Schmid V; School of Medicine and Health, TUM University Hospital, Munich, Germany.
Paterson S; Weinkauf C; Wang J; et al

GeroScience. 48(3):4827-4845, 2026 Jun.

Reduced peak oxygen uptake (VO2peak) is a hallmark of heart failure (HF)
and aging, but studies on VO2peak in older HF patients are limited. We
compared VO2peak in older HF patients versus controls and investigated
differences across the age continuum: young-old (YO, 60-69 years),
middle-old (MO, 70-79 years), and oldest-old (OO, >= 80 years). PubMed was
searched (1967 May 2024) for studies meeting the following inclusion
criteria: (1) HF patients with mean age >= 65 years; (2) VO2peak measured
via maximal cardiopulmonary exercise testing, and (3) control group for
aim 1. For aim 2, studies had to compare VO2peak within the age-subgroups.
Random-effects meta-analysis was conducted, comparing VO2peak (primary
aim, and Fick determinants when reported) between HF and controls (aim 1),
and VO2peak between older age-subgroups (aim 2). Results are presented as
weighted mean differences (WMD) with 95% confidence intervals. From 2788
screened articles, 38 studies were included. For aim 1, 30 studies (HF: n
= 1093, mean age 70 years, 46% female; controls: n = 942, mean age 69
years, 52% female) demonstrated a significantly lower VO2peak in HF (WMD –
8.8 mL/kg/min, [95% CI] – 10.3 to – 7.3 mL/kg/min). In the subset of
patients where Fick determinants were measured, peak cardiac output and
heart rate were lower in HF versus controls. For aim 2, eight studies
showed progressively lower VO2peak with age: MO vs. YO (- 1.5 mL/kg/min)
and OO vs. MO (- 1.2 mL/kg/min). Older HF patients exhibit significant
VO2peak reductions compared to controls, with progressively lower VO2peak
values observed across the older age continuum.

Rodo-Pin A; Pulmonology Department, Hospital del Mar- Barcelona,Spain.
Martin-Ontiyuelo C; Rodriguez-Fuster A;et al

Respiration. 105(8):864-872, 2026.

INTRODUCTION: To determine whether peak workload (Wpeak), expressed as a
percentage of predicted value during a cardiopulmonary exercise test
(CPET), can predict postoperative cardiopulmonary complications in
high-risk patients undergoing lung cancer resection.

METHODS: A retrospective cohort study was conducted on 226 consecutive
patients who underwent anatomical lung resection (lobectomy or
segmentectomy) for non-small cell lung cancer between 2013 and 2017. All
patients were considered high risk, with preoperative FEV1 and DLco <80%
predicted and underwent full CPET within 30 days prior to surgery. The
main endpoint was the occurrence of cardiopulmonary complications within
30 days postoperatively. The predictive ability of Wpeak (% predicted) for
complications was evaluated using ROC analysis and optimal cutoff was
identified. Outcomes were compared above and below this threshold.

RESULTS: A Wpeak threshold of 52% predicted was identified as the optimal
cutoff, with an area under the ROC curve of 0.59 (95% CI: 0.51-0.67; p =
0.015). Patients with Wpeak <=52% had a significantly higher rate of
postoperative complications (58% vs. 33%, p = 0.001), particularly
respiratory complications (47% vs. 28%, p = 0.008), and longer hospital
stays (mean 24 vs. 15 days, p = 0.002). They also had lower FEV1, DLco,
VO2peak, and heart rate responses compared to patients with Wpeak >52%.

CONCLUSIONS: Wpeak <=52% of predicted was associated with increased risk
of postoperative complications and longer hospitalization. Although the
discriminatory ability was modest (AUC 0.59), Wpeak <=52% predicted was
associated with higher postoperative complications and may serve as a
complementary tool for risk stratification, especially in resource-limited
settings. Further prospective validation is warranted.

Beg MA; The Royal Marsden Hospital, NHS Foundation Trust, London, UK.
Frountzas M; Oliver A; Plete NK; Akhbari AR;et al

Surgery. 196:110283, 2026 Aug.

