Ramirez-Velez R; Hospital Universitario de Navarra, Madrid, Spain
Oscoz-Ochandorena S; Garcia-Alonso Y; Garcia-Alonso N;
Legarra-Gorgonon G; Oteiza J; Lorea AE; Izquierdo M; Correa-Rodriguez M

Clinical Nutrition ESPEN. 58:253-262, 2023 Dec.

BACKGROUND & AIMS: Long COVID syndrome (LCS) involves persistent symptoms
experienced by many patients after recovering from coronavirus disease
2019 (COVID-19). We aimed to assess skeletal muscle energy metabolism,
which is closely related to substrate oxidation rates during exercise, in
patients with LCS compared with healthy controls. We also examined whether
muscle power output mediates the relationship between COVID-19 and
skeletal muscle energy metabolism.

METHODS: In this cross-sectional study, we enrolled 71 patients with LCS
and 63 healthy controls. We assessed clinical characteristics such as body
composition, physical activity, and muscle strength. We used
cardiopulmonary exercise testing to evaluate substrate oxidation rates
during graded exercise. We performed statistical analyses to compare group
characteristics and peak fat oxidation differences based on power output.

RESULTS: The two-way analysis of covariance (ANCOVA) results, adjusted
for covariates, showed that the patients with LCS had lower absolute
maximal fatty acid oxidation (MFO), relative MFO/fat free mass (FFM),
absolute carbohydrates oxidation (CHox), relative CHox/FFM, and oxygen
uptake (VO2) at maximum fat oxidation (g min-1) than the healthy controls
(P < 0.05). Moderation analysis indicated that muscle power output
significantly influenced the relationship between LCS and reduced peak fat
oxidation (interaction beta = -0.105 [95% confidence interval -0.174;
-0.036]; P = 0.026). Therefore, when muscle power output was below 388 W,
the effect of the LCS on MFO was significant (62% in our study sample P =
0.010). These findings suggest compromised mitochondrial bioenergetics and
muscle function, represented by lower peak fat oxidation rates, in the
patients with LCS compared with the healthy controls.

CONCLUSION: The patients with LCS had lower peak fat oxidation during
exercise compared with the healthy controls, potentially indicating
impairment in skeletal muscle function. The relationship between peak fat
oxidation and LCS appears to be mediated predominantly by muscle power
output. Additional research should continue investigating LCS pathogenesis
and the functional role of mitochondria.

James A; Department of Anaesthesia of many Hospitals in the UK – Marsden, Royal London, Plymouth Trust
Bruce D; Tetlow N; Patel ABU; Black E; Whitehead N; Ratcliff A; Jamie Humphreys A; MacDonald N; McDonnell G; Raobaikady R; Thirugnanasambanthar J; Ravindran JI; Whitehead N; Minto G; Abbott TEF; Jhanji S; Milliken D; Ackland GL;

BJA open [BJA Open] 2023 Nov 03; Vol. 8, pp. 100238.
Date of Electronic Publication: 2023 Nov 03 (Print Publication: 2023).

Background: Impaired vagal function in older individuals, quantified by the ‘gold standard’ delayed heart rate recovery after maximal exercise (HRR ^exercise ), is an independent predictor of cardiorespiratory capacity and mortality (particularly when HRR ≤12 beats min ^-1 ). Heart rate also often declines after orthostatic challenge (HRR ^orthostatic ), but the mechanism remains unclear. We tested whether HRR ^orthostatic reflects similar vagal autonomic characteristics as HRR ^exercise .
Methods: Prospective multicentre cohort study of subjects scheduled for cardiopulmonary exercise testing (CPET) as part of routine care. Before undergoing CPET, heart rate was measured with participants seated for 3 min, before standing for 3 min (HRR ^orthostatic). HRR ^exercise 1 min after the end of CPET was recorded. The primary outcome was the correlation between mean heart rate change every 10 s for 1 min after peak heart rate was attained on standing and after exercise for each participant. Secondary outcomes were HRR ^orthostatic and peak VO ₂ compared between individuals with HRR ^exercise <12 beats min ^-1 .
Results: A total of 87 participants (mean age: 64 yr [95%CI: 61-66]; 48 (55%) females) completed both tests.
Mean heart rate change every 10 s for 1 min after peak heart rate after standing and exercise was significantly correlated ( R ² =0.81; P <0.0001). HRR ^orthostatic was unchanged in individuals with HRR ^exercise ≤12 beats min ^-1 ( n =27), but was lower when HRR ^exercise >12 beats min ^-1 ( n =60; mean difference: 3 beats min ^-1 [95% confidence interval 1-5 beats min ^-1 ]; P <0.0001). Slower HRR ^orthostatic was associated with lower peak VO ₂ (mean difference: 3.7 ml kg ^-1 min ^-1 [95% confidence interval 0.7-6.8 ml kg ^-1 min ^-1 ]; P =0.039).
Conclusion: Prognostically significant heart rate recovery after exhaustive exercise is characterised by quantitative differences in heart rate recovery after orthostatic challenge. These data suggest that orthostatic challenge is a valid, simple test indicating vagal impairment.

