Tokodi M; Oláh A; Fábián A; Lakatos BK; Hizoh I; Ruppert M; Sayour AA; Barta BA; Kiss O; Sydó N; Csulak E;Ladányi Z;Merkely B; Kovács A; Radovits T

European heart journal. Cardiovascular Imaging [Eur Heart J Cardiovasc Imaging] 2021 Aug 25.
Date of Electronic Publication: 2021 Aug 25.

Aims: We sought to investigate the correlation between speckle-tracking echocardiography (STE)-derived myocardial work (MW) and invasively measured contractility in a rat model of athlete’s heart. We also assessed MW in elite athletes and explored its association with cardiopulmonary exercise test (CPET)-derived aerobic capacity.
Methods and Results: Sixteen rats underwent a 12-week swim training program and were compared to controls (n = 16). STE was performed to assess global longitudinal strain (GLS), which was followed by invasive pressure-volume analysis to measure contractility [slope of end-systolic pressure-volume relationship (ESPVR)]. Global MW index (GMWI) was calculated from GLS curves and left ventricular (LV) pressure recordings. In the human investigations, 20 elite swimmers and 20 healthy sedentary controls were enrolled. GMWI was calculated through the simultaneous evaluation of GLS and non-invasively approximated LV pressure curves at rest. All subjects underwent CPET to determine peak oxygen uptake (VO2/kg). Exercised rats exhibited higher values of GLS, GMWI, and ESPVR than controls (-20.9 ± 1.7 vs. -17.6 ± 1.9%, 2745 ± 280 vs. 2119 ± 272 mmHg·%, 3.72 ± 0.72 vs. 2.61 ± 0.40 mmHg/μL, all PExercise < 0.001). GMWI correlated robustly with ESPVR (r = 0.764, P < 0.001). In humans, regular exercise training was associated with decreased GLS (-17.6 ± 1.5 vs. -18.8 ± 0.9%, PExercise = 0.002) but increased values of GMWI at rest (1899 ± 136 vs. 1755 ± 234 mmHg·%, PExercise = 0.025). GMWI exhibited a positive correlation with VO2/kg (r = 0.527, P < 0.001).
Conclusions: GMWI precisely reflected LV contractility in a rat model of exercise-induced LV hypertrophy and captured the supernormal systolic performance in human athletes even at rest. Our findings endorse the utilization of MW analysis in the evaluation of the athlete’s heart.

Nayor M; Chernofsky A; Spartano NL; Tanguay M; Blodgett JB; Murthy VL; Malhotra R; Boston, MA, Houstis NE; Velagaleti RS; Murabito JM; Vasan RS; Shah RV; Lewis GD;

European heart journal [Eur Heart J] 2021 Aug 26. Date of Electronic Publication: 2021 Aug 26.

Aims: While greater physical activity (PA) is associated with improved health outcomes, the direct links between distinct components of PA, their changes over time, and cardiorespiratory fitness are incompletely understood.
Methods and Results: Maximum effort cardiopulmonary exercise testing (CPET) and objective PA measures [sedentary time (SED), steps/day, and moderate-vigorous PA (MVPA)] via accelerometers worn for 1 week concurrent with CPET and 7.8 years prior were obtained in 2070 Framingham Heart Study participants [age 54 ± 9 years, 51% women, SED 810 ± 83 min/day, steps/day 7737 ± 3520, MVPA 22.3 ± 20.3 min/day, peak oxygen uptake (VO2) 23.6 ± 6.9 mL/kg/min]. Adjusted for clinical risk factors, increases in steps/day and MVPA and reduced SED between the two assessments were associated with distinct aspects of cardiorespiratory fitness (measured by VO2) during initiation, early-moderate level, peak exercise, and recovery, with the highest effect estimates for MVPA (false discovery rate <5% for all). Findings were largely consistent across categories of age, sex, obesity, and cardiovascular risk. Increases of 17 min of MVPA/day [95% confidence interval (CI) 14-21] or 4312 steps/day (95% CI 3439-5781; ≈54 min at 80 steps/min), or reductions of 249 min of SED per day (95% CI 149-777) between the two exam cycles corresponded to a 5% (1.2 mL/kg/min) higher peak VO2. Individuals with high (above-mean) steps or MVPA demonstrated above average peak VO2 values regardless of whether they had high or low SED.
Conclusions: Our findings provide a detailed assessment of relations of different types of PA with multidimensional cardiorespiratory fitness measures and suggest favourable longitudinal changes in PA (and MVPA in particular) are associated with greater objective fitness.

Singh I; Joseph P; Heerdt PM; Cullinan M; Lutchmansingh D; Gulati M; Possick JD; Systrom DM; Waxman AB;

Chest [Chest] 2021 Aug 10. Date of Electronic Publication: 2021 Aug 10.