BACKGROUND: Locally advanced rectal cancers may require beyond total
mesorectal excision, including extensive procedures, such as total pelvic
exenteration. These operations carry significant morbidity.
Cardiopulmonary exercise testing is utilized to assess physiological
fitness before major surgery. However, limited evidence exists regarding
its predictive value in beyond total mesorectal excision. This study aimed
to determine whether preoperative cardiopulmonary exercise testing
parameters are associated with postoperative morbidity following beyond
total mesorectal excision, with subgroup analysis of patients undergoing
total pelvic exenteration.

METHODS: A retrospective cohort study was conducted at a tertiary center,
including consecutive patients who underwent cardiopulmonary exercise
testing prior to beyond total mesorectal excision between 2014 and 2021.
Associations between anaerobic threshold (AT VO2) and peak oxygen
consumption (VO2 peak) with major perioperative morbidity (Clavien-Dindo
>=3) were investigated. Receiver operating characteristic analysis
identified optimal cutoff values, which were used to dichotomize patients
into low- and high-risk groups. Groups were compared using chi2 and
Mann-Whitney U tests.

RESULTS: A total of 116 patients were included, of whom 62 underwent
total pelvic exenteration. In the overall beyond total mesorectal excision
cohort, cardiopulmonary exercise testing parameters could not demonstrate
any significant correlation with postoperative outcomes. However, in the
total pelvic exenteration subgroup, both AT VO2 (area under the curve
0.68; P = .035) and VO2 peak (area under the curve 0.73; P = .013) were
associated with significant morbidity. Receiver operating
characteristic-derived thresholds (AT VO2 <11.45 mL/kg/min; VO2 peak
<19.15 mL/kg/min) identified higher complication rates (30-31% vs 6-7%)
and longer hospital stay.

CONCLUSION: Cardiopulmonary exercise testing seems to present an
exploratory association with perioperative morbidity in patients
undergoing total pelvic exenteration but did not show any significant
association across the broader beyond total mesorectal excision cohort.
Incorporating cardiopulmonary exercise testing into preoperative
assessment may support risk stratification and targeted optimization
before complex rectal cancer surgery.

Hildebrand ND; Department of Surgery, Maastricht University,
Maastricht, the Netherlands;
Alhulaili ZM; Driessens H; Hoeijmakers LSM; Bongers BC; et al

European Journal of Surgical Oncology. 52(8):111913, 2026 Aug.

INTRODUCTION: Major complication rates after pancreatoduodenectomy (PD)
are high. Cardiorespiratory fitness and body composition are considered
important determinants of postoperative outcomes. This study evaluated the
association between a multimodal preoperative assessment of
cardiorespiratory fitness and body composition as core patient phenotypes
and the occurrence of major complications following PD.

METHODS: In this two-center retrospective cohort study (2022-2024),
patients undergoing PD were included. Preoperative cardiorespiratory
fitness was assessed using cardiopulmonary exercise testing (CPET) or the
modified steep ramp test (mSRT). Poor cardiorespiratory fitness was
defined as an oxygen uptake (VO2) at the ventilatory anaerobic threshold
(AT) < 11.0 mL/kg/min or VO2 at peak exercise (VO2peak) < 18.0 mL/kg/min
during CPET, or a work rate at peak exercise <2.1W/kg at the mSRT.
Preoperative body composition parameters were derived from abdominal
computed tomography scans. Low muscle mass based on skeletal muscle index
(SMI) and myosteatosis (defined as low skeletal muscle radiation
attenuation, SM-RA) were assessed. The primary outcome was 30-day major
complications (Clavien-Dindo >= III). Logistic regression analyses
identified predictors.

RESULTS: Among 175 eligible patients (mean +/- SD age 69.1 +/- 8.2 years,
44.6% female), 34.9% were unfit; 54.9% had low muscle mass and 35.4% had
myosteatosis. Major complications occurred in 37.7% and 8.0% required
unplanned intensive care unit (ICU) admission. Preoperative
cardiorespiratory fitness correlated moderately with SM-RA (rho =
0.36-0.47; all p < 0.001). Poor cardiorespiratory fitness was associated
with major complications in multivariable analysis (adjusted odds ratio
[aOR] 2.54, 95% CI 1.17-5.54, p=0.02). Combined myosteatosis and poor
cardiorespiratory fitness (n = 28, 16.0%) was associated with both major
complications (aOR 3.40, 95% CI 1.25-9.28, p = 0.02) and unplanned ICU
admission (aOR 4.62, 95% CI 1.06-20.16, p = 0.04).

