Open research questions in Cardiovascular and exercise physiology

What the literature leaves open

• Passive leg movement (PLM) offers a robust method for assessing vascular function; however, the interactions among age, endothelial-mediated vasodilatory mechanisms, and exercise training-induced PLM modulation remain poorly understood.

  The Impact of Age and Exercise Training on Endothelial-Mediated Mechanisms of Vasodilation during Passive Leg Movement in Males · 2026 · DOI

• Furthermore, considering the high variabil- ity of the MEF25% parameter and difficult trainability, applied training protocols were insufficient to induce lasting effects on small airway function.

  Effects of Resistance Respiratory Training on Respiratory Muscle Strength in Healthy Active Individuals · 2026 · DOI

• 20 To strengthen the evidence regarding the effectiveness of cycle ergometer- based training in improving balance and functional capacity, future research should consider studies with larger sample sizes to enhance external validity. Nonetheless, further investigations are warranted to refine the training protocol and clarify the physiological mechanisms involved.

  Low intensity cycle ergometer exercise improve balance in breast cancer women underwent chemotherapy · 2026 · DOI

• While the clinical significance of these potentially maladaptive changes at the individual level remains uncertain, at a population level high intensities and volumes of physical activity are consistently associated with reduced cardiovascular and all-cause mortality compared with sedentary behaviour, although the incremental survival benefit may plateau at very high exercise volumes.

  Does too much exercise damage the heart? A narrative review of the long-term cardiovascular effects of intense training · 2026 · DOI

• As a result, it remains unclear whether the observed improvements were primarily driven by aerobic exercise, respiratory training, or their interaction. Additionally, the cut-off values of the IPAQ-Short Form, which was used to assess physical activity and for which direct counterparts are lacking in the literature, appear relatively high. Future studies with a more diverse sample are warranted to further explore these effects.

  THE EFFECT OF AEROBIC EXERCISE TRAINING ON PHYSIOLOGICAL COST INDEX, PHYSICAL ACTIVITY, FUNCTIONAL CAPACITY, FATIGUE AND SLEEPINESS IN HEALTHY YOUNG ADULTS · 2026 · DOI

• Most studies investigating recovery in CrossFit® have focused on the effects of a single training session, whereas the cumulative effects of consecutive sessions within a training microcycle remain poorly understood.

  Time-Course of Recovery Following a Strength–Power Emphasized Crossfit® Microcycle · 2026 · DOI

• Future research is needed investigating the incidence and severity of EIGS and Ex-GIS in youth athletes com- peting in real-life ultramarathon events, with some key markers of EIGS rising to clinical significance in appli- cation of more extreme exercise stress (e.

  Exploration of Exercise-Induced Gastrointestinal Syndrome in Endurance-Trained Adolescents: Is There Cause for Concern in Regard to Ultra-endurance Event Participation · 2026 · DOI

• Although these findings provide preliminary support for the application of IT + BFR in male intermittent-sport athletes, several moderator results were based on limited evidence or showed limited robustness.

  Can blood flow restriction amplify the physiological and performance benefits of interval training in male intermittent-sport athletes? a systematic review and meta-analysis · 2026 · DOI

• Background Traditional percentage-based training (PBT) prescribes loads according to a fixed percentage of one-repetition maximum (1RM) but does not account for daily fluctuations in performance readiness.

  Relative effectiveness of different resistance training modalities on lower-body strength and explosive power: a systematic review and network meta-analysis · 2026 · DOI

