Mazaheri R; Sadeghian M; Nazarieh M; Niederseer D; Schmied C

International Journal of Environmental Research & Public Health
[Electronic Resource]. 18(24), 2021 12 08.

BACKGROUND: Peak oxygen consumption (VO2) measured by cardiopulmonary
exercise testing (CPET) is a significant predictor of mortality and future
transplantation in heart failure patients with severely reduced ejection
fraction (HFrEF). The present study evaluated the differences in peak VO2
and other prognostic variables between treadmill and cycle CPETs in these
patients.
METHODS: In this cross-over study design, thirty males with severe HFrEF
underwent CPET on both a treadmill and a cycle ergometer within 2-5 days
apart, and important CPET parameters between two exercise test modalities
were compared.
RESULTS: Peak VO2 was 23.12% higher on the treadmill than on cycle (20.55
+/- 3.3 vs. 16.69 +/- 3.01, p < 0.001, respectively). Minute ventilation
to carbon dioxide production (VE/VCO2) slope was not different between the
two CPET modes (p = 0.32). There was a strong positive correlation between
the VE/VCO2 slopes during treadmill and cycle testing (r = 0.79; p <
0.001). VE/VCO2 slope was not related to peak respiratory exchange ratio
(RER) in either modality (treadmill, r = 0.13, p = 0.48; cycle, r = 0.25,
p = 0.17). The RER level was significantly higher on the cycle ergometer
(p < 0.001).
CONCLUSION: Peak VO2 is higher on treadmill than on cycle ergometer in
severe HFrEF patients. In addition, VE/VCO2 slope is not a modality
dependent parameter and is not related to the patients’ effort during
CPET.

Jonathan Wagner, Max Niemeyer, Denis Infanger, Otmar Pfister, Jonathan Myers; Arno Schmidt-Trucksäss and Raphael Knaier

Frontiers in Physiology | www.frontiersin.org
November 2021 | Volume 12 | Article 775601

Objective: The aim of this study was to analyze whether V˙ O2-kinetics during
cardiopulmonary exercise testing (CPET) is a useful marker for the diagnosis of
heart failure (HF) and to determine which V˙ O2-kinetic parameter distinguishes healthy
participants and patients with HF.
Methods: A total of 526 healthy participants and 79 patients with HF between 20 and
90 years of age performed a CPET. The CPET was preceded by a 3-min low-intensity
warm-up and followed by a 3-min recovery bout. V˙ O2-kinetics was calculated from
the rest to exercise transition of the warm-up bout (on-kinetics), from the exercise to
recovery transition following ramp test termination (off-kinetics) and from the initial delay
of V˙ O2 during the warm-up to ramp test transition (ramp-kinetics).
Results: V˙ O2 off-kinetics showed the highest z-score differences between healthy
participants and patients with HF. Furthermore, off-kinetics was strongly associated
with V˙ O2peak. In contrast, ramp-kinetics and on-kinetics showed only minimal z-score
differences between healthy participants and patients with HF. The best on- and
off-kinetic parameters significantly improved a model to predict the disease severity.
However, there was no relevant additional value of V˙ O2-kinetics when V˙ O2peak was
part of the model.
Conclusion: V˙ O2 off-kinetics appears to be superior for distinguishing patients with HF
and healthy participants compared with V˙ O2 on-kinetics and ramp-kinetics. If V˙ O2peak
cannot be determined, V˙ O2 off-kinetics provides an acceptable substitute. However, the
additional value beyond that of V˙ O2peak cannot be provided by V˙ O2-kinetics.

