Waxman AB; Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (A.B.W., D.M.S.).
Systrom DM; Manimaran S; Lu J; Rischard FP;

Circulation. Heart failure [Circ Heart Fail] 2024 Apr 04, pp. e011227.
Date of Electronic Publication: 2024 Apr 04.

Background: This study aims to assess the impact of sotatercept on exercise tolerance, exercise capacity, and right ventricular function in pulmonary arterial hypertension.
Methods: SPECTRA (Sotatercept Phase 2 Exploratory Clinical Trial in PAH) was a phase 2a, single-arm, open-label, multicenter exploratory study that evaluated the effects of sotatercept by invasive cardiopulmonary exercise testing in participants with pulmonary arterial hypertension and World Health Organization functional class III on combination background therapy. The primary end point was the change in peak oxygen uptake from baseline to week 24. Cardiac magnetic resonance imaging was performed to assess right ventricular function.
Results: Among the 21 participants completing 24 weeks of treatment, there was a significant improvement from baseline in peak oxygen uptake, with a mean change of 102.74 mL/min ([95% CIs, 27.72-177.76]; P =0.0097). Sotatercept demonstrated improvements in secondary end points, including resting and peak exercise hemodynamics, and 6-minute walk distance versus baseline measures. Cardiac magnetic resonance imaging showed improvements from baseline at week 24 in right ventricular function.
Conclusions: The clinical efficacy and safety of sotatercept demonstrated in the SPECTRA study emphasize the potential of this therapy as a new treatment option for patients with pulmonary arterial hypertension. Improvements in right ventricular structure and function underscore the potential for sotatercept as a disease-modifying agent with reverse-remodeling capabilities.

Juarez M; Department of Internal Medicine, Texas Tech University Health Sciences Center, USA.
Castillo-Rodriguez C; Soliman D; Del Rio-Pertuz G; Nugent K;

Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101651414 Publication Model: Electronic Cited Medium: Internet ISSN: 2308-3425 (Electronic) Linking ISSN: 23083425 NLM ISO Abbreviation: J Cardiovasc Dev Dis Subsets: PubMed not MEDLINE

Cardiopulmonary exercise testing (CPET) provides important information for the assessment and management of patients with heart failure. This testing measures the respiratory and cardiac responses to exercise and allows measurement of the oxygen uptake (V˙O ₂ ) max and the relationship between minute ventilation (V˙E) and carbon dioxide excretion (V˙CO ₂ ). These two parameters help classify patients into categories that help predict prognosis, and patients with a V˙O ₂ < 14 mL/kg/min and V˙E/V˙CO ₂ slope >35 have a poor prognosis. This testing has been used in drug trials to determine complex physiologic responses to medications, such as angiotensin-converting enzyme inhibitors. For example, a study with enalapril demonstrated that the peak V˙O ₂ was 14.6 ± 1.6 mL/kg/min on placebo and 15.8 ± 2.0 mL/kg/min on enalapril after 15 days of treatment. The V˙E/V˙CO ₂ slopes were 43 ± 8 on placebo and 39 ± 7 on enalapril. Chronic heart failure and reduced physical activity measured by cardiopulmonary exercise testing are associated with increases in BNP, and several studies have demonstrated that cardiac rehabilitation is associated with reductions in BNP and increases in V˙O ₂ . Therefore, BNP measurements can help determine the benefits of cardiac rehabilitation and provide indirect estimates of changes in V˙O ₂ . In addition, measurement of microRNAs can determine the status of skeletal muscle used during physical activity and the changes associated with rehabilitation. However, CPET requires complicated technology, and simpler methods to measure physical activity could help clinicians to manage their patients. Recent advances in technology have led to the development of portable cardiopulmonary exercise testing equipment, which can be used in various routine physical activities, such as walking upstairs, sweeping the floor, and making the bed, to provide patients and clinicians a better understanding of the patient’s current symptoms. Finally, current smart watches can provide important information about the cardiorespiratory system, identify unexpected clinical problems, and help monitor the response to treatment. The organized use of these devices could contribute to the management of certain aspects of these patients’ care, such as monitoring the treatment of atrial fibrillation. This review article provides a comprehensive overview of the current use of CPET in heart failure patients and discusses exercise principles, methods, clinical applications, and prognostic implications.

Ait Ali L; Institute of Clinical Physiology, National Research Council, Pisa, Italy. & other Italian centres
Martini N;Listo E; Valenti E; Sotelo J; Salvadori S; Passino C; Monteleone A; Stagnaro N; Trocchio G; o, Italy.Marrone C; Raimondi F; Catapano G;

Pediatric cardiology [Pediatr Cardiol] 2024 Mar 22.
Date of Electronic Publication: 2024 Mar 22.