• This pilot study has several limitations. First, the sample size was small, which limits statistical power and generalizability. Second, no dietary intake monitoring or nutritional control was implemented, which may have influenced changes in body composition. Third, neither participants nor assessors the risk of performance and were blinded, measurement bias. Fourth, no follow­up assessment was conducted to determine whether the observed changes were maintained over time. Fifth, no correction for multiple comparisons was applied, increasing the risk of Type I error. Finally, the Apnea–Hypopnea Index (AHI) and other objective sleep­related outcomes were not the intervention, limiting conclusions regarding the impact of these interventions on OSA severity. Some calculated t­values were unexpectedly high relative to the sample size and magnitude of mean change. Although the analyses were performed using SPSS, these values should be interpreted cautiously, as they may reflect statistical instability associated with the small pilot sample. reassessed after R. Jayabharathi E­mail: [email protected] 1. Messineo, L., Bakker, J. P., Cronin, J., Yee, J., & White, D. P. (2024). Obstructive sleep apnea and obesity: A review of epidemiology, pathophysiology and the effect of weight­loss treatments. Sleep medicine reviews, 78, 101996. https://doi.org/10.1016/ j.smrv.2024.101996 2. Chang, J. L., Goldberg, A. N., Alt, J. A., Mohammed, A., Ashbrook, L., Auckley, D., Ayappa, I., Bakhtiar, H., Barrera, J. E., Bartley, B. L., Billings, M. E., Boon, M. S., Bosschieter, P., Braverman, I., Brodie, K., Cabrera­Muffly, C., Caesar, R., Cahali, M. B., Cai, Y., Cao, M. Rosen, I. M. (2023). International Consensus Statement on Obstructive Sleep Apnea. International forum of allergy & rhinology, 13(7), 1061–1482. https://doi.org/10.1002/alr.23079 3. Lee, W., Nagubadi, S., Kryger, M. H., & Mokhlesi, B. (2008). Epidemiology of Obstructive Sleep Apnea: a Population­based Perspective. Expert review of respiratory medicine, 2(3), 349–364. https://doi.org/10.1586/17476348.2.3.349 4. Romero­Corral, A., Caples, S. M., Lopez­Jimenez, F., & Somers, V. K. (2010). Interactions between obesity and obstructive sleep apnea: implications for treatment. Chest, 137(3), 711–719. https://doi.org/10.1378/chest.09­0360 5. Dempsey, J. A., Veasey, S. C., Morgan, B. J., & O'Donnell, C. P. (2010). Pathophysiology of sleep apnea. Physiological reviews, 90(1), 47–112. https://doi.org/10.1152/physrev.00043.2008 6. Isono, Shiroh. (2012). Obesity and obstructive sleep apnoea: Mechanisms for increased collapsibility of the passive pharyngeal airway. Respirology (Carlton, Vic.). 17. 32­42. 10.1111/j.1440­1843.2011.02093.x. 7. Eckert, D. J., & Malhotra, A. (2008). Pathophysiology of adult obstructive sleep apnea.

  Comparative effects of upper-body plyometric training and circuit interval training in obese adults with moderate obstructive sleep apnea: a pilot study · 2026 · DOI

• The study group consisted of 88 women. This number proved to be insufficient. Considering the intensity of the undertaken tra‐ ining, participants were assigned to one of four groups: high, moderate, low, and mixed intensity. Unequal group sizes may ha‐ ve hindered reliable statistical analysis. Additionally, the intensity of individual training sessions was determined based on the fit‐ ness club’s offer, without verification using, for example, the Borg scale. Due to the overlap of multiple variables, the main aim of the study proved difficult to achieve. The results should be treated as a pilot study. Undoubtedly, there is a need for further studies conducted on a much larger scale, with division by sex.

  Can high-intensity training cause rectus abdominis diastasis in women? A pilot study · 2026 · DOI

• Supplementary material None. Regular physical activity, particularly walking and exercises activating the calf muscles, should be rec- ommended as a cornerstone of supportive therapy in patients with CVI, as these interventions improve venous return and reduce venous stasis. Compres- sion therapy remains one of the most evidence-based nonpharmacological approaches in CVI management. Assessment of calf muscle pump efficiency with duplex Doppler ultrasound and plethysmographic methods may be useful in selected patients, espe- cially in advanced stages of disease. Although L- -carnitine may influence skeletal muscle metabolism and endothelial function, further clinical studies are required before firm recommendations regarding sup- plementation in CVI can be established.

  Influence of the calf muscle pump on the genesis, development, and therapy of chronic venous insufficiency · 2026 · DOI

• This study has a few limitations that should be considered. First, the use of two independent metabolic carts without cross- over testing between systems should be acknowledged. Because participants were tested exclusively on one system, direct inter- device agreement could not be formally evaluated. Although identical calibration procedures, ergometer models, testing protocols, and data processing methods were applied across systems, potential systematic differences between platforms cannot be excluded. Therefore, findings should be interpreted within-device cross-system as equivalence, and specific to young, healthy adults. Second, each constant work-rate trial lasted six minutes, which is generally sufficient to reach steady state in moderate and heavy domains but may not capture longer-term physiological variability or progressive ventilatory drift. Additionally, the analysis focused on phase III of V̇ O2 kinetics but was not aimed at exploring phases I and II, into dynamic responses. insight Another methodological consideration relates to the use of a evidence of limiting rather than Frontiers in Sports and Active Living 09 frontiersin.org Colosio et al. 10.3389/fspor.2026.1814527 that MRT single MRT-based correction to translate ramp-derived responses into constant-work-rate exercise intensities. Recent work has highlighted to represent a fixed is unlikely physiological constant across exercise intensities and conditions (32), which may limit the precision of this type of adjustment approach. Nevertheless, in the present study, this correction was applied systematically within participants using the same procedure across all conditions, thereby reducing random methodological variability. In addition, the selected exercise (33%Δ and 66%Δ within each domain) were intensities intentionally positioned sufficiently within the moderate, heavy, and severe domains to minimise the likelihood that small errors in MRT correction would alter domain allocation. Despite these precautions, some residual uncertainty in the precise estimation of target work rates cannot be excluded. Finally, although variability metrics were derived from all interpolated and 5 s averaged data points within the final minute of exercise rather than from a single 1 min average value, the processing approach used in the present study still represents a smoothed representation of the original breath-by-breath signal. This approach was intentionally chosen to improve comparability across exercise intensities by partially reducing the influence of differing breathing frequencies and irregular breath timing. However, it may also attenuate some short-term physiological fluctuations compared with analyses performed directly on raw breath- by-breath data.

