Category Archives: Publications

The metabolic signature of cardiorespiratory fitness: a protocol for a systematic review and meta-analysis.

Carrard J; Guerini C; Appenzeller-Herzog C; Infanger D; Königstein K; Streese L; Hinrichs T; Hanssen H;
Gallart-Ayala H; Ivanisevic J; Schmidt-Trucksäss A;

BMJ open sport & exercise medicine [BMJ Open Sport Exerc Med] 2021 Feb 19; Vol. 7 (1), pp. e001008. Date of Electronic Publication: 2021 Feb 19 (Print Publication: 2021).

Introduction: A low cardiorespiratory fitness (CRF) is a strong and independent predictor of cardiometabolic, cancer and all-cause mortality. To date, the mechanisms linking CRF with reduced mortality remain largely unknown. Metabolomics, which is a powerful metabolic phenotyping technology to unravel molecular mechanisms underlying complex phenotypes, could elucidate how CRF fosters human health.
Methods and Analysis: This study aims at systematically reviewing and meta-analysing the literature on metabolites of any human tissue sample, which are positively or negatively associated with CRF. Studies reporting estimated CRF will not be considered. No restrictions will be placed on the metabolomics technology used to measure metabolites. PubMed, Web of Science and EMBASE will be searched for relevant articles published until the date of the last search. Two authors will independently screen full texts of selected abstracts. References and citing articles of included articles will be screened for additional relevant publications. Data regarding study population, tissue samples, analytical technique, quality control, data processing, metabolites associated to CRF, cardiopulmonary exercise test protocol and exercise exhaustion criteria will be extracted. Methodological quality will be assessed using a modified version of QUADOMICS. Narrative synthesis as well as tabular/charted presentation of the extracted data will be included. If feasible, meta-analyses will be used to investigate the associations between identified metabolites and CRF. Potential sources of heterogeneity will be explored in meta-regressions.

Percentage of age-predicted cardiorespiratory fitness and risk of sudden cardiac death: a prospective cohort study.

Laukkanen JA; Kurl S; IKhan H; Kunutsor SK;

Heart rhythm [Heart Rhythm] 2021 Mar 06. Date of Electronic Publication: 2021 Mar 06.

Background: The inverse associations between cardiorespiratory fitness (CRF) and vascular outcomes are previously established. However, there has been no previous prospective evaluation of the relationship between percentage of age-predicted CRF (%age-predicted CRF) and risk of sudden cardiac death (SCD).
Objective: We aimed to assess the association of %age-predicted CRF with SCD risk in a long-term prospective cohort study.
Methods: Cardiorespiratory fitness was assessed using the gold standard respiratory gas exchange analyser in 2,276 men who underwent cardiopulmonary exercise testing. The age-predicted CRF estimated from a regression equation for age was converted to %age-predicted CRF using (achieved CRF/age-predicted CRF)*100. Hazard ratios (HRs) (95% confidence intervals, CIs) were calculated for SCD.
Results: During a median follow-up of 28.2 years, 260 SCDs occurred. There was a dose-response relationship between age-predicted CRF and SCD. A 1 standard deviation increase in %age-predicted CRF was associated with a decreased risk of SCD in analysis adjusted for established risk factors (HR 0.60; 95% CI 0.53-0.70), which remained consistent on further adjustment for several potential confounders including alcohol consumption, physical activity, socioeconomic status and systemic inflammation (HR 0.73; 95% CI 0.62-0.85). The corresponding adjusted HRs (95% CIs) were 0.34 (0.23-0.50) and 0.52 (0.34-0.79) respectively, when comparing extreme quartiles of %age-predicted CRF levels. The HRs for the associations of absolute CRF levels with SCD risk in the same participants were similar.
Conclusions: Percentage of age-predicted CRF is continuously, strongly and independently associated with risk of SCD and it is comparable to absolute CRF as a risk indicator for SCD.

“You can leave your mask on”: effects on cardiopulmonary parameters of different airway protection masks at rest and during maximal exercise.

Mapelli M; Salvioni E; De Martino F; Mattavelli I; Gugliandolo P; Vignati C; Farina S; Palermo P; Campodonico J; Maragna R; Lo Russo G; Bonomi A; Sciomer S; Agostoni P;

The European respiratory journal [Eur Respir J] 2021 Mar 07. Date of Electronic Publication: 2021 Mar 07.

