Hager A;

Eur Respir Rev 2021; 30: 200178 [DOI: 10.1183/16000617.0178-2020].

This review summarises various applications of how ventilatory equivalent (ventilatory efficiency or better
still ventilatory inefficiency) and the minute ventilation (VʹE)/carbon dioxide production (VʹCO2) slope
obtained from cardiopulmonary exercise testing (CPET) can be used in the diagnostic or prognostic
workup of patients with congenital heart disease.
The field of congenital heart disease comprises not only a very heterogeneous patient group with various
heart diseases, but also various conditions in different stages of repair, as well as the different residuals
seen in long-term follow-up. As such, various physiologic disarrangements must be considered in the
analysis of increased VʹE/VʹCO2 slope from CPET in patients with congenital heart disease. In addition to
congestive heart failure (CHF), cyanosis, unilateral pulmonary stenosis and pulmonary hypertension (PH)
provide the background for this finding. The predictive value of increased VʹE/VʹCO2 slope on prognosis
seems to be more important in conditions where circulatory failure is associated with failure of the
systemic ventricle. In cyanotic patients, those with Fontan circulation, or those with substantial mortality
from arrhythmia, the impact of VʹE/VʹCO2 on prognosis is not that important.

Guimarães GV; Ribeiro F; Castro RE; Roque JM; Machado ADT; Antunes-Correa LM; Ferreira SA; Bocchi EA;

International journal of cardiology [Int J Cardiol] 2021 Sep 07. Date of Electronic Publication: 2021 Sep 07.

Aims: Skeletal muscle dysfunction is a systemic consequence of heart failure (HF) that correlates with functional capacity. However, the impairment within the skeletal muscle is not well established. We investigated the effect of exercise training on peripheral muscular performance and oxygenation in HF patients.
Methods and Results: HF patients with ejection fraction ≤40% were randomized 2:1 to exercise training or control for 12 weeks. Muscle tissue oxygen was measured noninvasively by near-infrared spectroscopy (NIRS) during rest and a symptom-limited cardiopulmonary exercise test (CPET) before and after intervention. Measurements included skeletal muscle oxygenated hemoglobin concentration, deoxygenated hemoglobin concentration, total hemoglobin concentration, VO ₂ peak, VE/VCO ₂ slope, and heart rate. Muscle sympathetic nerve activity by microneurography, and muscle blood flow by plethysmography were also assessed at rest pre and post 12 weeks. Twenty-four participants (47.5 ± 7.4 years, 58% men, 75% no ischemic) were allocated to exercise training (ET, n = 16) or control (CG, n = 8). At baseline, no differences between groups were found. Exercise improved VO ₂ peak, slope VE/VCO ₂ , and heart rate. After the intervention, significant improvements at rest were seen in the ET group in muscle sympathetic nerve activity and muscle blood flow. Concomitantly, a significant decreased in Oxy-Hb (from 29.4 ± 20.4 to 15.7 ± 9.0 μmol, p = 0.01), Deoxi-Hb (from 16.3 ± 8.2 to 12.2 ± 6.0 μmol, p = 0.003) and HbT (from 45.7 ± 27.6 to 27.7 ± 13.4 μmol, p = 0.008) was detected at peak exercise after training. No changes were observed in the control group.
Conclusion: Exercise training improves skeletal muscle function and functional capacity in HF patients with reduced ejection fraction. This improvement was associated with increased oxygenation of the peripheral muscles, increased muscle blood flow, and decreased sympathetic nerve activity.

Szekely Y; Lichter Y; Sadon S; Lupu L; Taieb P; Banai A; Sapir O; Granot Y; Hochstadt A;Friedman S; Laufer-Perl M; Banai S; Topilsky Y;

Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography [J Am Soc Echocardiogr] 2021 Sep 08. Date of Electronic Publication: 2021 Sep 08.

