McHugh C; Cardiology Division, Massachusetts General Hospital, Boston,  USA.
Gustus SK; Petek BJ; Schoenike MW; Boyd KS; Kennett JB; VanAtta
C; Tower-Rader AF; Fifer MA; DiCarli MF; Wasfy MM

European Journal of Preventive Cardiology. 32(12):1112-1119, 2025 Sep 08. VI 1

AIMS: Cardiopulmonary exercise testing (CPET) is often used when athletes
present with suspected hypertrophic cardiomyopathy (HCM). While low peak
oxygen consumption (pVO2) augments concern for HCM, athletes with HCM
frequently display supranormal pVO2, which limits this parameter’s
diagnostic utility. We aimed to compare other CPET parameters in healthy
athletes and equally fit individuals with HCM.

METHODS AND RESULTS: Using cycle ergometer CPETs from a single centre, we
compared ventilatory efficiency and recovery kinetics between individuals
with HCM [percent predicted pVO2(ppVO2) > 80%, non-obstructive, no nodal
agents] and healthy athletes, matched (2:1 ratio) for age, sex, height,
weight and ppVO2. Consistent with matching, HCM (n = 30, 43.6 +/- 14.2
years) and athlete (n = 60, 43.8 +/- 14.9 years) groups had similar,
supranormal pVO2 (39.5 +/- 9.1 vs. 41.1 +/- 9.1 mL/kg/min, 125 +/- 26 vs.
124 +/- 25% predicted). Recovery kinetics were also similar. However, HCM
participants had worse ventilatory efficiency, including higher early
VE/VCO2 slope (25.4 +/- 4.7 vs. 23.4 +/- 3.1, P = 0.02), higher VE/VCO2
nadir (27.3 +/- 4.0 vs. 25.2 +/- 2.6, P = 0.004) and lower end-tidal CO2
at the ventilatory threshold (42.9 +/- 6.4 vs. 45.7 +/- 4.8 mmHg, P =
0.02). HCM participants were more likely to have abnormally high VE/VCO2
nadir (>30) than athletes (20 vs. 3%, P = 0.02).

CONCLUSION: Even in the setting of similar and supranormal pVO2,
ventilatory efficiency is worse in HCM participants vs. healthy athletes.
Our results demonstrate the utility of CPET beyond pVO2 assessment in
‘grey zone’ athlete cases in which the diagnosis of HCM is being debated.
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Other Abstract
plain-language-summary
We sought to examine exercise test findings in healthy athletes and
equally fit individuals with a form of heart enlargement that commonly
gets confused with ‘athlete’s heart’ called hypertrophic cardiomyopathy
(HCM) to see if elements of the exercise test could distinguish between
these two groups. This is relevant as fit individuals often present for
exercise testing as part of the work up to see if they have HCM or not,
and getting the answer right is important because HCM is amongst the most
common causes of sudden cardiac death in athletes.By design, individuals
with HCM in this study were equally fit as the athletes, with both groups
having fitness levels (‘VO2 max’ levels) around 25% higher than expected
for individuals of similar age and sex.Despite this similar and
supranormal fitness, individuals with HCM had worse ventilatory efficiency
than athletes. This is a metric that reflects how well the heart and lungs
work together to get rid of the waste gas carbon dioxide during exercise.
This finding should focus more attention on this parameter when exercise
tests are being performed to evaluate for HCM in clinical practice.

Driessens H; University of Groningen, Groningen, the Netherlands.
Hoeijmakers LSM; Zwerver ODJ; Wijma AG; Hildebrand ND;
Queisen RRYC; Kuikhoven M; den Dulk M; Olde Damink SWM; Klaase JM; Bongers BC

BACKGROUND: The widespread implementation of a preoperative assessment of
aerobic capacity requires a practical field test. This study investigated
the validity of the modified steep ramp test (SRT) for evaluating
preoperative aerobic capacity and to evaluate its usefulness for
preoperative risk assessment in patients planned for pancreatic surgery.

