Stubbs, D; University Division of Anaesthesia, Cambridge, United Kingdom
Grimes, L;  Ercole, A;

A systematic review. PLoS ONE 15(2): e0226480

RESEARCH ARTICLE

Introduction
Cardiopulmonary exercise testing (CPET) is widely used within the United Kingdom for pre-
operative risk stratification. Despite this, CPET’s performance in predicting adverse events
has not been systematically evaluated within the framework of classifier performance.
Methods
After prospective registration on PROSPERO (CRD42018095508) we systematically identi-
fied studies where CPET was used to aid in the prognostication of mortality, cardiorespira-
tory complications, and unplanned intensive care unit (ICU) admission in individuals
undergoing non-cardiopulmonary surgery. For all included studies we extracted or calcu-
lated measures of predictive performance whilst identifying and critiquing predictive models
encompassing CPET derived variables.
Results
We identified 36 studies for qualitative review, from 27 of which measures of classifier per-
formance could be calculated. We found studies to be highly heterogeneous in methodology
and quality with high potential for bias and confounding. We found seven studies that pre-
sented risk prediction models for outcomes of interest. Of these, only four studies outlined a
clear process of model development; assessment of discrimination and calibration were per-
formed in only two and only one study undertook internal validation. No scores were exter-
nally validated. Systematically identified and calculated measures of test performance for
CPET demonstrated mixed performance. Data was most complete for anaerobic threshold
(AT) based predictions: calculated sensitivities ranged from 20-100% when used for predict-
ing risk of mortality with high negative predictive values (96-100%). In contrast, positive
predictive value (PPV) was poor (2.9-42.1%). PPV appeared to be generally higher for
cardiorespiratory complications, with similar sensitivities. Similar patterns were seen for the
association of Peak VO2 (sensitivity 85.7-100%, PPV 2.7-5.9%) and VE/VCO2 (Sensitivity
27.8%-100%, PPV 3.4-7.1%) with mortality.
Conclusions
In general CPET’s ‘rule-out’ capability appears better than its ability to ‘rule-in’ complica-
tions. Poor PPV may reflect the frequency of complications in studied populations. Our cal-
culated estimates of classifier performance suggest the need for a balanced interpretation
of the pros and cons of CPET guided pre-operative risk stratification

McDonald JA; Department of Paediatrics, The University of Melbourne, Australia
Ye XT; Jones B; Zannino D; Konstantinov I; Brink J; Brizard
C; d’Udekem Y

Heart, Lung & Circulation. 33(8):1209-1214, 2024 Aug.

BACKGROUND: The exercise capacity long after repair of tetralogy of
Fallot, when performed exclusively with a transatrial repair, is unclear.
It is also unknown whether echocardiography and cardiopulmonary exercise
testing can predict the risk of reoperation in this patient group.
METHOD: We retrospectively reviewed the clinical records of 59 patients
who underwent cardiopulmonary exercise testing after transatrial Fallot
repair at a single centre. Patients underwent cardiopulmonary exercise
testing at a mean age of 16.6+/-4.4 years, and at 15.3+/-4.1 years after
Fallot repair.
RESULTS: At testing, the volume of oxygen consumption at maximal exercise
(VO2 max) was 71%+/-13% and the oxygen pulse was 80%+/-17% of predicted
values. Seventeen (17) patients (29%) had a VO2 max superior to 80% of the
predicted value. Thirty-two (32) patients (56%) had severe pulmonary
regurgitation, three (5%) had moderate pulmonary regurgitation, and 12
(21%) had mild pulmonary regurgitation. After a mean of 7.8+/-3.9 years
following cardiopulmonary exercise testing (23+/-5.3 years after the
repair), 21 (40%) patients underwent reoperation. Right ventricular
dilation and systolic function on echocardiography were both significantly
associated with subsequent reoperation rates. Patients who had severe
right ventricular dilation were eight times more likely to undergo
subsequent reoperation (hazard ratio 8.67; 1.82-41.3; p=0.007). No
cardiopulmonary exercise testing variable independently predicted
reoperation.
CONCLUSIONS: The exercise capacity at adolescence following transatrial
repair of tetralogy of Fallot is maintained at around 70% of predicted
values. Only the patients with normal right ventricular size and normal
right ventricular function seemed to be protected from reoperation over
the subsequent decade. We found no exercise variables which predicted
reoperation.

