Dierckx W; De Backer W; Ides K; De Meyer Y; Lauwers E; Franck E;

Physiological reports [Physiol Rep] 2023 Jun; Vol. 11 (12), pp. e15754.

Patients with post-acute sequelae of COVID-19 (PASC) present with a decrease in physical fitness. The aim of this paper is to reveal the relations between the remaining symptoms, blood volume distribution, exercise tolerance, static and dynamic lung volumes, and overall functioning. Patients with PASC were retrospectively studied. Pulmonary function tests (PFT), 6-minute walk test (6MWT), and cardiopulmonary exercise test were performed. Chest CT was taken and quantified. Patients were divided into two groups: minor functional limitations (MFL) and severe functional limitations (SFL) based on the completed Post-COVID-19 Functional Status scale (PCFS). Twenty one patients (3 M; 18 FM), mean age 44 (IQR 21) were studied. Eighteen completed the PCFS (8 MFL; 10 SFL). VO ₂ max was suboptimal in both groups (not significant). 6MWT was significantly higher in MFL-group (p = 0.043). Subjects with SFL, had significant lower TLC (p = 0.029). The MFL-group had more air trapping (p = 0.036). Throughout the sample, air trapping correlated significantly with residual volume (RV) in L (p < 0.001). An increase in air trapping was related to an increase in BV5 (p < 0.001). Mean BV5 was 65% (IQR 5%). BV5% in patients with PASC was higher than in patients with acute COVID-19 infection. This increase in BV5% in patients with PASC is thought to be driven by the air trapping in the lobes. This study reveals that symptoms are more driven by occlusion of the small airways. Patients with more physical complaints have significantly lower TLC. All subjects encounter physical limitations as indicated by suboptimal VO ₂ max. Treatment should focus on opening or re-opening of small airways by recruiting alveoli.

Gama F; Rocha B; Aguiar C; Strong C; Freitas P; Brízido C; Tralhão A; Durazzo A; Mendes M;

Heart, lung & circulation [Heart Lung Circ] 2023 Jun 15.
Date of Electronic Publication: 2023 Jun 15.

Background: Several heart failure (HF) prognostic risk scores are available to guide the ideal time for listing candidates for a heart transplant (HTx). The detection of exercise oscillatory ventilation (EOV) during cardiopulmonary exercise testing (CPET) is associated with advanced HF and a worse prognosis, and yet it is not accounted for in these risk scores. Therefore, this study aimed to assess whether EOV further adds prognostic value to HF scores.
Methods: A single-centre retrospective cohort study was undertaken of consecutive HF patients with reduced ejection fraction (HFrEF) who underwent CPET from 1996 to 2018. The Heart Failure Survival Score (HFSS), Seattle Heart Failure Model (SHFM), Meta-analysis Global Group In Chronic Heart Failure (MAGGIC), and Metabolic Exercise Cardiac Kidney Index (MECKI) were calculated. The added value of EOV on top of those scores was assessed using a Cox proportional hazard model. The added discriminative power was also assessed by receiver operating characteristic curve comparison.
Results: A total of 390 HF patients with a median age of 58 (IQR 50-65) years were investigated, of whom 78% were male and 54% had ischaemic heart disease. The median peak oxygen consumption was 15.7 mL/kg/min (IQR 12.8-20.1). Exercise oscillatory ventilation was detected in 153 (39.2%) patients. Over a median follow-up of 2 years, 61 patients died (49 due to a cardiovascular reason) and 54 had a HTx. Exercise oscillatory ventilation independently predicted the composite outcome of all-cause death and HTx. Furthermore, the presence of this ventilatory pattern significantly improved the prognostic performance of both HFSS and MAGGIC scores.
Conclusion: Exercise oscillatory ventilation was often found in a cohort of HF patients with reduced LVEF who underwent CPET. It was found that EOV added further prognostic value to contemporary HF scores, suggesting that this easily obtained parameter should be included in future modified HF scores.