T. Takken;  H. J. Hulzebos;

ObjectiveThe purpose of the present study was to investigate the association between cardiorespiratory fitness (CRF) measured as peak oxygen uptake (VO2peak, expressed in mL/min) and body mass index (BMI) in a large cohort of apparently healthy subjects.
MethodsBMI and VO2peak were measured in a cross-sectional study of 8470 apparently healthy adults. VO2peak (mL/min) was determined by an incremental cycle ergometer test to exhaustion. Linear regression analyses were performed to identify predictors of CRF.
ResultsThere was no difference in CRF between adults with a normal weight (BMI between 18.5–24.9 kg/m2) and those who were overweight (BMI 25.0–29.9 kg/m2). Subjects who were underweight (BMI < 18.5 kg/m2) as well as females who were obese (BMI ≥ 30.0 kg/m2) showed a reduced CRF compared to the normal and overweight groups. Age, height, and gender were significant predictors of CRF (R2 = 0.467, P < 0.0001); BMI did not add significantly to this relationship.
ConclusionOur findings indicate that BMI was not associated with CRF in addition to age, height, and gender. In subjects with a BMI < 18.5 kg/m2, CRF was lower compared to subjects with a BMI between 18.5 and 29.9 kg/m2. In obese subjects, CRF was only lower in females compared to females with a BMI between 18.5 and 29.9 kg/m2. Correcting CRF for BMI may be beneficial for subjects with a low BMI, and females with a BMI ≥ 30.0 kg/m2. The outcome of this study might help to improve the interpretation of exercise testing results in individuals with a low or high BMI.

T. Takken · H. J. Hulzebos

Journal of Science in Sport and Exercise https://doi.org/10.1007/s42978-021-00143-z

ObjectiveThe purpose of the present study was to investigate the association between cardiorespiratory fitness (CRF) measured as peak oxygen uptake (VO2peak, expressed in mL/min) and body mass index (BMI) in a large cohort of apparently healthy subjects.
MethodsBMI and VO2peak were measured in a cross-sectional study of 8470 apparently healthy adults. VO2peak (mL/min) was determined by an incremental cycle ergometer test to exhaustion. Linear regression analyses were performed to identify predictors of CRF.
ResultsThere was no difference in CRF between adults with a normal weight (BMI between 18.5–24.9 kg/m2) and those who were overweight (BMI 25.0–29.9 kg/m2). Subjects who were underweight (BMI < 18.5 kg/m2) as well as females who were obese (BMI ≥ 30.0 kg/m2) showed a reduced CRF compared to the normal and overweight groups. Age, height, and gender were significant predictors of CRF (R2 = 0.467, P < 0.0001); BMI did not add significantly to this relationship.
ConclusionOur findings indicate that BMI was not associated with CRF in addition to age, height, and gender. In subjects with a BMI < 18.5 kg/m2, CRF was lower compared to subjects with a BMI between 18.5 and 29.9 kg/m2. In obese subjects, CRF was only lower in females compared to females with a BMI between 18.5 and 29.9 kg/m2. Correcting CRF for BMI may be beneficial for subjects with a low BMI, and females with a BMI ≥ 30.0 kg/m2. The outcome of this study might help to improve the interpretation of exercise testing results in individuals with a low or high BMI.

Priel E; Wahab M; Mondal T; Freitag A; O’Byrne PM; Killian KJ; Satia I;

Current research in physiology [Curr Res Physiol] 2021 Oct 28; Vol. 4, pp. 235-242.
Date of Electronic Publication: 2021 Oct 28 (Print Publication: 2021).

Background: Beta blockers prolong life in patients with cardiovascular diseases. Negative chronotropic and inotropic effects carry the potential to adversely effect peripheral skeletal and airway smooth muscle contributing to further fatigue, dyspnea and exercise intolerance.
Research Questions: Do beta-blockers reduce maximal power output (MPO), VO2 max, cardiorespiratory responses, increase the perceived effort required to cycle and breath during cardiopulmonary exercise tests (CPET) and limit the capacity to exercise?
Methods: Retrospective observational study of subjects performing CPET to capacity from 1988 to 2012. Subjects with and without beta-blockers were compared: baseline physiological characteristics, MPO, VO ₂ max, heart rate max, ventilation responses and perceived exertion required to cycle and breathe (modified Borg scale). Forward stepwise linear additive regression was performed with MPO as the dependent factor with height, age, gender, muscle strength, FEV1 and DLCO as independent contributors.
Results: 42,771 subjects were included 7,787 were receiving beta-blocker [mean age 61 yrs, BMI 28.40 kg/m ² , 9% airflow obstruction (FEV1/FVC<0.7)] and 34,984 were not [mean age 51yrs, BMI 27.40 kg/m ² , 11% airflow obstruction]. Heart rate was lower by 18.2% (95% C.I. 18.15-18.38) (p<0.0001) while Oxygen pulse (VO ₂ /HR) was higher by 19.5% (95% C.I. 19.3-19.7) in those receiving beta blockers. Maximum power output (MPO) was 3.3% lower in those taking beta-blockers. The perceived effort required to cycle and breathe (mBorg) was 8% lower in those taking beta-blockers.
Interpretation: Increases in oxygen pulse minimize the reduction in exercise intolerance and symptom handicap associated with beta-blockers.