METHODS: Patients scheduled for pancreatic surgery who preoperatively
performed cardiopulmonary exercise testing (CPET) and the modified SRT
within 14 days were included. To assess its criterion validity, the
correlation between the achieved work rate at peak exercise (WRpeak) at
the modified SRT and oxygen uptake (VO2) at peak exercise (VO2peak) during
CPET was determined. To evaluate the ability of the modified SRT to
correctly classify patients as fit or unfit, receiver operating
characteristic (ROC) analyses were performed based on the CPET VO2peak
cutoff 18.0 ml.kg-1.min-1 and VO2 at the ventilatory anaerobic threshold
(VAT) cutoff 11.0 ml.kg-1.min-1.

RESULTS: Forty-eight patients (21 females) aged 68.7 +/- 7.6 years were
included. Modified SRT WRpeak (W/kg) demonstrated a very strong
correlation with CPET VO2peak (rho = 0.865, r = 0.926). The modified SRT
WRpeak cutoff to most accurately classify patients as fit or unfit was
2.095 W/kg for the CPET VO2peak cutoff (area under the curve (AUC) of
0.948) and the CPET VO2 at the VAT cutoff (AUC of 0.814).

CONCLUSIONS: The modified SRT is a valid short-term practical exercise
test to preoperatively assess aerobic capacity in patients undergoing
pancreatic surgery. A modified SRT performance below 2.1 W/kg seems
clinically most suitable to select candidates for further preoperative
CPET evaluation and/or prehabilitation, given its positive and negative
predictive value.

El Assaad I; Division of Cardiology & Cardiovascular Medicine, Cleveland, Ohio, USA.
Heilbronner AK; Zahka K; Hammond B; Patel A; Aziz PF

Journal of Cardiovascular Electrophysiology. 36(9):2287-2295, 2025 Sep. VI 1

OBJECTIVE: To describe our institutional experience with utilizing
cardiopulmonary exercise testing (CPET) to assess for chronotropic
suppression and to compare frequency of life-threatening events (LTEs) on
intentional “submaximal” treatment to those on maximal treatment.

METHODS: We queried our Inherited Arrhythmia Registry and identified
patients with LQTS who were on “submaximal” beta blocker doses (nadolol <
0.75-mg/kg/day & propranolol < 2 mg/kg/day) with at least 6 months follow
up. Adequate beta blockade effect was defined as at least 15% decrease
from maximal HR.

RESULTS: The study included 127 LQTS patients: 47% on maximal therapy,
43% on submaximal therapy, and 10% not receiving treatment. Thirty three
percent of patients were on submaximal therapy due to side effects, none
in patients less than 10 years of age. Baseline characteristics were
similar between the groups. There was no significant difference in LTEs
between maximal and submaximal therapy (8% vs. 5.4%, p = 0.72). During
CPET, patients on maximal therapy were more likely to exhibit adequate
chronotropic suppression (60% vs. 40%, p = 0.01). None of the patients on
submaximal therapy with adequate chronotropic effect experienced LTEs
during follow-up.

CONCLUSIONS: Adequate chronotropic suppression was achieved with
“submaximal” beta blocker dose in 40%. Despite similar baseline risk
profiles, LTEs were not significantly different in patients with
submaximal versus maximal therapy. CPET may be a useful modality to devise
an individualized treatment plan, especially in those who cannot tolerate
the recommended guideline directed dose.

Michielsen M; Department of Rehabilitation Sciences, KU Leuven, Leuven, Belgium.
Bekhuis Y; Claes J; Decorte E; De Wilde C; Gojevic T;
Costalunga L; Amyay S; Lazarou V; Daraki D; Kounalaki E; Chatzinikolaou P;
Goetschalckx K; Hansen D; Claessen G; De Craemer M; Cornelissen V

PLoS ONE [Electronic Resource]. 20(9):e0331737, 2025. VI 1

OBJECTIVE: This study investigates the mechanisms behind exercise capacity
in adults with type 2 diabetes mellitus (T2DM), focusing on central and
peripheral components, as described by the Fick equation.

METHODS: A cross-sectional study of 141 adults with T2DM was conducted,
using cardiopulmonary exercise testing, near-infrared spectroscopy (NIRS)
and exercise echocardiography. Participants with sufficient-quality NIRS
data were stratified into tertiles based on percentage predicted VO2peak.
Group comparisons and stepwise regression were used to examine the
contributions of central and peripheral components to VO2peak.

