Gao Y; Centre for Heart Research, University of Toronto, Canada
Moayedi Y; Foroutan F; Verma B; Kim B; Luca E; Brum M;
Brahmbhatt DH; Duhamel J; Simard A; McIntosh C; Ross HJ

Nature Medicine. 32(3):924-933, 2026 Mar.

Heart failure (HF) involves cycles of remission and exacerbation, which
are poorly characterized by static disease measures. Consumer wearables
have an understudied potential for daily monitoring of HF symptoms. Here
we report results from an observational cohort of free-living patients
over a median of 94.5 d with HF in the Ted Rogers Understanding
Exacerbations of HF (TRUE-HF) study. The study measured the ability of
Apple Watch data to predict peak oxygen uptake (pVO2) as measured using
in-clinic cardiopulmonary exercise testing (CPET). A deep learning model
was trained with data from 154 patients (46 women, 108 men) and validated
on a held-out set of 63 patients (24 women, 39 men) for determining
wearable-derived daily pVO2, which correlated strongly with CPET-measured
pVO2 (Pearson’s correlation = 0.85). Each 10% drop in wearable-derived
daily pVO2 was associated with a 3.62-fold increased hazard ratio (HR) for
unplanned healthcare events (95% confidence interval (CI), 1.37-9.55; P <
0.01), which occurred at a median of 7.4 d after the first 10% drop in
wearable-derived pVO2. These findings were externally validated in an
independent external cohort from the All of Us Research Program using a
crossplatform model that accounted for the reduced-sensor capacities
available in this external cohort. Using this reduced-sensor variant of
the model, drops in wearable-derived daily pVO2 were associated with
unplanned healthcare utilization (HR 1.32, 95% CI 1.03-1.69; P = 0.03),
which occurred at a median of 21 d after the first 10% drop in
wearable-derived pVO2. These results indicate that wearable-derived daily
pVO2 provides earlier and improved risk discrimination compared with
existing wearable fitness estimates and established clinical markers and
offers a scalable and generalizable approach for longitudinal HF research
and monitoring.

Tsuchiya A; Department of Cardiovascular Medicine, Hiroshima
Utsunomiya H; Kamigaichi A; Tsutani Y; Hamada A; Takeuchi M;
Hyodo Y; Mogami A; Takahari K; Ueda Y; Miyata Y; Okada M; Nakano Y

Circulation Journal. 90(4):376-387, 2026 Mar 25.

BACKGROUND: Decreased exercise tolerance after pulmonary resection for
lung cancer is strongly associated with a poor prognosis, but its
determinants remain underexplored. We investigated the mechanisms of
postoperative effort intolerance in lung cancer using combined
exercise-stress echocardiography and cardiopulmonary exercise testing
(ESE-CPET).

METHODS AND RESULTS: We prospectively analyzed 38 patients with suspected
non-small cell lung cancer who underwent pulmonary resection. Preoperative
and 6-month postoperative evaluations included resting echocardiography,
ESE-CPET, and pulmonary function tests. Pulmonary vascular function was
assessed using the mean pulmonary artery pressure/cardiac output (MPAP/CO)
slope (n=38). Postoperative peak oxygen consumption (VO2) significantly
decreased (19.4 vs. 17.3 mL/min/kg, P<0.001). Multiple regression analysis
identified left atrial reservoir strain (B 0.797 [95% confidence interval:
0.138-1.456], P=0.019) and number of resected segments (-5.448 [-10.99 to
-0.047], P=0.048) as independent predictors of postoperative change in
peak VO2. Subgroup analysis showed greater changes in systolic pulmonary
artery pressure during exercise (SPAP) and steeper postoperative MPAP/CO
slopes in patients with >=3 resected segments vs. <3 (P<0.001 and P=0.052
for time-group interaction). A preoperative MPAP/CO slope >2.0 predicted
larger increases in peak SPAP following >=3-segment resection (P=0.006),
signifying increased pulmonary vascular stress.

CONCLUSIONS: ESE-CPET demonstrated that extensive pulmonary resection
adversely affects postoperative exercise tolerance and pulmonary vascular
function, leading to greater SPAP and steeper MPAP/CO slopes.

Alkan M; Golden Jubilee National Hospital, Glasgow, Scotlan
Veldtman G; Deligianni F

Scientific Reports. 16(1), 2026 Feb 19.