Background: Some Coronavirus disease 2019 (COVID-19) patients who have recovered from their acute infection after experiencing only mild symptoms continue to exhibit persistent exertional limitation that is often unexplained by conventional investigative studies.
Research Question: What is the patho-physiological mechanism of exercise intolerance that underlies the post-COVID-19 long haul syndrome following COVID-19 in patients without cardio-pulmonary disease?
Study Design and Methods: This study examined the systemic and pulmonary hemodynamics, ventilation, and gas exchange in 10 post-COVID-19 patients without cardio-pulmonary disease during invasive cardiopulmonary exercise testing (iCPET) and compared the results to 10 age- and sex matched controls. These data were then used to define potential reasons for exertional limitation in the post-COVID-19 cohort.
Results: Post-COVID-19 patients exhibited markedly reduced peak exercise aerobic capacity (VO ₂ ) compared to controls (70±11%predicted vs. 131±45%predicted; p<0.0001). This reduction in peak VO ₂ was associated with impaired systemic oxygen extraction (i.e., narrow CaVO ₂ /CaO ₂ ) compared to controls (0.49±0.1 vs. 0.78±0.1, p<0.0001) despite a preserved peak cardiac index (7.8±3.1 vs. 8.4±2.3 L/min, p>0.05). Additionally, post-COVID-19 patients demonstrated greater ventilatory inefficiency (i.e., abnormal VE/VCO ₂ slope: 35±5 vs. 27±5, p=0.01) compared to controls without an increase in dead space ventilation.
Interpretation: Post-COVID-19 patients without cardiopulmonary disease demonstrate a marked reduction in peak VO ₂ from a peripheral rather than a central cardiac limit along with an exaggerated hyper-ventilatory response during exercise.

Salameh M; Pini L; Quadri F; Spreafico F; Bottone D; Tantucci C;

Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology [Allergy Asthma Clin Immunol] 2021 Aug 14; Vol. 17 (1), pp. 84.
Date of Electronic Publication: 2021 Aug 14.

Background: Physical effort is capable of triggering airway obstruction in asthmatics, the so-called exercise-induced bronchoconstriction in asthma (EIBa). This study was performed in subjects with mild persistent asthma, aiming to find predictors for developing EIBa.
Methods: In 20 subjects with mild asthma, measurements of baseline functional respiratory parameters and airways responsiveness by a methacholine challenge were obtained on the first day. A maximal, symptom-limited incremental cardiopulmonary exercise test (CPExT) was performed the day after, with subsequent, repeated maneuvers of maximal full forced expiration to monitor the FEV ₁ change at 1,3,5,7,10 and 15 min after the end of the exercise.
Results: 19 subjects completed the two-days protocol. No functional parameters both at rest and during effort were useful to predict EIBa after stopping exercise. In asthmatics with EIBa, mean Inspiratory Capacity (IC) did not increase with increasing ventilatory requirements during CPExT because 6 of them (50%) displayed dynamic pulmonary hyperinflation (DH), as documented by their progressive increase of end-expiratory lung volume. This subgroup, showing earlier post-exercise FEV ₁ fall, had significantly lower forced mean expiratory flow between 25% and 75% of forced vital capacity (FEF _25-75% ) at rest (p < 0.05) and higher airways responsiveness, expressed as PD ₂₀ FEV ₁ (p < 0.05) as compared with other asthmatics with EIBa.
Conclusions: No functional respiratory parameters seem to predict EIBa in mild asthmatics. However, in those with EIBa, a subgroup developed DH during exercise, and this was associated with a baseline reduced forced expiratory flow rates at lower lung volumes and higher airway hyperresponsiveness, suggesting a prominent small airways impairment.

Wadey CA; Weston ME; Dorobantu DM; Pieles GE; Stuart G;Barker AR; Taylor RS; Williams CA;

European journal of preventive cardiology [Eur J Prev Cardiol] 2021 Aug 18.
Date of Electronic Publication: 2021 Aug 18.

Aims: The role of cardiopulmonary exercise testing (CPET) in predicting major adverse cardiovascular events (MACE) in people with congenital heart disease (ConHD) is unknown. A systematic review with meta-analysis was conducted to report the associations between CPET parameters and MACE in people with ConHD.
Methods and Results: Electronic databases were systematically searched on 30 April 2020 for eligible publications. Two authors independently screened publications for inclusion, extracted study data, and performed risk of bias assessment. Primary meta-analysis pooled univariate hazard ratios across studies. A total of 34 studies (18 335 participants; 26.2 ± 10.1 years; 54% ± 16% male) were pooled into a meta-analysis. More than 20 different CPET prognostic factors were reported across 6 ConHD types. Of the 34 studies included in the meta-analysis, 10 (29%), 23 (68%), and 1 (3%) were judged as a low, medium, and high risk of bias, respectively. Primary univariate meta-analysis showed consistent evidence that improved peak and submaximal CPET measures are associated with a reduce risk of MACE. This association was supported by a secondary meta-analysis of multivariate estimates and individual studies that could not be numerically pooled.
Conclusion: Various maximal and submaximal CPET measures are prognostic of MACE across a variety of ConHD diagnoses. Further well-conducted prospective multicentre cohort studies are needed to confirm these findings.