Ratia N; Unit of Clinical Physiology,  Helsinki University Hospital, Helsinki, Finland.
Palu E; Lantto H;Ylikallio E; Luukkonen R; Suomalainen A; Auranen M;Piirilä P;

Frontiers in neurology [Front Neurol] 2023 Nov 08; Vol. 14, pp. 1277944.
Date of Electronic Publication: 2023 Nov 08 (Print Publication: 2023).

Introduction: Spinal muscular atrophy, Jokela type (SMAJ) is a rare autosomal dominantly hereditary form of spinal muscular atrophy caused by a point mutation c.197G>T in CHCHD10 . CHCHD10 is known to be involved in the regulation of mitochondrial function even though patients with SMAJ do not present with multiorgan symptoms of mitochondrial disease. We aimed to characterize the cardiopulmonary oxidative capacity of subjects with SMAJ compared to healthy controls and patients with mitochondrial myopathy.
Methods: Eleven patients with genetically verified SMAJ, 26 subjects with mitochondrial myopathy (MM), and 28 healthy volunteers underwent a cardiopulmonary exercise test with lactate and ammonia sampling. The effect of the diagnosis group on the test results was analysed using a linear model.
Results: Adjusted for sex, age, and BMI, the SMAJ group had lower power output ( p  < 0.001), maximal oxygen consumption (VO ₂ max) ( p  < 0.001), and mechanical efficiency ( p  < 0.001) compared to the healthy controls but like that in MM. In the SMAJ group and healthy controls, plasma lactate was lower than in MM measured at rest, light exercise, and 30 min after exercise ( p  ≤ 0.001-0.030) and otherwise lactate in SMAJ was lower than controls and MM, in longitudinal analysis p  = 0.018. In MM, the ventilatory equivalent for oxygen was higher ( p  = 0.040), and the fraction of end-tidal CO ₂ lower in maximal exercise compared to healthy controls ( p  = 0.023) and subjects with SMAJ.
Conclusion: In cardiopulmonary exercise test, subjects with SMAJ showed a similar decrease in power output and oxidative capacity as subjects with mitochondrial myopathy but did not exhibit findings typical of mitochondrial disease.

Squeo MR; Italian National Olympic Committee, Institute of Sport Medicine and Science, Roma, Italy.
Monosilio S; Gismondi A; Perrone M;Gregorace E; Lemme E; Di Gioia G; Mango R; Prosperi S;Spataro A; Maestrini V; Di Giacinto B; Pelliccia A;

BMJ open sport & exercise medicine [BMJ Open Sport Exerc Med] 2023 Nov 29; Vol. 9 (4), pp. e001610.
Date of Electronic Publication: 2023 Nov 29 (Print Publication: 2023).

Background: The Tokyo Olympic games were the only games postponed for a year in peacetime, which will be remembered as the COVID-19 Olympics. No data are currently available on the effect on athlete’s performance.
Aim: To examine the Italian Olympic athletes who have undergone the return to play (RTP) protocol after COVID-19 and their Olympic results.
Methods: 642 Potential Olympics (PO) athletes competing in 19 summer sport disciplines were evaluated through a preparticipation screening protocol and, when necessary, with the RTP protocol. The protocol comprised blood tests, 12-lead resting ECG, transthoracic echocardiogram, cardiopulmonary exercise test, 24-hour Holter-ECG monitoring and cardiovascular MR based on clinical indication.
Results: Of the 642 PO athletes evaluated, 384 participated at the Olympic Games, 254 being excluded for athletic reasons. 120 athletes of the total cohort of 642 PO were affected by COVID-19. They were evaluated with the RTP protocol before resuming physical activity after a mean detraining period of 30±13 days. Of them, 100 were selected for Olympic Games participation, 16 were excluded for athletic reasons and 4 were due to RTP results (2 for COVID-19-related myocarditis, 1 for pericarditis and 1 for complex ventricular arrhythmias). Among athletes with a history of COVID-19 allowed to resume physical activity after the RTP and selected for the Olympic Games, no one had abnormalities in cardiopulmonary exercise test parameters, and 28 became medal winners with 6 gold, 6 silver and 19 bronze medals.
Conclusions: Among athletes with COVID-19, there is a low prevalence of cardiac sequelae. For those athletes allowed to resume physical activity after the RTP evaluation, the infection and the forced period of inactivity didn’t have a negative impact on athletic performance.