CONCLUSION: Myosteatosis correlates with lower cardiorespiratory fitness.
The combination of preoperative myosteatosis and poor cardiorespiratory
fitness is associated with major complications and postoperative ICU
admission. In future preoperative assessment, these patient phenotypes may
help to refine personalized risk assessment and guide inclusions for
trials on targeted preventive interventions.

Smith JR, Department of Cardiovascular Medicine Mayo Clinic Rochester MN. USA
Medina-Inojosa JR, Chacin Suarez AS, Taylor JL, Fischer KM, et al

J Am Heart Assoc. 2026 Jul 17:e044403. doi: 10.1161/JAHA.125.044403.
Online ahead of print.

BACKGROUND: Cardiac rehabilitation (CR) leads to increased exercise capacity (VO2peak) and risk reduction of major adverse cardiovascular events (MACEs). Women exhibit blunted VO2peak improvements following CR. The purpose was to examine sex differences in the clinical predictors of VO2peak improvement and odds of MACEs following CR.
METHODS: From 1999 to 2017, all consecutive patients undergoing cardiopulmonary exercise testing before and after CR were included. Sex differences in peak exercise metrics in response to CR were compared. Multiple logistic regression models were fit to assess clinical predictors of VO2peak improvement (defined as >0% from pre-CR) and MACEs following CR for men and women.
RESULTS: A total of 513 men and 158 women were included. Men had greater increases in VO2peak than women following CR (P=0.001). For men, independent predictors of VO2peak improvement following CR included higher CR session attendance (odds ratio [OR], 1.04 [95% CI, 1.02-1.06]), peripheral artery disease (OR, 0.47 [95% CI, 0.25-0.86]), and pre-CR VO2peak (OR, 0.98 [95% CI, 0.97-0.99]) (all, P<0.02). Independent predictors of lower odds of MACEs following CR in men included higher number of CR sessions (OR, 0.97 [95% CI, 0.95-0.99]), pre-CR VO2peak (OR, 0.98 [95% CI, 0.97-0.99]), surgical CR indication (OR, 0.34 [95% CI, 0.18-0.68]), and no history of peripheral artery disease (OR, 2.94 [95% CI, 1.60-5.38]) (all, P<0.02). For women, the selected clinical characteristics were not statistically significant independent predictors of VO2peak improvement or odds of MACEs (except for diabetes) following CR.
CONCLUSIONS: These findings suggest that clinical predictors of VO2peak improvement and odds of MACEs following CR are sex specific.

Richardson JN; DeBakey Heart & Vascular Center, Houston, Texas, USA.
Martin CM

Methodist DeBakey cardiovascular journal. 22(3):124-135, 2026.

Advances in the management of congenital heart disease have resulted in a
rapidly expanding population of adults with congenital heart disease
(ACHD), among whom heart failure (HF) has emerged as a leading cause of
morbidity and mortality. HF in ACHD represents a distinct and
heterogeneous clinical entity shaped by lifelong abnormal loading
conditions, prior surgical interventions, arrhythmogenic substrates, and
limited representation in randomized clinical trials. The systemic
ventricle may be morphologically left, right, or single, each conferring
unique susceptibility to maladaptive remodeling, myocardial fibrosis,
valvular dysfunction, and progressive contractile decline. Accurate
diagnosis requires longitudinal, multimodal assessment incorporating
echocardiography, cardiovascular magnetic resonance, cardiopulmonary
exercise testing, biomarkers, rhythm surveillance, and selective invasive
hemodynamic evaluation. Management prioritizes identification and
correction of reversible contributors, including residual structural
lesions, atrioventricular valve regurgitation, arrhythmias, pulmonary
vascular disease, and extracardiac comorbidities. Pharmacologic therapy
remains largely extrapolated from acquired HF paradigms and demonstrates
variable efficacy across ACHD subgroups, underscoring the need for
physiology-driven individualized care within specialized centers. Advanced
therapies, including heart transplantation and mechanical circulatory
support, are increasingly utilized, with improving outcomes despite higher
perioperative complexity. This review presents a ventricle-based framework
for understanding the pathophysiology, evaluation, and management of HF in
ACHD and highlights critical gaps requiring further investigation.