RESULTS: Sixty-seven participants had insufficient quality NIRS data.
Those with lower-quality data were more likely to be female (p < 0.001)
and had a lower exercise capacity (p < 0.001). Among participants with
good-quality NIRS data, those in the lowest fitness tertile were older (p
< 0.01), had a longer diabetes duration (p = 0.04), lower eGFR (p < 0.001)
and more frequent use of beta-blockers (p = 0.02) and diuretics (p =
0.04). Significant differences were observed in peak cardiac output (p <
0.001) and NIRS-derived parameters across fitness groups. Multivariate
regression identified cardiac output as the strongest predictor of
VO2peak, while peripheral oxygen extraction did not improve model
performance.

CONCLUSION: Cardiac output is the primary determinant of exercise
capacity in adults with T2DM. This suggests that muscle perfusion may be
the main limiting factor in relatively fit individuals with T2DM. However,
cardiac output and local muscle perfusion are not directly equivalent, as
mechanical factors, such as intramuscular pressure during high-intensity
exercise, may prevent maximal perfusion.

Mikeš O; Third Department of Internal Medicine,  Charles University, Prague, Czech Republic.
Prázný M; Šoupal J; Marek J; Matoulek M; Tuka V;

Scientific reports [Sci Rep] 2025 Aug 13; Vol. 15 (1), pp. 29633.
Date of Electronic Publication: 2025 Aug 13.

Type 1 diabetes mellitus (T1DM) is a chronic disease that usually manifests at a younger age and is associated with higher morbidity and mortality compared to the general population. The objective of this study was to assess the blood pressure response to exercise in patients with T1DM with varying durations of diabetes and with respect to the determinants of systolic blood pressure (SBP) and diastolic blood pressure (DBP) during the exercise stress test. This cross-sectional exploratory study included 52 patients (35 with T1DM aged &lt; 35 years and 17 aged &gt; 35 years) and 25 control subjects. All participants were untrained and underwent a cardiopulmonary exercise stress test using a cycle ergometer and their BP was measured manually. Compared to control subjects, both younger and older patients with T1DM had higher SBP and DBP at submaximal exercise load 0,5 W/kg (SBP 124 ± 18; 142 ± 17; 146 ± 19 mmHg, p = 0.0004, respectively, and DBP 75 ± 10; 84 ± 7; 82 ± 7 mmHg, p = 0.0015, respectively), and at peak exercise (SBP 170 ± 24; 188 ± 26; 192 ± 23 mmHg, p = 0.0006, respectively. BP during exercise in T1DM patients in multivariate model was influenced by resting SBP, and diabetes duration. Patients with T1DM exhibited impaired BP control during exercise, which may serve as an early marker of heightened cardiovascular risk.

Mueller S; TUM University Hospital, Georg-Brauchle-Ring 56, 80992 Munich, Germany.
Kabelac M; Fegers-Wustrow I; Winzer EB; Gevaert AB; Beckers P;
Haller B; Edelmann F; Christle JW; Haykowsky MJ; Sachdev V; Kitzman DW;
Linke A; Adams V; Wisloff U; Pieske B; van Craenenbroeck E; Halle M

European Journal of Preventive Cardiology. 32(11):926-936, 2025 Aug 25.

AIMS: Exercise training (ET) is an effective therapy in heart failure with
preserved ejection fraction (HFpEF), but the influence of different ET
characteristics is unclear. We aimed to evaluate the associations between
ET frequency, duration, intensity [% heart rate reserve (%HRR)] and
estimated energy expenditure (EEE) with the change in peak oxygen
consumption (VO2) over 3 months of moderate continuous training (MCT,
5x/week) or high-intensity interval training (HIIT, 3x/week) in HFpEF.

METHODS AND RESULTS: ET duration and heart rate (HR) were recorded with a
smartphone application. EEE was calculated using the HR data during ET and
the individual HR-VO2 relationships during cardiopulmonary exercise
testing. Differences between groups and associations between ET
characteristics and peak VO2 change were assessed with linear regression
analyses. Peak VO2 improved by 9.2 +/- 13.2% after MCT and 8.7 +/- 15.9%
after HIIT (P = 0.67). The average EEE of 1 HIIT session was equivalent to
~1.42 MCT sessions and when adjusted for EEE, the mean difference between
MCT and HIIT was -0.1% (P = 0.98). For both MCT and HIIT, peak VO2 change
was positively associated with ET frequency (MCT: R2 = 0.103; HIIT: R2 =
0.149) and duration/week (MCT: R2 = 0.120; HIIT: R2 = 0.125; all P <
0.05). Average %HRR was negatively associated with peak VO2 change in MCT
(R2 = 0.101; P = 0.034), whereas no significant association was found in
HIIT (P = 0.234). Multiple regression analyses explained ~1/3 of the
variance in peak VO2 change.

