Author Archives: Paul Older

Determinants of Reclassification of Exercise Performance across Cardiopulmonary Exercise Testing Prediction Equations.

Abbaspour Kaboudan F;  Veterans Affairs Health Care System, San Francisco, USA
Zeng S; Abrham Y; Roman J; et al

Medicine & Science in Sports & Exercise. 58(11):2570-2580, 2026 Nov 01.

PURPOSE: Volume of oxygen uptake at peak exercise ( ) is a key indicator
of cardiorespiratory fitness used to assess surgical risk and clinical
trial outcomes. However, multiple prediction equations exist for its
interpretation, often yielding inconsistent classifications of exercise
performance. We aimed to determine how different prediction equations
affect exercise performance classification and identify factors
contributing to its variability.

METHODS: We performed a post hoc analysis of cardiopulmonary exercise
testing (CPET) data collected from 332 nonsmoking flight attendants who
participated in our previous studies examining the health effects of
occupational exposure to secondhand tobacco smoke. Percent-predicted was
calculated using seven prediction equations (Fitness Registry and the
Importance of Exercise National Database, Wasserman, Hansen-Wasserman,
Study of Health in Pomerania, Jones, Bruce, and Cooper-Storer). Reduced
exercise performance was defined as < 80 percent-predicted. Agreement
across equations was assessed using Cohen’s kappa. Associations with
dyspnea (modified Medical Research Council >= 1) were examined using
C-statistics to assess the discriminative performance of prediction
equations for this patient-centered outcome. The magnitude of change in
percent-predicted when switching from one equation to another
(“recalculation magnitude”) was quantified for individual participants,
and multivariable regression modeling was used to identify demographic and
anthropometric determinants of recalculation magnitude.

RESULTS: Participants were 56 +/- 12 years old, 86% female, with body
mass index = 24 +/- 4 kg/m 2 . Depending on the prediction equation, mean
percent-predicted varied widely (83%-113%), and the prevalence of reduced
exercise performance ranged from 7% to 51%. Agreement across equations
ranged from slight to substantial (kappa = 0.10-0.79). At an individual
level, switching between equations recalculated percent-predicted by -93%
to +84%, leading to bidirectional exercise performance reclassification of
6.6%-45.5% of participants. Body mass index was the strongest determinant
of recalculation magnitude, followed by age and sex. The discrimination
accuracy of prediction equations for dyspnea was modest (area under the
curve = 0.56-0.71), with the Study of Health in Pomerania equation showing
the best performance.

CONCLUSIONS: Different prediction equations yielded materially different
percent-predicted values and frequently changed exercise capacity
classification in a bidirectional manner. The observed discordance appears
to arise in substantial part from limitations in how demographic and
anthropometric factors, particularly body size, are modeled across
equations, underscoring the need for improved reference standards that
better capture physiological variability.

Cardiopulmonary Fitness and Exercise-Based Cardiac Rehabilitation in Patients With Myocarditis.

Zhang SS; Department of Cardiology, Beijing, China,
Jiang LY; Zuo HJ; Liu WJ

Cardiovascular therapeutics. 2026(1):e3611934, 2026.

BACKGROUND: Cardiorespiratory fitness (CRF) is a powerful predictor of
cardiovascular morbidity and mortality. The cardiopulmonary exercise test
(CPET) is considered a gold standard in assessing CRF. Patients with
myocarditis are recommended to abstain from exercise because of the risk
of sudden cardiac death (SCD). Therefore, the clinical benefit of
exercise-based cardiac rehabilitation (CR) has not been previously
established in this population.

OBJECTIVE: The aim of this study is to assess the CRF of myocarditis and
the safety and effectiveness of an exercise-based CR program in these
populations.

METHOD: A total of 70 consecutive patients with a diagnosis of
myocarditis admitted to Tongji Hospital, Tongji Medical College, Huazhong
University of Science and Technology between October 2021 and December
2024 were enrolled in the current study. CPET was performed within 3-6
months of hospital discharge. The exercise-based CR program was performed
for 3 months. The protocol included biomarker analysis, CPET, and
standard-of-care echocardiography (including resting left ventricular
ejection fraction and global longitudinal strain [GLS]). Data were
collected at admission and 3 months after discharge.