Vonbank K; Lehmann A; Bernitzky D; Gysan MR; Simon S; Schrott A;Burtscher M; Idzko M; Gompelmann D;

Frontiers in medicine [Front Med (Lausanne)] 2021 Dec 24; Vol. 8, pp. 773788.
Date of Electronic Publication: 2021 Dec 24 (Print Publication: 2021).

Objectives: Coronavirus disease 2019 (COVID-19) is a global pandemic affecting individuals to varying degrees. There is emerging evidence that even patients with mild symptoms will suffer from prolonged physical impairment. Methods: In this prospective observational study, lung function, and cardiopulmonary exercise testing have been performed in 100 patients for 3-6 months after COVID-19 diagnosis (post-CoVG). Depending on the severity of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, patients were divided into asymptomatic, or mild to moderate (mild post-CoVG), and severe post-CoVG [hospitalization with or without intensive care unit/non-invasive ventilation (ICU/NIV)]. Results have been compared with age, sex, and body mass index (BMI) matched control group (CG, N = 50).
Results: Both lung function (resting) and exercise capacity (peak workload, Wpeak and peak oxygen uptake, VO ₂ peak – % predicted) were considerably affected in patients with severe post-CoV (81.7 ± 27.6 and 86.1 ± 20.6%), compared to the mild post-CoVG (104.8 ± 24.0%, p = 0.001 and 100.4 ± 24.8; p = 0.003). In addition, also the submaximal exercise performance was significantly reduced in the severe post-CoVG (predicted VT1/VO ₂ peak; p = 0.013 and VT2/VO ₂ peak; p = 0.001). Multiple linear regression analyses revealed that 74 % (adjusted R² ) of the variance in relative VO ₂ peak of patients who had CoV could be explained by the following variables: lower age, male sex, lower BMI, higher DLCO, higher predicted heart rate (HR) peak, lower breathing reserve (BR), and lower SaO ₂ peak, which were related to higher relative VO ₂ peak values. Higher NT-proBNP and lower creatinine kinase (CK) values were seen in severe cases compared to patients who experienced mild CoV.
Discussion: Maximal and submaximal exercise performance in patients recovering from severe COVID-19 remain negatively affected for 3-6 months after COVID-19 diagnosis. The presented findings reveal that impaired pulmonary, cardiac, and skeletal muscle function contributed to the limitation of VO ₂ peak in those patients, which may have important implications on rehabilitation programs.

Burghard M; Takken T; Nap-van der Vlist MM; Nijhof SL; van der Ent CK; Heijerman HGM; Hulzebos HJE;

Therapeutic advances in respiratory disease [Ther Adv Respir Dis] 2022 Jan-Dec; Vol. 16, pp. 17534666211070143.