CONCLUSION: In HFpEF, isocaloric HIIT and MCT seem to be equally
effective over 3 months. Within each mode, increasing ET frequency or
duration/week may be more effective to improve peak VO2 than increasing ET
intensity. Copyright &#xa9; The Author(s) 2024. Published by Oxford
University Press on behalf of the European Society of Cardiology.

Shrestha, D; Lancaster Medical School, Lancaster University, Lancaster, United Kingdom.;
Wisely, N; Bampouras, T; Subar, D et al

PloS one,2025 Aug 12

• Background: Cardiopulmonary exercise testing (CPET) provides objective measures of cardiorespiratory fitness and can support surgical risk stratification. As socioeconomic status is a factor known to influence patient health and outcomes, we analysed how CPET-derived measures vary across levels of socioeconomic status in patients being considered for elective surgery.
• Methods: A database of patients who underwent CPET between 2011 and 2024 was analysed. Measures including oxygen consumption (V̇O₂) at gas exchange threshold (GET), peak V̇O₂, and ventilatory equivalent for carbon dioxide (VE/V̇CO₂) were compared across socioeconomic deprivation quintiles. Multivariable linear and logistic regression models assessed the effects of age, sex, body mass index (BMI), Revised Cardiac Risk Index (RCRI), and deprivation quintiles on CPET measures. Hierarchical regression models incorporating the Indices of Deprivation (IoD) domains and Access to Healthy Assets and Hazards (AHAH) scores determined whether wider social determinants of health explained the variance in CPET measures.
• Results: A total of 3344 patients (2476 male) were included, referred prior to procedures in vascular (2006), colorectal (650), upper GI (267), urology (205), and other (216) surgical specialties. Lower socioeconomic status was associated with younger age (p < 0.001), higher BMI (p = 0.022), higher smoking prevalence (p < 0.001), and RCRI ≥3 (p = 0.013). CPET measures were lower in the most deprived quintile (Q1) compared to the least (Q5): mean GET was 11.0 vs. 11.5 ml·kg-1·min-1 and peak V̇O2 was 14.8 vs. 16.3 ml·kg-1·min-1 (p < 0.05). Deprivation remained an independent predictor of lower GET and peak V̇O2, even after adjustment. Several IoD and AHAH domains explained small but significant variance in CPET measures.
• Conclusion: Patients from more deprived areas exhibit risk factors for poor health and lower cardiorespiratory fitness as measured by CPET. These findings add to our understanding of socioeconomic disparities in physiological reserve among surgical patients and may support the need for more holistic approaches to peri-operative care.

Willixhofer, R; Centro Cardiologico Monzino, IRCCS, Via Parea 4, Milan 20138, Italy.;
Mapelli, M; Baracchini, N; Campana, N; et al

