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: http://www.clinicaltrials.gov. ARISTOS-HF Clinical Trial number, NCT03013270).

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.

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.

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.

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 ( V ‘_{O 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 V ‘_{O 2} peak, respiratory exchange ratio (RER), minute ventilation ( V ‘_E ) 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 V ‘_{O 2} peak, RER and V ‘_E 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 V ‘_{O 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.

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.

van den Bosch E; Bossers SSM; Kamphuis VP; Boersma E; Breur JMPJ; Kapusta L; Bartelds B; Roest AAW; Kuipers IM; Blom NA; Koopman LP; Helbing WA;

Journal of the American Heart Association [J Am Heart Assoc] 2021 Feb; Vol. 10 (5), pp. e015022. Date of Electronic Publication: 2021 Feb 24.

Background Patients who have undergone the Fontan procedure are at high risk of circulatory failure. In an exploratory analysis we aimed to determine the prognostic value of blood biomarkers in a young cohort who have undergone the Fontan procedure.
Methods and Results In multicenter prospective studies patients who have undergone the Fontan procedure underwent blood sampling, cardiopulmonary exercise testing, and stress cardiac magnetic resonance imaging. Several biomarkers including NT-proBNP (N-terminal pro-B-type natriuretic peptide), GDF-15 (growth differentiation factor 15), Gal-3 (galectin-3), ST2 (suppression of tumorigenicity 2), DLK-1 (protein delta homolog 1), FABP-4 (fatty acid-binding protein 4), IGFBP-1 (insulin-like growth factor-binding protein 1), IGFBP-7, MMP-2 (matrix metalloproteinase 2), and vWF (von Willebrand factor) were assessed in blood at 9.6 (7.1-12.1) years after Fontan completion. After this baseline study measurement, follow-up information was collected on the incidence of adverse cardiac events, including cardiac death, out of hospital cardiac arrest, heart transplantation (listing), cardiac reintervention (severe events), hospitalization, and cardioversion/ablation for arrhythmias was collected and the relation with blood biomarkers was assessed by Cox proportional hazard analyses. The correlation between biomarkers and other clinical parameters was evaluated. We included 133 patients who have undergone the Fontan procedure, median age 13.2 (25th, 75th percentile 10.4-15.9) years, median age at Fontan 3.2 (2.5-3.9) years. After a median follow-up of 6.2 (4.9-6.9) years, 36 (27.1%) patients experienced an event of whom 13 (9.8%) had a severe event. NT-proBNP was associated with (all) events during follow-up and remained predictive after correction for age, sex, and dominant ventricle (hazard ratio, 1.89; CI, 1.32-2.68). The severe event-free survival was better in patients with low levels of GDF-15 ( P =0.005) and vWF ( P =0.008) and high levels of DLK-1 ( P =0.041). There was a positive correlation (β=0.33, P =0.003) between DLK-1 and stress cardiac magnetic resonance imaging functional reserve.
Conclusions NT-proBNP, GDF-15, vWF, DLK-1, ST-2 FABP-4, and IGFBP-7 levels relate to long-term outcome in young patients who have undergone the Fontan procedure.

The ventilatory efficiency and its clinical and prognostic value in cardiorespiratory disorders (ersjournals.com)

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Stephan Lang, Robert Herold, Alexander Kraft, Volker Harth, Alexandra M.

PLoS ONE 13(12):e0207648.
https://doi.org/10.1371/journal.pone.0207648

Spiroergometric measurements of persons who require oxygen insufflation due to illness
can be performed under conditions of increased inspiratory oxygen concentration (FIO2).
This increase in FIO2, however, often leads to errors in the calculation of oxygen consumption
(V_ O2). These inconsistencies are due to the application of the Haldane Transformation
(HT), an otherwise indispensable correction factor in the calculation of V_ O2 that becomes
inaccurate at higher FIO2 concentrations. A possible solution to this problem could be the
use of the ‘Eschenbacher transformation’ (ET) as an alternative correction factor. This study
examines the concentration of FIO2 at which the HT and the ET are valid, providing plausible
data of oxygen consumption corresponding to the wattage achieved during cycle ergometry.
Ten healthy volunteers underwent spiroergometric testing under standard conditions (FIO2 =
20.9%), as well as at FIO2 = 40% and 80%. When compared with the predicted values of
V_ O2, as calculated according to Wasserman et al. (2012), the data obtained show that both
the HT and ET are valid under normal conditions and at an increased FIO2 of 40%. At FIO2
concentrations of 80%, however, the V_ O2 values provided by the HT begin to lose plausibility,
whereas the ET continues to provide credible results. We conclude that the use of the ET
in place of the HT in spiroergometric measurements with increased FIO2 allows a reliable
evaluation of stress tests in patients requiring high doses of supplemental oxygen.

David C. Poole , Harry B. Rossiter , George A. Brooks and L. Bruce Gladden

J Physiol 599.3 (2021) ppp 737–767

Abstract The anaerobic threshold (AT) remains a widely recognized, and contentious, concept
in exercise physiology and medicine. As conceived by Karlman Wasserman, the AT coalesced
the increase of blood lactate concentration ([La−]), during a progressive exercise test, with an
excess pulmonary carbon dioxide output (˙VCO2 ). Its principal tenets were: limiting oxygen (O2)
delivery to exercisingmuscle→increased glycolysis, La− and H+ production→decreasedmuscle
and blood pH→with increased H+ buffered by blood [HCO3−]→increased CO2 release from
blood→increased ˙VCO2 and pulmonary ventilation. This schema stimulated scientific scrutiny
which challenged the fundamental premise that muscle anoxia was requisite for increased
muscle and blood [La−]. It is now recognized that insufficient O2 is not the primary basis for
lactataemia. Increased production and utilization of La− represent the response to increased
glycolytic flux elicited by increasing work rate, and determine the oxygen uptake (˙VO2) at which
La− accumulates in the arterial blood (the lactate threshold; LT). However, the threshold for a
sustained non-oxidative contribution to exercise energetics is the critical power, which occurs
at a metabolic rate often far above the LT and separates heavy from very heavy/severe-intensity
exercise. Lactate is nowappreciated as a crucial energy source,major gluconeogenic precursor and
signalling molecule but there is no ipso facto evidence formuscle dysoxia or anoxia. Non-invasive
estimation of LT using the gas exchange threshold (non-linear increase of ˙VCO2 versus ˙VO2 )
remains important in exercise training and in the clinic, but its conceptual basis should now be
understood in light of lactate shuttle biology.