Smarz K; Jaxa-Chamiec T; Zaborska B; Tysarowski M; Budaj A;

PloS one [PLoS One] 2021 Aug 05; Vol. 16 (8), pp. e0255682. Date of Electronic Publication: 2021 Aug 05
(Print Publication: 2021).

Exercise intolerance after acute myocardial infarction (AMI) is a predictor of worse prognosis, but its causes are complex and poorly studied. This study assessed the determinants of exercise intolerance using combined stress echocardiography and cardiopulmonary exercise testing (CPET-SE) in patients treated for AMI. We prospectively enrolled patients with left ventricular ejection fraction (LV EF) ≥40% for more than 4 weeks after the first AMI. Stroke volume, heart rate, and arteriovenous oxygen difference (A-VO2Diff) were assessed during symptom-limited CPET-SE. Patients were divided into four groups according to the percentage of predicted oxygen uptake (VO2) (Group 1, <50%; Group 2, 50-74%; Group 3, 75-99%; and Group 4, ≥100%). Among 81 patients (70% male, mean age 58 ± 11 years, 47% ST-segment elevation AMI) mean peak VO2 was 19.5 ± 5.4 mL/kg/min. A better exercise capacity was related to a higher percent predicted heart rate (Group 2 vs. Group 4, p <0.01), higher peak A-VO2Diff (Group 1 vs. Group 3, p <0.01) but without differences in stroke volume. Peak VO2 and percent predicted VO2 had a significant positive correlation with percent predicted heart rate at peak exercise (r = 0.28, p = 0.01 and r = 0.46, p < 0.001) and peak A-VO2Diff (r = 0.68, p <0.001 and r = 0.36, p = 0.001) but not with peak stroke volume. Exercise capacity in patients treated for AMI with LV EF ≥40% is related to heart rate response during exercise and peak peripheral oxygen extraction. CPET-SE enables non-invasive assessment of the mechanisms of exercise intolerance.

Hashimoto K; Hirashiki A; Kawamura K; Sugioka J; Mizuno Y; Tanioku S; Sato K; Ueda I; Itoh N;Nomoto K;
Kokubo M; Shimizu A; Kondo I;

Geriatrics & gerontology international [Geriatr Gerontol Int] 2021 Aug 06. Date of Electronic Publication: 2021
Aug 06.

Aim: Decreased use of life spaces, as reflected in decreased Life-Space Assessment (LSA) scores, is associated with poor prognosis in older adults. The purpose of this study was to examine factors affecting the extent of life-space activities in older adults with cardiovascular disease.
Methods: We carried out a prospective observational study in 98 older adults (minimum age 65 years; mean age 79.5 ± 7.4 years) who were admitted to our hospital due to cardiovascular disease. Once their medical condition was stable, they underwent cardiopulmonary exercise testing, echocardiography and physical evaluation, and completed questionnaires.
Results: The LSA score was significantly associated with the ability to drive a car (driving 95.1 ± 21.1 points, not driving 60.4 ± 30.3 points, P < 0.001). In addition, LSA was significantly correlated with age; peak VO ₂ ; brain natriuretic peptide; and Short Physical Performance Battery, Geriatric Depression Scale and Mini-Mental State Examination scores. In a multiple regression analysis, Short Physical Performance Battery and driving a car were significantly associated with LSA (β = 0.28, β = 0.37, respectively).
Conclusion: Assessment of motor function and social factors in addition to clinical cardiac function might be important to understand the complete context of life-space activity in older adults with cardiovascular disease.

Fermoyle CC; Stewart GM; Borlaug BA; Johnson BD;

Journal of the American Heart Association [J Am Heart Assoc] 2021 Aug 07, pp. e019950. Date of Electronic Publication: 2021 Aug 07.