Griffith GJ; Northwestern University Feinberg School of Medicine. Electronic address: garett.griffith@northwestern.edu.
Wang AP; Liem RI; Carr MR;Corson T; Ward K;

The American journal of cardiology [Am J Cardiol] 2023 Nov 30.
Date of Electronic Publication: 2023 Nov 30.

Pediatric patients are often referred to cardiopulmonary exercise testing (CPET) laboratories for assessment of exercise-related symptoms. For clinicians to understand results in the context of performance relative to peers, adequate fitness-based prediction equations must be available. However, reference equations for prediction of peak oxygen uptake (VO_2peak ) in pediatrics are largely developed from field-based testing and equations derived from CPET are primarily developed using adult data. Our objective was to develop a pediatric reference equation for VO_2peak .
Clinical CPET data from a validation cohort of 1,383 pediatric patients aged 6-18 years who achieved a peak RER≥1.00 were analyzed to identify clinical and exercise testing factors that contributed to the prediction of VO_2peak from tests performed using the Bruce protocol.
The resultant prediction equation was applied to a cross-validation cohort of 1,367 pediatric patients. Exercise duration, sex, weight, and age contributed to the prediction of VO_2peak , resulting in the following prediction equation (R ²  = 0.645, p < 0.001, SEE = 6.19mL/kg/min): VO_2peak (mL/kg/min) = 16.411+ 3.423 (exercise duration [minutes]) – 5.145 (sex [0=male, 1=female]) – 0.121 (weight [kg]) + 0.179 (age [years]). This equation was stable across the age range included in the present study, with differences ≤ 0.5mL/kg/min between mean measured and predicted VO_2peak in all age groups.
In conclusion, this study represents the largest pediatric CPET-derived VO_2peak prediction effort to date and this VO_2peak prediction equation provides clinicians who perform and interpret exercise tests on pediatric patients with a resource with which to better quantify fitness when CPET is not available.

Sarac DC; Department of Physiotherapy and Rehabilitation, Ankara, Turkiye;
Bayraktar D; Ozer Kaya D; Altug Gucenmez O; Oskay D;

Pediatric pulmonology [Pediatr Pulmonol] 2023 Dec 01.
Date of Electronic Publication: 2023 Dec 01.

Introduction: Although inspiratory muscle training (IMT) has proven effective in adult rheumatic diseases, its impact on juvenile idiopathic arthritis (JIA) remains unexplored. The present study aimed to investigate the effects of IMT in children with JIA.
Methods: Thirty-three children (13-18 years) with JIA were divided into two groups as exercise (n = 17) and control (n = 16). The exercise group performed IMT at home daily for 8 weeks. The initial IMT load was set as 60% of maximal inspiratory pressure (PI _max ) and increased by %10 of the initial load every 2 weeks. The control group received no additional intervention. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV ₁ ), FVC/FEV ₁ , PI _max , and maximal expiratory pressure (PE _max ) were evaluated. Peak oxygen consumption (VO _2max ), metabolic equivalents (METs), and maximal heart rate were measured with cardiopulmonary exercise test. Functional capacity and quality of life were assessed with 6-min walk distance and Pediatric Quality of Life Inventory 3.0 Arthritis Module. All participants were evaluated at baseline and post-treatment.
Results: FVC ( ↑ 0.20 (95% CI: 0.07/0.32) liters), FEV ₁ ( ↑ 0.14 (95% CI: 0.02/0.25) liters), PI _max (↑19.11 (95% CI: 9.52/28.71) cmH ₂ O), PE _max (↑12.41 (95% CI: 3.09/21.72) cmH ₂ O), VO _2peak (↑158.29 (95% CI: 63.85/252.73) ml/min), and METs (↑0.92 (95% CI: 0.34/1.49) [ml/kg/min]) significantly improved only in the exercise group (p < .05). The difference over time in FVC, FEV ₁ , PI _max , VO _2peak , and METs were significantly higher in exercise group compared to control group (p < .05).
Conclusions: IMT seems to be an effective option for improving respiratory functions and aerobic exercise capacity in JIA.

Madonna R; University Cardiology Division, Pisa University Hospital and University of Pisa, Italy;
Alberti M; Biondi F;Morganti R; ,Badagliacca R; Vizza CD; De Caterina R;

European journal of internal medicine [Eur J Intern Med] 2023 Dec 01.
Date of Electronic Publication: 2023 Dec 01.

