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11 pages, 703 KiB  
Article
Initial Implementation and Utilization of Cardiopulmonary Exercise Testing at a Pulmonary Department of an Academic Tertiary Care Center: An Overview
by Nimrod Kleinhaus, Yael Raviv, Itamar Ben Shitrit, Jonathan Wiesen, Liora Boehm Cohen, Michael Kassirer and Natalya Bilenko
J. Clin. Med. 2025, 14(11), 3676; https://doi.org/10.3390/jcm14113676 - 23 May 2025
Viewed by 227
Abstract
Background: Cardiopulmonary exercise testing (CPET) is a valuable diagnostic and prognostic tool for assessing the integrated function of the cardiopulmonary and muscular systems during exercise. The initiation of a CPET program is complex, and data on early implementation in academic centers remain relatively [...] Read more.
Background: Cardiopulmonary exercise testing (CPET) is a valuable diagnostic and prognostic tool for assessing the integrated function of the cardiopulmonary and muscular systems during exercise. The initiation of a CPET program is complex, and data on early implementation in academic centers remain relatively limited. Objective: to evaluate the initial integration of CPET within a pulmonary department, focusing on patient demographics, referral indications, test performance, and factors associated with anaerobic threshold achievement. Methods: A retrospective cohort study was conducted at a single tertiary care center, including all patients who underwent their first CPET between February 2016 and December 2022. Demographic, clinical, and functional parameters were extracted. Multivariable logistic regression was used to identify variables associated with anaerobic threshold achievement, defined as a respiratory exchange ratio (RER) ≥ 1.1. Results: The cohort included 434 patients (mean age 60.3 ± 14.1 years; 54% male; mean BMI 29.2 ± 5.6 kg/m2). The most common indication for testing was dyspnea (50%). Tests were most frequently terminated due to leg discomfort (39%) and dyspnea (38.8%). Achievement of RER ≥ 1.1 was independently associated with lower BMI (aOR = 0.91; 95% CI: 0.88–0.95; p < 0.001), higher FVC % predicted (aOR = 1.02; 95% CI: 1.00–1.03; p = 0.028), and greater minute ventilation volume (aOR = 1.02; 95% CI: 1.01–1.03; p < 0.001), and it was less likely in patients referred for cardiovascular disease (aOR = 0.37; 95% CI: 0.21–0.64; p < 0.001). No consistent temporal trend in RER achievement was observed across the study period. Conclusions: CPET was most commonly utilized in response to patient-reported dyspnea, with test termination frequently driven by subjective symptoms rather than objective clinical criteria. Anaerobic threshold achievement was more strongly associated with individual physiological characteristics than with institutional experience. These findings underscore the importance of patient preparation and pulmonary functional capacity in optimizing CPET performance. Full article
(This article belongs to the Section Respiratory Medicine)
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11 pages, 231 KiB  
Article
Autonomic Dysfunction and Low Cardio-Respiratory Fitness in Long-Term Post-COVID-19 Syndrome
by Radostina Cherneva, Zheyna Cherneva, Vania Youroukova, Tanya Kadiyska, Dinko Valev, Ebru Hayrula-Manaf and Vanyo Mitev
Biomedicines 2025, 13(5), 1138; https://doi.org/10.3390/biomedicines13051138 - 8 May 2025
Viewed by 408
Abstract
Purpose: Post-COVID-19 syndrome (PCS) is characterized by low cardio-respiratory fitness (CRF). Recent research focuses on the role of autonomic nervous system dysfunction (AD) as a potential contributor to the diminished exercise performance. The aim is to determine the prevalence of AD—chronotropic insufficiency (CI) [...] Read more.
