Neunhäuserer D;Hudelmaier M; Niederseer DVecchiato M; Wirth W; Steidle-Kloc E; Kaiser B; Lamprecht B;Ermolao A; Studnicka M;

Medicine and science in sports and exercise [Med Sci Sports Exerc] 2023 Aug 02.
Date of Electronic Publication: 2023 Aug 02.

Objective: Exercise training is a cornerstone of the treatment of COPD while the related inter-individual heterogeneity in skeletal muscle dysfunction and adaptations are not yet fully understood. We set out to investigate the effects of exercise training and supplemental oxygen on functional and structural peripheral muscle adaptation.
Methods: In this prospective, randomized, controlled, double-blind study, 28 patients with non-hypoxemic COPD (FEV1 45.92 ± 9.06%) performed six-weeks of combined endurance and strength training, three times a week while breathing either supplemental oxygen or medical air. The impact on exercise capacity, muscle strength and quadriceps femoris muscle cross-sectional area (CSA), was assessed by maximal cardiopulmonary exercise testing, ten-repetition maximum strength test of knee extension, and magnetic resonance imaging, respectively.
Results: After exercise training, patients demonstrated a significant increase of functional capacity, aerobic capacity, exercise tolerance, quadriceps muscle strength and bilateral CSA. Supplemental oxygen affected significantly the training impact on peak work rate when compared to medical air (+0.20 ± 0.03 vs +0.12 ± 0.03 Watt/kg, p = 0.047); a significant increase in CSA (+3.9 ± 1.3 cm2, p = 0.013) was only observed in the training group using oxygen. Supplemental oxygen and exercise induced peripheral desaturation were identified as significant opposing determinants of muscle gain during this exercise training intervention, which led to different adaptations of CSA between the respective subgroups.
Conclusions: The heterogenous functional and structural muscle adaptations seem determined by supplemental oxygen and exercise induced hypoxia. Indeed, supplemental oxygen may facilitate muscular training adaptations, particularly in limb muscle dysfunction, thereby contributing to the enhanced training responses on maximal aerobic and functional capacity.
Competing Interests: Conflict of Interest and Funding Source: The Salzburg COPD Exercise and Oxygen (SCOPE) study was supported by an unconditional and unrestricted grant by Air Liquide. All authors declare hereby to have no conflicts of interest. The results of this study are presented clearly, honestly and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by the American College of Sports Medicine.

Bertrand É; Caru M; Morel S; Bergeron Parenteau A; Belanger V; Laverdière C; Krajinovic M; Sinnett D; Levy E;
Marcil V; Curnier D;

Pediatric hematology and oncology [Pediatr Hematol Oncol] 2023 Jul 13, pp. 1-18.
Date of Electronic Publication: 2023 Jul 13.

Children with acute lymphoblastic leukemia (ALL) are at high risk of developing long-term cardiometabolic complications during their survivorship. Maximal fat oxidation (MFO) is a marker during exercise of cardiometabolic health, and is associated with metabolic risk factors. Our aim was to characterize the carbohydrate and fat oxidation during exercise in childhood ALL survivors. Indirect calorimetry was measured in 250 childhood ALL survivors to quantify substrate oxidation rates during a cardiopulmonary exercise test. A best-fit third-order polynomial curve was computed for fat oxidation rate (mg/min) against exercise intensity ( V ̇ O ₂ peak) and was used to determine the MFO and the peak fat oxidation (Fat _max ). The crossover point was also identified. Differences between prognostic risk groups were assessed (ie, standard risk [SR], high risk with and without cardio-protective agent dexrazoxane [HR + DEX and HR]). MFO, Fat _max and crossover point were not different between the groups ( p  = .078; p  = .765; p  = .726). Fat _max and crossover point were achieved at low exercise intensities. A higher MFO was achieved by men in the SR group (287.8 ± 111.2 mg/min) compared to those in HR + DEX (239.8 ± 97.0 mg/min) and HR groups (229.3 ± 98.9 mg/min) ( p  = .04). Childhood ALL survivors have low fat oxidation during exercise and oxidize carbohydrates at low exercise intensities, independently of the cumulative doses of doxorubicin they received. These findings alert clinicians on the long-term impact of cancer treatments on childhood ALL survivors’ substrate oxidation.

Hardin KM; Boston; Giverts I; Campain J; Farrell R; Cunningham T; Brooks L; Christ A; Wooster L; Bailey CS; Schoenike M; Sbarbaro J; Baggish A; Nayor M; Ho JE; Malhotra R; Shah R; Lewis GD;

Journal of cardiac failure [J Card Fail] 2023 Jul 17.
Date of Electronic Publication: 2023 Jul 17.

