do Nascimento DM; Machado KC; Bock PM; Saffi MAL; Goldraich LA; Silveira AD; Clausell N; Schaan BD;

BMC cardiovascular disorders [BMC Cardiovasc Disord] 2023 Jul 29; Vol. 23 (1), pp. 381.
Date of Electronic Publication: 2023 Jul 29.

Background: Functional training may be an effective non-pharmacological therapy for heart failure (HF). This study aimed to compare the effects of functional training with strength training on peak VO ₂ and quality of life in individuals with HF.
Methods: A randomized, parallel-design and examiner-blinded controlled clinical trial with concealed allocation, intention-to-treat and per-protocol analyses. Twenty-seven participants with chronic HF were randomly allocated to functional or strength training group, to perform a 12-week physical training, three times per week, totalizing 36 sessions. Primary outcomes were the difference on peak VO ₂ and quality of life assessed by cardiopulmonary exercise testing and Minnesota Living with Heart Failure Questionnaire, respectively. Secondary outcomes included functionality assessed by the Duke Activity Status Index and gait speed test, peripheral and inspiratory muscular strength, assessed by hand grip and manovacuometry testing, respectively, endothelial function by brachial artery flow-mediated dilation, and lean body mass by arm muscle circumference.
Results: Participants were aged 60 ± 7 years, with left ventricular ejection fraction 29 ± 8.5%. The functional and strength training groups showed the following results, respectively: peak VO ₂ increased by 1.4 ± 3.2 (16.9 ± 2.9 to 18.6 ± 4.8 mL.kg ^-1 .min ^-1 ; p time = 0.011) and 1.5 ± 2.5 mL.kg ^-1 .min ^-1 (16.8 ± 4.0 to 18.6 ± 5.5 mL.kg ^-1 .min ^-1 ; p time = 0.011), and quality of life score decreased by 14 ± 15 (25.8 ± 14.8 to 10.3 ± 7.8 points; p time = 0.001) and 12 ± 28 points (33.8 ± 23.8 to 19.0 ± 15.1 points; p time = 0.001), but no difference was observed between groups (peak VO ₂ : p interaction = 0.921 and quality of life: p interaction = 0.921). The functional and strength training increased the activity status index by 6.5 ± 12 and 5.2 ± 13 points (p time = 0.001), respectively, and gait speed by 0.2 ± 0.3 m/s (p  time = 0.002) in both groups.
Conclusions: Functional and strength training are equally effective in improving peak VO ₂ , quality of life, and functionality in individuals with HF. These findings suggest that functional training may be a promising and innovative exercise-based strategy to treat HF.

Biagini D; Pugliese NR; Vivaldi FM; Ghimenti S; Lenzi A; De Angelis F; Ripszam M; Bruderer T; Armenia S; Cappeli F; Taddei S;
Masi S; Francesco FD; Lomonaco T;

Journal of breath research [J Breath Res] 2023 Aug 09; Vol. 17 (4).
Date of Electronic Publication: 2023 Aug 09.

This paper describes the AEOLUS pilot study which combines breath analysis with cardiopulmonary exercise testing (CPET) and an echocardiographic examination for monitoring heart failure (HF) patients. Ten consecutive patients with a prior clinical diagnosis of HF with reduced left ventricular ejection fraction were prospectively enrolled together with 15 control patients with cardiovascular risk factors, including hypertension, type II diabetes or chronic ischemic heart disease. Breath samples were collected at rest and during CPET coupled with exercise stress echocardiography (CPET-ESE) protocol by means of needle trap micro-extraction and were analyzed through gas-chromatography coupled with mass spectrometry. The protocol also involved using of a selected ion flow tube mass spectrometer for a breath-by-breath isoprene and acetone analysis during exercise. At rest, HF patients showed increased breath levels of acetone and pentane, which are related to altered oxidation of fatty acids and oxidative stress, respectively. A significant positive correlation was observed between acetone and the gold standard biomarker NT-proBNP in plasma ( r = 0.646, p < 0.001), both measured at rest. During exercise, some exhaled volatiles (e.g., isoprene) mirrored ventilatory and/or hemodynamic adaptation, whereas others (e.g., sulfide compounds and 3-hydroxy-2-butanone) depended on their origin. At peak effort, acetone levels in HF patients differed significantly from those of the control group, suggesting an altered myocardial and systemic metabolic adaptation to exercise for HF patients. These preliminary data suggest that concomitant acquisition of CPET-ESE and breath analysis is feasible and might provide additional clinical information on the metabolic maladaptation of HF patients to exercise. Such information may refine the identification of patients at higher risk of disease worsening.