Purpose: Post-COVID-19 syndrome (PCS) is characterized by low cardio-respiratory fitness (CRF). Recent research focuses on the role of autonomic nervous system dysfunction (AD) as a potential contributor to the diminished exercise performance. The aim is to determine the prevalence of AD—chronotropic insufficiency (CI) and abnormal heart rate recovery (HRR) in long-term PCS subjects and to analyse their association with exercise capacity. Patients and Methods: A total of 192 subjects with a history of SARS-CoV-2 infection were included. Chronic Fatigue Syndrome Questionnaire (CFSQ) was applied, and two symptomatic and asymptomatic emerged. Forty-seven had post-COVID complaints, persisting up to thirty months post-acute episode. CI and HRR were determined during the cardio-pulmonary exercise test (CPET). Results: Symptomatic subjects were divided into mild (20) and moderate-severe (27), depending on the CFSQ score; forty-eight PCS subjects without complaints served as a control group. Subjects with moderate-severe PCS showed lower peak VO2 (24.13 ± 6.1 mL/min/kg vs. 26.73 ± 5.9 mL/min/kg, vs. 27.01 ± 6.3 mL/min/kg), as compared to the mild/asymptomatic subjects. Diminished physical activity was established in 10 (37%) of the moderate-severe, 7 (35%) of the mildly symptomatic and 14 (29%) of the asymptomatic groups. The occurrence of AD in the mild/moderate-severe and control groups were, respectively, CI 35% vs. 81.5% vs. 12.5%. Abnormal HRR was, respectively, 20% vs. 33% vs. 8%. None of the subjects had depleted breathing reserve, dynamic hyperinflation, exercise bronchospasm or desaturation. Neither CI nor abnormal HRR correlated to peak O2. Conclusions: AD is present among long-term PCS subjects and may limit the cardio-respiratory response to exercise but is not independently associated with it. Assuming the multiorgan ANS innervation, it is highly probable that AD has diverse pathological pathways in the various PCS phenotypes and contributes differently by cerebral, cardiovascular, respiratory, peripheral or mixed pathways to the diminished neuro-cognitive and physical performance. Full article
12 pages, 991 KiB  
Article
Vo2peak, Ve/VCO2, and Cardiac Remodeling Correlate with Long-Term Cardiovascular Outcome in Heart Failure Patients
by Antonio Pagliaro, Luna Cavigli, Roberta Molle, Elisabetta Iardino, Francesca Anselmi, Francesca Righini, Luca Martini, Valerio Zacà, Giulia Elena Mandoli, Maria Concetta Pastore, Marta Focardi, Matteo Cameli, Sonia Bernazzali, Massimo Maccherini, Marco Chiostri, Flavio D’Ascenzi and Serafina Valente
J. Cardiovasc. Dev. Dis. 2025, 12(5), 174; https://doi.org/10.3390/jcdd12050174 - 2 May 2025
Viewed by 296
Abstract
Accurate prognostic stratification in patients with chronic heart failure and reduced ejection fraction (HFrEF) remains a significant clinical challenge. Many different parameters, including left ventricular (LV) and right ventricular (RV) function and cardiopulmonary exercise testing (CPET) parameters, are available in the literature. LV [...] Read more.
Accurate prognostic stratification in patients with chronic heart failure and reduced ejection fraction (HFrEF) remains a significant clinical challenge. Many different parameters, including left ventricular (LV) and right ventricular (RV) function and cardiopulmonary exercise testing (CPET) parameters, are available in the literature. LV ejection fraction (LVEF) is the most used parameter in clinical practice. This study aimed to analyze CPET and echocardiographic data in patients under evaluation for heart transplantation (HTx) to identify the parameter that best correlates with cardiac events. Methods and Results. Echocardiography and CPET were performed in patients with HFrEF under evaluation for HTx. The population comprised 170 patients (mean age: 55 ± 9 years; 88% male; non-ischemic etiology: 63%). LVEF was 30.4 ± 7.6%, peak oxygen uptake (Vo2peak) was 17.08 ± 4.6 mL/Kg/min; minute ventilation (VE)/carbon dioxide production (Vco2) slope was 34.8 ± 8.7. During a follow-up of 4 ± 1 years, 37 hospitalizations, 4 deaths, 14 HTx, and 5 LV assist device implantation occurred. Patients who experienced major events had a lower Vo2peak (p < 0.005), higher VE/Vco2 slope (p < 0.005), greater LV end-systolic diameter (p < 0.005), and RV end-diastolic diameter (p < 0.005) than patients without events. Conversely, LVEF did not differ between these two groups. VE/Vco2 slope and RV dimensions significantly correlated with hard cardiac events (p = 0.019 and p = 0.008, respectively). Conclusions. In patients with HFrEF, parameters quantifying the system reserve (i.e., Vo2peak and VE/Vco2 slope) and those demonstrating advanced biventricular remodeling may help stratify the risk of cardiac events. Conversely, LVEF showed a limited prognostic value in this setting. Full article