Background: Whether systemic oxygen levels (SaO ₂ ) during exercise can provide a window into invasively derived exercise hemodynamic profiles in patients with undifferentiated dyspnea on exertion is unknown.
Methods: We performed cardiopulmonary exercise testing with invasive hemodynamic monitoring and arterial blood gas sampling in individuals referred for dyspnea on exertion. Receiver operator analysis was performed to distinguish heart failure with preserved ejection fraction from pulmonary arterial hypertension (PAH).
Results: Among 253 patients (mean ± SD, age 63±14 years, 55% female, arterial O ₂ (PaO ₂ ) 87±14mmHg, SaO ₂ 96±4%, resting pulmonary capillary wedge pressure (PCWP) 18±4mmHg and pulmonary vascular resistance (PVR) 2.7±1.2 Wood units), there was no exercise PCWP threshold, measured up to 49mmHg, above which hypoxemia was consistently observed. Exercise PaO ₂ was not correlated with exercise PCWP (rho=0.04, p=0.51) but did relate to exercise PVR (rho=-0.46, p<0.001). Exercise PaO ₂ and SaO ₂ levels distinguished left-heart predominant dysfunction from pulmonary vascular-predominant dysfunction with an AUC of 0.89 and 0.89, respectively.
Conclusion: Systemic O ₂ levels during exercise distinguish relative pre- and post-capillary pulmonary hemodynamic abnormalities in patients with undifferentiated dyspnea. Hypoxemia during upright exercise should not be attributed to isolated elevation in left heart filling pressures and should prompt consideration of pulmonary vascular dysfunction.

Fabiani I; Pugliese NR; Pedrizzetti G; Tonti G; Castiglione V; Chubuchny V; Taddei C; Gimelli A; Del Punta L;
Balletti A; Del Franco A; Masi S; Lombardi CM; Cameli M; Emdin M; Giannoni A;

ESC heart failure [ESC Heart Fail] 2023 Jul 17.
Date of Electronic Publication: 2023 Jul 17.

Aims: A novel tool for the evaluation of left ventricular (LV) systo-diastolic function through echo-derived haemodynamic forces (HDFs) has been recently proposed. The present study aimed to assess the predictive value of HDFs on (i) 6 month treatment response to sacubitril/valsartan in heart failure with reduced ejection fraction (HFrEF) patients and (ii) cardiovascular events.
Methods and Results: Eighty-nine consecutive HFrEF patients [70% males, 65 ± 9 years, LV ejection fraction (LVEF) 27 ± 7%] initiating sacubitril/valsartan underwent clinical, laboratory, ultrasound and cardiopulmonary exercise testing evaluations. Patients experiencing no adverse events and showing ≥50% reduction in plasma N-terminal pro-B-type natriuretic peptide and/or ≥10% LVEF increase over 6 months were considered responders. Patients were followed up for the composite endpoint of HF-related hospitalisation, atrial fibrillation and cardiovascular death. Forty-five (51%) patients were responders. Among baseline variables, only HDF-derived whole cardiac cycle LV strength (wLVS) was higher in responders (4.4 ± 1.3 vs. 3.6 ± 1.2; p = 0.01). wLVS was also the only independent predictor of sacubitril/valsartan response at multivariable logistic regression analysis [odds ratio 1.36; 95% confidence interval (CI) 1.10-1.67], with good accuracy at receiver operating characteristic (ROC) analysis [optimal cutpoint: ≥3.7%; area under the curve (AUC) = 0.736]. During a 33 month (23-41) median follow-up, a wLVS increase after 6 months (ΔwLVS) showed a high discrimination ability at time-dependent ROC analysis (optimal cut-off: ≥0.5%; AUC = 0.811), stratified prognosis (log-rank p < 0.0001) and remained an independent predictor for the composite endpoint (hazard ratio 0.76; 95% CI 0.61-0.95; p < 0.01), after adjusting for clinical and instrumental variables.
Conclusions: HDF analysis predicts sacubitril/valsartan response and might optimise decision-making in HFrEF patients.

Mrak M; Pavšič N; Žižek D; Ležaić L; Bunc M;

Journal of cardiovascular development and disease [J Cardiovasc Dev Dis] 2023 May 26; Vol. 10 (6).
Date of Electronic Publication: 2023 May 26.

