Hortegal R; Department of Cardiovascular Diseases, Mayo Clinic,
Rochester, MN, USA;
Reddy YNV; Jain CC; Borlaug BA; et al

Journal of Cardiac Failure. 32(8):1323-1332, 2026 Aug.

OBJECTIVES: Pulmonary artery wedge pressure (PAWP) and left ventricular
end-diastolic pressure (LVEDP) are central metrics for assessing filling
pressures. A moderate correlation between their resting values has been
reported, but their agreement during exercise and associated clinical
impact remain unclear. Moreover, their prognostic value is poorly
understood. The study’s objectives were to: (1) evaluate the correlation
between PAWP and LVEDP at rest and during peak exercise; and (2) assess
their ability to predict outcomes.

METHODS AND RESULTS: We studied a retrospective cohort of 161 patients
undergoing simultaneous resting and exercise PAWP and LVEDP measurements.
Associations among filling pressures, physiological variables, and
outcomes were evaluated. The primary endpoint was a composite of death,
hospitalization due to heart failure, or need for advanced heart failure
therapy. The cohort’s ages were 68 [53-76] years, and the body mass
indexes were 31.7 +/- 7.2 kg/m2; 49.1% were female. Resting PAWPs were 16
[11-20] mmHg, and LVEDPs were 19 [15-24] mmHg, increasing to 27 [21-32]
mmHg and 28 [23-34] mmHg during exercise, respectively. PAWPs and LVEDPs
showed moderate correlation (r=0.64 rest; r=0.67 exercise) and poor
agreement in detecting elevated filling pressures (Kappa rest 0.32;
exercise 0.39). PAWPs correlated better with other hemodynamic parameters
than LVEDPs, being associated with the composite outcome when >= 20 mmHg
at rest (hazard ratio 2.72, 95% confidence interval 1.42-5.19; P=0.002);
this persisted after adjusting for confounders. LVEDPs were not predictive
of the outcome.

CONCLUSIONS: PAWP was superior to LVEDP in identifying hemodynamic
abnormalities and the clinical endpoint, supporting emphasis on PAWP as
the primary metric of left heart filling pressures.

Wan Q; Institute of Respiratory Health, Guangzhou, China
Deng Z; Wu F; Zhou K; Tang G; et al

Respiratory Medicine. 261:109021, 2026 Sep.

INTRODUCTION: Exercise intolerance serves as a prognostic marker for poor
respiratory outcomes in mild-to-moderate COPD. However, the longitudinal
change in exercise tolerance and its association with disease progression
remains unknown. We aimed to explore the association of longitudinal
change in exercise tolerance with disease progression in mild-to-moderate
COPD.

METHODS: This community-based, prospective cohort study was conducted in
China from 2019 to 2024. The participants completed baseline
questionnaires, spirometry, chest computed tomography, and cardiopulmonary
exercise testing (CPET), and underwent annual acute exacerbation
assessment and spirometry over 3 years. Participants were categorized by
the longitudinal change in peak oxygen uptake from baseline to 3 years
into groups with non-declined or declined exercise tolerance.

RESULTS: Overall, 213 participants with mild-to-moderate COPD who
completed baseline and 3-year CPET were analyzed, including 131 (61.5%)
with exercise tolerance decline. For every 5% longitudinal decrease in
exercise tolerance, there was greater progression of air trapping
(adjusted difference=0.18%/year, 95% CI 0.01-0.34, P=0.033) and a faster
decline in postbronchodilator FEV1 (adjusted difference=-4.2ml/year, 95%
CI -8.3 to -0.1, P=0.044). Compared with the non-declined exercise
tolerance group, the group with exercise tolerance decline demonstrated
greater progression of emphysema (adjusted difference=0.40%/year, 95% CI
0.10-0.69, P=0.008) and air trapping (adjusted difference=1.26%/year, 95%
CI 0.41-1.84, P=0.002).

CONCLUSIONS: The longitudinal decrease in exercise tolerance over 3 years
was associated with accelerated lung function decline and air trapping
progression, suggesting it may be a marker associated with disease
progression in mild-to-moderate COPD.