  Exercise intensity influences variability and test-retest reliability of pulmonary gas-exchange measurements during constant work-rate cycling · 2026 · DOI

• Moderate-load BFR may represent a practical strategy for improving performance while reducing mechanical loading demands, although caution is warranted when generalizing beyond the present protocol.

  The effect of blood flow restriction combined with different resistance training on the improvement of athletic performance in male tactical personnel · 2026 · DOI

• In contrast, the potential role of isometric exercise in patients with CAD remains insufficiently characterized, with limited and heterogeneous evidence regarding study designs, intervention protocols, and outcome measures, despite emerging findings suggesting favorable cardiovascular and metabolic adaptations when implemented through controlled protocols.

  Effects of Isometric Exercise on Cardiovascular and Metabolic Outcomes in Patients with Coronary Artery Disease: a Systematic Review · 2026 · DOI

• Background: Peripheral muscle electrostimulation (PME), encompassing neuromuscular electrical stimulation (NMES) and functional electrical stimulation (FES), has been increasingly acknowledged as an effective adjunctive or complementary treatment to voluntary exercise in elderly cardiac patients who cannot perform sufficient amounts of exercise, for whom there is limited research on optimal protocols.

  Theoretical and Scientific Underpinnings of Peripheral Muscle Electrostimulation in Cardiac Rehabilitation of the Elderly: A Systematic Review · 2026 · DOI

• However, whether HIIT preserves physical, cognitive, and cardiovascular function, mitigates frailty, and improves brain and heart health in older adult female mice remains unknown.

  High Intensity Interval Training in Aged Female Mice Preserves Physical, Cognitive, and Cardiovascular Function · 2026 · DOI

• Time spent at or near maximal oxygen uptake (tV̇O 2 max) has emerged as a key marker of the adaptive potential of HIIT, yet HIIT configurations that maximise tV̇O₂max remain unclear.

  Time spent at or near V̇O₂max during high-intensity interval training - a systematic review and meta-analysis · 2026 · DOI

• Background: Exercise-based cardiac rehabilitation (CR) improves peak oxygen uptake ([V]O2peak) in patients with coronary heart disease (CHD); however, whether women and men exhibit similar adaptations across the steps of O2 transport remains unknown.

  Beyond sex differences: equivalent adaptations across the O2 transport chain after exercise-based cardiac rehabilitation in women and men with coronary heart disease · 2026 · DOI

• This study has some limitations. First, the group definition relied solely on the readmission count without adjunctive biomarkers and detailed HF phenotype characterization, which may have diluted subgroup specificity. Although LVEF-based HF phenotypes were additionally summarized, biomarkers reflecting HF severity, including B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide, were not collected. Therefore, detailed characterization of disease severity and physiological heterogeneity across HF groups remains limited. Second, excluding ADL-dependent patients and those with dementia limited the generalizability to high-need HF subgroups. Third, non-standardized environmental variability (room temperature/illumination/noise/home setting) and the single-session design precluded the assessment of day-to-day variability, thereby affecting reliability. Fourth, detailed medication data, including β-blockers, angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers/angiotensin receptor–neprilysin inhibitors, mineralocorticoid receptor antagonists, and diuretics, were not systematically collected. These therapies may have influenced HR, HRR, SBP, and autonomic responses; therefore, the findings should be interpreted cautiously. Fifth, medication timing (β-blockers, diuretics, and ACE inhibitors) was imperfectly controlled and could alter acute responses. Sixth, all participants wore the device on the left wrist, and hand dominance was not recorded, which may have influenced the ULSC due to laterality bias. Future protocols should correct for side dominance. Seventh, the assumed effect size (f = 0.25) lacked strong empirical grounding and should be viewed as a methodological limitation. For interpretation, SBP re-rise and the R-HF ~ 5-min HR peak are descriptive (exploratory) features; these patterns should therefore be interpreted cautiously because group × time interaction effects were not statistically significant. PLOS One | https://doi.org/10.1371/journal.pone.0351501 June 11, 2026 13 / 16 Moreover, short-epoch HRV during low-intensity nonstationary segments is not a simple surrogate for sympathovagal balance [8,9]. Looking ahead, areas under the curve, time-to-peak, and recovery time constants should be pre-registered; spline/time-series models, 30–60-min monitoring, and concurrent respiration/actigraphy with medication-timing sensitivity analyses could more robustly test the chain from “quality of recovery after ADL” → “function and outcomes.”

