Abbasi A;  Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, CA, USA.
Hansen N; Palade J; Paredes D; Meechoovet B; Van Keuren-Jensen
K; Pirrotte P; Stringer WW

Scientific Reports. 16(1):3469, 2026 Jan 26.
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Headings placed by Dr Paul Older not the authors

Background The Persistence of SARS-CoV-2 in tissues has been proposed as a driver of
prolonged symptoms in long COVID. Pulmonary rehabilitation with exercise
training is a well-established intervention for improving symptoms,
functional capacity, and inflammation in chronic cardiorespiratory
diseases. To investigate whether long COVID is associated with persistent
viral or immune-related signals, we analyzed the long RNA profile of
circulating extracellular vesicles (EVs) to determine the presence of
virus-related transcripts and assess changes in response to exercise
training.
Methods Fourteen adults with long COVID participated in this
single-center pilot clinical trial and completed a 10-week aerobic
exercise training program (twenty 1.5 h sessions). Serum-derived EV RNA
profiles were analyzed via sequencing at rest (T0) and peak
cardiopulmonary exercise testing (T1), before (V2) and after (V24)
exercise training.
Results Differentially expressed genes (DEGs) were identified
(q < 0.05), and pathway activation analysis was performed. Serum EVs
carried diverse RNA species, including protein-coding RNAs, long
non-coding RNAs, short non-coding RNAs, and pseudogenes, with no
virus-related RNAs detected. No significant DEGs were identified at rest
between pre- and post-training, nor in response to acute exercise at
pre-training. However, following training, 53 DEGs were found at peak
exercise (V24T1) compared to rest (V24T0), including three upregulated
genes (ANK3, FTO, FCN1) and 50 downregulated genes (TOP 5: MYL9, NRGN,
H2AC6, MAP3K7CL, B2M). These genes were primarily involved in inflammation
and metabolism. Pathway analysis revealed significant regulation of 100
pathways at post-training compared to pre training, predominantly
inactivated, including pathways involved in inflammation (STAT3 signaling)
and metabolism (O-linked glycosylation).
Conclusions Acute exercise and exercise
training modulated EV-associated gene expression in long COVID, primarily
through transcriptional downregulation. Suppression of inflammation- and
immune-related genes post-training highlights potential molecular
mechanisms underlying symptom improvement and identifies candidate
biomarkers of recovery biology in long COVID. Importantly, while exercise
training did not substantially alter EV RNA content at rest, it enhanced
the body’s ability to mount a dynamic EV-mediated molecular response
during exertion, reflecting improved physiological adaptability.

Jiang Y;  School of Medicine, Tongji University, Shanghai, 200065, China.
Shen T; Shi C; Li D; Zhan M; Li G; Qian L; Huang Q; Zheng L;
CheL; Wang L; Shen Y

BMC Cardiovascular Disorders. 26(1):91, 2025 Dec 27.
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BACKGROUND: Acute coronary syndrome (ACS) is a major global health burden
with a high risk of adverse outcomes. Existing predictive models (e.g.,
GRACE) primarily rely on static indicators and focus on short-term
prognosis, limiting their ability to comprehensively assess patient status
and predict long-term mortality. To address the need for improved
long-term risk prediction in this specific patient subgroup, this study
developed and validated a long-term mortality prediction model for ACS
patients incorporating cardiopulmonary exercise testing (CPET) and other
clinical indicators.

METHODS: This retrospective cohort study included ACS patients treated at
Tongji Hospital from January 1, 2007, to December 31, 2018. Demographic
data, medical histories, CPET indicators, laboratory indicators, and other
baseline data were collected, and all-cause mortality was followed up
until June 30, 2023. All data sets were randomly divided into derivation
and validation cohorts in a ratio of 7/3. Least absolute shrinkage and
selection operator regression and Cox multivariate analysis were used to
identify independent risk factors and a risk prediction model was
established using nomograms.

