Author Archives: Paul Older

Sex-specific differences of cardiopulmonary fitness and pulmonary function in exercise-based rehabilitation of patients with long-term post-COVID-19 syndrome.

Garbsch R; University of Witten/Herdecke, Witten, Germany.
Schafer H; Kotewitsch M; Mooren JM; Waranski M; Teschler M;
Vereckei K; Boll G; Mooren FC; Schmitz B

BMC Medicine. 22(1):446, 2024 Oct 08.

Post-COVID-19 Syndrome (PCS) entails a spectrum of symptoms,
including fatigue, reduced physical performance, dyspnea, cognitive
impairment, and psychological distress. Given the effectiveness of
exercise-based rehabilitation for PCS, this study examined the efficacy of
rehabilitation for PCS patients, focusing on sex-specific differences.
METHODS: Prospective cohort study during inpatient rehabilitation.
Cardiopulmonary exercise testing and spirometry were performed at
admission and discharge. Questionnaires were used to assess fatigue,
health-related quality of life, wellbeing, and workability for up to 6
months.
RESULTS: 145 patients (36% female, 47.1 +/- 12.7 years; 64% male, 52.0
+/- 9.1 years; p = 0.018) were referred to rehabilitation 262.0 +/- 128.8
days after infection (female, 285.5 +/- 140.6 days; male, 248.8 +/- 112.0
days; p = 0.110). Lead symptoms included fatigue/exercise intolerance
(81.4%), shortness of breath (74.5%), and cognitive dysfunction (52.4%).
Women presented with higher relative baseline exercise capacity (82.0 +/-
14.3%) than males (68.8 +/- 13.3%, p < 0.001), but showed greater
improvement in submaximal workload (p = 0.026). Men exhibited higher
values for FEV1, FEV1/VC, PEF, and MEF and lower VC at baseline (p <=
0.038), while FEV1/VC improvement more in women (p = 0.027). Higher
baseline fatigue and lower wellbeing was detected in women and correlated
with impaired pulmonary function (p < 0.05). Disease perception including
fatigue, health-related quality of life, wellbeing and workability
improved with rehabilitation for up to six-month.
CONCLUSIONS: Rehabilitation improves cardiopulmonary fitness, pulmonary
function and disease burden in women and men with long-term PCS. Women
with PCS may benefit from intensified respiratory muscle training.
Clinical assessment should include cardiopulmonary exercise testing and
pulmonary function tests and fatigue assessments for all PCS patients to
document limitations and tailor therapeutical strategies.

A Comparison of Outcome in Patient With and Without Undergoing Cardiopulmonary Exercise Testing (CPET).

Veeralakshmanan P; Department of Vascular Surgery, Birmingham, UK.
Juszczak M; Tiwari A

Vascular & Endovascular Surgery. 58(8):862-865, 2024 Nov.

BACKGROUND: Cardiopulmonary exercise testing (CPET) is a preoperative risk
stratification tool providing an objective measure of fitness and
functional capacity. There is however little evidence on the use of this
compared to non-physiological test in vascular surgery despite its current
use. This study investigates whether CPET perioperatively has value
alongside non-physiological testing for patients undergoing elective open
abdominal aortic aneurysm (AAA) repair.
METHOD: Retrospective data was collected at 2 vascular centres between
2015-2019 in a CPET centre vs non-CPET centre in patients undergoing
elective AAA repair. Outcomes measured included: length of stay in an
intensive care unit (ICU); total length of stay; post-operative
complications and acute kidney injury (AKI). Statistical analysis was
performed using IBM SPSS software.
RESULTS: There were 38 patients at each centre. The mean duration of stay
in ICU for patients in CPET centre was 2.5 +/- 2.13 days whilst in
non-CPET centre it was 3.68 +/- 4.08 days (P = 0.05). The mean duration of
stay in ICU and total length of stay was significantly shorter in CPET
centre (P = 0.05 and P = 0.015 respectively). Mortality in CPET centre was
2.63% and 5.26% in non-CPET centre (not significant). The number of
patients developing AKI post-operatively was 13.61% in CPET vs 28.95% in
non-CPET centre.
CONCLUSION: CPET tested patients have statistically significant lower
length of total and ICU stay compared to non-CPET patients. CPET is
therefore a useful adjunct in selecting patients for open surgery compared
to non-physiological testing. This study provides some evidence on the use
of this routinely but not validated assessment tool in aortic aneurysm
repair.

