Pieles GE; Hospital for Sick Children, University of Toronto, Canada & University College London, London, United Kingdom.;
Dorobantu DM; Caterini JE; Cifra B;Reyes J; Roldan Ramos S; Hannon E;Williams CA; Humpl T;Mertens L; Wells GD; Friedberg MK;

American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2024 Oct 01; Vol. 327 (4), pp. H749-H764.
Date of Electronic Publication: 2024 Jul 26.

Despite exercise intolerance being predictive of outcomes in pulmonary arterial hypertension (PAH), its underlying cardiac mechanisms are not well described. The aim of the study was to explore the biventricular response to exercise and its associations with cardiorespiratory fitness in children with PAH. Participants underwent incremental cardiopulmonary exercise testing and simultaneous exercise echocardiography on a recumbent cycle ergometer. Linear mixed models were used to assess cardiac function variance and associations between cardiac and metabolic parameters during exercise. Eleven participants were included with a mean age of 13.4 ± 2.9 yr old. Right ventricle (RV) systolic pressure (RVsp) increased from a mean of 59 ± 25 mmHg at rest to 130 ± 40 mmHg at peak exercise ( P < 0.001), whereas RV fractional area change (RV-FAC) and RV-free wall longitudinal strain (RVFW-S _l ) worsened (35.2 vs. 27%, P = 0.09 and -16.6 vs. -14.6%, P = 0.1, respectively). At low- and moderate-intensity exercise, RVsp was positively associated with stroke volume and O ₂ pulse ( P < 0.1). At high-intensity exercise, RV-FAC, RVFW-S _l , and left ventricular longitudinal strain were positively associated with oxygen uptake and O ₂ pulse ( P < 0.1), whereas stroke volume decreased toward peak ( P = 0.04). In children with PAH, the increase of pulmonary pressure alone does not limit peak exercise, but rather the concomitant reduced RV functional reserve, resulting in RV to pulmonary artery (RV-PA) uncoupling, worsening of interventricular interaction and LV dysfunction. A better mechanistic understanding of PAH exercise physiopathology can inform stress testing and cardiac rehabilitation in this population. NEW & NOTEWORTHY In children with pulmonary arterial hypertension, there is a marked increase in pulmonary artery pressure during physical activity, but this is not the underlying mechanism that limits exercise. Instead, right ventricle-to-pulmonary artery uncoupling occurs at the transition from moderate to high-intensity exercise and correlates with lower peak oxygen uptake. This highlights the more complex underlying pathological responses and the need for multiparametric assessment of cardiac function reserve in these patients when feasible.

Hsiao CC; Chang Gung Memorial Hospital, New Taipei, Taiwan,
Chou CY; Fang JT; Chang SC; Liu KC; Huang SC

Kidney & Blood Pressure Research. 49(1):735-744, 2024.

INTRODUCTION: Disparities in physical fitness between immediately before
dialysis (pre-D) and the day following dialysis (non-D) have not been
investigated despite potential adverse factors such as fluid status,
uremia, and electrolyte levels in the pre-dialysis period. The effect of
acute exercise immediately before hemodialysis (HD) on HD-related
hypotension remains unclear. We hypothesized that cardiopulmonary
performance and muscular strength would be inferior in the immediate pre-D
period compared to those non-D.

METHODS: Twenty patients receiving chronic HD treatments underwent
symptom-limited incremental cardiopulmonary exercise testing (CPET) and
isokinetic testing both 1-2 h prior to dialysis (pre-D) and non-D. This
investigation was a sub-study of a clinical trial assessing the efficacy
of a pre-D exercise training program. Blood pressure profiles during HD
post-CPET and pre-D exercise training were compared with those during
usual HD sessions.

RESULTS: No adverse events were observed during the 80 exercise tests.
Prior to dialysis, the nadir of the ventilatory equivalent of CO2 was
slightly elevated, the resting heart rate was lower, and the peak systolic
blood pressure was higher than those non-D. Contrary to our hypothesis,
peak <inline-formula>VO2</inline-formula> and quadriceps peak torque
showed no differences. Blood pressure profiles during HD post-exercise
were similar to those during sessions without prior exercise, except for a
lower resting systolic blood pressure at the beginning of HD.

CONCLUSION: Cardiopulmonary response and muscular strength in the 1-2 h
prior to HD were comparable with those on the day following HD, with only
minor clinically insignificant differences. Acute exercise prior to HD did
not affect the magnitude of hypotension during HD. This study suggests a
potential alternative timing for exercise training or testing in patients
undergoing chronic HD.

Masood IR; Children’s Hospital of Los Angeles,Los Angeles, USA.
Rezvan PH; Lee K; Vervaet H; Kuo C; Loss K; Menteer J; Souza A;
Freyer D; Su JA

Pediatric Cardiology. 45(7):1493-1502, 2024 Oct.

