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.

James MD; Respiratory Investigation Unit, Queen’s University, Kingston, Canada
McCleary J; Back GD; Alosta KA; et al

Copd: Journal of Chronic Obstructive Pulmonary Disease. 23(1):2650696,
2026 Mar 24.

A sizable fraction of dyspneic patients with only mild to moderate COPD
exhibit a heightened ventilatory response to exercise relative to
metabolic demands, i.e. a high ventilation (V.E)/CO2 output (V.CO2). The
lack of continuous assessment of gas exchange efficiency and estimates of
arterial CO2 partial pressure has hindered our understanding of the
physiological underpinnings of this dynamic phenomenon. We compared key
indices of gas exchange efficiency relative to the intra-breath CO2
profile as a function of expired volume using breath-by-breath volumetric
capnography in 30 patients (FEV1 = 76 +/- 17%) and 30 sex- and age-matched
controls during incremental cycle ergometry. Wasted ventilation in the
physiological dead space (VDphys) was calculated as the sum of airway and
alveolar (alv) dead space divided by tidal volume (VT). Transcutaneous
(tc) readings provided estimates of arterialised PCO2. Patients exhibited
lower exercise tolerance, reporting higher dyspnoea throughout exercise (p
< 0.05). Higher V.E/V.CO2 was associated with higher absolute (L) alveolar
dead space (VDalv), but similar VT; thus, both VDphys/VT and VDalv/VT were
consistently higher in patients (p < 0.05). V.E/V.CO2 was elevated (>=34)
in normocapnic patients (PtcCO2>=35 mmHg) who had a high VDphys/VT
(>=0.3); conversely, high V.E/V.CO2 coexisted with a lower VDphys/VT only
in hypocapnic subjects (p < 0.05). Higher VDalv and lower PtcCO2 were
independently associated with a high V.E/V.CO2 nadir and iso-work rate
dyspnoea (p < 0.001). Based on this innovative, high-density
data-acquisition approach, we conclude that both wasted ventilation and
alveolar hyperventilation, in a highly variable combination, contribute to
excessive ventilation in dyspneic patients with mild-to-moderate COPD

Mapelli M; Centro Cardiologico Monzino, IRCCS, Milan, Ital
Baracchini N; Campana N; Capovilla TM; et al

Scientific Reports. 16(1), 2026 Feb 17.

In hypertrophic cardiomyopathy (HCM), cardiopulmonary exercise testing
(CPET) is considered the gold standard for assessing exercise tolerance,
with O2-pulse commonly used as a surrogate for stroke volume (SV).
However, because SV reduction can be masked by increased oxygen
extraction, direct non-invasive measurement of SV is valuable. This study
involved 102 HCM patients (mean age 53 +/- 16 years, 78% male),
predominantly with a non-obstructive phenotype (74%), who underwent CPET
with SV measurement using Physioflow (PF). Abnormal O2-pulse kinetics were
observed in 12 patients, all confirmed by abnormal SV trends with PF.
Additionally, PF identified another 28 patients with altered SV kinetics.
Abnormal SV trends were associated with higher peak VE/VO2 ratios (42.6
[37.4-47.5] vs. 38.0 [33.6-41.3]) and lower end-tidal CO2 values (31.8 +/-
4.9 vs. 34.3 +/- 5.6 mmHg, p < 0.05). Patients with greater SV growth
during the final 25% of exercise showed improved anaerobic threshold VO2
(49.8 +/- 12.3% vs. 43.9 +/- 15.2% predicted peak VO2), VO2/work slope
(10.2 +/- 2.0 vs. 9.3 +/- 1.3 mL/min/Watt), and peak PetCO2 (34.5 +/- 5.6
vs. 32.3 +/- 5.2 mmHg), alongside a lower VE/VCO2 slope (28.7 [24.9-31.0]
vs. 31.3 [27.3-34.2], p < 0.05). Integrating PF and CPET may enhance the
detection of abnormal SV kinetics, which are associated with reduced
functional capacity in HCM patients.

McDowell R; University of Bath, Bath, UK.
Ogbonnaya C; Shannon H; Douglas H

BMC Pulmonary Medicine. 26(1), 2026 Feb 19.

