Category Archives: Abstracts

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.

Cardiopulmonary Response to Acute Exercise before Hemodialysis: A Pilot Study.

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.

Left Ventricle Size Correlates with Peak Exercise Capacity in Pediatric Cancer Survivors Exposed to Anthracycline Chemotherapy.

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.

Does High-Intensity Exercise Cause Acute Liver Injury in Patients with Fontan Circulation? A Prospective Pilot Study.

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.

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

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.

Prediction of exercise respiratory limitation from pulmonary function tests

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.