Background: During the COVID-19 pandemic, the use of protection masks is essential to reduce contagions. However, public opinion reports an associated subjective shortness of breath. We evaluated cardiorespiratory parameters at rest and during maximal exertion to highlight any differences with the use of protection masks.
Methods: Twelve healthy subjects underwent three cardiopulmonary exercise tests: without wearing protection mask, with surgical and with FFP2 mask. Dyspnea was assessed by Borg Scale. Standard pulmonary function tests were also performed.
Results: All the subjects (40.8±12.4 years; 6 males) completed the protocol with no adverse event. At spirometry, from no mask to surgical to FFP2, a progressive reduction of FEV 1 and FVC was observed (3.94±0.91 l, 3.23±0.81 l, 2.94±0.98 l and 4.70±1.21 l, 3.77±1.02 l, 3.52±1.21 l, respectively, p<0.001). Rest ventilation, O 2 uptake (V̇O 2 ) and CO 2 production (VCO 2 ) were progressively lower with a reduction of respiratory rate. At peak exercise, subjects revealed a progressively higher Borg scale when wearing surgical and FFP2. Accordingly, at peak exercise, V̇O 2 (31.0±23.4, 27.5±6.9, 28.2±8.8 ml/kg/min, p=0.001), ventilation (92±26, 76±22, 72±21 l, p=0.003), respiratory rate (42±8, 38±5, 37±4, p=0.04) and tidal volume (2.28±0.72, 2.05±0.60, 1.96±0.65 l, p=0.001) were gradually lower. We did not observed a significant difference in oxygen saturation.
Conclusions: Protection masks are associated with significant but modest worsening of spirometry and cardiorespiratory parameters at rest and peak exercise. The effect is driven by a ventilation reduction due to an increased airflow resistance. However, since exercise ventilatory limitation is far from being reached, their use is safe even during maximal exercise, with a slight reduction in performance.

Bicycle spiroergometry: comparison of standardized examination protocols for adolescents: is it necessary to define own standard values for each protocol?

Windhaber J; Steinbauer M; Holter M; Wieland A;Kogler K; Riedl R; Schober P; Castellani C; Singer G; Till H;

European journal of applied physiology [Eur J Appl Physiol] 2021 Mar 12. Date of Electronic Publication: 2021
Mar 12.

Purpose: To compare performance data of adolescents collected with five different bicycle spiroergometry protocols and to assess the necessity for establishing standard values for each protocol.
Methods: One-hundred-twenty adolescents completed two bicycle spiroergometries within 14 days. One of the two tests was performed based on our institutional weight-adapted protocol (P0). The other test was performed based on one out of four exercise protocols widely used for children and adolescents (P1, 2, 3 or 4) with 30 persons each. The two tests were performed in a random order. Routine parameters of cardiopulmonary exercise tests (CPET) such as VO 2 peak, maximum power, O 2 pulse, OUES, VE/VCO 2 slope as well as ventilatory and lactate thresholds were investigated. Agreement between protocols was evaluated by Bland-Altman analysis, coefficients of variation (CV) and intra-class correlation coefficients (ICC).
Results: None of the CPET parameters were significantly different between P0 and P1, 2, 3 or 4. For most of the parameters, low biases between P0 and P1-P4 were found and 95% confidence intervalls were narrow. CV and ICC values largely corresponded to well-defined analytical goals (CV < 10% and ICC > 0.9). Only maximal power (Pmax) showed differences in size and drift of the bias depending on the length of the step duration of the protocols.
Conclusion: Comparability between examination protocols has been shown for CPET parameters independent on step duration. Protocol-dependent standard values do not appear to be necessary. Only Pmax is dependent on the step duration, but in most cases, this has no significant influence on the fitness assessment.

Combined aerobic/resistance/inspiratory muscle training as the ‘optimum’ exercise programme for patients with chronic heart failure: ARISTOS-HF randomized clinical trial.

Laoutaris ID; Piotrowicz E; Kallistratos MS; Dritsas A; Dimaki N; Miliopoulos D; Andriopoulou M; Manolis AJ; Volterrani M; Piepoli MF; Coats AJS; Adamopoulos S;

European journal of preventive cardiology [Eur J Prev Cardiol] 2020 Dec 02. Date of Electronic Publication: 2020 Dec 02.