Kumar G B; All India Institute of Medical Sciences, Bhubaneswar, India.
S M; Ibrahimpur NS; M R; Meher BR

European Journal of Clinical Pharmacology. 82(9), 2026 Aug 12.

BACKGROUND: Management of symptomatic non-obstructive hypertrophic
cardiomyopathy (HCM) remains challenging, and evidence comparing
pharmacological therapies is limited. While several randomized controlled
trials (RCTs) have evaluated individual agents, direct comparisons across
multiple therapies are lacking. This study aimed to compare the efficacy
of available pharmacological treatments for non-obstructive HCM using
network meta-analysis.

METHODS: This frequentist network meta-analysis was conducted following
PRISMA-NMA guidelines. Randomized controlled trials evaluating
pharmacological therapies in adult patients with non-obstructive HCM were
identified through systematic searches of major databases. Continuous
outcomes were analyzed using mean differences (MD) with 95% confidence
intervals (CI), while NT-proBNP was analyzed using the ratio of means
(RoM). The primary outcome was change in peak oxygen consumption (peak
VO2). Secondary outcomes included VE/VCO2 slope, NT-proBNP levels, E/e’
ratio, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, and left
ventricular ejection fraction (LVEF).

RESULTS: Nine RCTs involving 1,057 patients were included. No
pharmacological therapy demonstrated a significant improvement in peak
VO2, the primary outcome. Mavacamten significantly reduced NT-proBNP
compared with placebo (RoM 0.42, 95% CI 0.32-0.56, I2 = 0%), whereas ARNI
and ninerafaxstat significantly improved VE/VCO2 slope, and candesartan
improved E/e’ ratio. No significant differences were observed for KCCQ
score or LVEF.

CONCLUSIONS: Different pharmacological therapies may provide benefits in
specific physiological domains in patients with non-obstructive HCM;
however, no single therapy demonstrated consistent improvements across all
evaluated outcomes. These findings highlight the heterogeneity of
treatment effects and suggest that targeting multiple pathophysiological
pathways may be important. Larger randomized and head-to-head comparative
studies are needed to define optimal management in this population.

Luput-Andrica IM; University of Medicine and Pharmacy
Timisoara, Romania.
Marinescu AR; Cut TG; Herlo A; et al

International Journal of Molecular Sciences. 27(15), 2026 Jul 28.
Headings by Dr Older

Background Despite the success of modern antiretroviral therapy in achieving
virological suppression, people living with HIV face an elevated risk of
cardiovascular diseases, particularly heart failure with preserved
ejection fraction.
Aims This study evaluates the cardiometabolic phenotype and
functional capacity in a Romanian HIV cohort to delineate the metabolic
footprint of chronic infection.
Methods In this cross-sectional study based on
prospectively collected, protocol-driven phenotyping, we evaluated 50
consecutive outpatients from a university-affiliated infectious diseases
clinic in Timisoara. Eligibility strictly required clinical stability and
sustained virological suppression (plasma HIV-RNA < 50 copies/mL for >=12
months).
Results The analysis revealed widespread metabolic dysregulation, with
52% exhibiting excess weight and 64% showing atherogenic dyslipidemia.
Integrase strand transfer inhibitor-based regimens were significantly
correlated with an increased body mass index (p = 0.034) and elevated LDL
cholesterol (aOR = 2.4, 95% CI [1.18-4.95], p = 0.022). Furthermore, we
observed a pronounced metabolic age gap (+4.5 +/- 2.8 years), defined as
the deviation of bioimpedance-estimated metabolic age from the patients’
chronological age. This gap (p = 0.028), alongside historical
immunodeficiency indicated by a low nadir CD4+ count (aOR = 0.998, 95% CI
[0.991-0.999], p = 0.021), strongly predicted exercise intolerance,
independent of current immune reconstruction. Sarcopenic obesity (present
in 18% of the cohort) and an elevated triglycerides-to-HDL ratio (aOR =
2.14, 95% CI [1.15-3.98], p = 0.016) emerged as robust independent
negative predictors of functional capacity. Additionally, subclinical
myocardial remodeling, evidenced by impaired Global Longitudinal Strain,
significantly predicted reduced aerobic capacity (aOR = 0.72, 95% CI
[0.58-0.89], p = 0.003).
Conclusions Consequently, contemporary HIV management must
transition beyond virological control to integrated cardiometabolic
screening. Utilizing cardiopulmonary exercise testing, echocardiography,
and metabolic biomarkers is critical for the early identification of
subclinical “functional HIV-associated frailty” and mitigating the
trajectory toward overt cardiovascular diseases.