RESULTS: A total of 299 patients were included in this cohort (211 in the
derivation cohort and 88 in the validation cohort), with an average age of
57.00 years, including 280 males (93.6%). The median follow-up time was
3821 days, and 46 cases (15.4%) reached the study endpoint. The derivation
cohort identified four independent predictive factors: age, blood urea
nitrogen (BUN), ejection fraction (EF), and heart rate reserve (HRR), and
a Nomogram scoring model was constructed based on these factors. The model
demonstrated good discrimination in the derivation cohort (C-index: 0.83)
but this decreased in the validation cohort (C-index: 0.72), suggesting
potential overfitting. Time-dependent calibration analysis showed poor
agreement at 5 years in the validation cohort (R2 = 0.1819), but improved
at 10 years (Slope = 0.8006, R2 = 0.5575) and 15 years (R2 = 0.5638). The
model’s applicability is strictly limited to the studied population: a
predominantly male, lower-risk subset of ACS survivors capable of
completing CPET.

CONCLUSIONS: A model based on four readily available variables-age, BUN,
EF, and the key CPET parameter, HRR-may have utility for predicting
long-term all-cause mortality. This model provides a preliminary tool for
the long-term management of a specific subpopulation of acute coronary
syndrome (ACS) survivors, namely a predominantly male, lower-risk cohort
with the capacity to complete CPET. Further external validation in similar
populations is required before prospective clinical application.

Berger L;  Institute of Aerospace Medicine, Cologne, GERMANY
Mulder E; Zange J; Frings-Meuthen P; Frett T; Simon P; Hoenemann
JN; Poczatek MJ; Laurie SS; Huang AS; Macias BR; Jordan J; Tank J;
Rittweger J; Schmitz MT; Pesta D

Medicine & Science in Sports & Exercise. 57(12):2887-2901, 2025 Dec 01.
VI 1

PURPOSE: During spaceflight, countermeasures are crucial to counteract
cardiorespiratory and musculoskeletal deconditioning, similar to effects
seen after prolonged immobilization. Within a bed rest study simulating
the effects of microgravity, we investigated the effectiveness of
submaximal aerobic exercise and postexercise venoconstrictive thigh cuffs
(VTC) for maintaining cardiorespiratory fitness and muscle function.

METHODS: Twenty-four males and females were randomly allocated to a
countermeasure ( n = 12, age = 34 +/- 9 yr, body mass index = 22.9 +/- 2.9
kg.m -2 ) or control group ( n = 12, age = 35 +/- 8 yr, body mass index =
23.3 +/- 2.0 kg.m -2 ). Participants underwent 30 d of strict 6degree
head-down tilt (HDT) bed rest. Six days per week, the countermeasure group
completed 60 min of submaximal cycling in HDT position, followed by 6 h of
VTC (50 +/- 5 mm Hg). The control group maintained HDT bed rest without
any countermeasure. Cardiorespiratory fitness and muscle strength were
assessed before and after bed rest via cardiopulmonary exercise testing
and isokinetic dynamometry, respectively.

RESULTS: Peak oxygen uptake was maintained in the countermeasure group
(-106 +/- 148 mL.min -1 ) compared with the control group (-607 +/- 343
mL.min -1 ; P < 0.001). The countermeasure also mitigated the decrease in
plasma volume (countermeasure: -147 +/- 95 mL vs control: -286 +/- 153 mL;
P = 0.014), peak estimated stroke volume (countermeasure: -6 +/- 5 mL vs
control: -21 +/- 13 mL; P < 0.001), and cardiac output (countermeasure:
-0.7 +/- 0.9 L.min -1 vs control: -3.8 +/- 2.1 L.min -1 ; P < 0.001). Both
groups showed reductions in fat-free mass and muscle strength after bed
rest.

CONCLUSIONS: Submaximal exercise with subsequent VTC preserves
cardiorespiratory fitness during bed rest, likely by maintaining peak
stroke volume and cardiac output. However, this countermeasure did not
prevent declines of fat-free mass and muscle strength.

