Abela M, Cardiovascular and Genomics Research Institute at St George’s, University of London, UK
Scicluna J, Debattista J, Scerri J, Marmara V, Scerri C, Felice T

Int J Cardiol. 2026 May 13:134555. doi: 10.1016/j.ijcard.2026.134555.
Online ahead of print.

INTRODUCTION: Cascade testing in gene-positive cardiomyopathy families facilitates the identification of relatives at risk of cardiomyopathy. Conventional clinical screening is often unremarkable, particularly in younger individuals. This study evaluated the potential role of cardiopulmonary exercise testing (CPET) in detecting subclinical disease among gene-positive phenotype-negative (G + P-) relatives.
METHODS: In this single-centre case series, relatives of probands with likely/definite pathogenic cardiomyopathy variants underwent cascade testing. Gene-positive relatives underwent extensive phenotyping (ECG, echocardiography, holter monitor, cardiac MRI). Individuals with morpho-functional abnormalities suggestive of early cardiomyopathy and those fulfilling diagnostic criteria were excluded. Consecutively recruited (March 2017-December 2024) G + P- relatives underwent CPET ergometry. Those who completed a maximal test were included. A cardiac limitation was defined as VO2MAX <80% and/or ≥ 2 abnormal CPET variables.
RESULTS: Twenty-two subjects were included (59.1% female, mean age of 32.1 ± 16.0 years). Most had a TTN (27.3%), ACTC1 (22.7%) and DSG2 (22.7%) variant. All subjects are under follow-up (42.4 ± 24.0 months). Nearly ¾ (72.7%) had evidence of cardiac limitation during CPET, irrespective of haemoglobin, creatinine and body mass index. More than a third (40.9%) had a reduced VO2MAX. Two thirds (59.1%) had abnormal stroke volume kinetics (O2/pulse). Nearly half (45.5%) had reduced ventilatory efficiency (VE/VCO2) and two thirds (63.6%) had reduced aerobic efficiency (VO2/WR). A fifth (22.7%) had ventricular arrhythmias at peak exercise.
CONCLUSION: This is the first proof-of-concept study to demonstrate that CPET in cardiomyopathy families can identify a considerable proportion of G + P- relatives with early cardiac functional limitations. Long-term surveillance, and larger prospective studies are warranted to validate these findings.

Mapelli M; Centro Cardiologico Monzino IRCCS, Milan, Italy.
Puttini F; Mattavelli I; Salvioni E; Galotta A; Ferrarini G;
Canevari M; Willixhofer R; Caputo R; Costantino S; Biroli M; Lustri C;
Grandi D; Teglia A; Valenti M; Agostoni P
Headings added by Dr Older

Background Body posture influences cardiovascular and respiratory responses during
exercise, yet in a clinical setting, differences in body positions are not
considered when comparing different methodologies analyzing physical
effort, such as cardiopulmonary exercise testing (CPET), stress echo, or
invasive hemodynamic. We aimed to investigate how upright (UP),
semirecumbent (SR), and supine (SP) positions affect key CPET variables
and cardiac output (CO) in healthy adults.
Methods Twelve healthy volunteers (30.9
+/- 4.4 yr; 50% female) performed three randomized CPETs in UP, SR, and SP
positions. Breath-by-breath gas exchange data [oxygen uptake (Vo2) carbon
dioxide production (Vco2), minute ventilation (Ve), tidal volume (TV),
respiratory rate (RR)] and hemodynamic parameters [CO by thoracic
bioimpedance, stroke volume (SV), heart rate (HR)] were continuously
monitored. Data were analyzed at rest, anaerobic threshold, iso-watt
stages, and peak exercise.
Results At rest and submaximal workloads, HR decreased,
and SV increased with more reclined positions, maintaining CO. Ve and TV
were lower in SR and SP positions, whereas RR and peripheral oxygen
saturation ([Formula: see text]) were unchanged. At peak exercise, Vo2,
Vco2, workload, and exercise duration declined progressively from UP to SP
(Vo2: 2,587 +/- 1,009, 2,520 +/- 982, 2,269 +/- 847 mL/min; P < 0.001),
with lower Ve driven by reduced TV. Despite reduced metabolic and
ventilatory demands, CO was unchanged via increased SV. Dyspnea perception
was lower in reclined postures. Body posture modulates cardiopulmonary
responses during exercise. Semirecumbent and supine positions reduce Vo2
and Ve preserving CO.
Conclusons These findings highlight the importance of
posture-specific reference values for accurate interpretation in clinical
practice. NEW & NOTEWORTHY Body position during exercise testing
profoundly affects cardiopulmonary responses, even in healthy individuals.
Results obtained in different postures are not directly comparable.
Upright, semirecumbent, and supine exercise produce systematic changes in
oxygen uptake, ventilation, workload, and dyspnea, with lower performance
in reclined positions. Despite this, cardiac output is preserved through
adjustments in heart rate and stroke volume, indicating that
posture-rather than cardiac dysfunction-drives differences. Without
posture-specific reference values, disease severity may be misinterpreted.