Girardi M; Gattoni C; Stringer WW;Rossiter HB; Casaburi R; Ferguson C; Capelli C;

American journal of physiology. Regulatory, integrative and comparative physiology [Am J Physiol Regul Integr Comp Physiol] 2023 Jul 31.
Date of Electronic Publication: 2023 Jul 31.

Identification of the breathing cycle forms the basis of any breath-by-breath gas exchange analysis. Classically, the breathing cycle is defined as the time interval between the beginning of two consecutive inspiration phases. Based on this definition, several research groups have developed algorithms designed to estimate the volume and rate of gas transferred across the alveolar membrane (“alveolar gas exchange”); however, most algorithms require measurement of lung volume at the beginning of the i ^th breath ( V _Li-1 – i.e., the end-expiratory lung volume of the preceding i ^th breath). The main limitation of these algorithms is that direct measurement of V _Li-1 is challenging and often unavailable. Two solutions avoid the requirement to measure V _Li-1 by redefining the breathing cycle. One method defines the breathing cycle as the time period between two equal fractional concentrations of lung expired oxygen ( F _O2 ) (or carbon dioxide; F _CO2 ), typically in the alveolar phase, whereas the other uses the time period between equal values of the F _O2 /F _N2 (or F _CO2 / F _N2 ) ratios. Thus, these methods identify the breathing cycle by analyzing the gas fraction traces rather than the gas flow signal. In this review, we define the traditional approach and two alternative definitions of the human breathing cycle and present the rationale for redefining this term. We also explore the strengths and limitations of the available approaches and provide implications for future studies.

Milani JGPO; Milani M; Cipriano GFB; Hansen D; Cipriano Junior G;

BMJ open sport & exercise medicine [BMJ Open Sport Exerc Med] 2023 Jul 31; Vol. 9 (3), pp. e001601.
Date of Electronic Publication: 2023 Jul 31 (Print Publication: 2023).

Objectives: To compare the elicited exercise responses at ventilatory thresholds (VTs: VT1 and VT2) identified by cardiopulmonary exercise testing (CPET) in patients with cardiovascular disease (CVD) with the guideline-directed exercise intensity domains; to propose equations to predict heart rate (HR) at VTs; and to compare the accuracy of prescription methods.
Methods: A cross-sectional study was performed with 972 maximal treadmill CPET on patients with CVD. First, VTs were identified and compared with guideline-directed exercise intensity domains. Second, multivariate linear regression analyses were performed to generate prediction equations for HR at VTs. Finally, the accuracy of prescription methods was assessed by the mean absolute percentage error (MAPE).
Results: Significant dispersions of individual responses were found for VTs, with the same relative intensity of exercise corresponding to different guideline-directed exercise intensity domains. A mathematical error inherent to methods based on percentages of peak effort was identified, which may help to explain the dispersions. Tailored multivariable equations yielded r ² of 0.726 for VT1 and 0.901 for VT2. MAPE for the novel VT1 equation was 6.0%, lower than that for guideline-based prescription methods (9.5 to 23.8%). MAPE for the novel VT2 equation was 4.3%, lower than guideline-based methods (5.8%-19.3%).
Conclusion: The guideline-based exercise intensity domains for cardiovascular rehabilitation revealed inconsistencies and heterogeneity, which limits the currently used methods. New multivariable equations for patients with CVD were developed and demonstrated better accuracy, indicating that this methodology may be a valid alternative when CPET is unavailable.