Hogwood AC; Division of Cardiology, Charlottesville, Virginia
Smarz K; Golino M; Tysarowski M; et al

Current Problems in Cardiology. 51(10):103382, 2026 Oct.

BACKGROUND: Modern treatment of ST-elevation myocardial infarction
(STEMI), emphasizing prompt reperfusion, has improved clinical outcomes by
preserving cardiac function. Despite this, cardiorespiratory fitness
remains impaired. The purpose of this study was to assess determinants of
cardiorespiratory fitness in patients with reperfused STEMI and preserved
cardiac function.

METHODS: We prospectively collected data from two patient cohorts with
reperfused STEMI who underwent cardiopulmonary exercise testing on either
a semi-supine cycle ergometer (Cohort 1) or treadmill (Cohort 2). Peak
oxygen consumption (VO2) was measured as mL.kg-1.min-1 and as
percent-predicted. Cardiac reserve was measured with Doppler
echocardiography using heart rate (HR), stroke volume (SV), and cardiac
output (CO) before and at peak exercise. Arterial-venous oxygen difference
(a-v O2diff) was calculated using the Fick equation.

RESULTS: We included ninety-five patients (58 [51-65] years, 34% female)
tested 41 [37-45] days after STEMI (Cohort 1: n = 39; Cohort 2: n = 56).
Resting LVEF was 55 [50-59] %, with 2 (2%) having <40%. E’ velocity was
8.8 [7.3-10.5] and E/e’ was 7.6 [6.5-9.2]. Peak VO2 was 20.0 [16.3-22.9]
mL.kg-1.min-1, and 74 (78%) and 24 (25%) patients had reduced peak VO2 at
<80% and <60% of predicted, respectively. A significant positive
correlation was observed between peak VO2 and peak CO (R = 0.42, p =
0.0001), SV (R = 0.24, p = 0.02), HR (R = 0.36, p = 0.006), and a-v O2diff
(R = 0.49, p < 0.0001). Peak HR and SV were each independent predictors of
peak VO2 using multivariate analyses (all p < 0.01).

CONCLUSION: Cardiorespiratory fitness remains impaired after successfully
reperfused recent STEMI, despite rather preserved resting cardiac
function. Cardiac and peripheral reserve partially explain the
impairments, and preserving these may improve fitness after STEMI.

Braggio M; Department of Diagnostics and Public Health, Verona, Italy.
Ceolan J; Minoia A; Villaboni S; Mazzi F; et al

BACKGROUND: Transfusion-dependent beta-thalassemia (TDT) is characterized
by reduced exercise capacity due to chronic hemolytic anemia, iron
overload cardiomyopathy, and potential skeletal muscle alterations. Early
cardiovascular and muscular dysfunction in the absence of cardiac iron
overload remains poorly characterized.

METHODS: In this exploratory study, 9 TDT patients without cardiac iron
overload and with normal body mass index (BMI) were matched with 9 healthy
controls. Cardiopulmonary exercise testing combined with lung ultrasound
(LUS-CPET) was used to assess exercise-induced lung congestion and
diastolic dysfunction. Serum biomarkers of endothelial activation (ICAM-1)
and muscle-metabolic function (FGF21, miR-577) were evaluated. Resting
echocardiography, handgrip strength, and body composition by bioelectrical
impedance analysis (BIA) were also assessed.