BACKGROUND: Cystic Fibrosis is an inherited, life-limiting condition
causing a range of symptoms including lowered exercise tolerance.
Approximately 95% of people with cystic fibrosis in the United Kingdom are
now eligible for new genetic modulator therapies. As a result, cystic
fibrosis centres are treating older populations in greater numbers.
Cardiopulmonary exercise testing measures aerobic capacity, however it is
resource intensive. Identifying whether routinely collected clinical
measures are associated with reduced aerobic capacity is needed to aid
prioritisation of cardiopulmonary exercise testing.
METHODS: Maximal
cardiopulmonary exercise testing data were collected from July 2022 to
January 2024, alongside routine clinical data (spirometry, body mass
index, diabetic status, Pseudomonas aeruginosa colonisation status,
modulator status, age and sex). Peak oxygen uptake was analysed as a
percentage predicted value (VO2peakpp).
RESULTS: Overall aerobic capacity
at the centre was low (mean peak oxygen uptake 79.16% predicted). No
relationship was identified between body mass index and aerobic capacity
(beta = 0.23, 95%CI -0.91, 1.37, p = 0.69). When adjusting for other
clinical measures, having cystic fibrosis related diabetes (beta=-17.56,
95%CI -27.17, -7.95, p < 0.001) and younger age (beta = 16.62, 95%CI 4.13,
29.12, p = 0.01) were associated with a reduction in VO2peakpp.
CONCLUSION
: Annual CPET for all pwCF may not be necessary or available. This service
evaluation found associations with younger age and CFRD and reduced
VO2peak who could be targeted

Fujisawa T; Department of Cardiology Ehime University Graduate
School of Medicine, Ehime, Japan
Kawakami H; Kurokawa K; Horie R; Tamaki S; et al

Heart Rhythm. 23(7):e1000-e1011, 2026 Jul.

BACKGROUND: The clinical importance of catheter ablation (CA) in
asymptomatic persistent atrial fibrillation (PeAF) remains uncertain,
given that current indications mainly focus on symptom relief.
Asymptomatic patients may have unrecognized impairments in exercise
capacity or quality of life (QoL), but prospective data are limited.

OBJECTIVE: This study aimed to prospectively evaluate changes in exercise
capacity and QoL after CA in patients with asymptomatic PeAF.

METHODS: This single-center prospective observational study enrolled
consecutive patients with clinically asymptomatic PeAF who underwent CA
between August 2021 and July 2024. Asymptomatic status was defined as
modified European Heart Rhythm Association class I without subjective
symptoms. Cardiopulmonary exercise testing-including anaerobic threshold,
peak oxygen (O2) uptake, metabolic equivalents, and O2 pulse-and QoL
assessments (Atrial Fibrillation Quality of Life Questionnaire and EuroQol
5-Dimension 5-Level) were performed at baseline and 3 and 12 months after
ablation. A symptomatic PeAF cohort assessed under the same protocol was
included for a secondary descriptive comparison.

RESULTS: Among the 68 patients with asymptomatic PeAF, 52 completed the
12-month evaluation. All cardiopulmonary exercise testing parameters
improved significantly after ablation (anaerobic threshold 12.8 -> 14.0
mL/kg/min; peak O2 uptake 18.0 -> 19.4 mL/kg/min; metabolic equivalents
5.3 -> 5.8; O2 pulse 9.4 -> 12.4 mL/beat; all P < .05). The Atrial
Fibrillation Quality of Life Questionnaire scores improved early and
remained stable, whereas the EuroQol 5-Dimension 5-Level score
significantly improved only at 12 months. Secondary comparison with
symptomatic patients showed higher exercise capacity in asymptomatic
patients at baseline and 12 months, whereas the QoL scores became
comparable after ablation.

CONCLUSION: CA in asymptomatic PeAF was associated with sustained
improvements in exercise capacity and QoL, suggesting that rhythm-control
therapy may provide functional benefit even without overt symptoms.

Kler A; Countess of Chester Hospital NHS Foundation Trust, UK
Tay J; Slawinski C; Welch C; Moug S; et al

Annals of the Royal College of Surgeons of England. 108(6):430-437, 2026 Jul.

INTRODUCTION: Surgical resection is the main treatment for non-metastatic
colorectal cancer (CRC). However, 6% of patients do not undergo surgery
owing to frailty, according to the National Bowel Cancer Audit (NBOCA).
The impact of preoperative evaluation and decision making on outcomes in
frail patients is underexplored. This study examines variation in decision
making for frail, older patients and the availability/use of resources by
colorectal multidisciplinary teams (MDTs) across United Kingdom (UK)
hospitals.

METHODS: A UK-wide questionnaire was distributed to colorectal MDTs via
the NBOCA newsletter and social media (18 May to 30 June 2021). Part A
assessed MDT structure and resource use; Part B explored MDT decisions for
two simulated 75-year-old patients with colonic and rectal cancer.

RESULTS: Twenty MDTs responded. Decisions were MDT-driven in 55% (n = 11)
and surgeon-driven in 45% (n = 9). Clinical examination (85%) and
performance status (90%) were most used. Resource utilisation during MDT
meetings varied across sites; for example, echocardiogram results were
available and considered in MDT decision making in only 15% of centres.
Cardiopulmonary exercise testing was used in 75%, anaesthetic assessment
in 80%, frailty scoring in 25%, and preoperative geriatric assessment in
5%. Management of right-sided cancer was more consistent; rectal cancer
decisions were more variable.

CONCLUSIONS: Variation exists across MDTs in the availability and use of
resources when managing frail CRC patients. There is less consensus for
rectal than caecal cancer. These findings highlight the need for
standardised MDT