RESULTS: A total of 70 patients with myocarditis were enrolled. Among
them, 47 patients completed the rehabilitation program and had complete
follow-up assessments, including cardiopulmonary exercise testing, and
were included in the final analysis. In comparison with NFM, patients with
FM were more often female, and had higher levels of creatine kinase (CK),
lactate dehydrogenase (LDH), urea nitrogen (UN), N-terminus probrain
natriuretic peptide (NT-proBNP), fasting blood glucose (FBG), and white
blood cell (WBC). For FM, echocardiography revealed more frequently signs
of left ventricular (LV) dysfunction in the form of a reduced ejection
fraction (p < 0.01), and lower GLS (p < 0.01) in contrast to NFM. CPET
results showed that FM patients had markedly lower exercise capacity,
impaired ventilatory efficiency, and pulmonary function (p < 0.05). After
the 3-month exercise-based CR program, both groups demonstrated
significant improvements in peak VO2, peak workload, and MVV. However, no
significant between-group differences were observed in the magnitude of
improvement in CRF.

CONCLUSION: CRF was substantially impaired in patients recovering from
myocarditis, particularly among those with fulminant presentations.
Participation in a structured 3-month exercise-based CR program was
feasible and was associated with favorable changes in exercise capacity
and cardiopulmonary performance.

Coronary Revascularization of Ischemic Territories Improves Myocardial Perfusion, Increases Submaximal Aerobic Capacity and Reduces Exercise-induced Angina in Patients With Chronic Coronary Syndrome.

Mosen H; Department of Clinical Physiology, Lund, Sweden.
Szekely A; Steding-Ehrenborg K; Akil Engblom S; et al

American Journal of Cardiology. 278:30-37, 2026 Nov 01.

Chronic coronary syndrome (CCS) is associated with reduced stress
perfusion, a predictor of adverse cardiovascular outcome. To what extent
myocardial perfusion is related to cardiorespiratory fitness is not
completely known. The aim was to investigate if change in myocardial
perfusion correlates to change in aerobic capacity after
revascularization. Sixty-two patients with suspected or established CCS
underwent cardiopulmonary exercise testing (CPET) and [13N]NH3 positron
emission tomography (PET) before and after elective invasive coronary
angiography. Thirty-six patients were revascularized and 26 were not. The
angiographer was blinded to the results from CPET and PET. Myocardial
perfusion was defined as decreased when below 2 ml/min/g and as myocardial
perfusion reserve (MPR) <2. Change in oxygen uptake at submaximal effort
(VO2 at AT) correlated positively to change in MPR in revascularized
patients (r = 0.36, p = 0.04), but not in conservatively treated patients
(r = 0.03, p = 0.90). Change in VO2 peak, however, did not correlate to
change in myocardial perfusion in any of the groups. Myocardial perfusion
at stress and MPR increased significantly after revascularization, when
baseline perfusion was decreased (p = 0.01 stress and p = 0.001 MPR,
respectively). Furthermore, the number of patients with exercise-induced
angina decreased significantly for the revascularized patients (42%
(14/33) at baseline versus 3% (1/33) at follow-up, p <0.001) whereas half
of the conservatively treated patients still had exercise-induced angina
at follow-up (42% (10/24) at baseline versus 21% (5/24) at follow-up, p =
0.12). In conclusion, change in myocardial perfusion correlates with
change in submaximal aerobic capacity after revascularization and
revascularization reduces exercise-induced angina.

Hemodynamic phenotyping in ME/CFS and ANOCA: complementary insights from coronary function testing and invasive cardiopulmonary exercise testing.

Mackay Z; Yale School of Medicine, USA
Shah S; Villalobos JG; Latif N; et al

American Journal of Physiology – Heart & Circulatory Physiology.
331(5):H1485-H1494, 2026 Nov 01.

