Category Archives: Abstracts

Utility of Cardiopulmonary Exercise Testing in Chronic Obstructive Pulmonary Disease: A Review.

Behnia M; Sietsema KE;  Harbor-UCLA Medical Center, Torrance, CA, USA.

International Journal of Copd. 18:2895-2910, 2023.

Chronic obstructive pulmonary disease (COPD) is a disease defined by
airflow obstruction with a high morbidity and mortality and significant
economic burden. Although pulmonary function testing is the cornerstone in
diagnosis of COPD, it cannot fully characterize disease severity or cause
of dyspnea because of disease heterogeneity and variable related and
comorbid conditions affecting cardiac, vascular, and musculoskeletal
systems. Cardiopulmonary exercise testing (CPET) is a valuable tool for
assessing physical function in a wide range of clinical conditions,
including COPD. Familiarity with measurements made during CPET and its
potential to aid in clinical decision-making related to COPD can thus be
useful to clinicians caring for this population. This review highlights
pulmonary and extrapulmonary impairments that can contribute to exercise
limitation in COPD. Key elements of CPET are identified with an emphasis
on measurements most relevant to COPD. Finally, clinical applications of
CPET demonstrated to be of value in the COPD setting are identified. These
include quantifying functional capacity, differentiating among potential
causes of symptoms and limitation, prognostication and risk assessment for
operative procedures, and guiding exercise prescription.

Haemodynamic and metabolic phenotyping of patients with aortic stenosis and preserved ejection fraction: A specific phenotype of heart failure with preserved ejection fraction?

De Biase N; University of Pisa, Pisa, Italy
Mazzola M; Del Punta L; Di Fiore V; De Carlo M; Giannini C;
Costa G; Paneni F; Mengozzi A; Nesti L; Gargani L; Masi S; Pugliese NR

European Journal of Heart Failure. 25(11):1947-1958, 2023 11.

AIMS: Degenerative aortic valve stenosis with preserved ejection fraction
(ASpEF) and heart failure with preserved ejection fraction (HFpEF) display
intriguing similarities. This study aimed to provide a non-invasive,
comparative analysis of ASpEF versus HFpEF at rest and during exercise.
METHODS AND RESULTS: We prospectively enrolled 148 patients with HFpEF
and 150 patients with degenerative moderate-to-severe ASpEF, together with
66 age- and sex-matched healthy controls. All subjects received a
comprehensive evaluation at rest and 351/364 (96%) performed a combined
cardiopulmonary exercise stress echocardiography test. Patients with ASpEF
eligible for transcatheter aortic valve replacement (n = 125) also
performed cardiac computed tomography (CT). HFpEF and ASpEF patients
showed similar demographic distribution and biohumoral profiles. Most
patients with ASpEF (134/150, 89%) had severe high-gradient aortic
stenosis; 6/150 (4%) had normal-flow, low-gradient ASpEF, while 10/150
(7%) had low-flow, low-gradient ASpEF. Both patient groups displayed
significantly lower peak oxygen consumption (VO2 ), peak cardiac output,
and peak arteriovenous oxygen difference compared to controls (all p <
0.01). ASpEF patients showed several extravalvular abnormalities at rest
and during exercise, similar to HFpEF (all p < 0.01 vs. controls).
Epicardial adipose tissue (EAT) thickness was significantly greater in
ASpEF than HFpEF and was inversely correlated with peak VO2 in all groups.
In ASpEF, EAT was directly related to echocardiography-derived disease
severity and CT-derived aortic valve calcium burden.
CONCLUSION: Functional capacity is similarly impaired in ASpEF and HFpEF
due to both peripheral and central components. Further investigation is
warranted to determine whether extravalvular alterations may affect
disease progression and prognosis in ASpEF even after valve intervention,
which could support the concept of ASpEF as a specific sub-phenotype of
HFpEF.

Proteomics and Precise Exercise Phenotypes in Heart Failure With Preserved Ejection Fraction: A Pilot Study.

Shah RV; Vanderbilt University Medical Center Nashville TN
Hwang SJ; Murthy VL; Zhao S; Tanriverdi K; Gajjar P; Duarte K;
Schoenike M; Farrell R; Brooks LC; Gopal DM; Ho JE; Girerd N; Vasan RS;
Levy D; Freedman JE; Lewis GD; Nayor M

Journal of the American Heart Association. 12(21):e029980, 2023 Nov 07.

BACKGROUND: While exercise impairments are central to symptoms and
diagnosis of heart failure with preserved ejection fraction (HFpEF), prior
studies of HFpEF biomarkers have mostly focused on resting phenotypes. We
combined precise exercise phenotypes with cardiovascular proteomics to
identify protein signatures of HFpEF exercise responses and new potential
therapeutic targets.
METHODS AND RESULTS: We analyzed 277 proteins (Olink) in 151 individuals
(N=103 HFpEF, 48 controls; 62+/-11 years; 56% women) with cardiopulmonary
exercise testing with invasive monitoring. Using ridge regression adjusted
for age/sex, we defined proteomic signatures of 5 physiological variables
involved in HFpEF: peak oxygen uptake, peak cardiac output, pulmonary
capillary wedge pressure/cardiac output slope, peak pulmonary vascular
resistance, and peak peripheral O2 extraction. Multiprotein signatures of
each of the exercise phenotypes captured a significant proportion of
variance in respective exercise phenotypes. Interrogating the importance
(ridge coefficient magnitude) of specific proteins in each signature
highlighted proteins with putative links to HFpEF pathophysiology (eg,
inflammatory, profibrotic proteins), and novel proteins linked to distinct
physiologies (eg, proteins involved in multiorgan [kidney, liver, muscle,
adipose] health) were implicated in impaired O2 extraction. In a separate
sample (N=522, 261 HF events), proteomic signatures of peak oxygen uptake
and pulmonary capillary wedge pressure/cardiac output slope were
associated with incident HFpEF (odds ratios, 0.67 [95% CI, 0.50-0.90] and
1.43 [95% CI, 1.11-1.85], respectively) with adjustment for clinical
factors and B-type natriuretic peptides.
CONCLUSIONS: The cardiovascular proteome is associated with precision
exercise phenotypes in HFpEF, suggesting novel mechanistic targets and
potential methods for risk stratification to prevent HFpEF early in its
pathogenesis.

Maximal oxidative capacity during exercise is associated with muscle power output in patients with long coronavirus disease 2019 (COVID-19) syndrome. A moderation analysis.

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.

Heart rate recovery after orthostatic challenge and cardiopulmonary exercise testing in older individuals: prospective multicentre observational cohort study.

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.

Lowered oxidative capacity in spinal muscular atrophy, Jokela type; comparison with mitochondrial muscle disease.

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.

Periodic health evaluation in athletes competing in Tokyo 2020: from SARS-CoV-2 to Olympic medals.

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.

A Reference Equation for VO 2peak for Pediatric Patients Undergoing Treadmill Cardiopulmonary Exercise Testing.

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 (VO2peak ) 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 VO2peak .
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 VO2peak 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 VO2peak , resulting in the following prediction equation (R 2  = 0.645, p < 0.001, SEE = 6.19mL/kg/min): VO2peak (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 VO2peak in all age groups.
In conclusion, this study represents the largest pediatric CPET-derived VO2peak prediction effort to date and this VO2peak 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.

The effects of inspiratory muscle training on cardiorespiratory functions in juvenile idiopathic arthritis: A randomized controlled trial.

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.

Chronic thromboembolic pulmonary disease: Association with exercise-induced pulmonary hypertension and right ventricle adaptation over time: Chronic thromboembolic pulmonary disease and exercise pulmonary hypertension.

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.