Objectives: [1] To investigate the cardiorespiratory fitness (CRF) levels in children and adolescents with cystic fibrosis (CF) with no ventilatory limitation (ventilatory reserve ⩾ 15%) during exercise, and [2] to assess which physiological factors are related to CRF.
Methods: A cross-sectional study design was used in 8- to 18-year-old children and adolescents with CF. Cardiopulmonary exercise testing was used to determine peak oxygen uptake normalized to body weight as a measure of CRF. Patients were defined as having ‘low CRF’ when CRF was less than 82%predicted. Physiological predictors used in this study were body mass index z-score, P. Aeruginosa lung infection, impaired glucose tolerance (IGT) including CF-related diabetes, CF-related liver disease, sweat chloride concentration, and self-reported physical activity. Backward likelihood ratio (LR) logistic regression analysis was used.
Results: Sixty children and adolescents (51.7% boys) with a median age of 15.3 years (25th-75th percentile: 12.9-17.0 years) and a mean percentage predicted forced expiratory volume in 1 second of 88.5% (±16.9) participated. Mean percentage predicted CRF (ppVO _2peak/kg ) was 81.4% (±12.4, range: 51%-105%). Thirty-three patients (55.0%) were classified as having ‘low CRF’. The final model that best predicted low CRF included IGT ( p  = 0.085; Exp(B) = 6.770) and P. Aeruginosa lung infection (p = 0.095; Exp(B) = 3.945). This model was able to explain between 26.7% and 35.6% of variance.
Conclusions: CRF is reduced in over half of children and adolescents with CF with normal ventilatory reserve. Glucose intolerance and P. Aeruginosa lung infection seem to be associated to low CRF in children and adolescents with CF.

Seo YG; Kim MK; Sung J; Jeong DS;

Reviews in cardiovascular medicine [Rev Cardiovasc Med] 2021 Dec 22; Vol. 22 (4), pp. 1595-1601.

Evidence of the effect of exercise therapy in patients who have undergone total thoracoscopic ablation is lacking. This study aimed to evaluate the effects of eight weeks exercise-based cardiac rehabilitation on cardiopulmonary fitness and adherence to exercise in patients who underwent total thoracoscopic ablation and followed a regimen of exercise therapy. Twenty-four patients were involved in the study and were divided into two groups. The exercise group underwent exercise therapy, which included aerobic and resistance exercises, twice a week as part of an eight weeks hospital-based outpatient cardiac rehabilitation program. Cardiopulmonary exercise test was used to evaluate exercise capacity and the International Physical Activity Questionnaire was utilized to identify the amount of physical activity and confirm adherence to exercise at six months postoperatively. There were significant differences between the groups in moderate activity level ( p = 0.004) and extent of total physical activity ( p = 0.0001). Complications such as recurrent atrial fibrillation did not occur during the exercise training. Exercise-based cardiac rehabilitation was beneficial in maintaining the activity level at six months postoperatively. Early exercise intervention at four weeks post-surgical ablation is a safe and effective therapy that can increase physical activity. Further studies are needed to verify the effect of exercise intervention in a larger sample size of patients who have undergone total thoracoscopic ablation.

Reuveny R; Luboshitz J; Bar-Dayan A; DiMenna FJ; Jones AM; Segel MJ;

Journal of vascular surgery. Venous and lymphatic disorders [J Vasc Surg Venous Lymphat Disord] 2021 Dec 24.
Date of Electronic Publication: 2021 Dec 24.

Objective: Pulmonary oxygen uptake (V̇O ₂ ) kinetics measured during initiation of exercise mirror energetic transition during daily activity. The aim of this study was to elucidate the pathophysiological mechanisms of exercise limitation of patients with chronic ilio-femoral vein obstruction after deep vein thrombosis by measuring V̇O ₂ kinetics compared to patients with peripheral arterial disease (PAD) and healthy individuals.
Methods: Eleven patients with ilio-femoral vein obstruction (7 man, age 20-65 yrs.), seven patients with PAD (all men, age 44-60 yrs.) and eight healthy participants (5 men, age 28-58 yrs.) were studied. Participants performed upper and lower-limb symptom-limited cardiopulmonary exercise tests on cycle ergometers; and four repeat lower-limb tests at a constant work-rate (WR) corresponding to 90% of the gas exchange threshold for determining V̇O ₂ kinetics.
Results: Phase I V̇O ₂ amplitude in the constant WR tests (% increase over resting V̇O ₂ ), representing the initial surge in cardiac output caused by the emptying of leg veins, was 59±19% in the ilio-femoral vein obstruction group, 73±22% in peripheral arterial disease and 85±26% in healthy participants (p=0.055 for ilio-femoral vein obstruction vs. healthy). Phase II V̇O ₂ kinetics, which largely reflect the kinetics of O ₂ consumption in the exercising muscles, were slower in ilio-femoral vein obstruction (tau = 42±6 s), and PAD (tau = 49±19 s), compared to healthy participants (23±4 s; p<0.01)
CONCLUSIONS: Slow phase II V̇O ₂ kinetics reflect a slow onset of muscular aerobic metabolism in both ilio-femoral vein obstruction and PAD. Low amplitude phase I of V̇O ₂ kinetics observed in ilio-femoral vein obstruction suggests a damped cardio-dynamic phase, consistent with reduced venous return from the obstructed veins. These abnormalities of V̇O ₂ kinetics may contribute to exercise intolerance in ilio-femoral vein obstruction and PAD.