We sought to evaluate the potential clinical role of 4D-flow cardiac magnetic resonance (CMR)-derived energetics and flow parameters in a cohort of patients’ post-Fontan palliation. In patients with Fontan circulation who underwent 4D-Flow CMR, streamlines distribution was evaluated, as well a 4D-flow CMR-derived energetics parameters as kinetic energy (KE) and energy loss (EL) normalized by volume. EL/KE index as a marker of flow efficiency was also calculated. Cardiopulmonary exercise test (CPET) was also performed in a subgroup of patients. The population study included 55 patients (mean age 22 ± 11 years). The analysis of the streamlines revealed a preferential distribution of the right superior vena cava flow for the right pulmonary artery (62.5 ± 35.4%) and a mild preferential flow for the left pulmonary artery (52.3 ± 40.6%) of the inferior vena cave-pulmonary arteries (IVC-PA) conduit. Patients with heart failure (HF) presented lower IVC/PA-conduit flow (0.75 ± 0.5 vs 1.3 ± 0.5 l/min/m ² , p = 0.004) and a higher mean flow-jet angle of the IVC-PA conduit (39.2 ± 22.8 vs 15.2 ± 8.9, p < 0.001) than the remaining patients. EL/KE index correlates inversely with VO ₂ /kg/min: R: – 0.45, p = 0.01 peak, minute ventilation (VE) R: – 0.466, p < 0.01, maximal voluntary ventilation: R:0.44, p = 0.001 and positively with the physiological dead space to the tidal volume ratio (VD/VT) peak: R: 0.58, p < 0.01. From our data, lower blood flow in IVC/PA conduit and eccentric flow was associated with HF whereas higher EL/KE index was associated with reduced functional capacity and impaired lung function. Larger studies are needed to confirm our results and to further improve the prognostic role of the 4D-Flow CMR in this challenging population.

Kim MS;  Pusan National University Hospital, Busan, Republic of Korea.
Bong W; Choi JH; Shin MJ; Lee BJ;

ESC heart failure [ESC Heart Fail] 2024 Mar 26.
Date of Electronic Publication: 2024 Mar 26.

Aims: Frailty is an obstacle to performing cardiopulmonary exercise test (CPET) in patients with chronic heart failure (CHF). We evaluated the usefulness of oxygen uptake efficiency slope (OUES) using a 6 min walk test (6MWT) with portable gas analysis compared with CPET-derived parameters in patients with CHF.
Methods and Results: Patients with CHF who underwent both the 6MWT with portable gas analysis and CPET between December 2016 and May 2020 were retrospectively investigated. The 6MWT-derived and echocardiographic parameters were compared with the OUES and peak oxygen consumption (VO ₂ ) from the CPET. Forty patients were analysed; 50% were male with a mean age of 55.45 ± 14.70 years. Twenty-six patients (65%) had New York Heart Association Functional Classification II or III dyspnoea. Twenty-five patients (62.5%) had heart failure (HF) with preserved ejection fraction (EF) (left ventricular EF > 50%), and nine patients (22.5%) had HF with reduced EF (EF < 40%). During the 6MWT, the peak VO ₂ was 14.97 ± 3.80 mL/kg/min, which was only 74% of the peak VO ₂ in the CPET, 20.18 ± 5.64 mL/kg/min. The OUES in the 6MWT was lower than that in the CPET (1528.87 ± 579.01 in the 6MWT vs. 1638.69 ± 601.31 in the CPET). The 6 min walk distance (6MWD) and OUES in the 6MWT were positively correlated with the OUES in the CPET (6MWD, r = 0.434, P = 0.005; OUES, r = 0.729, P < 0.001). The OUES in the 6MWT showed the strongest correlation with the OUES in the CPET. When we divided patients into two groups according to peak VO ₂ in the CPET, the correlation between OUES values of the 6MWT and that of the CPET was consistently confirmed (peak VO ₂  ≥ 20 mL/kg/min group, r = 0.661, P = 0.001; peak VO ₂  < 20 mL/kg/min group, r = 0.526, P = 0.021). In addition, the 6MWD, OUES, and peak VO ₂ in the 6MWT were associated with peak VO ₂ in the CPET (6MWD, r = 0.627, P < 0.001; OUES, r = 0.452, P = 0.003; and peak VO ₂ , r = 0.492, P = 0.001).
Conclusions: In frail patients with CHF who have difficulty performing maximal exercises, the OUES through the 6MWT may be applied instead of the OUES and peak VO ₂ from the CPET.

Melo Santos AC; de Melo EV; Sousa ACS; Oliveira JLM; Martins-Filho PR; Noronha NCM; do Nascimento CIS; Campos MDSB

Cardiology [Cardiology] 2024 Mar 26.
Date of Electronic Publication: 2024 Mar 26.