Wolf C; University of Pittsburgh & San Francisco, CA. USA
Blackwell TL; Johnson E; Glynn NW; Nicklas B; Kritchevsky SB;
Carnero EA; Cawthon PM; Cummings SR; Toledo FGS; Newman AB; Forman DE;
Goodpaster BH

Medicine & Science in Sports & Exercise. 56(9):1574-1584, 2024 Sep 01.

PURPOSE: Cardiorespiratory fitness (CRF) measured by peak oxygen
consumption (VO 2peak ) declines with aging and correlates with mortality
and morbidity. Cardiopulmonary exercise testing (CPET) is the criterion
method to assess CRF, but its feasibility, validity, and reliability in
older adults are unclear. Our objective was to design and implement a
dependable, safe, and reliable CPET protocol in older adults.
METHODS: VO 2peak was measured by CPET, performed using treadmill
exercise in 875 adults >=70 yr in the Study of Muscle, Mobility and Aging
(SOMMA). The protocol included a symptom-limited peak (maximal) exercise
and two submaximal walking speeds. An adjudication process was in place to
review tests for validity if they met any prespecified criteria (VO 2peak
<12.0 mL.kg -1 .min -1 ; maximum heart rate <100 bpm; respiratory exchange
ratio <1.05 and a rating of perceived exertion <15). A subset ( N = 30)
performed a repeat test to assess reproducibility.
RESULTS: CPET was safe and well tolerated, with 95.8% of participants
able to complete the VO 2peak phase of the protocol. Only 56 (6.4%)
participants had a risk alert and only two adverse events occurred: a fall
and atrial fibrillation. Mean +/- SD VO 2peak was 20.2 +/- 4.8 mL.kg -1
.min -1 , peak heart rate 142 +/- 18 bpm, and peak respiratory exchange
ratio 1.14 +/- 0.09. Adjudication was indicated in 47 tests; 20 were
evaluated as valid and 27 as invalid (18 data collection errors, 9 did not
reach VO 2peak ). Reproducibility of VO 2peak was high (intraclass
correlation coefficient = 0.97).
CONCLUSIONS: CPET was feasible, effective, and safe for older adults,
including many with multimorbidity or frailty. These data support a
broader implementation of CPET to provide insight into the role of CRF and
its underlying determinants of aging and age-related conditions.

Kennouche D; Universitaire de Saint-Etienne, Saint-Etienne, FRANCE.
Foschia C; Brownstein CG; Lapole T; Rimaud D; Royer N; LE Mat
F; Thiery G; Gauthier V; Giraux P; Oujamaa L; Sorg M; Verges S; Doutreleau
S; Marillier M; Prudent M; Bitker L; Feasson L; Gergele L; Stauffer E;
Guichon C; Gondin J; Morel J; Millet GY

Medicine & Science in Sports & Exercise. 56(9):1563-1573, 2024 Sep 01.

PURPOSE: Approximately 30% of people infected with COVID-19 require
hospitalization, and 20% of them are admitted to an intensive care unit
(ICU). Most of these patients experience symptoms of fatigue weeks
post-ICU, so understanding the factors associated with fatigue in this
population is crucial.
METHODS: Fifty-nine patients (38-78 yr) hospitalized in ICU for COVID-19
infection for 32 (6-80) d, including 23 (3-57) d of mechanical
ventilation, visited the laboratory on two separate occasions. The first
visit occurred 52 +/- 15 d after discharge and was dedicated to
questionnaires, blood sampling, and cardiopulmonary exercise testing,
whereas measurements of the knee extensors neuromuscular function and
performance fatigability were performed in the second visit 7 +/- 2 d
later.
RESULTS: Using the FACIT-F questionnaire, 56% of patients were classified
as fatigued. Fatigued patients had worse lung function score than
non-fatigued (i.e., 2.9 +/- 0.8 L vs 3.6 +/- 0.8 L; 2.4 +/- 0.7 L vs 3.0
+/- 0.7 L for forced vital capacity and forced expiratory volume in 1 s,
respectively), and forced vital capacity was identified as a predictor of
being fatigued. Maximal voluntary activation was lower in fatigued
patients than non-fatigued patients (82% +/- 14% vs 91% +/- 3%) and was
the only neuromuscular variable that discriminated between fatigued and
non-fatigued patients. Patient-reported outcomes also showed differences
between fatigued and non-fatigued patients for sleep, physical activity,
depression, and quality of life ( P < 0.05).
CONCLUSIONS: COVID-19 survivors showed altered respiratory function 4 to
8 wk after discharge, which was further deteriorated in fatigued patients.
Fatigue was also associated with lower voluntary activation and
patient-reported impairments (i.e., sleep satisfaction, quality of life,
or depressive state). The present study reinforces the importance of
exercise intervention and rehabilitation to counteract cardiorespir