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11 pages, 240 KiB  
Article
Cardio-Respiratory Fitness and Fatigue in Post-COVID-19 Syndrome—A Three-Year Update
by Radostina Cherneva, Zheyna Cherneva, Vania Youroukova, Tanya Kadiyska, Dinko Valev, Ebru Myuyun Hayrula-Manaf and Vanyo Mitev
Biomedicines 2025, 13(5), 1097; https://doi.org/10.3390/biomedicines13051097 - 30 Apr 2025
Viewed by 403
Abstract
Background: Post-COVID-19 syndrome (PCS) is defined as the persistence of symptoms 3 months after acute SARS-CoV-2 infection. The long-term prevalence and clinical progression of PCS has not been established. Our aim was to investigate the symptoms in PCS patients, explore the degree of [...] Read more.
Background: Post-COVID-19 syndrome (PCS) is defined as the persistence of symptoms 3 months after acute SARS-CoV-2 infection. The long-term prevalence and clinical progression of PCS has not been established. Our aim was to investigate the symptoms in PCS patients, explore the degree of physical activity, according to the fatigue severity score, and analyze its association with basic cardio-pulmonary exercise testing (CPET) parameters. Methods: A total of 192 subjects with history of SARSCoV-2 infection were included. They filled in the Chronic Fatigue Syndrome Questionnaire (CFSQ) and were divided into symptomatic and asymptomatic groups. Forty-seven had persistent post-COVID complaints—reduced physical capacity, fatigue, dyspnea, sleep disturbances, muscle pain. CPET was performed and the pathophysiological parameters in the different fatigue severity groups were compared. Results: Subjects with persistent long-term PCS were divided into two groups—mild (20) and moderate–severe (27), depending on the CFSQ score; forty-eight PCS subjects without complaints served as a control group. The average period between the acute illness and the study was 1028 ± 214 days. Subjects with moderate–severe PCS had more symptoms during CPET (73.6% vs. 24.8% vs. 17.4%), as compared to mild/asymptomatic. The rate of perceived effort was subjective and did not correspond to the workload, heart, or breathing rate in the symptomatic group. These subjects were unable to reach the anaerobic threshold, compared to mild/asymptomatic subjects (51.8% vs. 25%, vs. 12.5%). Patients with moderate–severe PCS showed lower peak VO2 (24.13 ± 6.1 mL/min/kg vs. 26.73 ± 5.9 mL/min/kg, vs. 27.01 ± 6.3 mL/min/kg), as compared to mild/asymptomatic subjects. Conclusions: Long-term PCS is still present in up to 24% of the general population, more than thirty months after the acute episode. It is characterized by increased perception of symptom burden and diminished aerobic metabolism. A third of the long-term PCS exhibit lower cardio-respiratory fitness, independently from the severity of the symptoms. Full article
13 pages, 1096 KiB  
Article
The Influence of Genotype on the Cardiopulmonary Test Response in Patients Affected by Hypertrophic Cardiomyopathy
by Maria Felicia Gagliardi, Gabriella Malfatto, Claudia Baratto, Alessia Giglio, Valeria Rella, Paolo Cerea, Davide Mariani, Sabrina Salerno, Silvia Ravaro, Silvia Castelletti, Gerardina Fratianni, Chiara Alberio, Matteo Pedrazzini, Mariam Khujadze, Luigi P. Badano, Denisa Muraru, Gianfranco Parati, Franco Cecchi, Sergio Caravita and Lia Crotti
Cardiogenetics 2025, 15(2), 12; https://doi.org/10.3390/cardiogenetics15020012 - 29 Apr 2025
Viewed by 568
Abstract
In hypertrophic cardiomyopathy (HCM), the presence of pathogenic/likely pathogenic (P/LP) disease-causing genetic variants may indicate a worse prognosis. Few data exist on the effects of these genetic variants on cardiopulmonary exercise test (CPET) performance in HCM patients. We analysed asymptomatic and slightly symptomatic [...] Read more.
