC) analysis. Positive predictive values (PPVs) and negative predictive values (NPVs) are presented.
Results: The two thresholds, <30 (90% sensitivity) and >41 (90% specificity), created three risk groups: low risk (VE/VCO ₂ slope <30, n=44, 28%); intermediate risk (VE/VCO ₂ slope 30-41, n=95, 60%) and high risk (VE/VCO ₂ slope >41, n=19, 12%). The frequency of complications differed between groups: 5%, 16% and 47% (P<0.001). Using two thresholds compared to one threshold increased the overall model quality (reaching AUC 0.70, 95% confidence interval: 0.59-0.81), and identified a high sensitivity threshold (VE/VCO ₂ slope <30) which generated a NPV of 95% but importantly, also a high specificity threshold (VE/VCO ₂ slope >41) with a PPV of 47%.
Conclusions: Risk stratification based on three risk groups from the preoperative VE/VCO ₂ slope increased the model quality, was more discriminative and generated better PPV and NPV compared to traditional risk stratification into two risk groups.

Ozemek C;  University of Illinois, Chicago, IL, USA.
Hardwick J; Bonikowske A; Christle J;German C; Reddy S; Arena R;Faghy M;

Progress in cardiovascular diseases [Prog Cardiovasc Dis] 2024 Feb 26.
Date of Electronic Publication: 2024 Feb 26.

Graded exercise testing is a widely accepted tool for revealing cardiac ischemia and/or arrhythmias in clinical settings. Cardiopulmonary exercise testing (CPET) measures expired gases during a graded exercise test making it a versatile tool that helps reveal underlying physiologic abnormalities that are in many cases only present with exertion. It also characterizes one’s health status and clinical trajectory, informs the therapeutic plan, evaluates the efficacy of therapy, and provides submaximal and maximal information that can be used to tailor an exercise intervention. Practitioners can also modify the mode and protocol to allow individuals of all ages, fitness levels, and most disease states to perform a CPET. When used to its full potential, CPET can be a key tool used to optimize care in primary and secondary prevention settings.

Harber MP; Clinical Exercise Physiology, Chicago, IL, USA
Myers J; Bonikowske AR; Muntaner-Mas A; Molina-Garcia P; Arena R; Healthy Ortega FB;

Progress in cardiovascular diseases [Prog Cardiovasc Dis] 2024 Feb 26.
Date of Electronic Publication: 2024 Feb 26.

Cardiorespiratory fitness (CRF) is a well-established biomarker that has applications to all adults across the health and disease spectrum. Despite the overwhelming evidence supporting the prognostic utility of CRF, it remains vastly underutilized. CRF is optimally measured via cardiopulmonary exercise testing which may not be feasible to implement on a large scale. Therefore, it is prudent to develop ways to accurately estimate CRF that can be applied in clinical and community settings. As such, several prediction equations incorporating non-exercise information that is readily available from routine clinical encounters have been developed that provide an adequate reflection of CRF that could be implemented to raise awareness of the importance of CRF. Further, technological advances in smartphone apps and consumer-grade wearables have demonstrated promise to provide reasonable estimates of CRF that are widely available, which could enhance the utilization of CRF in both clinical and community settings.

Faghy MA; University of Derby, Derby, UK;  & Sheffield Hallam University, Sheffield, UK. &  Illinois Chicago, Chicago, IL, USA
Dalton C; Duncan R; Arena R; Ashton REM;

Progress in cardiovascular diseases [Prog Cardiovasc Dis] 2024 Feb 26.
Date of Electronic Publication: 2024 Feb 26.

Cardio-respiratory fitness (CRF) is well-established in the clinical domains as an integrative measure of the body’s physiological capability and capacity to transport and utilise oxygen during controlled bouts of physical exertion. Long COVID is associated with >200 different symptoms and is estimated to affect ~150 million people worldwide. The most widely reported impact is reduced quality of life and functional status due to highly sensitive and cyclical symptoms that manifest and are augmented following exposure to physical, emotional, orthostatic, and cognitive stimuli, more commonly known as post-exertional symptom exacerbation (PESE) which prevents millions from engaging in routine daily activities. The use of cardiopulmonary exercise testing (CPET) is commonplace in the assessment of integrated physiology; CPET will undoubtedly play an integral role in furthering the pathophysiology and mechanistic knowledge that will inform bespoke Long COVID treatment and management strategies. An inherent risk of previous attempts to utilise CPET protocols in patients with chronic disease is that these are compounded by PESE and have induced a worsening of symptoms for patients that can last for days or weeks. To do this effectively and to meet the global need, the complex multi-system pathophysiology of Long COVID must be considered to ensure the design and implementation of research that is both safe for participants and capable of advancing mechanistic understanding.

Hoedemakers S; Departments of Cardiology, Jessa Hospital, Hasselt, Belgium.
Pugliese NR; Stassen J; Vanoppen A; Claessens J; Gojevic T; Bekhuis Y; Falter M; Moura Ferreira S; Dhont S; De Biase N; Del Punta L; Di Fiore V; De Carlo M; Giannini C; Colli A; Cardiac, Dulgheru RE; Yilmaz A; Claessen G; Bertrand P;Droogmans S; Lancellotti P; Cosyns B; Verbrugge FH; Herbots L; Masi S; Verwerft J;

Circulation [Circulation] 2024 Feb 27.
Date of Electronic Publication: 2024 Feb 27.