Aims: An ‘optimum’ universally agreed exercise programme for heart failure (HF) patients has not been found. ARISTOS-HF randomized clinical trial evaluates whether combined aerobic training (AT)/resistance training (RT)/inspiratory muscle training (IMT) (ARIS) is superior to AT/RT, AT/IMT or AT in improving aerobic capacity, left ventricular dimensions, and secondary functional outcomes.
Methods and Results: Eighty-eight patients of New York Heart Association II-III, left ventricular ejection fraction  ≤ 35% were randomized to an ARIS, AT/RT, AT/IMT, or AT group, exercising 3 times/week, 180 min/week for 12 weeks. Pre- and post-training, peakVO2 was evaluated with cardiopulmonary exercise testing, left ventricular dimensions using echocardiography, walking distance with the 6-min walk test (6MWT), quality of life by the Minnesota Living with HF Questionnaire (MLwHFQ), while a programme preference survey (PPS) was used. Seventy-four patients of [mean 95% (confidence interval, CI)] age 66.1 (64.3-67.9) years and peakVO2 17.3 (16.4-18.2) mL/kg/min were finally analysed. Between-group analysis showed a trend for increased peakVO2 (mL/kg/min) [mean contrasts (95% CI)] in the ARIS group [ARIS vs. AT/RT 1.71 (0.163-3.25)(.), vs. AT/IMT 1.50 (0.0152-2.99)(.), vs. AT 1.38 (-0.142 to 2.9)(.)], additional benefits in circulatory power (mL/kg/min⋅mmHg) [ARIS vs. AT/RT 376 (60.7-690)*, vs. AT/IMT 423 (121-725)*, vs. AT 345 (35.4-656)*], left ventricular end-systolic diameter (mm) [ARIS vs. AT/RT -2.11 (-3.65 to (-0.561))*, vs. AT -2.47 (-4.01 to (-0.929))**], 6MWT (m) [ARIS vs. AT/IMT 45.6 (18.3-72.9)**, vs. AT 55.2 (27.6-82.7)****], MLwHFQ [ARIS vs. AT/RT -7.79 (-11 to (-4.62))****, vs. AT -8.96 (-12.1 to (-5.84))****], and in PPS score [mean (95% CI)] [ARIS, 4.8 (4.7-5) vs. AT, 4.4 (4.2-4.7)*] [(.) P ≤ 0.1; *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001; ****P ≤ 0.0001].
Conclusion: ARISTOS-HF trial recommends exercise training for 180 min/week and supports the prescription of the ARIS training regime for HF patients (Clinical Trial Registration: ARISTOS-HF Clinical Trial number, NCT03013270).

Safety and feasibility of upper limb cardiopulmonary exercise test in Friedreich ataxia.

Pane C; Salzano A; Trinchillo A; Del Prete C; Casali C; Marcotulli C; Defazio G; Guardasole V; Vastarella R;
Giallauria F; Puorro G; Marsili A; De Michele G; Filla A; Cittadini A; Saccà F;

European journal of preventive cardiology [Eur J Prev Cardiol] 2020 Dec 09. Date of Electronic Publication: 2020 Dec 09.

Aims: To explore the feasibility of upper limbs cardiopulmonary exercise test (CPET) in Friedreich ataxia (FRDA) patients and to compare the results with sex, age, and body mass index (BMI) matched cohort of healthy controls (HC).
Methods and Results: Cardiopulmonary exercise test was performed using an upper limbs cycle ergometer on fasting subjects. Peak oxygen uptake (peak VO2) was recorded as the mean value of VO2 during a 20 s period at the maximal effort of the test at an appropriate respiratory exchange rate. The ventilatory anaerobic threshold (AT) was detected by the use of the V-slope method. We performed echocardiography with an ultrasound system equipped with a 2.5 MHz multifrequency transducer for complete M-mode, two-dimensional, Doppler, and Tissue Doppler Imaging analyses. We studied 55 FRDA and 54 healthy matched controls (HC). Peak VO2 showed a significant 31% reduction in FRDA patients compared to HC (15.2 ± 5.7 vs. 22.0 ± 6.1 mL/kg/min; P < 0.001). Peak workload was reduced by 41% in FRDA (42.9 ± 12.5 vs. 73.1 ± 21.2 W; P < 0.001). In FRDA patients, peak VO2 is inversely correlated with the Scale for Assessment and Rating of Ataxia score, disease duration, and 9HPT performance, and directly correlated with activities of daily living. The AT occurred at 48% of peak workload time in FRDA patients and at 85% in HC (P < 0.001).
Conclusions: Upper limb CPET is useful in the assessment of exercise tolerance and a possible tool to determine the functional severity of the mitochondrial oxidative defect in patients with FRDA. The cardiopulmonary exercise test is an ideal functional endpoint for Phases II and III trials through a simple, non-invasive, and safe exercise test.