Vecchiato M; University of Padova, Padova, ITALY.
Aghi A; Nerini R; Borasio N; Gasperetti A; Quinto G; Battista
F; Bettini S; DI Vincenzo A; Ermolao A; Busetto L; Neunhaeuserer D

Medicine & Science in Sports & Exercise. 56(9):1732-1739, 2024 Sep 01.

PURPOSE: Cardiorespiratory fitness (CRF) is a critical marker of overall
health and a key predictor of morbidity and mortality, but the existing
prediction equations for CRF are primarily derived from general
populations and may not be suitable for patients with obesity.
METHODS: Predicted CRF from different non-exercise prediction equations
was compared with measured CRF of patients with obesity who underwent
maximal cardiopulmonary exercise testing (CPET). Multiple linear
regression was used to develop a population-specific nonexercise CRF
prediction model for treadmill exercise including age, sex, weight,
height, and physical activity level as determinants.
RESULTS: Six hundred sixty patients underwent CPET during the study
period. Within the entire cohort, R2 values had a range of 0.24 to 0.46.
Predicted CRF was statistically different from measured CRF for 19 of the
21 included equations. Only 50% of patients were correctly classified into
the measured CRF categories according to predicted CRF. A multiple model
for CRF prediction (mL.min -1 ) was generated ( R2 = 0.78) and validated
using two cross-validation methods.
CONCLUSIONS: Most used equations provide inaccurate estimates of CRF in
patients with obesity, particularly in cases of severe obesity and low
CRF. Therefore, a new prediction equation was developed and validated
specifically for patients with obesity, offering a more precise tool for
clinical CPET interpretation and risk stratification in this population.

Ariyaratnam JP; Royal Adelaide Hospital, Adelaide, Australia
Elliott AD; Mishima RS; Kadhim K; Emami M; Fitzgerald JL;
Middeldorp M; Sanders P

JACC. Clinical Electrophysiology. 10(7 Pt 2):1608-1619, 2024 Jul.

BACKGROUND: Reduced cardiorespiratory fitness (CRF) is an independent risk
factor for the progression of atrial fibrillation (AF). We hypothesized
that reduced CRF is associated with structural, functional, and electrical
remodeling of the left atrium.
OBJECTIVES: This study sought to correlate objectively assessed CRF with
functional and electrical left atrial (LA) parameters using invasive and
noninvasive assessments.
METHODS: Consecutive patients with symptomatic AF undergoing catheter
ablation were recruited. CRF was objectively quantified pre-ablation by
using cardiopulmonary exercise testing. Using peak oxygen consumption,
participants were classified as preserved CRF (>20 mL/kg/min) or reduced
CRF (<20 mL/kg/min). LA stiffness was assessed invasively with hemodynamic
monitoring and imaging during high-volume LA saline infusion. LA stiffness
was calculated as DELTALA diameter/DELTALA pressure over the course of the
infusion. LA function was assessed with echocardiographic measures of LA
emptying fraction and LA strain. Electrical remodeling was assessed by
using high-density electroanatomical maps for LA voltage and conduction.
RESULTS: In total, 100 participants were recruited; 43 had reduced CRF
and 57 had preserved CRF. Patients with reduced CRF displayed elevated LA
stiffness (P = 0.004), reduced LA emptying fraction (P = 0.006), and
reduced LA reservoir strain (P < 0.001). Reduced CRF was also associated
with reduced LA voltage (P = 0.039) with greater heterogeneity (P = 0.027)
and conduction slowing (P = 0.04) with greater conduction heterogeneity (P
= 0.02). On multivariable analysis, peak oxygen consumption was
independently associated with LA stiffness (P = 0.003) and LA conduction
velocities (P = 0.04)
CONCLUSIONS: Reduced CRF in patients with AF is independently associated
with worse LA disease involving functional and electrical changes.
Improving CRF may be a target for restoring LA function in AF.