Introduction: Left bundle branch block (LBBB) disrupts the electrical activation of the left ventricle (LV), potentially impairing its systolic function, leading to LBBB-induced cardiomyopathy. This study examined cardiopulmonary exercise test (CPET) variables in patients with and without LBBB and assessed the longitudinal development of left ventricular ejection fraction (LVEF).
Method: An observational, comparative clinical study was executed in two stages at a private hospital in Brazil. The sample consisted of 27 individuals: 11 with LBBB and 16 without LBBB, all with preserved LVEF (>50%) and without confirmed ischemia. CPET variables were assessed, and after four years, participants had a transthoracic echocardiogram (TTE) for LVEF re-evaluation. Groups were compared using the t-test or the Chi-square (X²) test. Multivariate analysis of covariance (MANCOVA) determined effect magnitude.
Results: Patients with LBBB demonstrated significant differences in CPET variables, particularly in predicted peak V̇O2, predicted peak PO2, V̇E/V̇CO2 slope, and T½V̇O2. They also exhibited a more significant decline in LVEF over a four-year span compared to the patients without LBBB. Although initial preservation of LVEF, changes in contractile patterns due to LBBB interfered with its systolic function, suggesting early ventricular dysfunction indicated by a reduction in LVEF and an increase in the V̇E/V̇CO2 slope. Despite differences in cardiopulmonary function and changes in LVEF over time between patients with and without LBBB, the effect size was considered mild to moderate.
Conclusions: LBBB patients with initially preserved LVEF displayed reduced exercise tolerance and a decrease in LVEF over time, emphasizing the need for vigilant monitoring and early intervention in these patients.

Larsson P; Faculty of Medicine, University of Oslo, Oslo, Norway.
Edvardsen E; Gay CL; Ursin M; Mack U; Lerdal A;

Topics in stroke rehabilitation [Top Stroke Rehabil] 2024 Mar 27, pp. 1-11.
Date of Electronic Publication: 2024 Mar 27.

Background: Research on cardiorespiratory fitness (CRF) in relation to physical activity (PA) and fatigue after stroke is limited. Increased knowledge of interrelationships between these factors can help optimize rehabilitation strategies and improve health-outcomes.
Objectives: We aimed to: 1) evaluate CRF, PA, and fatigue, 2) characterize patients with impaired versus non-impaired CRF, and 3) examine associations of CRF with PA and fatigue, three months after first-ever ischemic stroke.
Methods: In this cross-sectional study CRF was measured as peak oxygen uptake (VO _2peak ) by cardiopulmonary exercise testing. PA was measured using accelerometers. Fatigue was assessed with the 7-item Fatigue Severity Scale (FSS).
Results: The sample (n=74, mean age 64±13 years, 36% women) had a mean VO _2peak of 27.0±8.7 (86% of predicted). Fifty-one percent met the World Health Organization’s recommendation of ≥150 min of moderate PA/week. Mean steps-per-day was 9316±4424 (113% of predicted). Thirty-five percent of the sample had moderate-to-high fatigue (FSS≥4), mean FSS score was 3.2±1.8.  Patients with impaired CRF (VO _2peak <80% of predicted) had higher body-fat-percent (p<0.01), less moderate-to-vigorous PA (MVPA) (p<0.01) and a trend toward higher fatigue (p=0.053) compared to the non-impaired. Backward regression analysis showed that higher CRF was associated with more MVPA (unstandardized beta [95% CI]: 0.38 [0.15, 0.63], p=0.002) and less fatigue (unstandardized beta [95% CI]: -3.9 [-6.4, -1.6], p=0.004).
Conclusions: Stroke patients had lower CRF compared to reference values. Impaired CRF was mainly related to overweight. Higher CRF was associated with more MVPA and less fatigue. Exercise after stroke may be especially beneficial for patients with impaired CRF.

Watanabe T; Department of Cardiovascular Medicine, Kyushu University,J apan.
Tohyama T; Ikeda M; Fujino T; Hashimoto T; Matsushima S;
Kishimoto J; Todaka K; Kinugawa S; Tsutsui H; Ide T

European Journal of Preventive Cardiology. 31(4):448-457, 2024 Mar 04. VI 1

AIMS: Exercise intolerance is a clinical feature of patients with heart
failure (HF). Cardiopulmonary exercise testing (CPET) is the first-line
examination for assessing exercise capacity in patients with HF. However,
the need for extensive experience in assessing anaerobic threshold (AT)
and the potential risk associated with the excessive exercise load when
measuring peak oxygen uptake (peak VO2) limit the utility of CPET. This
study aimed to use deep-learning approaches to identify AT in real time
during testing (defined as real-time AT) and to predict peak VO2 at
real-time AT.
METHODS AND RESULTS: This study included the time-series data of CPET
recorded at the Department of Cardiovascular Medicine, Kyushu University
Hospital. Two deep neural network models were developed to: (i) estimate
the AT probability using breath-by-breath data and (ii) predict peak VO2
using the data at the real-time AT. The eligible CPET contained 1472
records of 1053 participants aged 18-90 years and 20% were used for model
evaluation. The developed model identified real-time AT with 0.82 for
correlation coefficient (Corr) and 1.20 mL/kg/min for mean absolute error
(MAE), and the corresponding AT time with 0.86 for Corr and 0.66 min for
MAE. The peak VO2 prediction model achieved 0.87 for Corr and 2.25
mL/kg/min for MAE.
CONCLUSION: Deep-learning models for real-time CPET analysis can
accurately identify AT and predict peak VO2. The developed models can be a
competent assistant system to assess a patient’s condition in real time,
expanding CPET utility.

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.