O’Shea O; Casey S;Giblin C; Stephenson A; Carroll TP; McElvaney NG; McDonough SM;

International journal of chronic obstructive pulmonary disease [Int J Chron Obstruct Pulmon Dis] 2023 Jun 16; Vol. 18, pp. 1231-1250.
Date of Electronic Publication: 2023 Jun 16 (Print Publication: 2023).

Alpha-1 antitrypsin deficiency (AATD) is a hereditary disorder and a genetic risk factor for chronic obstructive pulmonary disease (COPD). Physical activity (PA) is important for the prevention and treatment of chronic disease. Little is known about PA in people with AATD. Therefore, we aimed to map the research undertaken to improve and/or measure PA, sedentary behaviour (SB) or exercise in people with AATD. Searches were conducted in CINAHL, Medline, EMBASE and clinical trial databases for studies published in 2021. Databases were searched for keywords (physical activity, AATD, exercise, sedentary behavior) as well as synonyms of these terms, which were connected using Boolean operators. The search yielded 360 records; 37 records were included for review. All included studies (n = 37) assessed exercise capacity; 22 studies reported the use of the six-minute walk test, the incremental shuttle walk test and cardiopulmonary exercise testing were reported in three studies each. Other objective measures of exercise capacity included a submaximal treadmill test, the Naughton protocol treadmill test, cycle ergometer maximal test, endurance shuttle walk test, constant cycle work rate test, a peak work rate test and the number of flights of stairs a participant was able to walk without stopping. A number of participant self-reported measures of exercise capacity were noted. Only one study aimed to analyze the effects of an intensive fitness intervention on daily PA. One further study reported on an exercise intervention and objectively measured PA at baseline. No studies measured SB. The assessment of PA and use of PA as an intervention in AATD is limited, and research into SB absent. Future research should measure PA and SB levels in people with AATD and explore interventions to enhance PA in this susceptible population.
Competing Interests: Professor Noel G McElvaney reports grants from Grifols, Csl Behring; advisory board for vertex and inhibrx, outside the submitted work. The authors report no other conflicts of interest in this work.

Milne KM; Cowan J; Schaeffer MR; Voduc N; Chirinos JA; Abdallah SJ; Guenette JA;

ERJ open research [ERJ Open Res] 2023 Jun 19; Vol. 9 (3).
Date of Electronic Publication: 2023 Jun 19 (Print Publication: 2023).