This single-center cohort study sought to evaluate the association between
myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and angina
with nonobstructive coronary arteries (ANOCA), by determining the observed
frequency of ME/CFS among patients with ANOCA diagnosed by coronary
function testing (CFT). In addition, we performed an exploratory analysis
of the diagnostic utility of invasive cardiopulmonary exercise testing
(iCPET) in ME/CFS patients with CFT-confirmed ANOCA, with the aim of
identifying the predominant physiological mechanism responsible for
exertional limitation in this population. Systematic medical record review
of 261 patients with CFT-confirmed ANOCA was performed using standardized
diagnostic criteria to identify concurrent ME/CFS diagnosis. ME/CFS was
identified in 47 patients, representing an observed frequency of 18%. The
only statistically significant difference between ANOCA patients with and
without ME/CFS was a higher frequency of connective tissue disease in the
ME/CFS group (P = 0.0221). In a separate cohort of 27 patients with ME/CFS
who underwent iCPET, 24 patients (89%) had CFT-confirmed ANOCA. The
diagnosis of ANOCA by CFT prompted a change in medical management in 81%
of patients in this cohort. iCPET revealed a primary peripheral limitation
to exercise, characterized by impaired peak systemic oxygen extraction
despite normal peak oxygen delivery. This study demonstrates a clinically
significant association between ME/CFS and ANOCA. These findings
underscore the clinical value of CFT in patients with ME/CFS and
exertional chest pain and highlight iCPET as a complementary tool for
hemodynamic phenotyping in this population. Prospective studies
incorporating simultaneous CFT and iCPET with molecular phenotyping are
warranted. NEW & NOTEWORTHY This study demonstrates a clinically
significant association between myalgic encephalomyelitis/chronic fatigue
syndrome (ME/CFS) and angina with nonobstructive coronary arteries
(ANOCA), with 18% of patients with coronary function testing-confirmed
ANOCA meeting diagnostic criteria for ME/CFS. Invasive cardiopulmonary
exercise testing (iCPET) in patients with concurrent ME/CFS and ANOCA
reveals a primary peripheral, not cardiac, limitation to exercise. These
findings highlight the complementary roles of coronary function testing
and iCPET for hemodynamic phenotyping in this underrecognized patient
population.

Myocardial Fibrosis and Reverse Remodeling After Valve Replacement in Chronic Aortic Regurgitation.

Thornton GD; Institute of Cardiovascular Science University College London, UK
Bennett JB; Aziminia N; Tapia L; Birkinshaw A; et al

JAMA Cardiology. 11(10):981-990, 2026 Oct 01

Importance: Patients undergoing aortic valve replacement (AVR) for chronic
severe aortic regurgitation (AR) based on current guideline-based
thresholds may have irreversible myocardial scarring.

Objective: To quantify reverse remodeling, functional recovery, and
symptomatic change after AVR and assess whether myocardial fibrosis is
associated with incomplete recovery.

Design, Setting, and Participants: In this prospective longitudinal
observational study, patients with chronic severe AR referred for AVR by a
cardiology team were included. Key exclusion criteria were previous valve
surgery, moderate or greater valve disease, and other primary
cardiomyopathies. Included patients underwent paired biomarkers,
echocardiography, cardiopulmonary exercise testing, and cardiovascular
magnetic resonance (CMR) at baseline and at a median of 7 months after
AVR. The study took place at 2 tertiary cardiothoracic centers in London,
United Kingdom, with enrollment from August 2021 to October 2023. Data
were analyzed from January to April 2026.

Exposure: AVR.

Main Outcomes and Measures: Left ventricular (LV) reverse remodeling
(change in LV end-diastolic volume [LVEDV] and LV mass) post-AVR and
preoperative correlates of incomplete recovery, with prespecified focus on
CMR fibrosis markers (late gadolinium enhancement [LGE] and extracellular
volume [ECV]).