Cancer survivors exposed to anthracycline chemotherapy are at risk for
developing cardiomyopathy, which may have delayed clinical manifestation.
In a retrospective cross-sectional study, we evaluated the utility of
cardiopulmonary exercise testing (CPET) for detecting early cardiac
disease in 35 pediatric cancer survivors by examining the associations
between peak exercise capacity (measured via percent predicted peak VO2)
and resting left ventricular (LV) function on echocardiography and cardiac
magnetic resonance imaging (cMRI). We additionally assessed the
relationships between LV size on resting echocardiography or cMRI and
percent predicted peak VO2 since LV growth arrest can occur in
anthracycline-exposed patients prior to changes in LV systolic function.
We found reduced exercise capacity in this cohort, with low percent
predicted peak VO2 (62%, IQR: 53-75%). While most patients in our
pediatric cohort had normal LV systolic function, we observed associations
between percent predicted peak VO2 and echocardiographic and cMRI measures
of LV size. These findings indicate that CPET may be more sensitive in
manifesting early anthracycline-induced cardiomyopathy than
echocardiography in pediatric cancer survivors. Our study also highlights
the importance of assessing LV size in addition to function in pediatric
cancer survivors exposed to anthracyclines.

Gumm A; Department of Pediatrics, Medical College of Wisconsin, USA.
Ginde S; Hoffman G; Liegl M; Mack C; Simpson P; Vo N; Telega G;
Vitola B; Chugh A

The Fontan procedure results in chronic hepatic congestion and
Fontan-associated liver disease (FALD) characterized by progressive liver
fibrosis and cirrhosis. Exercise is recommended in this population, but
may accelerate the progression of FALD from abrupt elevations in central
venous pressure. The aim of this study was to assess if acute liver injury
occurs after high-intensity exercise in patients with Fontan physiology.
Ten patients were enrolled. Nine had normal systolic ventricular function
and one had an ejection fraction < 40%. During cardiopulmonary exercise
testing, patients had near-infrared spectroscopy (NIRS) to measure oxygen
saturation of multiple organs, including the liver, and underwent pre- and
post-exercise testing with liver elastography, laboratory markers, and
cytokines to assess liver injury. The hepatic and renal NIRS showed a
statistically significant decrease in oxygenation during exercise, and the
hepatic NIRS had the slowest recovery compared to renal, cerebral, and
peripheral muscle NIRS. A clinically significant increase in shear wave
velocity occurred after exercise testing only in the one patient with
systolic dysfunction. There was a statistically significant, albeit
trivial, increase in ALT and GGT after exercise. Fibrogenic cytokines
traditionally associated with FALD did not increase significantly in our
cohort; however, pro-inflammatory cytokines that predispose to
fibrogenesis did significantly rise during exercise. Although patients
with Fontan circulation demonstrated a significant reduction in hepatic
tissue oxygenation based on NIRS saturations during exercise, there was no
clinical evidence of acute increase in liver congestion or acute liver
injury following high-intensity exercise.

Pieles GE; University of Toronto, Toronto, Ontario, Canada. and other sites
Dorobantu DM; Caterini JE; Cifra B; Reyes J; Roldan Ramos S;
Hannon E; Williams CA; Humpl T; Mertens L; Wells GD; Friedberg MK

American Journal of Physiology – Heart & Circulatory Physiology.
327(4):H749-H764, 2024 Oct 01.

Despite exercise intolerance being predictive of outcomes in pulmonary
arterial hypertension (PAH), its underlying cardiac mechanisms are not
well described. The aim of the study was to explore the biventricular
response to exercise and its associations with cardiorespiratory fitness
in children with PAH. Participants underwent incremental cardiopulmonary
exercise testing and simultaneous exercise echocardiography on a recumbent
cycle ergometer. Linear mixed models were used to assess cardiac function
variance and associations between cardiac and metabolic parameters during
exercise. Eleven participants were included with a mean age of 13.4 +/-
2.9 yr old. Right ventricle (RV) systolic pressure (RVsp) increased from a
mean of 59 +/- 25 mmHg at rest to 130 +/- 40 mmHg at peak exercise (P <
0.001), whereas RV fractional area change (RV-FAC) and RV-free wall
longitudinal strain (RVFW-Sl) worsened (35.2 vs. 27%, P = 0.09 and -16.6
vs. -14.6%, P = 0.1, respectively). At low- and moderate-intensity
exercise, RVsp was positively associated with stroke volume and O2 pulse
(P < 0.1). At high-intensity exercise, RV-FAC, RVFW-Sl, and left
ventricular longitudinal strain were positively associated with oxygen
uptake and O2 pulse (P < 0.1), whereas stroke volume decreased toward peak
(P = 0.04). In children with PAH, the increase of pulmonary pressure alone
does not limit peak exercise, but rather the concomitant reduced RV
functional reserve, resulting in RV to pulmonary artery (RV-PA)
uncoupling, worsening of interventricular interaction and LV dysfunction.
A better mechanistic understanding of PAH exercise physiopathology can
inform stress testing and cardiac rehabilitation in this population. NEW &
NOTEWORTHY In children with pulmonary arterial hypertension, there is a
marked increase in pulmonary artery pressure during physical activity, but
this is not the underlying mechanism that limits exercise. Instead, right
ventricle-to-pulmonary artery uncoupling occurs at the transition from
moderate to high-intensity exercise and correlates with lower peak oxygen
uptake. This highlights the more complex underlying pathological responses
and the need for multiparametric assessment of cardiac function reserve in
these patients when feasible.

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