European journal of preventive cardiology,2025 Aug 07

• Aims: Hypertrophic cardiomyopathy (HCM) is associated with functional limitations during exercise. We aimed to evaluate oxygen pulse (O2p) as a stroke volume (SV) surrogate and to propose a new HCM classification (RoMa) based on haemodynamic profiles during exercise: predicted peak O2p (O2pp) and peak heart rate (HRpp).
• Methods and Results: This multicentre, prospective study included 90 clinically stable HCM patients who underwent cardiopulmonary exercise testing with simultaneous impedance cardiography (PhysioFlow®). We assessed the relationship between SV and O2p. Patients were stratified into four groups based on HRpp (≥80% predicted) and O2pp (≥100% predicted): RoMa I (high HRpp-high O2pp), RoMa II (high HRpp-low O2pp), RoMa III (low HRpp-high O2pp), and RoMa IV (low HRpp-low O2pp). Oxygen uptake (VO2), minute ventilation-to-carbon dioxide production (VE/VCO2) slope, SV, and mitral regurgitation (MR) were analysed. Patients (80% male, 53 [42-64] years) had preserved left ventricular ejection fraction (62 [58-68]%) and peakVO2 (23.1 ± 7.8 mL/min/kg = 81 ± 21% predicted). SV correlated with O2p (r = 0.48, P < 0.001; β = 3.59, P < 0.001). Resting moderate to severe MR was more prevalent in RoMa class IV (41%) vs. RoMa I (18%, P = 0.038). PeakVO2 declined across groups, from 29.7 ± 8.3 (RoMa I) to 16.2 ± 5.1 mL/min/kg (RoMa IV, P < 0.001). VE/VCO2 slope increased from 26.4 ± 4.5 (RoMa I) to 38.6 ± 6.0 (RoMa IV, P = 0.002). Peak SV decreased from 128.7 ± 24.8 (RoMa I) to 104.7 ± 28.0 mL (RoMa IV, P = 0.019), while rest to peak SV difference dropped from 38.6 (30.4-52.8) to 15.8 (8.2-27.9) mL (P = 0.002).
• Conclusion: SV and O2p are significantly related, and the RoMa classification effectively distinguished HCM patients.
• Key Findings: O2p is a reliable indicator of SV, helping to better understand exercise limitations in HCM patients.The newly introduced RoMa classification effectively distinguishes different levels of exercise impairment in HCM, linking poorer heart function to lower oxygen uptake and higher breathing inefficiency.

Takken, T; Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.
Ruuls, T; Van der Kamp, M;Thio, B; et al

Expert review of respiratory medicine,2025 Aug 14

• Introduction: Cardiopulmonary exercise testing (CPET) is a diagnostic-integrated tool for evaluating cardiovascular, ventilatory, and metabolic functional limitations in children with respiratory diseases. Recently, novel applications have emerged, revealing dynamic abnormalities that may go unnoticed in standard static cardiac and pulmonary function tests. Given its clinical importance and novel research findings, updated recommendations are warranted.
• Areas Covered: We conducted a narrative review based on a literature search up to April 2025. This review provides an update on the application of CPET in pediatric respiratory diseases, covering physiological differences to adults, non-traditional CPET metrics such as the oxygen uptake efficiency slope (OUES), tidal volume to inspiratory time ratio (VT/Ti), and recent reference values. Indications, contraindications, and standardized protocols are discussed, alongside emerging trends in CPET technology.
• Expert Opinion: CPET is a potent tool for assessing, evaluating, and diagnosing pediatric respiratory diseases. Standardized protocols, age-specific reference values, and novel CPET parameters enhance clinical utility. Future research should refine interpretation, integrate artificial intelligence for data analysis, and facilitate CPET for younger children.

Arena R; Department of Physical Therapy, College of Applied Science, University of Illinois, Chicago, IL, USA;
Myers J; Pronk NP;

Current problems in cardiology [Curr Probl Cardiol] 2025 Aug 05; Vol. 50 (10), pp. 103144.
Date of Electronic Publication: 2025 Aug 05.

A human’s ability to transfer oxygen from the environment to skeletal muscle and conversely remove carbon dioxide from skeletal muscle back to the environment during physical exertion is a critical representation of healthy longevity and functional capacity. Cardiorespiratory fitness (CRF) is the accepted construct for the assessment of oxygen consumption (VO ₂ ) and carbon dioxide production (VCO ₂ ) – CRF is most accurately quantified through cardiopulmonary exercise testing (CPET) in the clinical setting. All pharmacological interventions, from experimental to approved and on the market, are meant to impact one or more human physiological processes. In this context, the graphical primer on the physiological process of VO ₂ and VCO ₂ presented herein should facilitate the thought process on how pharmacology interacts with the factors that influence the capacity for physical exertion. Exercise is medicine and CRF is a vital sign and as such, the former should be prescribed to all capable individuals, and the latter should be considered a primary efficacy outcome measure in clinical and research settings. There is an opportunity to synergize and further enhance patient outcomes when pharmacologic and exercise interventions are considered integrated and in combination- a concept recently defined as pharma-cise – the graphical primer is proposed to facilitate application of this concept.