Sabino-Carvalho JL; Department of VA Health Care System, Decatur, GA.
Li S; Mekonnen E; Mammino K; Nocera JR; Park J

Medicine & Science in Sports & Exercise. 57(12):2621-2629, 2025 Dec 01.
VI 1

PURPOSE: Parasympathetic reactivation is essential for the rapid decrease
in heart rate following exercise and delayed heart rate recovery (HRR)
post-exercise is linked to poor clinical outcomes. Chronic kidney disease
(CKD) is associated with autonomic dysfunction including reduced
parasympathetic activity. Exercise training may improve parasympathetic
reactivation. Therefore, this study aimed to test whether CKD patients
experience delayed HRR due to impaired vagal reactivation and if 12 wk of
aerobic exercise can improve HRR.

METHODS: Twenty-seven CKD patients (stages III and IV, estimated
glomerular filtration rate 15-59 mL.min -1 .1.73 m -2 ) and 18 age-matched
controls underwent cardiopulmonary exercise testing. HRR was assessed
through heart rate decay (HRR60s) and heart rate variability (HRV) during
the first 60 s of recovery. Recovery kinetics were modeled to calculate
the time constant ( tau ). CKD patients were then randomly assigned to
aerobic exercise or non-aerobic stretching interventions for 12 wk (3 d.wk
-1 ), and cardiopulmonary exercise testing was repeated post-intervention.

RESULTS: CKD patients exhibited significantly blunted HRR60s
(DELTAHRR60s: -11 +/- 4 vs -17 +/- 6 bpm, P = 0.001) and a longer recovery
time constant ( tau : 142 +/- 33 vs 116 +/- 21 s, P = 0.004) compared with
controls. HRV indices increased less post-exercise in CKD patients
compared with controls (DELTARMSSD: 0.3 +/- 1 vs 1.6 +/- 1 ms, P = 0.001).
Twelve weeks of aerobic exercise did not improve HRR60s (DELTAHRR60s: pre
-12 +/- 4 bpm vs post -12 +/- 7 bpm, P = 0.971) or HRV indices (all P >
0.108).

CONCLUSIONS: CKD patients have decreased HRR post-exercise due to
impaired cardiac vagal reactivation. Twelve weeks of aerobic exercise
training did not improve cardiac vagal reactivation. Future studies should
explore different exercise modalities and manipulate training variables
such as intensity, volume, and frequency to assess their potential impact
on cardiac vagal reactivation in patients with CKD.

Belanger N; Department of Cardiology  Gutenberg-University Mainz,  Mainz, Germany.
Zeid S; Velmeden D; Schulz A; Koeck T; Rausch F; Foos B; Kazemi-Asrar F; Lackner KJ;
Gori T; Munzel T; Prochaska JH; Simon P; Wild PS

Cardiovascular Diabetology. 25(1):26, 2026 Jan 08.
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BACKGROUND: Cardiac autonomic dysfunction plays a pivotal role in the
heart failure syndrome. Metabolic dysregulation affects both autonomic
function and heart failure, but these relationships remain incompletely
understood. This study aimed at investigating the role of glucose and
insulin metabolism for parasympathetic reactivation.

METHODS: Data from the MyoVasc study (NCT04064450), a prospective heart
failure cohort study, were analyzed. Participants underwent a highly
standardized 5-hour examination, including venous blood sampling. To
assess the impact of glucose and insulin metabolism (HbA1c, HOMA-IR, and
C-peptide) on parasympathetic reactivation as reflected by heart rate
recovery 60 s (HRR60) after cardiopulmonary exercise testing,
multivariable linear regression models with adjustment for sex, age,
clinical profile (cardiovascular risk factors and comorbidities) and
medication were calculated in cross-sectional and longitudinal settings.
Additional adjustment for complementary glucose or insulin status was
performed to assess the dependency of each other. Analyses were carried
out in symptomatic heart failure and across the spectrum of glucose
metabolism dysfunction.