Cardiopulmonary exercise pattern in patients with persistent dyspnoea after recovery from COVID-19.

Mohr A; Dannerbeck L; Lange TJ; Pfeifer M; Blaas S; Salzberger B; Hitzenbichler F; Koch M;

Multidisciplinary respiratory medicine [Multidiscip Respir Med] 2021 Jan 25; Vol. 16 (1), pp. 732. Date of Electronic Publication: 2021 Jan 25 (Print Publication: 2021).

Cause and mechanisms of persistent dyspnoea after recovery from COVID-19 are not well described. The objective is to describe causal factors for persistent dyspnoea in patients after COVID-19. We examined patients reporting dyspnoea after recovery from COVID-19 by cardiopulmonary exercise testing. After exclusion of patients with pre-existing lung diseases, ten patients (mean age 50±13.1 years) were retrospectively analysed between May 14 th and September 15 th , 2020. On chest computed tomography, five patients showed residual ground glass opacities, and one patient showed streaky residua. A slight reduction of the mean diffusion capacity of the lung for carbon monoxide was noted in the cohort. Mean peak oxygen uptake was reduced with 1512±232 ml/min (72.7% predicted), while mean peak work rate was preserved with 131±29 W (92.4% predicted). Mean alveolar-arterial oxygen gradient (AaDO 2 ) at peak exercise was 25.6±11.8 mmHg. Mean value of lactate post exercise was 5.6±1.8 mmol/l. A gap between peak work rate in (92.4% predicted) to peak oxygen uptake (72.3% pred.) was detected in our study cohort. Mean value of lactate post exercise was high in our study population and even higher (n.s.) compared to the subgroup of patients with reduced peak oxygen uptake and other obvious reason for limitation. Both observations support the hypothesis of anaerobic metabolism. The main reason for dyspnoea may therefore be muscular.

Comparative analysis between available challenge tests in the hyperventilation syndrome.

Tiotiu A; Ioan I; Poussel M; Schweitzer C; Kafi SA;

Respiratory medicine [Respir Med] 2021 Feb 12; Vol. 179, pp. 106329. Date of Electronic Publication: 2021 Feb 12.

Background: The hyperventilation syndrome (HVS) is characterized by somatic/ psychological symptoms due to sustained hypocapnia and respiratory alkalosis without any organic disease.
Objective: The purpose of this study was to compare ventilatory parameters and symptoms reproducibility during the hyperventilation provocation test (HVPT) and cardiopulmonary exercise test (CPET) as diagnostic tools in patients with HVS, and to identify the most frequent etiologies of the HVS by a systematic assessment.
Methods: After exclusion of organic causes, 59 patients with HVS according to Nijmegen’s questionnaire (NQ) score ≥23 with associated hypocapnia (PaCO 2 /PET CO2 <35 mm Hg) were studied.
Results: The most frequent comorbidities of HVS were anxiety and asthma (respectively 95% and 73% of patients). All patients described ≥3 symptoms of NQ during the HVPT vs 14% of patients during the CPET (p<0.01). For similar maximal ventilation (61 L/min during HVPT vs 60 L/min during CPET), the median level of PET CO2  decreased from 30 mmHg at baseline to 15 mmHg during hyperventilation and increased from 31 mmHg at baseline to 34 mmHg at peak exercise (all p<0.01). No significant difference for the ventilatory parameters was found between patients with HVS (n = 16) and patients with HVS + asthma (n = 43).
Conclusions: In term of symptoms reproducibility, HVPT is a better diagnostic tool than CPET for HVS. An important proportion of patients with HVS has an atypical asthma previously misdiagnosed. The exercise-induced hyperventilation did not induce abnormal reduction in PET CO2 , suggesting that the exercise could be a therapeutic tool in HVS.