Background: Large number of patients around the world are recovering from COVID-19; many of them report persistence of symptoms.
Objectives: We sought to test pulmonary, cardiovascular and peripheral responses to exercise in patients recovering from COVID-19.
Methods: We prospectively evaluated patients who recovered from COVID-19 using a combined anatomic/functional assessment. All patients underwent clinical examination, laboratory tests, and a combined stress echocardiography and cardiopulmonary exercise test. We measured left ventricular volumes, ejection fraction, stroke volume, heart rate, E/e’ ratio, right ventricular function, VO ₂ , lung volumes, Ventilatory efficiency, O ₂ saturation and muscle O ₂ extraction in all effort stages and compared them to historical controls.
Results: A total of 71 patients were assessed 90.6±26 days after onset of COVID-19 symptoms. Only 23 (33%) were asymptomatic. The most common symptoms were fatigue (34%), muscle weakness/pain (27%) and dyspnea (22%). VO ₂ was lower among post-COVID-19 patients compared to controls (p=0.03, group by time interaction p=0.007). Reduction in peak VO ₂ was due to a combination of chronotropic incompetence (75% of post-COVID-19 patients vs. 8% of controls, p<0.0001) and insufficient increase in stroke volume during exercise (p=0.0007, group by time interaction p=0.03). Stroke volume limitation was mostly explained by diminished increase in left ventricular end-diastolic volume (p=0.1, group by time interaction p=0.03) and insufficient increase in ejection fraction (p=0.01, group by time interaction p=0.01). Post-COVID-19 patients had higher peripheral O ₂ extraction (p=0.004) and did not have significantly different respiratory and gas exchange parameters compared to controls.
Conclusions: Patients recovering from COVID-19 have symptoms associated with objective reduction in peak VO ₂ . The mechanism of this reduction is complex and mainly involves a combination of attenuated heart rate and stroke volume reserve.

Gervasi SF; Orvieto S; Sollazzo F; Bianco M; Cuccaro F; Zeppilli P; Palmieri V;

European journal of physical and rehabilitation medicine [Eur J Phys Rehabil Med] 2021 Sep 09.
Date of Electronic Publication: 2021 Sep 09.

Background: Although peak oxygen uptake (VO2peak) is considered the most useful index of functional capacity, it’s difficult to interpret the results of cardiopulmonary exercise testing (CPET) in individuals with spinal cord injury (SCI). In fact, VO2peak is usually normalized for total body weight, but body composition in persons with SCI largely varies depending on physical activity and time since injury, with a progressive loss of fat-free mass (FFM). This can lead to a misinterpretation of the cardiopulmonary fitness in this population.
Aim: Our study proposes a methodology of evaluation, based on bioelectrical impedance analysis (BIA), which could provide more individualized and accurate data in sportsmen with SCI.
Design: Case-control study.
Setting: Ambulatory evaluations at the Sports Medicine Unit of the Fondazione IRCSS Policlinico A. Gemelli, Rome, Italy.
Methods and Population: Comparison of data derived from BIA, echocardiography and CPET between 10 male sportsmen with complete, high SCI (Group T) and 10 able-bodied controls (Group C).
Results: Mean VO2peak, weight-normalized VO2peak, Fat-Free Mass (FFM)-normalized VO2peak and body cellular mass (BCM)-normalized values were significantly lower in Group T. At the same heart rate (on average the 55% of the maximal theoretical for age), mean of absolute VO2, weight-normalized VO2 and FFM-normalized VO2 were still significantly lower in Group T. Considering the BCM- normalized VO2, the Group T showed greater values than controls, 39.4 (7.8) vs 31.1 (8.5) ml/Kg/min.
Conclusions: Body composition is a crucial factor for properly interpreting a CPET in individuals with SCI. In particular, normalization of VO2peak values for the BCM seems the most reliable tool to assess the real functional capacity in this population.
Clinical Rehabilitation Impact: A more accurate definition of the aerobic power and functional capacity of people with SCI can improve the monitoring of rehabilitations protocols and physical exercise in this population.

Segreti A; Verolino G; Crispino SP; Agostoni P;

Heart failure clinics [Heart Fail Clin] 2021 Oct; Vol. 17 (4), pp. 635-646. Date of Electronic Publication: 2021 Jul 24.

Patients with advanced heart failure (AdHF) have a reduced quality of life and poor prognosis. A heart transplant (HT) is an effective treatment for such patients. Still, because of a shortage of donor organs, the final decision to place a patient without contraindications on the HT waiting list is based on detailed risk-benefit analysis. Cardiopulmonary exercise tests (CPETs) play a pivotal role in guiding selection in patients with AdHF considered for an HT. Furthermore, several validated multivariable predicting scores obtained through various techniques, including the CPETs, are available and part of the decision-making process for HT listing.

Satia I; Priel E; Al-Khazraji BK; Jones G; Freitag A; O’Byrne PM; Killian KJ;

The European respiratory journal [Eur Respir J] 2021 Aug 26; Vol. 58 (2).
Date of Electronic Publication: 2021 Aug 26 (Print Publication: 2021).