Background
Hemodynamic perturbations in heart failure with preserved ejection fraction (HFpEF) may alter the distribution of blood in the lungs, impair gas transfer from the alveoli into the pulmonary capillaries, and reduce lung diffusing capacity. We hypothesized that impairments in lung diffusing capacity for carbon monoxide (DL _CO ) in HFpEF would be associated with high mean pulmonary capillary wedge pressures during exercise.
Methods and Results
Rebreathe DL _CO and invasive hemodynamics were measured simultaneously during exercise in patients with exertional dyspnea. Pulmonary pressure waveforms and breath-by-breath pulmonary gas exchange were recorded at rest, 20 W, and symptom-limited maximal exercise. Patients with HFpEF (n=20; 15 women, aged 65±11 years, body mass index 36±8 kg/m ² ) achieved a lower symptom-limited maximal workload (52±27 W versus 106±42 W) compared with controls with noncardiac dyspnea (n=10; 7 women, aged 55±10 years, body mass index 30±5 kg/m ² ). DL _CO was lower in patients with HFpEF compared with controls at rest (DL _CO 10.4±2.9 mL/min per mm Hg versus 16.4±6.9 mL/min per mm Hg, P <0.01) and symptom-limited maximal exercise (DL _CO 14.6±4.7 mL/min per mm Hg versus 23.8±10.8 mL/min per mm Hg, P <0.01) because of a lower alveolar-capillary membrane conductance in HFpEF (rest 16.8±6.6 mL/min per mm Hg versus 28.4±11.8 mL/min per mm Hg, P <0.01; symptom-limited maximal exercise 25.0±6.7 mL/min per mm Hg versus 45.5±22.2 mL/min per mm Hg, P <0.01). DL _CO was lower in HFpEF for a given mean pulmonary artery pressure, mean pulmonary capillary wedge pressure, pulmonary arterial compliance, and transpulmonary gradient.
Conclusions
Lung diffusing capacity is lower at rest and during exercise in HFpEF due to impaired gas conductance across the alveolar-capillary membrane. DL _CO is impaired for a given pulmonary capillary wedge pressure and pulmonary arterial compliance. These data provide new insight into the complex relationships between hemodynamic perturbations and gas exchange abnormalities in HFpEF.

Gonze BB; Ostolin TLVDP; Barbosa ACB; Matheus AC; Sperandio EF; Gagliardi ART; Arantes RL; Romiti M;
Dourado VZ;

PloS one [PLoS One] 2021 Aug 09; Vol. 16 (8), pp. e0255724. Date of Electronic Publication: 2021 Aug 09 (Print Publication: 2021).

Purpose: Obese individuals have reduced performance in cardiopulmonary exercise testing (CPET), mainly considering peak values of variables such as oxygen uptake ([Formula: see text]), carbon dioxide production ([Formula: see text]), tidal volume (Vt), minute ventilation ([Formula: see text]) and heart rate (HR). The CPET interpretation and prognostic value can be improved through submaximal ratios analysis of key variables like [Formula: see text], [Formula: see text], [Formula: see text] [Formula: see text] and oxygen uptake efficiency slope (OUES). The obesity influence on these responses has not yet been investigated. Our purpose was to evaluate the influence of adulthood obesity on maximal and submaximal physiological responses during CPET, emphasizing the analysis of submaximal dynamic variables.
Methods: We analyzed 1,594 CPETs of adults (755 obese participants, Body Mass Index ≥ 30 kg/m2) and compared the obtained variables among non-obese (normal weight and overweight) and obese groups (obesity classes I, II and III) through multivariate covariance analyses.
Result: Obesity influenced the majority of evaluated maximal and submaximal responses with worsened CPET performance. Cardiovascular, metabolic and gas exchange variables were the most influenced by obesity. Other maximal and submaximal responses were altered only in morbidly obese. Only a few cardiovascular and ventilatory variables presented inconsistent results. Additionally, Vtmax, [Formula: see text], Vt/Inspiratory Capacity, Vt/Forced Vital Capacity, Lowest [Formula: see text], [Formula: see text], and the y-intercepts of [Formula: see text] did not significantly differ regardless of obesity.
Conclusion: Obesity expressively influences the majority of CPET variables. However, the prognostic values of the main ventilatory efficiency responses remain unchanged. These dynamic responses are not dependent on maximum effort and may be useful in detecting incipient ventilatory disorder. Our results present great practical applicability in identifying exercise limitation, regardless of overweight and obesity.

Olekšák F; Dvoran P; Jakušová Ľ; Ďurdík P; Igaz M; Bánovčin P;

Acta medica (Hradec Kralove) [Acta Medica (Hradec Kralove)] 2021; Vol. 64 (2), pp. 119-124.

Background: The reference values of young athletes for cardiopulmonary exercise testing are lacking. Expert opinions encourage production of local values specific for certain population.
Patients and Methods: The study population consisted of 136 healthy male caucasian athletic children and adolescents coming from one specific football school in northern Slovakia. Exercise testing with continuous electrocardiography was performed, and ventilatory parameters, oxygen uptake (VO2), and carbon dioxide (CO2) production were measured continuously with a respiratory gas analysis system.
Results: Peak VO2max/kg was changing very little across the childhood, whereas the peak work rate, heart rate and O2Pulse were. Linear regression analysis showed a significant effect of age on VE/VCO2.
Conclusion: This work provides a reference values for the most important cardiopulmonary variables that can be obtained during cardiopulmonary exercise testing in athletic children.