In hypertrophic cardiomyopathy (HCM), the presence of pathogenic/likely pathogenic (P/LP) disease-causing genetic variants may indicate a worse prognosis. Few data exist on the effects of these genetic variants on cardiopulmonary exercise test (CPET) performance in HCM patients. We analysed asymptomatic and slightly symptomatic HCM patients (NYHA I-II) whose genetic analysis and CPET were available; at baseline, left ventricular function was normal and severe left ventricular outflow trait obstruction was excluded. Out of 120 HCM patients, we excluded 13 carrying variants of uncertain significance; of the remaining 107 patients, 54 were genotype negative [gene (−)], and 53 had a P/LP variant in sarcomeric genes [gene (+)]. Patients in the two groups had similar NYHA class, cardiovascular risk factors and echocardiographic characteristics. Gene (+) patients showed a lower peak VO2% and O2 pulse % (p < 0.05). Moreover, among gene (+), patients with P/LP variants in the so called “thin-filament” genes (TNNT2, TPM1 and MYL3) had the poorest CPET results. In asymptomatic or slightly symptomatic HCM patients with similar echocardiographic characteristics, exercise tolerance is affected by the genetic background. Indeed, exercise capacity is poorer in gene (+) compared to gene (−) patients and those carrying P/LP variants in “thin-filament” genes show the worst performance. Full article
(This article belongs to the Section Cardiovascular Genetics in Clinical Practice)
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19 pages, 532 KiB  
Article
Integrated Diagnostics for Atrial Fibrillation Recurrence: Exploratory Results from the PLACEBO Trial
by Aristi Boulmpou, Theodoros Moysiadis, Georgios Zormpas, Eleftherios Teperikidis, Konstantina Tsioni, Maria Toumpourleka, Maria Zidrou, Georgios Giannakoulas, Vassilios Vassilikos and Christodoulos Papadopoulos
Diagnostics 2025, 15(9), 1105; https://doi.org/10.3390/diagnostics15091105 - 27 Apr 2025
Viewed by 376
Abstract
Background: Atrial fibrillation is a prevalent arrhythmia with significant morbidity and recurrence challenges. Paroxysmal atrial fibrillation (PAF) is characterized by episodic occurrences and unpredictable recurrences; therefore, it demands innovative diagnostic approaches to predict relapses and guide management. Objectives: This pilot, exploratory [...] Read more.
Background: Atrial fibrillation is a prevalent arrhythmia with significant morbidity and recurrence challenges. Paroxysmal atrial fibrillation (PAF) is characterized by episodic occurrences and unpredictable recurrences; therefore, it demands innovative diagnostic approaches to predict relapses and guide management. Objectives: This pilot, exploratory study evaluates the feasibility and prognostic value of integrating cardiopulmonary exercise testing (CPET), echocardiographic indices, and plasma biomarkers for predicting PAF recurrence. Methods: The PLACEBO trial is a single-center, prospective observational study of 73 adults with PAF in sinus rhythm at baseline. Comprehensive assessments included CPET, transthoracic echocardiography, 24 h electrocardiographic Holter monitoring with heart rate variability (HRV) metrics, and plasma biomarkers, such as galectin-3 (GAL3). Recurrence was defined as any documented AF episode lasting ≥30 s within 12 months of follow-up. Results: Binary logistic regression revealed that the standard deviation of RR intervals (SDRR) and GAL3 were significant predictors of recurrence. Particularly, higher SDRR [odds ratio (OR): 1.061, p = 0.021] and GAL3 > 10.95 ng/mL (OR: 5.206, p = 0.006) were associated with recurrence. Moreover, lower right ventricular fractional area change (RV FAC) exhibited a marginally significant association with recurrence (OR: 0.927, p = 0.062). CPET parameters demonstrated limited prognostic value in this cohort. Conclusion: This pilot study demonstrates that integrating novel echocardiographic indices, biomarkers, and HRV metrics is feasible and may provide valuable prognostic insights for PAF recurrence. Larger multicenter studies are needed to validate these findings and optimize personalized risk stratification strategies. Full article