Background: Recent guidelines redefined exercise pulmonary hypertension as a mean pulmonary artery pressure/cardiac output (mPAP/CO) slope >3 mm Hg·L ^-1 ·min ^-1 . A peak systolic pulmonary artery pressure >60 mm Hg during exercise has been associated with an increased risk of cardiovascular death, heart failure rehospitalization, and aortic valve replacement in aortic valve stenosis. The prognostic value of the mPAP/CO slope in aortic valve stenosis remains unknown.
Methods: In this prospective cohort study, consecutive patients (n=143; age, 73±11 years) with an aortic valve area ≤1.5 cm ² underwent cardiopulmonary exercise testing with echocardiography. They were subsequently evaluated for the occurrence of cardiovascular events (ie, cardiovascular death, heart failure hospitalization, new-onset atrial fibrillation, and aortic valve replacement) during a follow-up period of 1 year. Findings were externally validated (validation cohort, n=141).
Results: One cardiovascular death, 32 aortic valve replacements, 9 new-onset atrial fibrillation episodes, and 4 heart failure hospitalizations occurred in the derivation cohort, whereas 5 cardiovascular deaths, 32 aortic valve replacements, 1 new-onset atrial fibrillation episode, and 10 heart failure hospitalizations were observed in the validation cohort. Peak aortic velocity (odds ratio [OR] per SD, 1.48; P =0.036), indexed left atrial volume (OR per SD, 2.15; P =0.001), E/e’ at rest (OR per SD, 1.61; P =0.012), mPAP/CO slope (OR per SD, 2.01; P =0.002), and age-, sex-, and height-based predicted peak exercise oxygen uptake (OR per SD, 0.59; P =0.007) were independently associated with cardiovascular events at 1 year, whereas peak systolic pulmonary artery pressure was not (OR per SD, 1.28; P =0.219). Peak Vo ₂ (percent) and mPAP/CO slope provided incremental prognostic value in addition to indexed left atrial volume and aortic valve area ( P <0.001). These results were confirmed in the validation cohort.
Conclusions: In moderate and severe aortic valve stenosis, mPAP/CO slope and percent-predicted peak Vo ₂ were independent predictors of cardiovascular events, whereas peak systolic pulmonary artery pressure was not. In addition to aortic valve area and indexed left atrial volume, percent-predicted peak Vo ₂ and mPAP/CO slope cumulatively improved risk stratification.

Fouzas S;  University of Patras School of Medicine, 26504 Patras, Greece.
Nourloglou A; Vervenioti A; Karatza A; Anthracopoulos M; Dimitriou G;

Children (Basel). 2024 Feb 4;11(2):198. doi: 10.3390/children11020198.

Data on exercise tolerance of children born non-extremely preterm are sparse. We aimed to explore the cardiopulmonary exercise testing (CPET) characteristics in this population. We studied 63 children (age 7-12 years) born at 290/7-366/7 weeks of gestation (34 were late preterm, 29 were preterm) and 63 age-matched, term-born controls. All performed spirometry and CPET (cycle ergometry). There were no differences in activity levels and spirometric parameters between the group of preterm-born children and controls. A peak oxygen uptake (VO2peak) of <80% was noted in 25.4% of the term-born and 49.2% of preterm-born children (p = 0.001). Term-born participants presented similar VO2peak to late-preterm children but higher than those born at <340/7 weeks of gestation (p = 0.002). Ventilatory limitation was noted in 4.8% of term and 7.9% of preterm participants, while only one preterm child presented cardiovascular limitation. Children born before 34 weeks of gestation had higher respiratory rates and smaller tidal volumes at maximum exercise, as well as lower oxygen uptake for the level of generated work. We conclude that school-age children born at 29-34 weeks of gestation may present decreased exercise performance attributed to an altered ventilatory response to exercise and impaired O2 utilization by their skeletal muscles rather than other cardiopulmonary limiting factors.

Tanihata, A; Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine
Shibata, A; Yoshida, T; Kitada, R; Izumiya, Y; Fukuda, D;

Heart Vessels. 2024 Feb 27. doi: 10.1007/s00380-024-02358-w. Online ahead of print.

Exercise intolerance is a symptom of chronic heart failure (CHF). The magnitude of exercise tolerance, as measured by peak oxygen uptake (peak VO2), is strongly associated with prognosis in patients with CHF. We aimed to evaluate the factors associated with improved exercise tolerance in patients with HF. In this prospective study, we recruited patients who were diagnosed with non-ischemic cardiomyopathy between September 2017 and September 2021. All patients underwent cardiopulmonary exercise testing at discharge and 6 months after enrollment. The patients were stratified according to whether peak VO2 was increased or not at 6 months. One hundred patients with a reduced left-ventricular ejection fraction (LVEF < 50%) were enrolled. Improvement of peak VO2 was observed in 74 patients. In male patients, hemoglobin level was higher in the increased peak VO2 group than in the non-increased group (15.0 ± 1.9 g/dL vs. 13.1 ± 2.1 g/dL; p < 0.01). Baseline hemoglobin level was positively correlated with the percentage change in peak VO2 (Spearman’s r = 0.248, p = 0.040). Kaplan-Meier analysis demonstrated that adverse cardiac events were significantly less frequent in the increased peak VO2 group than in the non-increased group (log-rank test, p = 0.032). Multivariate logistic regression analysis identified hemoglobin level as an independent predictor of improved peak VO2 [odds ratio (OR) 1.60; 95% confidence interval (CI) 1.05-2.44; p = 0.027]. Baseline hemoglobin level is an independent predictor of improved peak VO2 in male patients with non-ischemic cardiomyopathy.