Results: Seventy-two patients (median [IQR] age, 60 [6-70] years; 59
[82%] male, 35 [49%] with bicuspid aortic valve) completed paired studies.
Median (IQR) regurgitant volume fell from 61 (38-83) mL to 5 (3-8) mL;
median (IQR) LVEDV fell 44% from 273 (211-307) mL to 153 (130-177) mL; and
median (IQR) LV mass fell 21% from 200 (159-226) g to 158 (137-184) g (all
P < .001). Indexed intracellular volume declined 21% and indexed
extracellular volume 15% (26 mL/m2 to 22 mL/m2; P < .001), raising
extracellular volume fraction (ECV%) from 27.4% to 29.1% (P < .001). LGE
as a percentage of LV mass was unchanged (2.3% to 2.4%; P = .36); baseline
LGE burden was associated with less regression of LV mass (chi22 = 29.4; P
< .001) and LVEDV at 7 months (chi21 = 7.9; P = .007). New York Heart
Association class and quality of life improved (median [IQR] EQ-5D index
improved from 0.89 [0.78-1.00] to 0.94 [0.81-1.00]; P < .001), but maximum
oxygen consumption was unchanged (22.6 mL/kg/min to 21 mL/kg/min; P =
.08). N-terminal pro-B-type natriuretic peptide decreased slightly (228
pg/mL to 198 pg/mL; P = .27), with a larger fall in patients with evidence
of decompensation (n = 31; 469 pg/mL to 279 pg/mL; P = .02).

Conclusions and Relevance: In this study, AVR was associated with
substantial reverse remodeling at 7 months, including regression of
hypertrophy and a fall in indexed extracellular (matrix) volume; the
extracellular volume fraction rose, as cellular regression outpaced matrix
regression. Focal scar, as a proportion of myocardium, was unchanged.
Preoperative focal scar was independently associated with less recovery
and may mark incomplete remodeling. Objective functional recovery did not
improve at this time point.

Ventilatory thresholds are detectable using DFA-alpha1 at group level but not individual level during swimming, cycling and running

Nieto-Jimenez, C., School of Physical Therapy, University Andres Bello, Viña del mar, Chile.
Naranjo-Orellana, J., Medina-Porcile, C.L., Gawn, J., et al

Physiol Int 2026

BACKGROUND: Ventilatory thresholds (VT1 and VT2) determined from gas-exchange criteria during cardiopulmonary exercise testing (CPET) provide reference points for exercise-intensity prescription, but their routine use is limited in applied settings. Detrended fluctuation analysis alpha 1 (DFA-alpha1) has emerged as a potential non-invasive marker of physiological transitions during exercise.
OBJECTIVE: To quantify and compare DFA-alpha1 values against CPET-derived ventilatory thresholds and between exercise modes during constant-load swimming, cycling, and running in trained triathletes.
METHODS: Seventeen triathletes (13 men, 4 women) completed maximal incremental CPETs in swimming, cycling, and running, after which constant-load trials were undertaken at VT1 and VT2, as determined from CPET using standard ventilatory criteria. R-R intervals were recorded with a Polar V800 and Polar H10 and processed in Kubios HRV Scientific v4.2.0. DFA-alpha1 was calculated using a 120-s moving window with 5-s updates. Between-modality comparisons were performed using repeated-measures ANOVA.
RESULTS: At VT1, V O2, heart rate, and PetCO2 differed by modality, whereas DFA-alpha1 did not differ significantly between swimming, cycling, and running (0.74 +/- 0.30, 0.75 +/- 0.21, and 0.65 +/- 0.20, respectively; P = 0.456). At VT2, V O2 and heart rate again differed by modality, whereas DFA-alpha1 showed no significant differences between modalities but wide between participant variability (0.42 +/- 0.13, 0.37 +/- 0.11, and 0.47 +/- 0.13, respectively; P = 0.061).
CONCLUSION: At the group level, mean DFA-alpha1 values were numerically close to previously proposed values for VT1 ( approximately 0.75) and VT2 ( approximately 0.50). However, the marked inter-individual dispersion across modalities limits the use of fixed DFA-alpha1 values for individual identification of VT1 and VT2. These findings indicate descriptive group-level correspondence rather than individual-level validity or agreement.