RESULTS: At rest, cardiac output and diastolic function were comparable
between groups. However, during LUS-CPET, TDT patients exhibited
significantly lower VO2max, O2 pulse, and chronotropic index, along with
increased B-lines, consistent with exercise-induced diastolic dysfunction.
TDT patients also showed reduced lean body mass and handgrip strength.
FGF21 levels were elevated at rest and post-exercise, whereas miR-577
levels were reduced. Post-exercise ICAM-1 levels were significantly higher
in TDT patients compared to controls.

CONCLUSIONS: LUS-CPET may represent a useful non-invasive approach to
identify early exercise-induced diastolic dysfunction in TDT patients
without cardiac iron overload. Altered FGF21 and miR-577 profiles suggest
the presence of metabolic dysregulation associated with early skeletal
muscle deconditioning.

Liu R; Beijing Friendship Hospital, China and other centres in USA and Brazil
Arena R; Santos-de-Araujo AD; Borghi-Silva A; Popovic D

Current Problems in Cardiology. 51(10):103399, 2026 Oct.

BACKGROUND: Atherosclerotic cardiovascular disease remains a leading cause
of morbidity and mortality worldwide. Established risk equations guide
prevention but rely mainly on static, clinic-based variables and
incompletely capture physical activity, sedentary behavior, and
cardiorespiratory fitness.

METHODS: This narrative review synthesizes evidence from epidemiological
studies, clinical trials, and methodological frameworks on the roles of
physical activity, sedentary behavior, and cardiorespiratory fitness in
cardiovascular risk prediction, with emphasis on digital phenotyping,
mechanistic exercise physiology, and multimodal clinical prediction
models.

RESULTS: Cardiorespiratory fitness reflects integrated physiological
reserve and is strongly associated with cardiovascular and all-cause
outcomes. Cardiopulmonary exercise testing extends fitness assessment by
identifying mechanisms of exercise limitation, including cardiac,
ventilatory, autonomic, pulmonary vascular, and peripheral contributors.
Wearable technologies provide longitudinal, real-world measures of
physical activity and sedentary behavior that complement static clinical
risk factors. Multimodal models integrating electronic health records,
electrocardiography, imaging, wearable signals, and exercise testing may
support more personalized and actionable risk stratification. However, the
current evidence base remains limited by insufficient external and
prospective validation, incomplete calibration reporting, limited
decision-analytic evaluation, and inadequate assessment of subgroup
performance and equity.

CONCLUSIONS: Physical activity and cardiorespiratory fitness should be
considered clinically relevant and modifiable phenotypes in contemporary
cardiovascular risk prediction. Future models should prioritize
standardized measurement, mechanistic validation of digital phenotypes,
calibration, external validation, subgroup evaluation, workflow
feasibility, and prospective evidence of clinical utility before
widespread implementation.

Wypyrsczyk L; Johannes Gutenberg-University Mainz,  Germany
Kuhn M; Dreismickenbecker E; Neu MA; et al

Pediatric Hematology & Oncology. 43(5):227-240, 2026 Aug.
Headings by Dr Older

Background The 6-min cycling test (6MCT), a submaximal endurance test, has not yet
been applied in pediatric oncology. This study evaluates its feasibility
and validity in 71 childhood cancer patients (9.6 +/- 4.0 years).
Methods For validation, 46 patients additionally underwent cardiopulmonary exercise
testing (CPET). Performance in the 6MCT (total revolutions) was correlated
with peak oxygen uptake (VO2peak) and peak work rate (WRpeak) using
Spearman’s correlation. Linear regressions assessed the predictive value
of VO2peak and WRpeak on 6MCT performance. Sixty-six participants (93%)
successfully completed the 6MCT, averaging 550 +/- 129 revolutions.
Results Revolutions correlated moderately with VO2peak (rho = 0.46, p = 0.001) and
strongly with WRpeak (rho = 0.64, p < 0.001). VO2peak significantly
predicted 6MCT performance (p = 0.001, R2 = 0.214), whereas WRpeak
explained more variance (p < 0.001, R2 = 0.488).
Conclusions The results demonstrate that the 6MCT is a feasible, valid endurance assessment in this
population, offering a promising alternative when gold standard testing is
not available.