Cardiopulmonary exercise testing (CPET) provides a comprehensive
assessment of functional capacity by measuring key physiological variables
including oxygen consumption ([Formula: see text]), carbon dioxide
production ([Formula: see text]), and pulmonary ventilation (VE) during
exercise. Previous research has identified peak [Formula: see text] and
[Formula: see text] ratio as robust predictors of mortality risk in
chronic heart failure (CHF) patients as well as in congenital heart
disease (CHD). This study utilises CPET variables as surrogate mortality
endpoints for patients with CHD. To our knowledge, this represents the
first successful implementation of an advanced machine learning approach
that predicts CPET outcomes by integrating electrocardiograms (ECGs) with
information derived from clinical letters. Our methodology began with
extracting unstructured patient information from clinical letters using
natural language processing techniques, organising this data into a
structured database. We then digitised ECGs to obtain quantifiable
waveforms and established comprehensive data linkages. The core innovation
of our approach lies in exploiting the Riemannian geometric properties of
covariance matrices derived from both 12-lead ECGs and clinical text data
to develop robust regression and classification models. Through extensive
ablation studies, we demonstrated that the integration of ECG signals with
clinical documentation, enhanced by covariance augmentation techniques in
Riemannian space, consistently produced superior predictive performance
compared to conventional approaches.

Stenberg H; Department of Clinical Sciences Lund, Lund University, Sweden.
Tufvesson E; Mosen H; Skarping I

Scandinavian Journal of Primary Health Care. 44(1):2623877, 2026 Dec.

BACKGROUND: Post COVID-19 condition remains a complex and challenging
issue, with diverse manifestations, despite accumulating research and
clinical experience. Dyspnea is one of the most common symptoms reported
in post COVID-19 condition. Cardiopulmonary exercise testing (CPET) offers
a cohesive assessment of dyspnea and exercise limitations. The Nijmegen
questionnaire is a form for assessment of dysfunctional breathing.

AIM: The aim was to explore relationships between self-reported post
COVID-19 respiratory symptoms, assessed by Nijmegen questionnaire, and the
results of a 6-minute walk test (6MWT) and CPET, in patients with mild
primary infection of COVID-19, managed within primary healthcare.

METHODS: A total of 15 participants with long-term dyspnea after a mild
COVID-19 infection were prospectively included at primary healthcare
facilities between July 2021 and April 2022. At inclusion, all subjects
performed a 6MWT and answered the Nijmegen questionnaire. All subjects
underwent CPET within 4 months of study inclusion. We estimated
correlations between Nijmegen score (both total score and a subset of the
questionnaire focusing on respiratory symptoms), and the 6MWT and CPET
derived variables, respectively.

RESULTS: Nijmegen scores (both total and particularly a respiratory
subset) were inversely correlated to 6MWT walking distance, but not to
spirometric parameters. Subjects with more self-reported symptoms had
higher end-tidal O2 and lower end-tidal CO2, indicating mild
hyperventilation. Nijmegen scores also correlated with CPET variables
reflecting breathing pattern.

CONCLUSIONS: Nijmegen score was associated with CPET variables and
walking distance at 6MWT. Post COVID-19 condition could be associated with
mild hyperventilation, also in subjects without overt dysfunctional
breathing pattern.

Gamble DT; School of Medicine and Dentistry, University of Aberdeen, United Kingdom.
Ross J; Khan H; Cheyne L; Rudd A; Srivanasan J; Horgan G; Hogg
D; Myint PK; Newby DE; Williams C; Gray SR; Dawson D

Circulation: Heart Failure. 19(3):e013229, 2026 Mar.

BACKGROUND: Takotsubo cardiomyopathy is an acute cardiac emergency
presenting with severe left ventricular dysfunction. Physical exercise
training or cognitive behavioral therapy may enhance myocardial recovery
after takotsubo cardiomyopathy.

METHODS: In a prospective multicenter clinical trial conducted between
February 2020 and August 2023, patients with acute takotsubo
cardiomyopathy were randomized 1:1:1 to physical exercise training,
cognitive behavioral therapy, or standard care for 12 weeks after index
presentation. The primary end point was resting phosphocreatine/gamma-ATP
ratio assessed by 31P-magnetic resonance spectroscopy. Secondary end
points were the rate of oxygen consumption at peak exercise on
cardiopulmonary exercise testing, 6-minute walk distance, left ventricular
global longitudinal strain, and the Minnesota Living With Heart Failure
Questionnaire. Twelve-week changes in outcome were compared between
allocated trial interventions.

RESULTS: Seventy-six participants were recruited: the median age was 66
years, and 91% were women. Compared with standard care, the primary end
point of myocardial phosphocreatine/gamma-ATP ratio was improved by
physical exercise training (0.4 [95% CI, 0.1-0.8]; P=0.016) and cognitive
behavioral therapy (0.3 [0.01-0.7]; P=0.043). Both physical exercise
training and cognitive behavioral therapy improved rate of oxygen
consumption at peak exercise (4.7 [1.4-8.0] and 4.0 [1.5-6.4] mL/min per
kg; P=0.001 and 0.004, respectively) and 6-minute walk distance (92.6
[24.7-160.6] and 73.3 [7.9-138.8] m; P=0.004 and 0.029, respectively)
compared with standard care. There were no differences in global
longitudinal strain or symptom burden.