Vianna MVA; Ávila MR; Figueiredo PHS; Lima VP; Carvalho LMS; da Cruz Ferreira PH; de Oliveira LFF; Silva WT; de Almeida ILGI; Lacerda ACR; Mendonça VA; de Castro Faria SC; Mediano MFF; Costa HS;

Heart & lung : the journal of critical care [Heart Lung] 2023 Jul 31; Vol. 62, pp. 152-156.
Date of Electronic Publication: 2023 Jul 31.

Background: Functional impairment can be detected from the onset of heart disease in patients with Chagas cardiomyopathy (ChC) and the prognostic value of the end-tidal carbon dioxide at peak exercise (PETCO ₂ peak) should be investigated.
Objective: To verify the prognostic value of PETCO ₂ peak in patients with ChC.
Methods: Seventy-six patients with ChC (49.2 ± 9.8 years, NYHA I-III) were evaluated by echocardiography and Cardiopulmonary Exercise Testing. Patients were followed up to four years and the end-point was defined as cardiovascular death, stroke, or cardiac transplantation.
Results: At the end of the follow-up period (29.0 ± 16.0 months), 16 patients (21%) had experienced adverse events. The area under the receiver operating characteristic (ROC) curve to identify the risk of adverse events by PETCO ₂ peak in patients with ChC was 0.83 (95% CI: 0.69 to 0.97), and the value of 32 mmHg was the optimal cut point (70% of sensitivity and 85% of specificity). In the Kaplan-Meier diagram, there was a significant difference (p<0.001) between patients with reduced (≤ 32 mmHg) and preserved PETCO ₂ peak (>32 mmHg). In the final Cox multivariate model, only reduced PETCO ₂ peak (HR 4.435; 95% CI: 1.228 to 16.016, p = 0.023) and VO _2peak (HR 0.869; 95% CI: 0.778 to 0.971, p = 0.013) remained as independent predictors of poor outcome in ChC patients.
Conclusion: Reduced PETCO ₂ peak and VO2 _peak demonstrated valuable prognostic value in patients with ChC. The cutoff points for both functional variables can be used during risk stratification and may help in the development of therapeutic strategies in ChC patients.

Amedro P; Matecki S; Pereira Dos Santos T; Guillaumont S; Rhodes J; Yin SM; Hager A; Hock J; De La Villeon G; Moreau J;
Requirand A; Souilla L; Vincenti M; Picot MC; Huguet H; Mura T; Gavotto A;

Sports medicine – open [Sports Med Open] 2023 Aug 01; Vol. 9 (1), pp. 68.
Date of Electronic Publication: 2023 Aug 01.

Background: The evaluation of health status by cardiopulmonary exercise test (CPET) has shown increasing interest in the paediatric population. Our group recently established reference Z-score values for paediatric cycle ergometer VO _2max , applicable to normal and extreme weights, from a cohort of 1141 healthy children. There are currently no validated reference values for the other CPET parameters in the paediatric population. This study aimed to establish, from the same cohort, reference Z-score values for the main paediatric cycle ergometer CPET parameters, apart from VO _2max .
Results: In this cross-sectional study, 909 healthy children aged 5-18 years old underwent a CPET. Linear, quadratic, and polynomial mathematical regression equations were applied to identify the best CPET parameters Z-scores, according to anthropometric parameters (sex, age, height, weight, and BMI). This study provided Z-scores for maximal CPET parameters (heart rate, respiratory exchange ratio, workload, and oxygen pulse), submaximal CPET parameters (ventilatory anaerobic threshold, VE/VCO ₂ slope, and oxygen uptake efficiency slope), and maximum ventilatory CPET parameters (tidal volume, respiratory rate, breathing reserve, and ventilatory equivalent for CO ₂ and O ₂ ).
Conclusions: This study defined paediatric reference Z-score values for the main cycle ergometer CPET parameters, in addition to the existing reference values for VO _2max , applicable to children of normal and extreme weights. Providing Z-scores for CPET parameters in the paediatric population should be useful in the follow-up of children with various chronic diseases. Thus, new paediatric research fields are opening up, such as prognostic studies and clinical trials using cardiopulmonary fitness outcomes. Trial registration NCT04876209-Registered 6 May 2021-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04876209 .

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.