Objectives: Dyspnoea is a common persistent symptom post-coronavirus disease 2019 (COVID-19) illness. However, the mechanisms underlying dyspnoea in the post-COVID-19 syndrome remain unclear. The aim of our study was to examine dyspnoea quality and intensity, burden of mental health symptoms, and differences in exercise responses in people with and without persistent dyspnoea following COVID-19.
Methods: 49 participants with mild-to-critical COVID-19 were included in this cross-sectional study 4 months after acute illness. Between-group comparisons were made in those with and without persistent dyspnoea (defined as modified Medical Research Council dyspnoea score ≥1). Participants completed standardised dyspnoea and mental health symptom questionnaires, pulmonary function tests, and incremental cardiopulmonary exercise testing.
Results: Exertional dyspnoea intensity and unpleasantness were increased in the dyspnoea group. The dyspnoea group described dyspnoea qualities of suffocating and tightness at peak exercise (p<0.05). Ventilatory equivalent for carbon dioxide ( V ‘ _E / V ‘ _{CO 2} ) nadir was higher (32±5 versus 28±3, p<0.001) and anaerobic threshold was lower (41±12 versus 49±11% predicted maximum oxygen uptake, p=0.04) in the dyspnoea group, indicating ventilatory inefficiency and deconditioning in this group. The dyspnoea group experienced greater symptoms of anxiety, depression and post-traumatic stress (all p<0.05). A subset of participants demonstrated gas-exchange and breathing pattern abnormalities suggestive of dysfunctional breathing.
Conclusions: People with persistent dyspnoea following COVID-19 experience a specific dyspnoea quality phenotype. Dyspnoea post-COVID-19 is related to abnormal pulmonary gas exchange and deconditioning and is linked to increased symptoms of anxiety, depression and post-traumatic stress.
Competing Interests: Conflict of interest: K.L. Lavoie reports consulting fees from AbbVie, Takeda, Astellas, Boehringer Ingelheim, AstraZeneca, Janssen, Novartis, GSK, Bausch and Sojecci Inc., outside the submitted work; payment or honoraria from AbbVie, Boehringer Ingelheim, Takeda, Pfizer, Merck, GSK, Astra-Zeneca, Novartis, Janssen, Bayer, Mundi Pharma, Bayer, Air Liquide, Astellas and Xfacto, outside the submitted work; and participation on a Data Safety Monitoring Board or Advisory Board for Astra-Zeneca, GSK and Bausch, outside the submitted work. Conflict of interest: J. Cowan reports support for the present manuscript from The Ottawa Hospital Foundation; grants or contracts from Octapharma and Takeda, outside the submitted work; payment or honoraria from GSK, Sanofi, EMD Serono, Alexion and Takeda, outside the submitted work; and support for attending meetings and/or travel from Octapharma, outside the submitted work. Conflict of interest: J.A. Chirinos reports grants or contracts from University of Pennsylvania research grants from National Institutes of Health, Fukuda-Denshi, Bristol-Myers Squibb, Microsoft and Abbott, outside the submitted work; consulting fees from Bayer, Sanifit, Fukuda-Denshi, Bristol-Myers Squibb, JNJ, Edwards Life Sciences, Merck, NGM Biopharmaceuticals and the Galway-Mayo Institute of Technology, outside the submitted work; patents planned, issued or pending: inventor in a University of Pennsylvania patent for the use of inorganic nitrates/nitrites for the treatment of Heart Failure and Preserved Ejection Fraction and for the use of biomarkers in heart failure with preserved ejection fraction, outside the submitted work; participant on advisory board for BMS, outside the submitted work; Vice President of North American Artery Society, outside the submitted work; received research device loans from Atcor Medical, Fukuda-Denshi, Uscom, NDD Medical Technologies, Microsoft and MicroVision Medical, outside the submitted work; received payments for editorial roles from the American Heart Association, the American College of Cardiology and Wiley, outside the submitted work. Conflict of interest: J.A. Guenette is an associate editor of this journal. Conflict of interest: The remaining authors have nothing to disclose.

Ahmed B; Shaw S; Pratt O; Forde C; Lal S; Carlson Cbe G;

Clinical nutrition ESPEN [Clin Nutr ESPEN] 2023 Aug; Vol. 56, pp. 152-157.
Date of Electronic Publication: 2023 May 19.

Background: Parenteral nutrition (PN) deficient in mitochondrial substrates and thiamine may lead to acidosis. This, combined with fatigue seen in patients with intestinal failure (IF), may suggest suboptimal oxidative metabolism. We therefore studied oxygen utilisation in otherwise apparently well-nourished individuals with intestinal failure receiving long term PN.
Methods: This was a retrospective analysis conducted in a tertiary IF institution, from 2010 to 2019, comparing treadmill/bicycle cardiopulmonary exercise test (CPET) derived variables including peak oxygen consumption (VO _{2 peak} ), anaerobic threshold (AT) and ventilatory efficiency (minute ventilation (VE)/CO ₂ output (VCO ₂ ) of patients with IF (cases) to those without (controls), matched in a 1:2 ratio for age ( ± 3 years), gender, use of beta-blockers and physiology parameters of p-POSSUM score ( ± 5). All subjects were free of sepsis and metastatic malignancy. Mann-Whitney or Student’s t-test for continuous and Fisher’s exact or chi-squared test for categorical variables were used as appropriate. Data shown represent mean or median values.
Results: Participants (31 cases, 62 controls) were comparable in age (65.4 vs. 65.3, p = 0.98); p-POSSUM parameters (18.0 vs. 17.0, p = 0.45); gender (p = 1.00); smoking status (p = 0.52); use of beta-blockers (p = 1.00) and ≤10 mg/day of oral steroids (p = 0.34). Participants had been on PN for 11.0 (6.0-24.0) months and were adequately nourished (requirements 27.6 kcal/kg/day, replacement 23.5 kcal/kg/day). No differences were found between VO _{2 peak} (15.2 vs. 14.6 ml/kg/min, p = 0.96), AT (10.4 vs. 11.0 ml/kg/min, p = 0.44) and VE/VCO ₂ (33.0 vs. 33.0, p = 0.96) of the examined groups.
Conclusion: Patients with intestinal failure receiving PN who are apparently well-nourished also appear to have normal oxygen utilisation, suggesting alternative causes for fatigue. More studies will be required to determine whether CPET could reliably be used to assess perioperative risk in this group of patients.