Reliability of maximum oxygen uptake in cardiopulmonary exercise testing with continuous laryngoscopy.

Engan M; Hammer IJ; Bekken M; Halvorsen T; Fretheim-Kelly ZL; Vollsæter M; Bovim LPV; Røksund OD; Clemm H;

ERJ open research [ERJ Open Res] 2021 Feb 15; Vol. 7 (1). Date of Electronic Publication: 2021 Feb 15 (Print Publication: 2021).

Aims: A cardiopulmonary exercise test (CPET) is the gold standard to evaluate symptom-limiting exercise intolerance, while continuous laryngoscopy performed during exercise (CLE) is required to diagnose exercise-induced laryngeal obstruction. Combining CPET with CLE would save time and resources; however, the CPET data may be distorted by the extra equipment. We therefore aimed to study whether CPET with CLE influences peak oxygen uptake ( VO 2 peak) and other gas exchange parameters when compared to a regular CPET.
Methods: Forty healthy athletes without exercise-related breathing problems, 15-35 years of age, performed CPET to peak exercise with and without an added CLE set-up, in randomised order 2-4 days apart, applying an identical computerised treadmill protocol.
Results: At peak exercise, the mean difference (95% confidence interval) between CPET with and without extra CLE set-up for VO 2 peak, respiratory exchange ratio (RER), minute ventilation ( VE ) and heart rate (HR) was 0.2 (-0.4 to 0.8) mL·kg -1 ·min -1 , 0.01(-0.007 to 0.027) units, 2.6 (-1.3 to 6.5) L·min -1 and 1.4 (-0.8 to 3.5) beats·min -1 , respectively. Agreement (95% limits of agreement) for VO 2 peak, RER and VE was 0.2 (±3.7) mL·kg -1 ·min -1 , 0.01 (±0.10) units and 2.6 (±24.0) L·min -1 , respectively. No systematic or proportional bias was found except for the completed distance, which was 49 m (95% CI 16 to 82 m) longer during CPET.
Conclusion: Parameters of gas exchange, including VO 2 peak and RER, obtained from a maximal CPET performed with the extra CLE set-up can be used interchangeably with data obtained from standard CPET, thus preventing unnecessary additional testing.

A more effective alternative to the 6-minute walk test for the assessment of functional capacity in patients with pulmonary hypertension.

Marsico A; Dal Corso S; Farah de Carvalho E; Arakelian V; Phillips S; Stirbulov R; Polonio I; Navarro F;
Consolim-Colombo F; Cahalin LP; Malosa Sampaio LM;

European journal of physical and rehabilitation medicine [Eur J Phys Rehabil Med] 2021 Feb 23. Date of Electronic Publication: 2021 Feb 23.

Background: The prognosis of Pulmonary Hypertension (PH) is directly correlated with the functional capacity (FC). The most common FC test is the 6-Minute Walk Test (6MWT), however, there is evidence to suggest that the 6MWT does not reflect the real FC in PH patients.
Objective: To compare physiological responses among three field walk tests and cardiopulmonary exercise testing (CPET) in patients with pulmonary hypertension (PH), and to determine the determinants of distance walked in the field walk tests.
Design: Cross sectional.
Setting: Outpatient clinic.
Participants: 26 volunteers (49.8 ± 14.6 years), WHO functional class II-III and a mean pulmonary artery pressure of 45 mmHg.
Interventions: Patients underwent three field walk test: 6MWT, incremental shuttle walk test (ISWT), and endurance shuttle walk test (ESWT) and CPET on different, nonconsecutive days.
Main Outcome Measures: Heart rate and perception of effort at the peak of exercise.
Results: The ISWT achieved maximum levels of effort without significant difference in any physiologic response compared to CPET. The physiological responses during ISWT were significantly higher than 6MWT and ESWT responses.
Conclusions: The ISWT produced the greatest physiologic response of the field tests safely for which reason it appears to be the most effective test to assess FC of PH patients.