The evolving role of cardiopulmonary exercise testing in ischemic heart disease – state of the art review. [Review]

Chaudhry S;Chicago, Illinois, USA & University of Toronto, Toronto, Canada.
Kumar N; Arena R; Verma S

Current Opinion in Cardiology. 38(6):552-572, 2023 Nov 01.

PURPOSE OF REVIEW: Cardiopulmonary exercise testing (CPET) is the gold
standard for directly assessing cardiorespiratory fitness (CRF) and has a
relatively new and evolving role in evaluating atherosclerotic heart
disease, particularly in detecting cardiac dysfunction caused by ischemic
heart disease. The purpose of this review is to assess the current
literature on the link between cardiovascular (CV) risk factors, cardiac
dysfunction and CRF assessed by CPET.
RECENT FINDINGS: We summarize the basics of exercise physiology and the
key determinants of CRF. Prognostically, several studies have been
published relating directly measured CRF by CPET and outcomes allowing for
more precise risk assessment. Diagnostically, this review describes in
detail what is considered healthy and abnormal cardiac function assessed
by CPET. New studies demonstrate that cardiac dysfunction on CPET is a
common finding in asymptomatic individuals and is associated with CV risk
factors and lower CRF. This review covers how key CPET parameters change
as individuals transition from the asymptomatic to the symptomatic stage
with progressively decreasing CRF. Finally, a supplement with case studies
with long-term longitudinal data demonstrating how CPET can be used in
daily clinical decision making is presented.
SUMMARY: In summary, CPET is a powerful tool to provide individualized CV
risk assessment, monitor the effectiveness of therapeutic interventions,
and provide meaningful feedback to help patients guide their path to
improve CRF when routinely used in the outpatient setting.

A Summed Score From Cardiopulmonary Exercise Test Parameters Predicts 1-Year Mortality in Newly Diagnosed Interstitial Lung Disease.

Cheng YY; Veterans General Hospital, Taichung 40705, Taiwan.
Lee YC; Liao YW; Liu MC; Wu YC; Hsu CY; Yu YH; Fu PK

Respiratory Care. 69(10):1305-1313, 2024 Sep 26.

BACKGROUND: Cardiopulmonary exercise testing (CPET) is a unique diagnostic
tool that assesses the functional capacity of the heart, lungs, and
peripheral oxidative system in an integrated manner. However, the clinical
utility of CPET for evaluating interstitial lung disease (ILD) remains
uncertain. The objective of this study was to determine the predictive
value of CPET for mortality in subjects with ILD.
METHODS: We prospectively enrolled subjects with ILD who underwent CPET
at a tertiary medical center in Taiwan and followed up their survival
status for 12 months. Mortality prediction was based on comparing CPET
parameters between subjects who survived and those who died. We further
analyzed CPET parameters that showed significant differences using
receiver operating characteristic curves to identify their optimal cutoff
values.
RESULTS: A total of 106 newly diagnosed subjects with ILD underwent CPET,
and the 1-y mortality rate was 7.5%. Six CPET variables were found to be
significant predictors of mortality: peak oxygen consumption, oxygen
pulse, end-tidal partial pressure of carbon dioxide, heart rate recovery 1
min after CPET, minute ventilation to carbon dioxide output slope, and
functional aerobic impairment. We calculated a summed score by adding the
number of CPET variables that exceeded their cutoff values. Subjects with
a summed score of 6 had a 1-y survival rate of only 25%, whereas subjects
with scores of 0-5 had a survival rate of 98%.
CONCLUSIONS: In conclusion, the summed score represents a useful tool for
screening patients with ILD who can undergo a CPET to determine their
prognosis.