Wernhart S; Balcer B; Rassaf T; Luedike P;

Journal of clinical medicine [J Clin Med] 2023 May 25; Vol. 12 (11).
Date of Electronic Publication: 2023 May 25.

(1) Background: The exercise capacity of patients with a left ventricular assist device (LVAD) remains limited despite mechanical support. Higher dead space ventilation (V _D /V _T ) may be a surrogate for right ventricular to pulmonary artery uncoupling (RV-PA) during cardiopulmonary exercise testing (CPET) to explain persistent exercise limitations.
(2) Methods: We investigated 197 patients with heart failure and reduced ejection fraction with ( n = 89) and without (HFrEF, n = 108) LVAD. As a primary outcome NTproBNP, CPET, and echocardiographic variables were analyzed for their potential to discriminate between HFrEF and LVAD. As a secondary outcome CPET variables were evaluated for a composite of hospitalization due to worsening heart failure and overall mortality over 22 months.
(3) Results: NTproBNP (OR 0.6315, 0.5037-0.7647) and RV function (OR 0.45, 0.34-0.56) discriminated between LVAD and HFrEF. The rise of endtidal CO ₂ (OR 4.25, 1.31-15.81) and V _D /V _T (OR 1.23, 1.10-1.40) were higher in LVAD patients. Group (OR 2.01, 1.07-3.85), VE/VCO ₂ (OR 1.04, 1.00-1.08), and ventilatory power (OR 0.74, 0.55-0.98) were best associated with rehospitalization and mortality.
(4) Conclusions: LVAD patients displayed higher V _D /V _T compared to HFrEF. Higher V _D /V _T as a surrogate for RV-PA uncoupling could be another marker of persistent exercise limitations in LVAD patients.

Mounsey LA; Witkin AS; Hardin CC; Rodriguez-Lopez J;

Annals of the American Thoracic Society [Ann Am Thorac Soc] 2023 Jun 13.
Date of Electronic Publication: 2023 Jun 13.

NO abstract available

Keteyian SJ; Steenson K; Grimshaw C; Mandel N; Koester-Qualters W; Berry R; Kerrigan DJ;Ehrman JK;
Peterson EL; Brawner CA;

Journal of cardiopulmonary rehabilitation and prevention [J Cardiopulm Rehabil Prev] 2023 Jun 14.
Date of Electronic Publication: 2023 Jun 14.

Purpose: Among patients in cardiac rehabilitation (CR) on beta-adrenergic blockade (βB) therapy, this study describes the frequency for which target heart rate (THR) values computed using a predicted maximal heart rate (HRmax), correspond to a THR computed using a measured HRmax in the guideline-based heart rate reserve (HRreserve) method.
Methods: Before CR, patients completed a cardiopulmonary exercise test to measure HRmax, with the data used to determine THR via the HRreserve method. Additionally, predicted HRmax was computed for all patients using the 220 – age equation and two disease-specific equations, with the predicted values used to calculate THR via the straight percent and HRreserve methods. The THR was also computed using resting heart rate (HR) +20 and +30 bpm.
Results: Mean predicted HRmax using the 220 – age equation (161 ± 11 bpm) and the disease-specific equations (123 ± 9 bpm) differed (P < .001) from measured HRmax (133 ± 21 bpm). Also, THR computed using predicted HRmax resulted in values that were infrequently within the guideline-based HRreserve range calculated using measured HRmax. Specifically, 0 to ≤61% of patients would have had an exercise training HR that fell within the guideline-based range of 50-80% of measured HRreserve. Use of standing resting HR +20 or +30 bpm would have resulted in 100% and 48%, respectively, of patients exercising below 50% of HRreserve.
Conclusions: A THR computed using either predicted HRmax or resting HR +20 or +30 bpm seldom results in a prescribed exercise intensity that is consistent with guideline recommendations for patients in CR.