Exercise-induced bronchoconstriction (EIBc) is a recognised response to exercise in asthmatic subjects and athletes but is less well understood in an unselected broad population. Exercise-induced bronchodilation (EIBd) has received even less attention. The objective of this study was to investigate the effects of age, sex, forced expiratory volume in 1 s (FEV ₁ ) and airflow limitation (FEV ₁ /forced vital capacity (FVC) <0.7) on the prevalence of EIBc and EIBd.This was a retrospective study based on incremental cardiopulmonary exercise testing on cycle ergometry to symptom limitation performed between 1988 and 2012. FEV ₁ was measured before and 10 min after exercise. EIBc was defined as a percentage fall in FEV ₁ post-exercise below the 5th percentile, while EIBd was defined as a percentage increase in FEV ₁ above the 95th percentile.35 258 subjects aged 6-95 years were included in the study (mean age 53 years, 60% male) and 10.3% had airflow limitation (FEV ₁ /FVC <0.7). The lowest 5% of subjects demonstrated a ≥7.6% fall in FEV ₁ post-exercise (EIBc), while the highest 5% demonstrated a >11% increase in FEV ₁ post-exercise (EIBd). The probability of both EIBc and EIBd increased with age and was highest in females across all ages (OR 1.76, 95% CI 1.60-1.94; p<0.0001). The probability of EIBc increased as FEV ₁ % pred declined (<40%: OR 4.38, 95% CI 3.04-6.31; p<0.0001), with a >2-fold increased likelihood in females (OR 2.31, 95% CI 1.71-3.11; p<0.0001), with a trend with airflow limitation (p=0.06). The probability of EIBd increased as FEV ₁ % pred declined, in the presence of airflow limitation (OR 1.55, 95% CI 1.24-1.95; p=0.0001), but sex had no effect.EIBc and EIBd can be demonstrated at the population level, and are influenced by age, sex, FEV ₁ % pred and airflow limitation.

Del Buono MG; Mihalick V;Damonte JI; Billingsley H; Kadayira D;Ho AC;Talasaz A; Carbone S; Markley R;Turlington J; Lu J; Federmann E; Arena R; Van Tassell B; Abbate A;Canada JM;

The American journal of cardiology [Am J Cardiol] 2021 Aug 28. Date of Electronic Publication: 2021 Aug 28.

There is limited understanding on the potential differences in the pathophysiology between de novo heart failure with reduced ejection fraction (HFrEF) and acute on chronic HFrEF. The aim of this study was to assess differences in cardiorespiratory fitness (CRF) parameters between de novo heart failure and acute on chronic HFrEF using cardiopulmonary exercise testing (CPX). We retrospectively analyzed CPX data measured within 2 weeks of discharge following acute hospitalization for HFrEF. Data are reported as median and interquartile range or frequency and percentage (%). We included 102 patients: 32 (31%) women, 81 (79%) black, 57 (51 to 64) years of age, BMI of 34 (29 to 39) Kg/m ² . Of these, 26 (25%) had de novo HFrEF and 76 (75%) had acute on chronic HFrEF. When compared with acute on chronic, patients with de novo HFrEF had a significantly higher peak oxygen consumption (VO ₂ ) (16.5 [12.2 to 19.4] vs 12.8 [10.1 to 15.3] ml·kg ^-1 ·min ^-1 , p <0.001), %-predicted peak VO ₂ (58% [51 to 75] vs 49% [42 to 59]) p = 0.012), peak heart rate (134 [117 to 147] vs 117 [104 to 136] beats/min, p = 0.004), peak oxygen pulse (12.2 [10.5 to 15.5] vs 9.9 [8.0 to 13.1] ml/beat, p = 0.022) and circulatory power (2,823 [1,973 to 3,299] vs 1,902 [1,372 to 2,512] mm Hg·ml·kg ^-1 ·min ^-1 , p = 0.002). No significant difference in resting left ventricular ejection fraction was found between groups. In conclusion, patients with de novo HFrEF have better CRF parameters than those with acute on chronic HFrEF. These differences are not explained by resting left ventricular systolic function but may be related to greater preservation in cardiac reserve during exercise in de novo HFrEF patients.

West MA; Baker WC; Munro A; Jack S; Grocott MP; Underwood TJ;Levett DZ;

Journal of surgical oncology [J Surg Oncol] 2021 Aug 31. Date of Electronic Publication: 2021 Aug 31.

Background: Sarcopenia (low skeletal muscle mass), myosteatosis (low skeletal muscle radiation-attenuation) and fitness are independently associated with postoperative outcomes in oesophago-gastric cancer. This study aimed to investigate (1) the effect of neoadjuvant therapy (NAT) on sarcopenia, myosteatosis and cardiopulmonary exercise testing (CPET), (2) the relationship between these parameters, and (3) their association with postoperative morbidity and survival.
Methods: Body composition analysis used single slice computed tomography (CT) images from chest (superior to aortic arch) and abdominal CT scans (third lumbar vertebrae). Oxygen uptake at anaerobic threshold (VO ₂ at AT) and at peak exercise (VO ₂ Peak) were measured using CPET. Measurements were performed before and after NAT and an adjusted regression model assessed their association.
Results: Of the 184 patients recruited, 100 underwent surgical resection. Following NAT skeletal muscle mass, radiation-attenuation and fitness reduced significantly (p < 0.001). When adjusted for age, sex, and body mass index, only pectoralis muscle mass was associated with VO ₂ Peak (p = 0.001). VO2 at AT and Peak were associated with 1-year survival, while neither sarcopenia nor myosteatosis were associated with morbidity or survival.
Conclusion: Skeletal muscle and CPET variables reduced following NAT and were positively associated with each other. Cardiorespiratory function significantly contributes to short-term survival after oesophago-gastric cancer surgery.