Rondaij T; Institute of Physiology, University of Ljubljana,  Slovenia.
Jesih J; Dovc K; Battelino T; Potocnik N

Frontiers in Endocrinology. 17:1813865, 2026.

Introduction: Type 1 diabetes (T1D) is associated with an increased risk
of cardiovascular and autonomic complications. Although cardiopulmonary
exercise testing (CPET) is a valuable tool for assessing cardiorespiratory
function, data on physiological response to maximal exertion in
adolescents with T1D remain limited and inconsistent. This study aimed to
compare cardiovascular, respiratory, metabolic, and microvascular
responses to CPET in adolescents with T1D and healthy peers.

Methods: Sixteen participants aged 11-16 years (eight with T1D and eight
healthy controls), matched for anthropometric characteristics, underwent
CPET on a cycle ergometer. Respiratory gas exchange, heart rate, heart
rate variability, blood pressure, blood glucose, lactate concentration,
skin blood flow, skin temperature, and cutaneous vascular conductance were
measured at predefined time points during rest, exercise, and recovery.
Blood glucose, lactate concentration, and skin microvascular variables
were assessed at rest and during recovery.

Results: Adolescents with T1D demonstrated a significantly lower
VO2/power output slope and a higher ventilatory equivalent for oxygen at
maximal effort, suggesting altered oxygen uptake efficiency. Maximal power
output and maximal oxygen consumption did not differ between groups. Heart
rate responses and heart rate variability were similar throughout testing.
However, finger skin blood flow and cutaneous vascular conductance were
significantly lower in the T1D group at rest and during recovery.

Conclusion: Adolescents with T1D showed preserved cardiovascular function
and comparable overall exercise capacity to healthy peers, despite subtle
impairments in oxygen utilization and reduced skin microvascular function.
These findings indicate that even at a young age, T1D is associated with
altered metabolic, respiratory, and microvascular responses to maximal
exercise. The results suggest that peripheral, rather than central
mechanisms may underlie these differences, potentially involving glucose
levels or synthetic insulin effects on vascular endothelium.

Gollie JM; Research and Development Washington DC VA Columbria USA
Kokkinos PF; Patel SS; Libin AV; Holley AB; Shara NM; Hazel CG;
Kim DJ; Blackman MR