Background and Aim: Chronic thromboembolic pulmonary disease (CTEPD) is a progressive condition caused by fibrotic thrombi and vascular remodeling in the pulmonary circulation despite prolonged anticoagulation. We evaluated clinical factors associated with CTEPD, as well as its impact on functional capacity, pulmonary haemodynamics at rest and after exercise, and right ventricle (RV) morphology and function.
Methods: We compared 33 consecutive patients with a history of acute pulmonary embolism and either normal pulmonary vascular imaging (negative Q-scan, group 1, n = 16) or persistent defects on lung perfusion scan (positive Q-scan) despite oral anticoagulation at 4 months (group 2, n = 17). Investigations included thrombotic load, the Pulmonary Embolism Severity Index (PESI) score, functional class, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), cardiopulmonary exercise test (CPET) and echocardiographic parameters at rest and after exercise (ESE), at 4 and at 24 months.
Results: Compared with group 1, group 2 featured a higher PESI score (p = 0.02) and a higher thrombotic load (p = 0.004) at hospital admission. At 4 months, group 2 developed exercise-induced pulmonary hypertension (Ex-PH) at CPET (p < 0.001) and ESE (p < 0.001). At 24 months group 2 showed higher NT-proBNP (p < 0.001), WHO-FC (p < 0.001), systolic (p<0.001) and diastolic (p = 0.037) RV dysfunction and worse RV-arterial coupling (p < 0.001) despite maintaining a low or intermediate echocardiographic probability of PH.
Conclusions: This is the first “proof of concept” study showing that patients with a positive Q-scan frequently develop Ex-PH and RV functional deterioration as well as reduced functional capacity, generating the hypothesis that Ex-PH could help detect the progression to CTEPD.

Zimmerman D; Department of Pediatrics, Children’s Hospital Los Angeles,  California;
Shwayder M; Souza A; Su JA; Votava-Smith J; Wagner-Lees S; Kaneta K; Cheng A; Szmuszkovicz J;

Pediatrics [Pediatrics] 2023 Dec 01; Vol. 152 (6).

Objectives: To assess the prevalence of residual cardiovascular pathology by cardiac MRI (CMR), ambulatory rhythm monitoring, and cardiopulmonary exercise testing (CPET) in patients ∼6 months after multisystem inflammatory disease in children (MIS-C).
Methods: Patients seen for MIS-C follow-up were referred for CMR, ambulatory rhythm monitoring, and CPET ∼6 months after illness. Patients were included if they had ≥1 follow-up study performed by the time of data collection. MIS-C was diagnosed on the basis of the Centers for Disease Control and Prevention criteria. Myocardial injury during acute illness was defined as serum Troponin-I level >0.05 ng/mL or diminished left ventricular systolic function on echocardiogram.
Results: Sixty-nine of 153 patients seen for MIS-C follow-up had ≥1 follow-up cardiac study between October 2020-June 2022. Thirty-seven (54%) had evidence of myocardial injury during acute illness. Of these, 12 of 26 (46%) had ≥1 abnormality on CMR, 4 of 33 (12%) had abnormal ambulatory rhythm monitor results, and 18 of 22 (82%) had reduced functional capacity on CPET. Of the 37 patients without apparent myocardial injury, 11 of 21 (52%) had ≥1 abnormality on CMR, 1 of 24 (4%) had an abnormal ambulatory rhythm monitor result, and 11 of 15 (73%) had reduced functional capacity on CPET. The prevalence of abnormal findings was not statistically significantly different between groups.
Conclusions: The high prevalence of abnormal findings on follow-up cardiac studies and lack of significant difference between patients with and without apparent myocardial injury during hospitalization suggests that all patients treated for MIS-C warrant cardiology follow-up.

Flaherty D. J.;  Haque A.; Vascular Surgery, University of Manchester, Manchester, GBR.

Cureus 2023 Vol. 15 Issue 11 Pages e48271

Background The prevalence of cardiovascular disease and incidence of major adverse cardiovascular events (MACEs) is very high among the abdominal aortic aneurysm (AAA) surveillance population. Formal assessments of and interventions to reduce cardiovascular risk are not a routine part of the surveillance programme at present. However, its potential importance is highlighted by incidental findings during the AAA Get Fit Trial, a randomised controlled trial which included baseline cardiopulmonary exercise testing (CPET). We speculate that CPET can act as an opportunistic screening programme to identify cardiovascular disease in AAA surveillance patients.
Methods The AAA Get Fit Trial was a prospective, randomised controlled trial at a tertiary vascular centre, Manchester University NHS Foundation Trust, conducted between November 2017 and August 2019. Patients underwent CPET at baseline, 8, 16, 24 and 36 weeks as well as clinical history and examination and blood tests. We report on incidental cardiovascular abnormalities diagnosed during the trial.
Results Of the 59 participants in the trial, four (6.8%) were identified to have abnormal findings suggestive of unstable cardiovascular disease. On subsequent further investigation, two patients were diagnosed and treated for severe coronary artery disease after abnormal ECG findings were noted during CPET. One patient was diagnosed with unstable angina after obtaining a detailed history on baseline assessment which was treated medically before going on to have a successful elective AAA repair. Conclusions There is a high incidence of MACEs among this high-risk population both pre and perioperatively. Identifying and treating cardiovascular disease among t