RESULTS: The analysis sample included 1,588 individuals (median age 64.0
years [IQR 55.0;72.0]; 33% women) in a fasting state. Symptomatic heart
failure was present in 43.7% of the subjects. Median HRR60 was 21.0 beats
per minute (IQR 14.0;28.0). In multivariable regression analysis with
adjustment for age, sex, clinical profile, and medication, both HbA1c
([Formula: see text]per SD -0.074, 95% CI [- 0.122;-0.026], P = 0.003) and
HOMA-IR ([Formula: see text]per SD -0.113 [- 0.165;-0.062], P < 0.0001)
predicted HRR60. Additional adjustment for both glucose and insulin
status, respectively, demonstrated that HOMA-IR ([Formula: see text]per SD
-0.097 [- 0.155;-0.040], P < 0.0001), but not HbA1c ([Formula: see
text]per SD -0.030 [- 0.084;0.025], P = 0.28), was independently related
to HRR60. This finding was confirmed in subgroups with heart failure and
type 2 diabetes. In all analyses, C-peptide was related to HRR60
independently of HbA1c with higher effect estimates than HOMA-IR
([Formula: see text]per SD -0.171 [- 0.225;-0.117], P < 0.0001). Finally,
higher HbA1c ([Formula: see text]per SD -0.094, [- 0.171;-0.017], P =
0.017) and C-peptide ([Formula: see text]per SD -0.076, [- 0.159;0.007], P
= 0.075) were more strongly associated with a lower HRR60 after two years
of follow-up.

CONCLUSIONS: This study demonstrates the relevance of insulin status for
vagal activity of cardiac autonomic function, particularly in heart
failure. The pathophysiological implications underlying the relationship
between insulin status and parasympathetic activity merit further
mechanistic exploration.

Timóteo AT, Department of Cardiology, Santa Marta Hospital,  Lisbon, Portugal
Rosa SA, Branco LM, Galrinho A, Rio PS, Thomas B, Ferreira RC

Int J Cardiovasc Imaging. 2026 Jan 27. doi: 10.1007/s10554-026-03635-7. Online ahead of print.

Right ventricular (RV) to pulmonary arterial (PA) uncoupling measures RV exhaustion. There is limited evidence regarding the association between RV to PA coupling and hypertrophic cardiomyopathy (HCM). Evaluate RV to PA uncoupling in patients with HCM. Prospective cohort study in 62 patients with HCM without obstructive epicardial coronary disease. Echocardiography was used to assess RV to PA coupling as the ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP). Coronary flow reserve in the left anterior descending artery (CVFR_LAD) was a surrogate marker for coronary microvascular dysfunction. Cardiopulmonary exercise testing (CPET) and cardiac magnetic resonance (CMR) were also performed. Mean age was 55 (15) years, 65% males. Mean TAPSE/PASP was 0.56 (0.23). The independent predictors of RV to PA coupling were age (β: - 0.184), left atrial volume index (β: - 0.641), CFVR_LAD (β: 0.183) and the extent of LGE in the LV (β: - 0.262). 43.5% showed reduced exercise tolerance. Independent predictors of peak VO2 were male gender (β: 0.349), age (β: - 0.286), global radial strain (β: 0.249) and TAPSE/PASP (β: 0.253). TAPSE/PASP showed a modest predictive accuracy for peak VO2 < 20 ml/Kg/min (AUC 0.671, p = 0.022), with the best cut-off set at 0.60 mm/mmHg (sensitivity 85% and specificity 47%). A TAPSE / PASP ≤ 0.60 mm/mmHg was present in 66% of patients. In patients with HCM, both coronary microvascular dysfunction and fibrosis are associated with RV to PA coupling, which is a determinant of exercise tolerance.