American Journal of Physiology – Renal Physiology. 330(5):F631-F640, 2026 May 01

Headings by Dr Older

Background
Peak oxygen consumption (Vo2peak) is reduced in patients with chronic
kidney disease (CKD). Although cardiovascular and skeletal muscle factors
are implicated in the declines of Vo2peak, few studies have evaluated
muscle oxygenation responses during exercise. We hypothesized that lower
Vo2peak in CKD would be associated with attenuated responses in muscle
oxygenation compared with those without CKD.
Methods
Forty-six male Veterans [CKD stages 3 and 4, n = 23; referent controls (REF), n = 23] completed the
study. Cardiopulmonary exercise testing was performed on a treadmill using
the modified Bruce protocol. Peak change in dominant medial gastrocnemius
deoxygenated hemoglobin/myoglobin {DELTA[deoxy(Hb-Mb)]peak}, total
hemoglobin/myoglobin {DELTA[total(Hb-Mb)]peak}, tissue saturation index
(DELTATSI), and DELTATSI reoxygenation half-time recovery
(DELTATSIreoxy1/2time) were assessed via near-infrared spectroscopy
(NIRS).
Results
Vo2peak, exercise time, HRpeak, Vo2 at gas-exchange threshold
(GET), and exercise time after GET were lower in the CKD group versus the
REF group (P = 0.002, P < 0.001, P = 0.020, P = 0.044, and P = 0.005,
respectively). For NIRS outcomes, DELTA[total(Hb-Mb)]peak was lower, and
DELTATSIreoxy1/2time prolonged, in the CKD group compared with the REF
group (P = 0.032 and P = 0.031, respectively). Vo2peak was positively
associated with HRpeak (CKD, r = 0.57, P = 0.005; REF, r = 0.63, P =
0.001) and DELTA[total(Hb-Mb)]peak (CKD, r = 0.63, P = 0.001; REF, r =
0.52, P = 0.012) in both groups. Conversely, Vo2peak was positively
associated with DELTA[deoxy(Hb-Mb)]peak in the CKD group only (r = 0.64, P
< 0.001).
Conclusions
These findings suggest that skeletal muscle impairments, in
addition to cardiovascular impairments, contribute to reduced Vo2peak in
patients with CKD. NEW & NOTEWORTHY Peak oxygen consumption is associated
with peak heart rate, oxygen extraction, and microvascular blood volume in
patients with chronic kidney disease (CKD), highlighting the importance of
cardiovascular and skeletal muscle health in this patient population.
Future studies are necessary to determine which exercise approaches are
most efficacious at enhancing cardiorespiratory fitness and whether, and
to what extent, improvements in cardiorespiratory fitness result from
changes in cardiovascular factors, skeletal muscle factors, or a
combination of both.

Bas Van Hooren;  Institute of Nutrition and Translational Research in Metabolism (NUTRIM),Maastricht, the Netherland
Tjeu Souren; Bart C. Bongers

Scandinavian Journal of Medicine & Science in Sports, 2026; 36:e70297
Headings by Dr Older

Aims The present study had three main objectives: (a) to evaluate the in-field validity of different commercially available cardiopul-
monary exercise testing (CPET) systems when used by end-users following typical calibration procedures, (b) to measure the
variability in accuracy among identical CPET units, and (c) to explore the relationship between the age of the units, as well as
the maintenance practices, and their measurement accuracy.
Methods Fifty-seven CPET systems, calibrated and operated by end-users inclinical practice, research, or sports settings,
were assessed against a metabolic simulator that simulates breath-by-breath gas ex-
change. The values measured by each system [minute ventilation (V̇E), oxygen uptake (V̇O2), carbon dioxide production (V̇CO2),
and respiratory exchange ratio (RER)] were compared to the simulated values to evaluate the accuracy. Absolute percentage
errors during the simulations ranged from 1.41% to 24.6% for V̇E, 3.29%–10.6% for V̇O2, 2.86%–13.3% for V̇CO2, and 1.90%–10.0%
for RER. Inter-unit variability (%) ranged from 1.98% to 12.7% for V̇O2, 1.49%–8.10% for V̇CO2, and 1.93%–4.24% for RER.
Results No consistent relationship between system age and accuracy was observed, nor between annual maintenance and accuracy. The validity
of metabolic carts for measuring respiratory gas variables varied significantly even between identical systems, despite passing
manufacturers’ calibration checks. Furthermore, inter-unit variability of most systems exceeded intra-unit test-retest variability,
thus necessitating caution when using devices interchangeably, as this may increase measurement noise, even within the same
laboratory. Most inaccuracies seemed related to technological errors, although some user errors were also identified, indicating
the need for a holistic approach to identify errors.

Pandit A; Biomedical Research Center, Baton Rouge,  USA.
Gupta M; Arabie DA; Milton P; Elbatreek M; Goodchild T; Lefer
DJ; Francis J; Moll D; Allerton TD

Obesity. 34(5):984-996, 2026 May.