CONCLUSIONS: In patients with acute takotsubo cardiomyopathy, a 12-week
intervention with exercise training or cognitive behavioral therapy
improved left ventricular myocardial energetics and exercise performance
without demonstrable effects on symptoms of heart failure

Kritikou S; Aristotle University of Thessaloniki, Thessaloniki, GREECE.
Zafeiridis A; Markopoulou A; Boutou A; Zacharias A; Rampiadou
C; Kounti G; Gkalgkouranas I; Kastritseas L; Chloros D; Stanopoulos I;
Pitsiou G; Dipla K

Medicine & Science in Sports & Exercise. 58(4):650-660, 2026 Apr 01.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a progressive lung
disease characterized by exertional dyspnea, desaturation, and exercise
intolerance. Desaturation may contribute to cerebral hypoxia during
exercise, and in turn, to exercise intolerance. Although pulmonary
rehabilitation (PR) has been shown to improve functional capacity and
symptom management, it remains unclear whether these benefits are
partially mediated by improved brain oxygenation.

PURPOSE: To evaluate whether a 12-month PR program enhances cerebral
oxygenation during exercise in patients with IPF. Secondary outcomes
included exercise capacity, cognitive function, depression/anxiety, and
physical activity levels.

METHODS: Sixteen patients with IPF (68.7 +/- 6.4 yr), on antifibrotic
therapy, completed a 12-mo supervised PR intervention involving aerobic,
resistance, flexibility, and breathing exercises. Pre- and
post-intervention assessments included spirometry, cardiopulmonary
exercise testing, cerebral oxygenation via near-infrared-spectroscopy,
Mini-Mental State Examination, Hospital Anxiety/Depression Scale, and
International Physical Activity Questionnaire.

RESULTS: After the PR intervention, cerebral oxygenated hemoglobin (O 2
Hb mean-response ) during exercise was higher ( P = 0.04) compared with
pre-PR exercise testing. Isowork O 2 Hb responses (at 50% and 75% of
pre-PR peak workload) were significantly elevated ( P = 0.006). The PR
intervention resulted in improved VO 2 peak ( P = 0.01), cardiopulmonary
exercise testing duration, and peak workload ( P = 0.02). Hospital
Anxiety/Depression Scale anxiety/depression scores decreased ( P = 0.01; P
< 0.001); the Mini-Mental State Examination was not significantly changed
( P = 0.054). Physical activity levels increased from “low” to “moderate”
( P < 0.001). Training-induced cerebral oxygenation improvements were
significantly correlated with improvements in exercise capacity (VO 2 peak
% predicted , r = 0.54, P = 0.03; Workload peakr = 0.54, P = 0.03) and
mMRC. ( r = 0.63, P = 0.01).

CONCLUSIONS: A 12-month PR program enhanced cerebral oxygenation during
exercise, improved exercise capacity, physical activity levels, and
psychological well-being of IPF patients. Importantly, our findings
suggest a potential association between improved cerebral oxygenation and
enhanced exercise capacity in IPF.

Lee Y; Department of Radiological Sciences Medical & Imaging Informatics (MII) Group Los Angeles CA
Feng J; Rahrooh A; Bui AAT; Cooper CB; Hsu JJ

Journal of the American Heart Association. 15(6):e045734, 2026 Mar 17.

BACKGROUND: Cardiorespiratory fitness, as measured by peak oxygen uptake
during cardiopulmonary exercise testing, is a prognostic indicator. We aim
to predict peak oxygen uptake from submaximal variables on cardiopulmonary
exercise testing to assess cardiorespiratory fitness when maximal exertion
is not possible.

METHODS: Data from 13535 cardiopulmonary exercise testings were
collected, and patients were divided into a normal group (NG; n=1076) and
other group (OG; n=9823). Regression models to predict maximum oxygen
consumption were trained and evaluated on the NG, OG, and combined groups
(NG+OG) using stratified 5-fold cross-validation. We trained different
models using demographic, resting and submaximal variables.

RESULTS: Optimal models were Bayesian Ridge for the NG and Light Gradient
Boosting Machine for the other groups. The mean (SD) R2 when using
demographic and rest variables was 0.690 (0.027) for the NG, 0.546 (0.012)
for the OG, and 0.562 (0.015) for the NG+OG. When using demographic, rest
and submaximal variables, performance increased to 0.796 (0.020) for the
NG, 0.732 (0.009) for the OG, and 0.761 (0.008) for the NG+OG. Oxygen
consumption at the first ventilatory threshold, minute ventilation at the
second ventilatory threshold, and forced expiratory volume in 1 second
were important features across the models trained with rest and submaximal
variables. Minute ventilation at the second ventilatory threshold had
negative effects, while oxygen consumption at the first ventilatory
threshold and forced expiratory volume in 1 second had positive effects on
maximum oxygen consumption prediction. In exploratory analyses, the
inclusion of chronotropic index improved model performance.