  Dressing-induced hemodynamic instability in patients with heart failure: Implications for nursing care · 2026 · DOI

• (min/wee (sessions × min/per k) ~63 ~114 week) ~3×20 ~4×15 ~4×30 ~5×20 COM = Combined aerobic and resistance training, HIIT = High-intensity interval training; Intensity coding was extracted from the Compendium of Metabolic Equivalent Values for Physical Activities in Adults: code 01305: Bicycling, high intensity interval training; Code 02035: Circuit training, moderate effort 4.3 Innovations and limitations This study provides several methodological advances over earlier meta-analyses of exercise and VAT reduction in adults with overweight or obesity. Whereas previous syntheses have relied largely on conventional pairwise meta-analysis, we combined network meta-analysis with Bayesian dose-response modelling to evaluate four exercise modalities within a unified analytical framework. This design not only enables a broader comparison of relative efficacy but also incorporates exercise dose, thereby offering more clinically relevant evidence regarding both the optimal exercise modality and the tailoring of training load at the individual level. Several limitations should also be considered. First, clinical and methodological heterogeneity existed across the included studies, with potential sources including VAT measurement method; demographic and adiposity-related characteristics such as age, sex, race/ethnicity, and obesity classification; and intervention-related factors such as intervention duration and MET-min/week. Because the number of studies available for further stratified analyses was limited, and race/ethnicity and obesity-class-specific outcomes were not consistently reported, stratification or covariate adjustment by these factors may have resulted in sparse networks and unstable estimates. Therefore, these variables were not statistically adjusted for in the primary network meta-analysis or SUCRA-based ranking, and caution is warranted when interpreting the pooled estimates and treatment rankings. As more primary studies become available, sufficiently powered subgroup analyses and meta-regression will be needed to clarify whether these factors modify the effects of exercise interventions on VAT. Second, although MET-min/week is a practical standardized metric for exercise dose, it integrates exercise intensity, session duration, and weekly frequency and therefore cannot fully disentangle the independent contribution of each intervention component. In addition, differences in progression, adherence, and supervision were not fully ARTICLE IN PRESS ARTICLE IN PRESS ACCEPTED MANUSCRIPT captured. Third, to isolate the independent effect of exercise, studies combining exercise with dietary interventions were excluded. However, in real-world weight management and VAT reduction programs, exercise is often implemented together with dietary modification. Therefore, the exclusion of combined exercise and dietary interventions may limit the external validity and generalizability of the findings to comprehensive lifestyle programs.

  Optimal exercise modality and dose for reducing visceral adipose tissue in overweight or obese adults: a network meta-analysis and dose-response study · 2026 · DOI

• section. We Chinese were included. These two languages represent the primary publication in biomedical research and encompass the vast majority of high-quality cardiovascular rehabilitation trials.

  Exercise modalities and dose-response for LVEF Improvement in heart failure patients: a systematic review and network meta-analysis · 2026 · DOI

• The time between participants completing the intervention and the interviews being conducted was greater than antic- ipated. As such, reflections on experiences may have been distorted based on participants current knowledge, beliefs, PLOS One | https://doi.org/10.1371/journal.pone.0350509 May 29, 2026 14 / 17 and expectations [28]. As a collective, participants that accepted the offer of an interview were thankful for the reha- bilitation offered and, therefore, may have provided responses that they believed would support the programme. The research team attempted to minimize social desirability through ensuring privacy and communicating anonymity proce- dures. Furthermore, if the interviewer suspected socially desirable responses, they used indirect questions and probes for more information [29]. Whilst we aimed to minimize bias, the research team acknowledge the potential for participa- tion bias potentially leading to positively skewed outcomes. While barriers to participation were identified (more negative outcomes) and explained by those interviewed, those who did not volunteer to participate may have offered different experiences and insights. Further, 18 of 19 participants were male, limiting the generalizability of our findings. The requirement of VoIP technology for interviews may have systematically excluded older or socio-economically disadvan- taged patients.