Heart failure with preserved ejection fraction (HFpEF) now represents the
dominant form of heart failure in the United States. Approximately 80% of
HFpEF patients also live with obesity. This review highlights the central
role of obesity in driving the pathophysiology and clinical presentation
of HFpEF, particularly exercise intolerance, which is the hallmark symptom
of heart failure. We summarize evidence that obesity promotes early
concentric remodeling, diastolic dysfunction, and atrial enlargement while
reducing the diagnostic utility of natriuretic peptides. We also examine
how cardiopulmonary exercise testing (CPET), the gold standard for
assessing exercise capacity, reveals obesity-related impairments in peak
oxygen uptake, chronotropic response, and pulmonary pressures. Beyond
cardiac contributions, obesity amplifies peripheral drivers of exercise
intolerance, including vascular stiffening, endothelial dysfunction,
impaired skeletal muscle oxygen utilization, mitochondrial dysfunction,
and myosteatosis. We also discuss new evidence that the chronic
inflammatory response can drive central and peripheral dysfunction
(systemic fibrosis and skeletal muscle atrophy) to reduce functional
capacity in HFpEF. Together, these findings position obesity as a central,
modifiable determinant of HFpEF and underscore the need for mechanistic
studies targeting skeletal muscle, vascular, and inflammatory pathways.

Tsai YL; Veterans General Hospital, Taichung City, Taiwan.
Chang KM; Chin CS; Hsu CY; Yu YH; Cheng YY; Fu PK

Respirology. 31(5):498-508, 2026 May.

BACKGROUND AND OBJECTIVE: Our previous study demonstrated that a summed
score derived from six cardiopulmonary exercise testing (CPET) parameters
could predict 1-year mortality in patients with interstitial lung disease
(ILD). However, its long-term prognostic value across different ILD
aetiologies remains unclear. This study aimed to assess the predictive
performance of CPET-derived parameters for long-term outcomes in patients
with idiopathic pulmonary fibrosis (IPF) and connective tissue
disease-associated ILD (CTD-ILD).

METHODS: In this prospective cohort study, 210 patients newly diagnosed
with ILD between 2018 and 2022 at a tertiary medical centre underwent
CPET. A CPET-derived summed score was evaluated for its association with a
composite outcome of all-cause mortality or lung transplantation. Cox
regression and receiver operating characteristic curve analyses were used
to examine predictive ability and identify the optimal cutoff value.
Kaplan-Meier survival analysis and log-rank tests compared event-free
survival in IPF and CTD-ILD patients.

RESULTS: A summed score incorporating five CPET-derived variables was an
independent predictor of the composite outcome. Patients with scores of
2-5 had markedly lower event-free survival (44.2%) than those with scores
of 0-1 (88.3%). The score demonstrated consistent predictive value in both
IPF and CTD-ILD.

CONCLUSION: The CPET-derived summed score is a useful prognostic tool for
predicting all-cause mortality or the need for lung transplantation in
newly diagnosed ILD patients. It also retains predictive accuracy for
long-term outcomes in both IPF and CTD-ILD. External validation in other
ILD subtypes is warranted.

Billany RE; Division of Cardiovascular Sciences,, Leicester, UK.
Vadaszy N; Burns S; Chowdhury R; Ford EC; Mubaarak Z;
Sohansoha GK; Yeo JL; Dattani A; Cowley AC; Gulsin GS; Bishop NC; Smith
AC; McCann GP; Graham-Brown MP

Clinical Rehabilitation. 40(5):587-602, 2026 May.