Coronary sinus reducer (CSR) implantation is a new treatment option for patients with refractory angina pectoris. However, there is no evidence from a randomized trial that would show an improvement in exercise capacity after this treatment.
The aim of this study was to evaluate the influence of CSR treatment on maximal oxygen consumption and compare it to a sham procedure.
Twenty-five patients with refractory angina pectoris (Canadian Cardiovascular Society (CCS) class II-IV) were randomized to a CSR implantation ( n = 13) or a sham procedure ( n = 12). At baseline and after 6 months of follow-up, the patients underwent symptom-limited cardiopulmonary exercise testing with an adjusted ramp protocol and assessment of angina pectoris using the CCS scale and Seattle angina pectoris questionnaire (SAQ). In the CSR group, maximal oxygen consumption increased from 15.56 ± 4.05 to 18.4 ± 5.2 mL/kg/min ( p = 0.03) but did not change in the sham group ( p = 0.53); p for intergroup comparison was 0.03. In contrast, there was no difference in the improvement of the CCS class or SAQ domains.
To conclude, in patients with refractory angina and optimized medical therapy, CSR implantation may improve oxygen consumption beyond that of optimal medical therapy.

Gryglewska-Wawrzak K; Cienkowski K; Cienkowska A; Banach M; Bielecka-Dabrowa A;

Journal of cardiovascular development and disease [J Cardiovasc Dev Dis] 2023 Jun 03; Vol. 10 (6).
Date of Electronic Publication: 2023 Jun 03.

Coronavirus disease 2019 (COVID-19) is a severe respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Heart failure (HF) is associated with a worse prognosis for patients with this viral infection, highlighting the importance of early detection and effective treatment strategies. HF can also be a consequence of COVID-19-related myocardial damage. To optimise the treatment of these patients, one needs to understand the interactions between this disease and viruses. Until now, the validity of the screening for cardiovascular complications after COVID-19 has not been confirmed. There were also no patients in whom such diagnostics seemed appropriate. Until appropriate recommendations are made, diagnosis procedures must be individualised based on the course of the acute phase and clinical symptoms reported or submitted after COVID-19. Clinical phenomena are the criteria for determining the recommended test panel. We present a structured approach to COVID-19 patients with heart involvement.

Pigakis KM; Stavrou VT; Pantazopoulos I; , Greece.Daniil Z; Kontopodi-Pigaki AK; Gourgoulianis K;

Advances in respiratory medicine [Adv Respir Med] 2023 Jun 07; Vol. 91 (3), pp. 239-253.
Date of Electronic Publication: 2023 Jun 07.

Background: Exercise-induced bronchoconstriction (EIB) is a common problem in elite athletes. Classical pathways in the development of EIB include the osmotic and thermal theory as well as the presence of epithelial injury in the airway, with local water loss being the main trigger of EIB. This study aimed to investigate the effects of systemic hydration on pulmonary function and to establish whether it can reverse dehydration-induced alterations in pulmonary function.
Materials and Methods: This follow-up study was performed among professional cyclists, without a history of asthma and/or atopy. Anthropometric characteristics were recorded for all participants, and the training age was determined. In addition, pulmonary function tests and specific markers such as fractional exhaled nitric oxide (FeNO) and immunoglobulin E (IgE) were measured. All the athletes underwent body composition analysis and cardiopulmonary exercise testing (CPET). After CPET, spirometry was followed at the 3rd, 5th, 10th, 15th, and 30th min. This study was divided into two phases: before and after hydration. Cyclists, who experienced a decrease in Forced Expiratory Volume in one second (FEV ₁ ) ≥ 10% and/or Maximal Mild-Expiratory Flow Rate (MEF _25-75 ) ≥ 20% after CPET in relation to the results of the spirometry before CPET, repeated the test in 15-20 days, following instructions for hydration.
Results: One hundred male cyclists ( n = 100) participated in Phase A. After exercise, there was a decrease in all spirometric parameters ( p < 0.001). In Phase B, after hydration, in all comparisons, the changes in spirometric values were significantly lower than those in Phase A ( p < 0.001).
Conclusions: The findings of this study suggest that professional cyclists have non-beneficial effects on respiratory function. Additionally, we found that systemic hydration has a positive effect on spirometry in cyclists. Of particular interest are small airways, which appear to be affected independently or in combination with the decrease in FEV ₁ . Our data suggest that pulmonary function improves systemic after hydration.

Tomlinson OW; Barker AR; Fulford J; Wilson P; Shelley J; Oades PJ; Williams CA

Frontiers in pediatrics [Front Pediatr] 2023 Jun 14; Vol. 11, pp. 1211547.
Date of Electronic Publication: 2023 Jun 14 (Print Publication: 2023).