  Participant lived experiences of high-intensity interval training in UK cardiac rehabilitation (HIIT or MISS UK): A qualitative study · 2026 · DOI

• It would be valuable to explore follow up programmes after CR. That is, what motivates participants to continue exercising after CR, what deters participants, and does this differ based on the type of exercise (e.g., HIIT/ MISS). The perceptions and experiences of intervention practitioners would also be insightful.

  Participant lived experiences of high-intensity interval training in UK cardiac rehabilitation (HIIT or MISS UK): A qualitative study · 2026 · DOI

• Although the present study has confirmed the positive effects of a 24-week BFR−FT intervention on athletic performance and body composition in high-level basketball players, several limitations warrant consideration. First, the sample size was relatively small due to the challenges associated with recruiting high-level athletes, despite meeting the minimum requirement based on power analysis.

  Effects of long-term functional training combined with blood flow restriction training on athletic performance and body composition in basketball athletes · 2026 · DOI

Most-cited papers in Cardiovascular and exercise physiology

• Limiting factors for maximum oxygen uptake and determinants of endurance performance · Medicine & Science in Sports & Exercise · 2000 · 1,613 citations
• Effects of Exercise on Glycemic Control and Body Mass in Type 2 Diabetes Mellitus · JAMA · 2001 · 1,403 citations
• Acute effects of moderate aerobic exercise on specific aspects of executive function in different age and fitness groups: A meta‐analysis · Psychophysiology · 2016 · 474 citations
• The acute versus the chronic response to exercise · Medicine & Science in Sports & Exercise · 2001 · 346 citations
• Resistance exercise as a treatment for sarcopenia: prescription and delivery · Age and Ageing · 2022 · 276 citations
• Balance Training for Neuromuscular Control and Performance Enhancement: A Systematic Review · Journal of Athletic Training · 2010 · 271 citations
• Resistance Exercise Training Alters Mitochondrial Function in Human Skeletal Muscle · Medicine & Science in Sports & Exercise · 2014 · 255 citations
• The Relevance of Sex Differences in Performance Fatigability · Medicine & Science in Sports & Exercise · 2016 · 254 citations
• Reliability and Intensity of the Six-Minute Walk Test in Healthy Elderly Subjects · Medicine & Science in Sports & Exercise · 2003 · 243 citations
• Impact of Resistance Training in Cancer Survivors · Medicine & Science in Sports & Exercise · 2013 · 241 citations

Most recent work

• The effect of blood flow restriction resistance exercise on arm muscle strength and isokinetic contraction parameters · BMC Sports Science, Medicine and Rehabilitation · 2026
• Association between Cardiorespiratory Fitness and Glycemic Control in Individuals with Type 2 Diabetes Mellitus · Exercise and Quality of Life · 2026
• Long-Term Effects of High-Intensity Training following Lung Cancer Surgery - A Five-Year Follow-Up of a Randomized Controlled Trial · Medicine & Science in Sports & Exercise · 2026
• Reduced task-related quadriceps sEMG and limited functional transfer after 4-week low-load blood flow restriction training: a pilot randomized controlled study · Frontiers in Physiology · 2026
• Efficacy of different high-intensity interval training versus moderate-intensity continuous training for body composition and cardiorespiratory fitness in obese/overweight patients: a systematic review and network meta-analysis · BMC Sports Science, Medicine and Rehabilitation · 2026
• Dual-resistance respiratory muscle training with a novel individualized respiratory exercise device: a randomized controlled trial · Irish Journal of Medical Science (1971 -) · 2026
• Artificial Intelligence-Driven Enhancement of Sports Wellness in the Elderly via an Adaptive Transfer Learning-Based Backpropagation Neural Network · Journal of Mechanics in Medicine and Biology · 2026
• Blood flow restriction training for lower limb injury prevention and rehabilitation in dancers: a scoping review of current evidence and future directions · BMC Sports Science, Medicine and Rehabilitation · 2026
• Combined effects of inspiratory and core muscle training on respiratory and core muscle function, limb muscle oxygenation and swimming performance · Journal of Sports Sciences · 2026
• Optimal Exercise Modalities and Dosages for Blood Pressure Reduction in Adults With Prehypertension and Established Hypertension: A Network Meta‐Analysis and Dose–Response Relationship Study · Journal of the American Heart Association · 2026

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