An Acute Alcoholic Beer Dose Impaired Exercise Performance: A Double-Blind, Placebo-Controlled Crossover Trial

de Lima, F.R., Exercise Psychophysiology Research Group  São Paulo,  Brazil.
de Salles Painelli, V., Canestri, R., Santos, T.M ,.et al

Int J Sport Nutr Exerc Metab 2026 1-10

PURPOSE: We investigated whether a small dose of alcoholic beer ingested before a running exercise bout impaired performance and changed psychophysiological responses to exercise.
METHODS: After three sessions of familiarizations, 16 healthy and physically active men (25.8 +/- 5.1 years, 175.0 +/- 5.4 cm, and 76 +/- 6.5 kg) performed a 30-min running time trial in a double-blind and placebo-controlled crossover design, after ingesting either beer (alcohol 4.8% v/v; 0.3 g/kg) or nonalcoholic beer (placebo). Performance, cardiopulmonary (oxygen consumption, ventilation, respiratory exchange ratio, and heart rate), and perceptual (perceived exertion, affect, and motivation) variables were assessed throughout the trial and averaged every 5 min during exercise. Running economy was assessed during steady-state running at 8 km/hr. The data were analyzed through t tests and repeated-measures mixed models (p < .05).
RESULTS: The ingestion of beer significantly decreased the average speed by 4.7% (p = .04; d = 0.21) and total distance covered by 4.3% (p = .007; d = 0.26) when compared with placebo. The ingestion of beer also impaired the running economy by 1.1% (p = .01; d = 0.39) and increased respiratory exchange ratio throughout the exercise bout (p = .004, d = 1.07). No beer-by-time interaction effects were detected in cardiopulmonary outcomes (p > .05). CONCLUSIONS: A small dose of alcoholic beer reduced the exercise capacity of healthy individuals, likely due to an impairment in running economy.

A nonexercise equation to predict VO(2) peak in chronic heart failure: Integrating clinical variables for prognostic assessment

Borghi-Silva, A., Cardiopulmonary Physiotherapy Laboratory,  São Carlos, Brazil;
Santos-de-Araujo, A.D., Montalvo, S., Christle, J.W. & Myers, J.

Prog Cardiovasc Dis 2026

BACKGROUND: Peak oxygen consumption (pVO2) has been widely recognized to identify potential pathophysiological mechanisms of exercise intolerance and to stratify risk in patients with heart failure (HF).
AIMS: To develop a non-exercise equation to estimate pVO2 (esVO2) and to determine its association with all-cause mortality.
METHODS: A total of 5176 HF patients (age 48 +/- 17 years) who underwent a CPET for clinical reasons, and were followed between May 2011, and December 1, 2023. Clinical and historical variables and forced expiratory volume in 1-s (FEV(1)) were used in a stepwise multivariate regression analysis to predict pVO2 measured from CPET. Kaplan-Meier curves and Cox proportional hazards analyses were used to determine the association between esVO2 and all-cause mortality.
RESULTS: The first esVO2 model was significantly associated with pVO2 (multiple R = 0.73, P < 0.001). Two other models considered gender separately (male: multiple R = 0.72, P < 0.001 and female (multiple R = 0.70, P < 0.001). A fourth model was proposed when spirometry is not available (age, BMI, resting SBP, HR and gender (multiple R = 0.69, P < 0.001)). The fifth proposed model included history of atrial fibrillation and previous stroke (multiple R = 0.70, P < 0.001). Kaplan-Meier survival curves differentiated patients according to esVO2 and pVO2 </= and > 14 mL/kg(-1) per min(-1). Univariate Cox proportional hazard analyses indicated significant prognostic value when esVO2 and pVO2 were </= 14 mL/kg(-1) per min(-1) (P = 0.001).
CONCLUSIONS: Multivariable nonexercise models combining spirometry and/or clinical variables commonly obtained during a clinical assessment predict pVO2 reasonably accurately in HF.