Background: Increased maximal oxygen uptake (V̇O _2max ) is beneficial in children with cystic fibrosis (CF) but remains lower compared to healthy peers. Intrinsic metabolic deficiencies within skeletal muscle (muscle “quality”) and skeletal muscle size (muscle “quantity”) are both proposed as potential causes for the lower V̇O _2max , although exact mechanisms remain unknown. This study utilises gold-standard methodologies to control for the residual effects of muscle size from V̇O _2max to address this “quality” vs. “quantity” debate.
Methods: Fourteen children (7 CF vs. 7 age- and sex-matched controls) were recruited. Parameters of muscle size – muscle cross-sectional area (mCSA) and thigh muscle volume (TMV) were derived from magnetic resonance imaging, and V̇O _2max obtained via cardiopulmonary exercise testing. Allometric scaling removed residual effects of muscle size, and independent samples t -tests and effect sizes (ES) identified differences between groups in V̇O _2max , once mCSA and TMV were controlled for.
Results: V̇O _2max was shown to be lower in the CF group, relative to controls, with large ES being identified when allometrically scaled to mCSA (ES = 1.76) and TMV (ES = 0.92). Reduced peak work rate was also identified in the CF group when allometrically controlled for mCSA (ES = 1.18) and TMV (ES = 0.45).
Conclusions: A lower V̇O _2max was still observed in children with CF after allometrically scaling for muscle size, suggesting reduced muscle “quality” in CF (as muscle “quantity” is fully controlled for). This observation likely reflects intrinsic metabolic defects within CF skeletal muscle.

Althunayyan A; Alborikan S; Badiani S; Wong K; Uppal R; CPatel N; Petersen SE; Lloyd G; Bhattacharyya S;

The American journal of cardiology [Am J Cardiol] 2023 Jun 20; Vol. 201, pp. 8-15.
Date of Electronic Publication: 2023 Jun 20.

The current guidelines recommend intervention in severe degenerative mitral regurgitation (MR) in symptomatic patients or asymptomatic patients with left ventricular dilatation or dysfunction. The insidious onset of symptoms may mean that patients do not report their symptoms. The role of systematic exercise testing for symptoms in MR is not clearly defined. A total of 97 patients with moderate to severe asymptomatic MR underwent exercise echocardiography combined with cardiopulmonary exercise testing. The predictors of exercise-induced dyspnea, symptom-free survival, and mitral valve intervention were identified. A total of 18 patients (19%) developed limiting dyspnea on exercise. Spontaneous symptom-free survival at 24 months was significantly higher in those without exercise-induced symptoms than those with exercise-induced symptoms, p <0.0001. The only independent predictors of spontaneous symptoms at 2 years were effective regurgitant orifice area (odds ratio 27.45, 95% confidence interval [CI] 1.43 to 528.40, p = 0.03) and exercise-induced symptoms (odds ratio 11.56, 95% CI 1.71 to 78.09, p = 0.01). The only independent predictor of surgery was indexed left ventricular systolic volumes (odds ratio 1.17, 95% CI 1.04 to 1.30, p = 0.006). Where only the patients who underwent surgery due to symptoms were included, the only independent predictor was exercise-induced symptoms (odds ratio 13.94, 95% CI 1.39 to 140.27, p = 0.025). In conclusion, in patients with primary asymptomatic degenerative MR, 1/5 develop revealed symptoms during exercise. This predicts a subsequent development of spontaneous symptoms and mitral valve intervention due to symptoms.
Competing Interests: Declaration of Competing Interest Dr. Petersen reports a relation with Circle Cardiovascular Imaging Inc., Calgary, Alberta, Canada (SEP) that includes consulting or advisory. The remaining authors have no conflicts of interest to declare.

Batten K; Bhattacharya K; Simar D; Broderick C;

Journal of inherited metabolic disease [J Inherit Metab Dis] 2023 Jun 22.
Date of Electronic Publication: 2023 Jun 22.

Skeletal muscle is a dynamic organ requiring tight regulation of energy metabolism in order to provide bursts of energy for effective function. Several inborn errors of muscle energy metabolism (IEMEM) affect skeletal muscle function and therefore the ability to initiate and sustain physical activity. Exercise testing can be valuable in supporting diagnosis, however its use remains limited due to the inconsistency in data to inform its application in IEMEM populations. While exercise testing is often used in adults with IEMEM, its use in children is far more limited. Once a physiological limitation has been identified and the aetiology defined, habitual exercise can assist with improving functional capacity, with reports supporting favourable adaptations in adult patients with IEMEM. Despite the potential benefits of structured exercise programs, data in paediatric populations remain limited. This review will focus on the utilisation and limitations of exercise testing and prescription for both adults and children, in the management of McArdle Disease, long chain fatty acid oxidation disorders, and myopathic mitochondrial respiratory chain disorders.