Carvalho RB; Marmett B; Dorneles GP; da Silva IM; Romão PRT; da Silva Júnior FMR; Rhoden CR;

Environmental geochemistry and health [Environ Geochem Health] 2021 Aug 20. Date of Electronic Publication: 2021 Aug 20.

Ozone (O ₃ ) represents a great threat to human health, contributing to respiratory diseases and premature mortality. This pollutant is often considered a critical pollutant in regions of southern Brazil. Exposure to this pollutant during vigorous physical activity should be the subject of thorough investigations due to the increased ventilation rate and altered breathing pattern present during vigorous physical activity that result in greater inhalation of O ₃ . Thus, this study aimed to evaluate the health risk of exposure to low, mean, and high concentrations of O ₃ during different durations of exercise in the city of Rio Grande (southern Brazil). Healthy young men (n = 45) performed cardiopulmonary exercise testing, and ventilation rate data were collected to predict total ventilation and pollutant inhalation during a 5 km running session. The O ₃ concentration in the city of Rio Grande was obtained from data reported by the Copernicus Atmosphere Monitoring Service (CAMS). The environmental health risk was calculated based on the potential intake dose. The lowest, mean, and highest concentrations of O ₃ detected during the monitoring period were 32.5, 64.9, and 115.2 µg/m ³ , respectively. In all evaluated scenarios, there was a toxicological risk (RQ > 1), except when exercising when the O ₃ concentration was lowest for the shortest length of time (p < 0.001). As the concentration of O ₃ and the duration of the exposure increase, the health risk is increased. Therefore, O ₃ concentration and duration of exposure are factors influencing the health risk of exercising. These findings are extremely relevant in cities that have high levels of O ₃ , such as the city of Rio Grande.

Forrer A; Scheiwiller PM; Mademilov M; Lichtblau M; Marazhapov NH; Saxer S; Bader P; Appenzeller P;
Aydaralieva S; Muratbekova A; Sooronbaev TM; Ulrich S; Bloch KE; Furian M;

High altitude medicine & biology [High Alt Med Biol] 2021 Aug 24. Date of Electronic Publication: 2021 Aug 24.

Introduction: Life-long exposure to hypobaric hypoxia induces physiologic adaptations in highlanders that may modify exercise performance; however, reference data for altitude populations are scant.
Methods: Life-long residents of the Tien Shan mountain range, 2,500 – 3,500 m, Kyrgyzstan, free of cardiopulmonary disease, underwent cardiopulmonary cycle exercise tests with a progressive ramp protocol to exhaustion at 3,250 m. ECG, breath-by-breath pulmonary gas exchange, and oxygen saturation by pulse oximetry (SpO ₂ ) were measured.
Results: Among 81 highlanders, age (mean ± SD) 48 ± 10 years, 46% women, SpO ₂ at rest was 88% ± 2%, peak oxygen uptake (V’O ₂ peak) was 21.6 ± 5.9 mL/kg/min (76% ± 15% predicted for a low-altitude reference population); peak work rate (Wpeak) was 117 ± 37 W (77% ± 17% predicted), SpO ₂ at peak was 84% ± 5%, heart rate reserve (220 – age – maximal heart rate) was 28 ± 17/min, ventilatory reserve (maximal voluntary ventilation – maximal minute ventilation) was 68 ± 32 l/min, and respiratory exchange ratio was 1.03 ± 0.09. Peak BORG-CR10 dyspnea and leg fatigue scores were 5.1 ± 2.0 and 6.3 ± 2.1. In multivariable linear regression analyses, age and sex were robust determinants of Wpeak, V’O ₂ peak, and metabolic equivalent (MET) at peak, whereas body mass index, resting systolic blood pressure, and mean pulmonary artery pressure were not.
Conclusions: The current study shows that V’O ₂ peak and Wpeak of highlanders studied at 3,250 m, near their altitude of residence, were reduced by about one quarter compared with mean predicted values for lowlanders. The provided prediction models for V’O ₂ peak, Wpeak, and METs in central Asian highlanders might be valuable for comparisons with other high altitude populations.