Objectives (1) Explore the effects of a 12-week home-based rehabilitation
programme on cardiorespiratory fitness in kidney transplant recipients;
(2) Compare cardiorespiratory fitness parameters in kidney transplant
recipients and age-sex matched healthy volunteers to aid the justification
for routine rehabilitation programmes.
Design  Pilot randomised controlled
trial with nested case-control. Setting Home-based rehabilitation;
hospital-based outcome assessments. Participants Pilot randomised
controlled trial: 50 stable kidney transplant recipients (>1 year
post-transplant) (randomised 1:1; n = 25 control and n = 25 intervention).
Nested case-control: 30 kidney transplant recipients and 30 healthy
volunteers. InterventionA 12-week home-based aerobic and resistance
rehabilitation programme or guideline-directed care control.Main
measuresCardiorespiratory fitness measured by cardiopulmonary exercise
testing.
Results Pilot randomised controlled trial: After adjusting for
baseline, follow-up values were significantly greater in intervention
compared to control for peak oxygen uptake (VO2peak) mL/kg/min, (+1.50, p
= .03) and maximum workload (+8 W, p = .04) but not VO2peak L/min or
variables at the gas exchange threshold. Higher frequency of aerobic
exercise sessions was associated with greater improvements in
cardiorespiratory fitness (R2 = .252, p = .040). Nested case-control:
VO2peak was reduced in kidney transplant recipients compared to healthy
volunteers (18.81 +/- 4.61 vs 24.06 +/- 5.72 mL/kg/min; p < .01), as was
VO2 at the gas exchange threshold (11.70 +/- 2.67 vs 14.47 +/- 3.39
mL/kg/min; p < .01).
Conclusions A 12-week home-based rehabilitation
programme induced a significant improvement in some cardiorespiratory
fitness variables and higher frequency of aerobic exercise associated with
greater improvements. Cardiorespiratory fitness is significantly impaired
in kidney transplant recipients compared to age-sex-matched healthy
volunteers. Together, these findings highlight the clinical importance of
promoting aerobic exercise and the integration of rehabilitation
programmes into routine care for this population.

Robin Willixhofera, Marlus Karstena,b, Arianna Galottaa, Elisabetta Salvionia, Carlo Vignatia,
Alice Bonomia, Anna Apostoloa, Mauro Continia, Pietro Palermoa, Jeness Campodonicoa,
Beatrice Pezzutoa, Stefania Farinaa, Massimo Mapellia, Irene Mattavellia, Piergiusepe Agostonia,c,*

a) Centro Cardiologico Monzino IRCCS, Milan,
b) Cardiovascular Health and Exercise Research Group (GEPCardio), Department of
Physiotherapy, Graduate Program in Physiotherapy, Santa Catarina State University (UDESC),
Florianopolis, Santa Catarina, Brazil
c) Department of Clinical Sciences and Community Health, Cardiovascular Section, University of
Milan, 20122 Milan, Italy.

Paper not yet published but accepted for publication

Background

Cardiopulmonary exercise testing (CPET) is the gold standard for assessing exertional dyspnea,
providing peak oxygen uptake (VO2), and the VE/VCO2 slope. Different metabolic carts may
introduce systematic variability, confounding longitudinal assessments and multicenter trials.
We evaluated intra-device reliability and inter-device comparability of CPET parameters.

Methods
In this prospective, single-center, within-subject, repeated-measures, multi-device comparison
study 34 healthy adults (35±11 years; 59% males) completed eight CPETs: two per cart, on four
systems (MGC Ultima™ CPX, COSMED Quark CPET™, Schiller PowerCube® Ergo, Vyaire
Vyntus™ CPX). Tests used randomized order, ramp protocols on cycle ergometer, and
standardized calibration, masks, and timing (2–10 days apart; within 40 days). Breath by breath
data were 10-second averaged. Analyses included paired tests for intra-device reliability, repeated-
measures ANOVA for inter-device comparisons, and iso-workload evaluation at 25–100% of
lowest peak workload (ISO-Wpeak).

Results
Intra-device reliability was high, with no significant differences in VO2, heart rate or workload at
anaerobic threshold (AT), respiratory compensation point (RCP) or peak. Minor variances
occurred in resting VO2 (COSMED: 56ml/min, p=0.0427) and peak ventilation (Medical Graphic
9 l/min, p<0.05). Inter-device comparability showed no differences in peak VO2 and the VE/VCO2
slope calculated up to the RCP. The VE/VCO2 slope assessed as the full slope however, showed
significant differences between machines (p=0.0048). Across standardized ISO-Wpeak (25%,
50%, 75%, and 100% of ISO-Wpeak), VO2 values were largely comparable between devices, with
significant differences only for VO2 (ml/kg/min) at 25% ISO-Wpeak (p=0.022).

Conclusion
Under standardized conditions, the tested metabolic carts yield comparable values both for intra-
device reliability and inter-device comparability.