Balakrishnan B; Cleveland Clinic, Cleveland, Ohio, USA,
Marakini A; Detloff L; Mahalwar G; Lane JE; Paul D; Tonelli AR

Respiration. 105(7):715-726, 2026.

Introduction: Pulmonary vascular abnormalities coexist with interstitial
lung disease (ILD), leading to a spectrum of physiologic impairments. We
hypothesized that ILD patients with exercise intolerance have a
heterogenous hemodynamic profile when assessed by invasive cardiopulmonary
exercise testing (iCPET).

METHODS: From January 2018 to December 2023, we prospectively performed
iCPET for several conditions. The primary outcome of the study was to
assess the hemodynamic phenotypes both at rest and during exercise of ILD
patients with exercise intolerance, which cannot be fully explained by the
severity of ILD.

RESULTS: Of the 43 ILD patients included in the study, 10 (23%) had no
pulmonary hypertension (PH), 16 (37%) had no PH with pulmonary vascular
resistance (PVR) >2 WU, 7 (16%) had precapillary PH, 7 (16%) had
postcapillary or combined pre- and postcapillary PH, and 3 (7%) had
unclassified PH. Four (9%) patients had exercise PH. Forced vital
capacity, diffusion capacity for carbon monoxide, peak oxygen consumption,
and resting partial pressure of oxygen (PaO2) were significantly lower
across the no PH to precapillary PH spectrum. Peak exercise PaO2 decreased
(97 +/- 25, 73 +/- 15, and 62 +/- 10 mm Hg, p = 0.001) while mPAP/CO slope
(1.9 +/- 1.1, 3.1 +/- 2.1, and 5.1 +/- 2.7, p = 0.009) and PAWP/CO slope
(0.9 +/- 0.7, 0.9 +/- 0.7, and 3.0 +/- 3.0, p = 0.007) increased from no
PH, to no PH with high PVR, to precapillary PH. No associations were noted
for gender, presence of fibrotic ILD and scleroderma, and mPAP/CO >3 WU
across this spectrum.

CONCLUSION: Patients with ILD and exercise intolerance have several
hemodynamic phenotypes with parameters that reveal worse exercise
performance from no PH to no PH with elevated PVR to precapillary PH

Bohovicova L; Masaryk Memorial Cancer Institute, Brno, Czech Republic.
Sumberova K; Buresova I; Palacova M; et al

Scientific Reports. 16(1), 2026 May 07.

Background
Breast cancer survivors are at increased risk of cardiovascular and
autonomic dysfunction following adjuvant chemotherapy, and exercise
interventions may help mitigate these effects. This randomized prospective
study evaluated the effects of a supervised, online-delivered exercise
intervention on cardiorespiratory fitness, cardiac autonomic modulation,
body composition, and quality of life in breast cancer survivors after
chemotherapy.
Methods
Seventy-two women were allocated to an exercise group or
usual care. The intervention consisted of a 12-week home-based exercise
program conducted online, with aerobic intensity individualized to 60-80%
of peak oxygen uptake. Cardiorespiratory fitness was assessed using
cardiopulmonary exercise testing and the 6-min walk test, while heart rate
variability was monitored longitudinally and analyzed using linear
mixed-effects models. Body composition and patient-reported outcomes were
assessed at baseline, post-chemotherapy, and post-intervention.
Results
The online supervised exercise resulted in a significant improvement in peak oxygen
uptake (+ 2.1 ml kg-1 min-1), which exceeded changes observed in the
control group (p = 0.009). Improvements in 6-min walk distance and
recovery of heart rate variability occurred irrespective of group
allocation. Changes in body composition, quality of life and the
improvement of heart rate variability metrics did not differ between
groups.

Lee J; Department of Thoracic & Cardiovascular Surgery, Pusan
National University Hospital, Korea
Cho HS; Cho JS; Kim YD; Ahn HY; Kim SH

Interdisciplinary Cardiovascular and Thoracic Surgery. 41(7), 2026 Jul 01.

OBJECTIVES: We examined whether cardiopulmonary exercise testing (CPET)
variables predict 30-day postoperative complications in patients
undergoing anatomical resection for non-small cell lung cancer (NSCLC).