CONCLUSIONS: Our peak oxygen uptake prediction model demonstrated strong
performance using submaximal exercise variables. This methodology offers a
means to assess prognostic markers for individuals who might not achieve
maximal exhaustion during cardiopulmonary exercise testing.

Button B;  Monash University, Melbourne, Australia,
Dharmakumara M; Wilson L; Parry N; Hartley F; Borg B; T Keating D

Canadian Respiratory Journal. 2026(1):e9062245, 2026.

BACKGROUND: The Alfred Step Test Exercise Protocol (A-STEP) and
feasibility study were previously published. The aim here was to determine
the validity of the A-STEP compared to cycle ergometry (CPET) in adults
with CF.

METHODS: The A-STEP and CPET were carried out in random order 2 weeks
apart. A wearable, portable metabolic system was used to measure
breath-by-breath and minute-by-minute sampling of O2, CO2, heart rate, and
VO2. The main outcome measures were VO2max and HRmax.

RESULTS: Seven stable-state adults (3 male) on CFTR modulator therapy
with a mean (SD) and range of age 38.2 (13.4) 26-64 years; height 169.9
(10.9) 149.7-185.3 cm; BMI 22.8 (2.10) 19.5-28 kg/m2; FEV1 79.4 (18.9)
38.0-106.0; and FVC 95.1 (16.7) 63.0-114.0 percent predicted (pp)
completed both A-STEP and CPET. The VO2Max had high correlation and good
agreement between the A-STEP 31.3 (5.9) and CPET 29.8 (6.2) mL/min/kg, r =
0.88. The HRMAX was strongly correlated with the A-STEP 174 (17) bpm and
95.7 (7.4) pp versus 168 (15) bpm and 92.4 (5.3) pp with r = 0.92 and
0.86, respectively. The SpO2Nadir for A-STEP was 91.0 (4.0) and CPET 92.0
(3.3), r = 0.82. The VO2 at the anaerobic threshold (VO2@AT) occurred
significantly earlier for the CPET at 1021 (260) versus A-STEP 1361 (234)
mL/minute, p < 0.05. The VEMax for CPET was 84.1 (18.8) and A-STEP 73.5
(15.8) L/minute, p < 0.05. The AWESCORE also ensured baseline stability.
The number of levels completed during the A-STEP was 10.7 (12.9) ranging
from 9 to 15.

CONCLUSION: The A-STEP may be a portable, valid surrogate to
cardiopulmonary exercise testing using cycle ergometry.

Sietsema, Kathy E; David Geffen School of Medicine at UCLA, Torrance, California.
Rossiter, Harry B.

Seminars in Respiratory & Critical Care Medicine. 44(5):661-680, 2023 Oct.

Aerobic, or endurance, exercise is an energy requiring process supported
primarily by energy from oxidative adenosine triphosphate synthesis. The
consumption of oxygen and production of carbon dioxide in muscle cells are
dynamically linked to oxygen uptake (VO2) and carbon dioxide output (VCO2)
at the lung by integrated functions of cardiovascular, pulmonary,
hematologic, and neurohumoral systems. Maximum oxygen uptake (VO2max) is
the standard expression of aerobic capacity and a predictor of outcomes in
diverse populations. While commonly limited in young fit individuals by
the capacity to deliver oxygen to exercising muscle, (VO2max) may become
limited by impairment within any of the multiple systems supporting
cellular or atmospheric gas exchange. In the range of available power
outputs, endurance exercise can be partitioned into different intensity
domains representing distinct metabolic profiles and tolerances for
sustained activity. Estimates of both VO2max and the lactate threshold,
which marks the upper limit of moderate-intensity exercise, can be
determined from measures of gas exchange from respired breath during
whole-body exercise. Cardiopulmonary exercise testing (CPET) includes
measurement of VO2 and VCO2 along with heart rate and other variables
reflecting cardiac and pulmonary responses to exercise. Clinical CPET is
conducted for persons with known medical conditions to quantify
impairment, contribute to prognostic assessments, and help discriminate
among proximal causes of symptoms or limitations for an individual. CPET
is also conducted in persons without known disease as part of the
diagnostic evaluation of unexplained symptoms. Although CPET quantifies a
limited sample of the complex functions and interactions underlying
exercise performance, both its specific and global findings are uniquely
valuable. Some specific findings can aid in individualized diagnosis and
treatment decisions. At the same time, CPET provides a holistic summary of
an individual’s exercise function, including effects not only of the
primary diagnosis, but also of secondary and coexisting conditions.