Floriani AF; S. Valentino Hospital, Montebelluna, Italy.
Menzella F

Expert Review of Respiratory Medicine. 20(8):963-974, 2026 Aug.

INTRODUCTION: Persistent exertional dyspnea remains a major unmet need in
patients with difficult-to-treat and severe asthma, even in the era of
optimized inhaled therapy and biologics. Resting lung function and
inflammatory biomarkers often fail to explain exercise intolerance,
leading to empirical step-up therapy without clear physiological
justification.

AREAS COVERED: This review discusses the role of cardiopulmonary exercise
testing (CPET) in the evaluation of exertional dyspnea in
difficult-to-treat and severe asthma, within the treatable traits
framework. The review focuses on the main CPET-derived physiological
patterns, including ventilatory limitation, dynamic hyperinflation,
ventilatory inefficiency, dysfunctional breathing, deconditioning,
cardiovascular limitation, exercise-induced laryngeal obstruction, and
normal exercise physiology. It also examines how CPET may influence
step-up decisions, support trait-directed interventions, and inform
pharmacoeconomic considerations. A pragmatic clinical framework for
selective integration of CPET into severe asthma assessment is proposed.

EXPERT OPINION: CPET may represent a valuable physiological adjunct in
selected patients with difficult-to-treat or severe asthma and persistent
exertional dyspnea insufficiently explained by resting assessments. Its
integration into the assessment pathway may help contextualize symptoms,
distinguish asthma-driven exercise limitation from non-inflammatory or
non-asthmatic causes of dyspnea, and support more mechanism-based
management. However, current evidence supports CPET primarily as a tool
for physiological phenotyping and trait reclassification rather than as a
prospectively validated guide to treatment escalation, biologic
stewardship, or long-term outcome improvement.

Rojas Vega S; German Sport University Cologne, Germany,
Solera-Herrera A; Vafa R; Acero-Moreno D; et al

Journal of Diabetes Research. 2026(1):e1311227, 2026.

BACKGROUND: Diabetes is associated with an increased risk of cognitive
dysfunction. We are aimed at examining cognitive performance in people
with Type 2 diabetes mellitus (T2DM) and their correlation with physical
activity (PA)/fitness level and mood.

METHODS: A cross-sectional study involving 47 individuals with T2DM, 30
diabetes-free individuals (controls): ages of 40-65 years and without
dementia. Subjects were evaluated using a neuropsychological test battery
that included Stroop, VLMT, CORSI, TMT and neuropsychiatric scales. The
Global Physical Activity Questionnaire (GPAQ) was assessed. Physical
fitness was evaluated using a maximal cardiopulmonary exercise testing
(CPX).

RESULTS: Compared with controls, people with T2DM had lower
cardiorespiratory fitness (CRF) and more frequent cognitive performance
below 1 SD of the normative value. Those individuals with T2DM, who
displayed low fitness, showed significantly poorer cognitive inhibition
(Stroop, p < 0.001), processing speed (TMT-A, p < 0.001), cognitive
flexibility (TMT-B, p < 0.001), visuospatial memory (CORSI, p < 0.001) and
memory consolidation (VLMT, p < 0.001). Higher ventilatory and metabolic
CRF markers and higher PA levels correlated significantly with higher
cognitive performance. None of the neuropsychological or psychiatric
background variables correlated significantly with any of the cognitive
scales.

CONCLUSIONS: Individual CRF markers and PA levels correlated positively
with cognitive performance in people with T2DM and in nondiabetic
individuals. However, individuals with T2DM showed at least two to three
times more frequent cognitive performances more than 1 SD below norm as
compared with controls. Among people with T2DM, those with low aerobic
fitness/PA levels showed significantly lower cognitive performance,
especially in the attention-concentration, executive functioning, episodic
memory and visuospatial processing domains.