Ludwig V; Technical University of Munich, Munich, Germany
Freiberger A; Muller J; Hock J; Ewert P; Hager A

Journal of Cardiopulmonary Rehabilitation & Prevention. 46(1):16-27, 2026

PURPOSE: Expiratory flow limitation (EFL) and dynamic hyperinflation (DH)
may significantly impact exercise capacity in patients with heart disease.
Although commonly linked to lung diseases, recent evidence highlights
their role in cardiovascular disease (CVD), contributing to exercise
intolerance. This systematic review examines studies from the past decade
on pulmonary function during exercise, measured using inspiratory capacity
(IC) maneuvers, in patients with CVD, emphasizing prevalence and clinical
significance.

REVIEW METHODS: A systematic literature search in PubMed, Scopus, and
Cochrane (January 2014-February 2024) explored pulmonary function during
exercise in patients with CVD. Two independent reviewers assessed studies
using established Quality Assessment Tools.

SUMMARY: Seven studies including 231 patients with CVD (mean age 31-66
yr, predominantly male) used cardiopulmonary exercise testing to evaluate
exercise-induced DH or EFL with varying definitions. Study quality was
mixed. Patients with myocardial infarction showed EFL at moderate
exercise, while patients with stable coronary artery disease exhibited EFL
only at high intensities. Up to 50% of patients with pulmonary arterial
hypertension have DH during peak exercise (P < .05). In patients with
heart failure, 25% experienced DH, while others maintained stable
breathing. Patients who are post-Fontan displayed pulmonary inefficiencies
without DH. Methodological variability precludes definitive conclusions on
DH prevalence in patients with CVD. However, reduced IC during exercise,
DH, and EFL occur in a substantial proportion of patients, indicating a
lower EFL threshold and earlier ventilatory constraints. Further research
into heart-lung integration during exercise is crucial for developing
personalized treatments and improving clinical management in those
patients.

Milani M; Hasselt University, REVAL/BIOMED, Hasselt, Belgium (
Milani JGPO; Machado FVC; Cipriano GFB;et al

Journal of Cardiopulmonary Rehabilitation & Prevention. 46(1):35-43, 2026

PURPOSE: A low breathing reserve (peak ventilation [Epeak]/estimated
maximum ventilation [Emax] <= 15%) is recommended as the decision node to
indicate abnormal ventilatory limitation during incremental cycle
ergometry. Given higher Epeak during weight-bearing exercise, we aim to
establish which coefficients should multiply the forced expiratory volume
in 1 second (FEV1) to reduce the prevalence of a low breathing reserve in
healthy subjects undergoing treadmill exercise.

METHODS: We determined the coefficients for FEV1 multiplication
associated with <5% prevalence of a low breathing reserve in 3544 healthy
individuals aged 20 to 80 years. We then contrasted their performance in
differentiating healthy subjects (N = 148) from patients with chronic
obstructive pulmonary disease (COPD) (N = 133) in an external validation
sample.

RESULTS: A low breathing reserve was found in 22% and 6% of women versus
48% and 17% of men when FEV1 was multiplied by 35 and 40, respectively.
Sex-adjusted coefficients required to decrease the prevalence of a low
breathing reserve ranged from 33 and 48 in women versus 36.5 and 50 in men
in those showing peak oxygen uptake <80% and >120% predicted,
respectively. Breathing reserve using the new sex- and fitness-adjusted
coefficients were superior to previous values in differentiating health
from disease, regardless of COPD severity.

CONCLUSION: Higher coefficients for FEV1 multiplication are required to
estimate Emax at peak treadmill exercise in men than in women, increasing
as a function of cardiorespiratory fitness in both sexes. These data are
poised to improve the yield of cardiopulmonary exercise tests in
accurately indicating pathological ventilatory limitation in patients with
respiratory diseases.

Tseng WH; Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
Chiu CH; Chang SY; Yang LY; Huang SC

Annals of Surgical Oncology. 33(2):889-904, 2026 Feb.