Legris V; Thibault B; Dupuis J; White M; Asgar AW; Fortier A; Pitre C; Bouabdallaoui N; Henri C; O’Meara E; Ducharme A;

ESC heart failure [ESC Heart Fail] 2021 Dec 24. Date of Electronic Publication: 2021 Dec 24.

Aims: Right ventricular (RV) dysfunction, pulmonary hypertension, and exercise intolerance have prognostic values, but their interrelation is not fully understood. We investigated how RV function alone and its coupling with pulmonary circulation (RV-PA) predict cardio-respiratory fitness in patients with heart failure and reduced ejection fraction (HFrEF).
Methods and Results: The Evaluation of Resynchronization Therapy for Heart Failure (EARTH) study included 205 HFrEF patients with narrow (n = 85) and prolonged (n = 120) QRS duration undergoing implantable cardioverter defibrillator implantation. All patients underwent a comprehensive evaluation with exercise tolerance tests and echocardiography. We investigated the correlations at baseline between RV parameters {size, function [tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RV-FAC), and RV myocardial performance index (RV-MPI)], pulmonary artery systolic pressure (PASP), and tricuspid regurgitation}; left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVi), and left atrial volume index (LAVi); and cardiopulmonary exercise test (CPET) [peak VO ₂ , minute ventilation/carbon dioxide production (VE/VCO ₂ ), 6 min walk distance (6MWD), and submaximal exercise duration (SED)]. We also studied the relationship between RV-PA coupling (TAPSE/PASP ratio) and echocardiographic parameters in patients with both data available. Univariate and multivariate linear regression models were used. Patients enrolled in EARTH (overall population) were mostly male (73.2%), mean age 61.0 ± 9.8 years, New York Heart Association class II-III (87.8%), mean LVEF of 26.6 ± 7.7%, and reduced peak VO ₂ (15.1 ± 4.6 mL/kg/min). Of these, 100 had both TAPSE and PASP available (TAPSE/PASP population): they exhibited higher BNP, wider QRS duration, larger LVEDVi, with more having tricuspid regurgitation compared with the 105 patients for whom these values were not available (all P < 0.05). RV-FAC (β = 7.5), LAVi (β = -0.1), and sex (female, β = -1.9) predicted peak VO ₂ in the overall population (all P = 0.01). When available, TAPSE/PASP ratio was the only echocardiographic parameter associated with peak VO ₂ (β = 6.8; P < 0.01), a threshold ≤0.45 predicting a peak VO ₂  ≤ 14 mL/kg/min (0.39 for VO ₂  ≤ 12). RV-MPI was the only echocardiographic parameter associated with ventilatory inefficiency (VE/VCO ₂ ) and 6MWD (β = 21.9 and β = -69.3, respectively, both P ≤ 0.01) in the overall population. In presence of TAPSE/PASP, it became an important predictor for those two CPET (β = -18.0 and β = 72.4, respectively, both P < 0.01), together with RV-MPI (β = 18.5, P < 0.01) for VE/VCO ₂ . Tricuspid regurgitation predicted SED (β = -3.2, P = 0.03).
Conclusions: Right ventricular function assessed by echocardiography (RV-MPI and RV-FAC) is closely associated with exercise tolerance in patients with HFrEF. When the TAPSE/PASP ratio is available, this marker of RV-PA coupling becomes the stronger echocardiographic predictor of exercise capacity in this population, highlighting its potential role as a screening tool to identify patients with reduced exercise capacity and potentially triage them to formal peak VO ₂ and/or evaluation for advanced HF therapies.