Cardiac size-exercise coupling in Paralympic athletes with spinal cord injury: the role of lesion level

Di Gioia, G., National Italian Olympic Committee, Rome, Italy.
Ferrera, A., Ginelli, D., Maestrini, V., et al

Eur J Appl Physiol 2026
Headings by Dr Older

Background
Spinal cord injury (SCI) alters autonomic cardiovascular regulation and may limit the translation of cardiac structural adaptation into aerobic performance. Whether spinal cord neurological level modifies cardiac size-exercise coupling in elite athletes remains under investigation.
Methods
We enrolled 178 Paralympic athletes with SCI (33% high SCI, above T6). Athletes underwent transthoracic echocardiography and cardiopulmonary exercise testing. SCI level was analyzed as the main predictor of cardiac structure and exercise performance. Multivariable linear regression models were adjusted for age, sex, and body weight, with additional sensitivity analyses including sport category. Mediation analyses evaluated the role of indexed left ventricular end-diastolic volume (LVEDV/BSA), and interaction models tested effect modification of the LVEDV-VO₂max relationship by SCI level.
Results
Athletes with low SCI exhibited larger LVEDV/BSA (60.6 ± 14.7 vs. 51.9 ± 11.9 mL\m², p < 0.0001) and higher VO₂ max (31.0 ± 9.4 vs. 21.0 ± 9.3 mL\kg\min, p < 0.0001) than those with high SCI. In adjusted models, high SCI independently predicted lower VO₂max (β=-8.88, 95% CI – 11.71 to – 6.05, p < 0.0001) and O₂ pulse (β=-3.38, 95% CI – 5.07 to – 1.70, p = 0.0002), persisting after adjustment for sport category (VO₂: β=-6.64, p = 0.001; O₂ pulse: β=-1.87, p = 0.004). LVEDV/BSA partially mediated the association between SCI level and VO₂ max (β = 0.323 per mL\m², p = 0.0002).
Conclusions
A significant SCI×LVEDV/BSA interaction (β=-1.229, 95% CI – 2.548 to – 1.090, p = 0.002) indicated attenuation of cardiac size-exercise coupling in high SCI. Level of spinal cord lesion independently influences cardiac remodeling and aerobic performance and modifies how cardiac size translates into functional capacity. High-level SCI is associated with a lesion-dependent uncoupling of cardiac structure and exercise performance.

Prediction of oxygen uptake at peak exercise in patients with inflammatory bowel disease using submaximal cardiopulmonary exercise testing and the steep ramp test as a practical field test

Demers, K., Maastricht University Medical Center+, Maastricht, the Netherlands.
van Kuijk, S.M.J., Pierik, M.J., Jonkers, D., Stassen, L.P.S. & Bongers, B.C.

PLoS One 2026 10 e0354707

PURPOSE: To develop predictive equations for oxygen uptake at peak exercise (VO2peak) measured during a cardiopulmonary exercise test (CPET) for patients with inflammatory bowel disease (IBD) using submaximal CPET-derived parameters and the steep ramp test, along with demographic and clinical characteristics.
METHODS: This study included patients with IBD in remission or with mild-to-moderate disease activity who performed a CPET and a steep ramp test within 14 days. Submaximal CPET-derived parameters included oxygen uptake (VO2) at the ventilatory anaerobic threshold (VAT) and oxygen uptake efficiency slope (OUES), while the outcome of the steep ramp test was the work rate achieved at peak exercise (WRpeak).
RESULTS: Predictive regression equations with submaximal VO2 at the VAT and with OUES, when combined with age and body fat percentage, explained >89% of the variance in VO2peak (optimism-adjusted R2 = 0.895 and 0.938). Predictive capacity increased when both VO2 at the VAT and OUES were combined in a predictive regression equation, together with age, body fat percentage, and clinically active disease (optimism-adjusted R2 = 0.951). Steep ramp test WRpeak explained 89% of the variance in VO2peak (optimism-adjusted R2 = 0.892).
CONCLUSION: The highly predictive equations developed in this study support the use of the submaximal CPET and the steep ramp test as alternatives for assessing VO2peak in patients with IBD in remission or with mild-to-moderate disease activity in clinical and research settings.