BACKGROUND: Cardiopulmonary exercise testing (CPET) parameters, such as
ventilatory equivalent for carbon dioxide (VE/VCO2), peak oxygen
consumption (VO2peak), and anaerobic threshold (AT), have been proposed as
potential predictors of postoperative complications. Yet, few systematic
analyses have examined the association between CPET variables and major
complications after esophagectomy, as defined by the Clavien-Dindo
classification. Associations with cardiopulmonary complications and
mortality also require updating on the basis of trial sequential analysis
(TSA).

MATERIALS AND METHODS: Systematic searches were conducted to identify
relevant studies reporting preoperative CPET values and major
complications, cardiopulmonary complications, and 1-year mortality.
Standardized mean differences (SMD, random-effects model) were calculated
and TSA was conducted to evaluate the robustness of evidence in the
previous and current meta-analyses.

RESULTS: A total of 12 studies met inclusion criteria. VO2peak was
correlated with major complications (SMD = – 0.42; 95% CI – 0.70 to –
0.14, p = 0.0032) and cardiopulmonary complications (SMD = – 0.39; 95% CI
– 0.65 to – 0.13, p = 0.0032). AT showed similar but weaker associations
with both outcomes (SMD = – 0.33 and – 0.22; 95% CI – 0.63 to – 0.03 and
CI – 0.40 to – 0.04, p = 0.033 and 0.018, respectively). VE/VCO2
demonstrated no meaningful relationship with major complications. In
addition, the present study found neither VO2peak nor AT was associated
with 1-year mortality after esophagectomy.

CONCLUSIONS: VO2peak and AT were inversely associated with morbidity
after esophagectomy, while VE/VCO2 offered limited prognostic value and
none predict 1-year survival. VO2peak is a key predictor of major and
cardiopulmonary complications after esophagectomy and warrants further
investigation, either alone or as part of a composite model.

Blumer V; Baim Institute for Clinical Research, Boston, Massachusetts, USA.
Januzzi JL Jr; Liu Y; Butler J; Ezekowitz JA; et al

JACC Heart Failure. 14(1):102433, 2026 Jan.

OBJECTIVES: This analysis focuses on sex differences in baseline
characteristics of study participants with DbCM at high risk for
progression to overt HF and sex-based treatment responses to high-dose
AT-001, a novel aldose reductase inhibitor.

METHODS: The ARISE-HF trial was a Phase 3, randomized, international,
placebo-controlled study designed to evaluate the efficacy and safety of
AT-001 in study participants with DbCM.

RESULTS: Of 691 participants, 348 (50.4%) were women. At baseline, women
had higher N-terminal pro-B-type natriuretic peptide concentrations (92 vs
60 ng/L; P < 0.001), lower peak oxygen uptake (13.87 vs 17.59 mL/kg/min; P
< 0.001), shorter cardiopulmonary exercise testing durations (8.47 vs
11.05 minutes; P < 0.001), and worse quality of life and health status
(Kansas City Cardiomyopathy Questionnaire overall summary score 87.79 vs
92.55; P < 0.001; Physical Activity Scale for the Elderly score 137.87 vs
171.09; P < 0.001) compared with men. Despite these differences, there
were no significant sex differences in the efficacy or tolerability of
high-dose AT-001 compared with placebo. The placebo-corrected oxygen
uptake change was 0.26 for women and 0.27 for men (P = 0.58), and changes
from baseline to month 15 in Kansas City Cardiomyopathy Questionnaire and
Physical Activity Scale for the Elderly scores showed no significant sex
differences (all P > 0.05).

CONCLUSIONS: Despite baseline differences between women and men with
DbCM, the efficacy and safety of high-dose AT-001 are comparable across
sexes. These findings highlight the presence of sex-specific
characteristics in DbCM and underscore the importance of further research
to understand potential sex-specific mechanisms. (Aldose Reductase
Inhibition for Stabilization of Exercise Capacity in Heart Failure Trial
[ARISE-HF]; NCT04083339).