METHODS: Consecutive patients who underwent segmentectomy or greater
between January 2023 and March 2025 at a single tertiary centre were
reviewed. All patients underwent CPET within 30 days preoperatively. Data
on demographics, comorbidities, pulmonary function, operative factors, and
outcomes were collected. Associations were assessed using univariable and
multivariable logistic regression; discrimination was evaluated with
receiver operating characteristic curve (ROC). Results with 2-sided alpha
= 0.05 were considered significant. Statistical analyses were conducted
with R 4.4.2 (stats).

RESULTS: Among 353 patients (mean age 68.4 +/- 8.4 years; 58.1% male
individuals), 33 (9.4%) experienced complications. Patients were older
(71.8 vs 68.0 years) and more often male individuals (81.8% vs 55.6%) than
controls; they had lower body mass index (BMI) (23.1 vs 24.4 kg/m2) and
lower forced expiratory volume in 1 second/forced vital capacity
(FEV1/FVC) (69.5% vs 72.7%). In the univariable analysis, age (odds ratio
[OR] 1.07), female sex (OR 0.28 vs male), BMI (OR 0.88 per kg/m2),
FEV1/FVC (OR 0.96 per %), ventilatory equivalent for carbon dioxide
(VE/VCO2) slope (OR 1.06 per unit), attained stage (OR 0.66 per stage),
and operation time (OR 1.58 per hour) were associated with complications.
In the multivariable analysis, BMI (OR 0.86, 95% confidence interval [CI]
0.75-1.00), FEV1/FVC (OR 0.94, 95% CI, 0.90-0.99), and VE/VCO2 slope (OR
1.06, 95% CI, 1.00-1.11) remained independent predictors. Receiver
operating characteristic curves showed poor discrimination: peak oxygen
consumption (VO2peak) area under the curve (AUC), 0.52; anaerobic
threshold (AT), 0.59; VE/VCO2 slope, 0.40; and AT time 0.43. Dichotomized
cut-offs were generally non-informative.

CONCLUSIONS: Individual CPET variables had limited discriminative
accuracy (AUC < 0.6). Cardiopulmonary exercise testing should complement
clinical and spirometric predictors rather than serve as a stand-alone
gatekeeper.

Magri D; Sant’Andrea Hospital, ‘Sapienza’ University of Rome, Italy
Ermolaev N; Castiglione V; Willixhofer R; et al

ESC heart failure. 13(4), 2026 Jul 04.

INTRODUCTION: Chronotropic incompetence (CI) is a frequent but
underappreciated feature of cardiac amyloidosis and may contribute to
exercise intolerance. However, its prognostic significance remains
incompletely defined. We investigated the prevalence, functional
correlates, and prognostic value of chronotropic incompetence in patients
with transthyretin amyloid cardiomyopathy.

METHODS: In this multicentre retrospective study, 212 stable outpatients
with transthyretin amyloid cardiomyopathy, in sinus rhythm and naive to
disease-specific therapy, underwent maximal cardiopulmonary exercise
testing. Chronotropic response was assessed as peak heart rate expressed
as a percentage of the age-predicted value (pHR%). Chronotropic
incompetence prevalence was evaluated using clinically relevant
thresholds. Prognostic performance for 1-year cardiovascular mortality was
assessed using Cox regression, receiver operating characteristic analysis,
and Kaplan-Meier estimates.

RESULTS: Chronotropic incompetence defined by a pHR% <=75% was present in
35% of patients and was associated with markedly impaired functional
capacity, including lower peak oxygen uptake and reduced ventilatory
efficiency. During 1-year follow-up, 10 cardiovascular deaths occurred.
Among exercise-derived variables, pHR% demonstrated strong prognostic
value, with each 1% increase associated with a 5.5% relative reduction in
cardiovascular mortality risk (hazard ratio 0.945; P = .011). A pHR%
threshold of 75% provided optimal discrimination (area under the curve
0.71) and identified a subgroup with significantly lower survival
(log-rank P < .05).

CONCLUSION: A blunted chronotropic response is common in transthyretin
amyloid cardiomyopathy and conveys adverse short-term prognosis. A pHR%
<=75% represents a clinically meaningful and easily obtainable threshold
for functional and prognostic stratification, offering a pragmatic
alternative when comprehensive cardiopulmonary exercise testing assessment
is not available.