Amedro P; Mura T; Matecki S;  Guillaumont S; Requirand A; Jeandel C; Kollen L; Gavotto A;

European journal of preventive cardiology [Eur J Prev Cardiol] 2023 Jun 14.
Date of Electronic Publication: 2023 Jun 14.

Aims: Overweight and obesity in children with congenital heart disease (CHD) represent an alarming cardiovascular risk. Promotion of physical activity and cardiac rehabilitation in this population requires assessing the level of aerobic fitness (VO2max) by a cardiopulmonary exercise test (CPET). Nevertheless, the interpretation of CPET in overweight/obese children with CHD remains challenging as VO2max is affected by both the cardiac condition and the body mass index (BMI). The new paediatric VO2max Z-score reference equations, based on a logarithmic function of VO2max, height and BMI, were applied to overweight/obese children with a CHD, and compared to overweight/obese children without any other chronic condition.
Methods and Results: In this cross-sectional controlled study, 344 children with a BMI>85th percentile underwent a CPET (54% boys; mean age 11.5±3.1 years; 100 CHD; 244 controls). Using the VO2max Z-score equations, aerobic fitness was significantly lower in obese/overweight CHD children than in matched obese/overweight control children (-0.43±1.27 vs. -0.01±1.09; p=0.02, respectively) and the proportion of children with impaired aerobic fitness was significantly more important in obese/overweight CHD children than in matched controls (17% vs.6%, p=0.02, respectively). The paediatric VO2max Z-score reference equations also identified specific complex CHD at risk of aerobic fitness impairment (univentricular heart, right outflow tract anomalies). Using Cooper’s weight and height-based linear equations, similar matched-comparisons analyses found no significant group differences.
Conclusions: As opposed to the existing linear models, the new paediatric VO2max Z-score equations can discriminate the aerobic fitness of obese/overweight children with CHD from that of obese/overweight children without any chronic disease.

Omar M; Omote K; Sorimachi H; Popovic D; Kanwar A; Alogna A; Reddy YNV; Lim KG;Shah SJ; Borlaug BA;

European journal of heart failure [Eur J Heart Fail] 2023 Jun 14.
Date of Electronic Publication: 2023 Jun 14.

Background & Aims: It is widely held that heart failure (HF) does not cause exertional hypoxemia, based upon studies in HF with reduced ejection fraction (EF), but this may not apply to patients with HF and preserved EF (HFpEF). Here, we characterize the prevalence, pathophysiology, and clinical implications of exertional arterial hypoxemia in HFpEF.
Methods & Results: Patients with HFpEF (n=539) and no coexisting lung disease underwent invasive cardiopulmonary exercise testing with simultaneous blood and expired gas analysis. Exertional hypoxemia (oxyhemoglobin saturation <94%) was observed in 136 patients (25%). As compared to those without hypoxemia (n=403), patients with hypoxemia were older and more obese. Patients with HFpEF and hypoxemia had higher cardiac filling pressures, higher pulmonary vascular pressures, greater alveolar-arterial O ₂ difference, increased dead space fraction, and greater physiologic shunt compared to those without hypoxemia. These differences were replicated in a sensitivity analysis where patients with spirometric abnormalities were excluded. Regression analyses revealed that increases in pulmonary arterial and capillary pressures were related to lower PaO ₂ , especially during exercise. BMI was not correlated with the arterial PaO ₂ , and hypoxemia was associated with increased risk for death over 2.8 (IQR 0.7-5.5) years of follow up, even after adjusting for age, sex, and BMI (HR 2.00 (95%CI: 1.01-3.96), p=0.046).
Conclusion: Between 10-25% of patients with HFpEF display arterial desaturation during exercise that is not ascribable to lung disease. Exertional hypoxemia is associated with more severe hemodynamic abnormalities and increased mortality. Further study is required to better understand the mechanisms and treatment of gas exchange abnormalities in HFpEF.