Shlomi D; Tel-Aviv University, Tel Aviv, Israel.
Beck T; Reuveny R; Segel MJ

Pulmonology. 30(5):452-458, 2024 Sep-Oct.

BACKGROUND: Evaluation of unexplained exercise intolerance is best
resolved by cardiopulmonary exercise testing (CPET) which enables the
determination of the exercise limiting system in most cases.
Traditionally, pulmonary function tests (PFTs) at rest are not used for
the prediction of a respiratory limitation on CPET.
OBJECTIVE: We sought cut-off values on PFTs that might, a priori, rule-in
or rule-out a respiratory limitation in CPET.
METHODS: Patients who underwent CPET in our institute were divided into
two groups according to spirometry: obstructive and non-obstructive. Each
group was randomly divided 2:1 into derivation and validation cohorts
respectively. We analyzed selected PFTs parameters in the derivation
groups in order to establish maximal and minimal cut-off values for which
a respiratory limitation could be ruled-in or ruled-out. We then validated
these values in the validation cohorts.
RESULTS: Of 593 patients who underwent a CPET, 126 were in the
obstructive and 467 in the non-obstructive group. In patients with
obstructive lung disease, forced expiratory volume in 1 second (FEV1) >=
61% predicted could rule out a respiratory limitation, while FEV1 <= 33%
predicted was always associated with a respiratory limitation. For
patients with non-obstructive spirometry, FEV1 of >= 73% predicted could
rule-out a respiratory limitation. Application of this algorithm might
have saved up to 47% and 71% of CPETs in our obstructive and
non-obstructive groups, respectively.
CONCLUSION: Presence or absence of a respiratory limitation on CPET can
be predicted in some cases based on a PFTs performed at rest.

Siuba MT; Department of Critical Care Medicine, Cleveland, USA
Sharpe MG; Lane J; Toth D; Paul D; Wang X; Tonelli AR

European Journal of Preventive Cardiology. 31(12):1550-1552, 2024 Sep 06.

No abstract available

Yu HK; Mackay Memorial Hospital, Taipei, Taiwan.
Chen CY; Chen YC; Cheng CH; Chen CY; Hu GC

Journal of Cardiopulmonary Rehabilitation & Prevention. 44(5):311-316,
2024 Sep 01.

PURPOSE: Following acute myocardial infarction (AMI), patients with
diabetes mellitus (DM) have a poorer prognosis than those without DM. This
study aimed to investigate the benefit of cardiac rehabilitation on
cardiorespiratory fitness in patients with AMI, examining whether this
effect varied depending on DM and glycated hemoglobin (HbA1c) levels.
METHODS: Data were collected from the medical records of 324 patients
diagnosed with AMI who were subsequently referred to participate in a
supervised exercise-based cardiac rehabilitation program.
Cardiorespiratory fitness was assessed using cardiopulmonary exercise
testing before and at 3 and 6 mo after the start of cardiac
rehabilitation. Linear mixed models were used to evaluate changes in
cardiorespiratory fitness between patients with and without DM during the
follow-up period.
RESULTS: In total, 106 patients (33%) had DM. Both patients with and
without DM showed a significant improvement in cardiorespiratory fitness
from baseline to the 6-mo follow-up. However, the improvement was
significantly lower in patients with DM than in those without DM (1.9 +/-
1.5 vs. 3.7 +/- 3.2 mL/kg/min, P < .001). Among patients with DM, those
with HbA1c levels < 7% showed a greater improvement in cardiorespiratory
fitness than those with HbA1c >= 7% (2.7 +/- 1.5 vs. 1.1 +/- 1.8
mL/kg/min, P < .001) during the follow-up period.
CONCLUSIONS: Improvements in cardiorespiratory fitness following cardiac
rehabilitation were significantly lower in patients with AMI and DM. The
response to cardiac rehabilitation in patients is influenced by HbA1c
levels. These findings suggest potential implications for individualizing
cardiac rehabilitation programming and ensuring optimal glycemic control
in patients with AMI and DM.

Staes M; University Hospitals Leuven, Belgium.
Gyselinck I; Goetschalckx K; Troosters T; Janssens W

European Respiratory Review. 33(173), 2024 Jul.

Abstract
Cardiopulmonary exercise testing (CPET) is a comprehensive and invaluable
assessment used to identify the mechanisms that limit exercise capacity.
However, its interpretation remains poorly standardised. This scoping
review aims to investigate which limitations to exercise are
differentiated by the use of incremental CPET in literature and which
criteria are used to identify them. We performed a systematic, electronic
literature search of PubMed, Embase, Cochrane CENTRAL, Web of Science and
Scopus. All types of publications that reported identification criteria
for at least one limitation to exercise based on clinical parameters and
CPET variables were eligible for inclusion. 86 publications were included,
of which 57 were primary literature and 29 were secondary literature. In
general, at the level of the cardiovascular system, a distinction was
often made between a normal physiological limitation and a pathological
one. Within the respiratory system, ventilatory limitation, commonly
identified by a low breathing reserve, and gas exchange limitation, mostly
identified by a high minute ventilation/carbon dioxide production slope
and/or oxygen desaturation, were often described. Multiple terms were used
to describe a limitation in the peripheral muscle, but all variables used
to identify this limitation lacked specificity. Deconditioning was a
frequently mentioned exercise limiting factor, but there was no consensus
on how to identify it through CPET. There is large heterogeneity in the
terminology, the classification and the identification criteria of
limitations to exercise that are distinguished using incremental CPET.
Standardising the interpretation of CPET is essential to establish an
objective and consistent framework.

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.