Clusters of multidimensional exercise response patterns and estimated heart failure risk in the Framingham Heart Study.

Miller PE; University School of Medicine, Boston, MA, USA
Gajjar P; Mitchell GF; Khan SS; Vasan RS; Larson MG; Lewis GD;
Shah RV; Nayor M

ESC heart failure. 11(5):3279-3289, 2024 Oct.

AIMS: New tools are needed to identify heart failure (HF) risk earlier in
its course. We evaluated the association of multidimensional
cardiopulmonary exercise testing (CPET) phenotypes with subclinical risk
markers and predicted long-term HF risk in a large community-based cohort.

METHODS AND RESULTS: We studied 2532 Framingham Heart Study participants
[age 53 +/- 9 years, 52% women, body mass index (BMI) 28.0 +/- 5.3 kg/m2,
peak oxygen uptake (VO2) 21.1 +/- 5.9 kg/m2 in women, 26.4 +/- 6.7 kg/m2
in men] who underwent maximum effort CPET and were not taking
atrioventricular nodal blocking agents. Higher peak VO2 was associated
with a lower estimated HF risk score (Spearman correlation r: -0.60 in men
and -0.55 in women, P < 0.0001), with an observed overlap of estimated
risk across peak VO2 categories. Hierarchical clustering of 26 separate
CPET phenotypes (values residualized on age, sex, and BMI to provide
uniformity across these variables) identified three clusters with distinct
exercise physiologies: Cluster 1-impaired oxygen kinetics; Cluster
2-impaired vascular; and Cluster 3-favourable exercise response. These
clusters were similar in age, sex distribution, and BMI but displayed
distinct associations with relevant subclinical phenotypes [Cluster
1-higher subcutaneous and visceral fat and lower pulmonary function;
Cluster 2-higher carotid-femoral pulse wave velocity (CFPWV); and Cluster
3-lower CFPWV, C-reactive protein, fat volumes, and higher lung function;
all false discovery rate < 5%]. Cluster membership provided incremental
variance explained (adjusted R2 increment of 0.10 in women and men, P <
0.0001 for both) when compared with peak VO2 alone in association with
predicted HF risk.

CONCLUSIONS: Integrated CPET response patterns identify physiologically
relevant profiles with distinct associations to subclinical phenotypes
that are largely independent of standard risk factor-based assessment,
which may suggest alternate pathways for prevention.

Exercise intensity prescription in cardiovascular rehabilitation: bridging the gap between best evidence and clinical practice.

Milani JGPO; Hasselt University, Hasselt, Belgium.; Graduate Programme in Health Sciences and Technologies, University of Brasilia (UnB), Brasilia, Brazil.
Milani M; Verboven K; Cipriano G Jr; Hansen D;

Frontiers in cardiovascular medicine [Front Cardiovasc Med] 2024 Aug 27; Vol. 11, pp. 1380639.
Date of Electronic Publication: 2024 Aug 27 (Print Publication: 2024).

Optimizing endurance exercise intensity prescription is crucial to maximize the clinical benefits and minimize complications for individuals at risk for or with cardiovascular disease (CVD). However, standardization remains incomplete due to variations in clinical guidelines. This review provides a practical and updated guide for health professionals on how to prescribe endurance exercise intensity for cardiovascular rehabilitation (CR) populations, addressing international guidelines, practical applicability across diverse clinical settings and resource availabilities. In the context of CR, cardiopulmonary exercise test (CPET) is considered the gold standard assessment, and prescription based on ventilatory thresholds (VTs) is the preferable methodology. In settings where this approach isn’t accessible, which is frequently the case in low-resource environments, approximating VTs involves combining objective assessments-ideally, exercise tests without gas exchange analyses, but at least alternative functional tests like the 6-minute walk test-with subjective methods for adjusting prescriptions, such as Borg’s ratings of perceived exertion and the Talk Test. Therefore, enhancing exercise intensity prescription and offering personalized physical activity guidance to patients at risk for or with CVD rely on aligning workouts with individual physiological changes. A tailored prescription promotes a consistent and impactful exercise routine for enhancing health outcomes, considering patient preferences and motivations. Consequently, the selection and implementation of the best possible approach should consider available resources, with an ongoing emphasis on strategies to improve the delivery quality of exercise training in the context of FITT-VP prescription model (frequency, intensity, time, type, volume, and progression).

Identifying limitations to exercise with incremental cardiopulmonary exercise testing: a scoping review.

Staes M; Laboratory of Respiratory Diseases and Thoracic Surgery,  Leuven, Belgium.;
Gyselinck I; Goetschalckx K;Troosters T; Janssens W;

European respiratory review : an official journal of the European Respiratory Society [Eur Respir Rev] 2024 Sep 04; Vol. 33 (173).
Date of Electronic Publication: 2024 Sep 04 (Print Publication: 2024).

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.
Competing Interests: Conflict of interest: I. Gyselinck reports grants from Research Foundation Flanders, and support for attending meetings from AstraZeneca. W. Janssens reports grants from AstraZeneca and Chiesi, consultation fees from AstraZeneca, Chiesi, GSK and Sanofi, payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Chiesi and GSK, support for attending meetings from AstraZeneca and Chiesi, and the following financial (or non-financial) interests: co-founder and chairholder of ARTIQ, a spin-off company of KULeuven.

A detailed analysis of body composition in relation to cardiopulmonary exercise test indices.

Karlsson P; Department of Medical Sciences: Clinical Physiology, Uppsala University, Uppsala, Sweden.
Strand R; Kullberg J; DMichaëlsson K; DeAhlström H; Division of Radiology, Lind L; Malinovschi A;

Scientific reports [Sci Rep] 2024 Sep 16; Vol. 14 (1), pp. 21633.
Date of Electronic Publication: 2024 Sep 16.

A cardiopulmonary exercise test (CPET) is a test assessing an individual’s physiological response during exercise. Results may be affected by body composition, which is best evaluated through imaging techniques like magnetic resonance imaging (MRI). The aim of this study was to assess relationships between body composition and indices obtained from CPET. A total of 234 participants (112 female), all aged 50 years, underwent CPETs and whole-body MRI scans (> 1 million voxels). Voxel-wise statistical analysis of tissue volume and fat content was carried out with a method called Imiomics and related to the CPET indices peak oxygen consumption (V̇O 2peak ), V̇O 2peak scaled by body weight (V̇O 2kg ) and by total lean mass (V̇O 2lean ), ventilatory efficiency (V̇E/V̇CO 2 -slope), work efficiency (ΔV̇O 2 /ΔWR) and peak exercise respiratory exchange ratio (RERpeak). V̇O 2peak showed the highest positive correlation with volume of skeletal muscle. V̇O 2kg negatively correlated with tissue volume in subcutaneous fat, particularly gluteal fat. RERpeak negatively correlated with tissue volume in skeletal muscle, subcutaneous fat, visceral fat and liver. Some associations differed between sexes: in females ΔV̇O 2 /ΔWR correlated positively with tissue volume of subcutaneous fat and V̇E/V̇CO 2 -slope with tissue volume of visceral fat, and, in males, V̇O 2peak correlated positively to lung volume. In conclusion, voxel-based Imiomics provided detailed insights into how CPET indices were related to the tissue volume and fat content of different body structures.

Biventricular responses to exercise and their relation to cardiorespiratory fitness in pediatric pulmonary hypertension.

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.