(This article belongs to the Special Issue The Future of Cardiac Imaging in the Diagnosis)
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12 pages, 565 KiB  
Article
Key Resting Echocardiographic Parameters for the Estimation of Exercise Parameters of Peak VO2, Heart Rate Recovery, and Ventilatory Efficiency
by Kalyan Chaliki, Arundhati Sharma, Anubhuti Sharma, Claire Yee, Hari Chaliki and Satyajit Reddy
J. Clin. Med. 2025, 14(9), 3013; https://doi.org/10.3390/jcm14093013 - 27 Apr 2025
Viewed by 374
Abstract
Background/Objectives: The peak oxygen consumption (VO2) during cardiopulmonary exercise testing (CPET) is a strong predictor of all-cause mortality. The cardiac output, a key determinant of VO2, can be assessed using resting echocardiographic parameters. The heart rate recovery and ventilatory efficiency (VE/VCO2 slope) [...] Read more.
Background/Objectives: The peak oxygen consumption (VO2) during cardiopulmonary exercise testing (CPET) is a strong predictor of all-cause mortality. The cardiac output, a key determinant of VO2, can be assessed using resting echocardiographic parameters. The heart rate recovery and ventilatory efficiency (VE/VCO2 slope) from CPET offer additional insights into cardiovascular fitness. Methods: This study aimed to identify resting echocardiographic parameters that predict the percentage of predicted peak VO2, heart rate recovery, and VE/VCO2 slope in a general cardiology population. This retrospective analysis included 1909 patients who underwent echocardiography within 3 months of CPET from 2017 to 2022. Patients with potentially confounding co-morbid conditions were removed. Spearman correlations were used to compare 19 echocardiographic parameters to peak VO2, heart rate recovery, and the VE/VCO2 slope, followed by multiple linear regression of peak VO2. Results: Eleven echocardiographic parameters correlated with peak VO2, with the strongest correlations seen with the left ventricular stroke volume index (R = 0.284, p < 0.001), mitral valve medial annular a’ wave velocity (R = 0.142, p < 0.0001), and mitral E-to-e’ ratio (R = −0.117, p < 0.0001). The left ventricular diastolic parameters and mitral E/A ratio correlated strongly with the heart rate recovery and VE/VCO2 slope. The multiple linear regression analysis identified the left ventricular mass index, stroke volume index, mitral valve E wave velocity, tricuspid valve regurgitation peak systolic velocity, tricuspid lateral annular systolic velocity S’, and left atrial volume index as independent predictors of peak VO2 (R2 = 0.191). Conclusions: The left ventricular stroke volume, diastolic function, and RV systolic function markers are significant predictors of cardiopulmonary fitness, aiding clinical decision-making in patients without CPET data. Full article
(This article belongs to the Section Cardiovascular Medicine)
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13 pages, 1179 KiB  
Article
Is Cardiopulmonary Exercise Testing Predictive of Survival Outcomes in Patients Undergoing Surgery for Ovarian Cancer?
by Velangani Bhavya Swetha Rongali, Joanne Knight, Chloe Banfield, Porfyrios Korompelis, Stuart Rundle and Anke Smits
Cancers 2025, 17(9), 1460; https://doi.org/10.3390/cancers17091460 - 26 Apr 2025
Viewed by 1011
Abstract
Preoperative cardiopulmonary exercise testing (CPET) provides an objective measure of a patient’s functional capacity under stress. However, the association between CPET and long-term outcomes for women with ovarian cancer have not been assessed. The aim was to determine whether cardiorespiratory fitness, as measured [...] Read more.
Preoperative cardiopulmonary exercise testing (CPET) provides an objective measure of a patient’s functional capacity under stress. However, the association between CPET and long-term outcomes for women with ovarian cancer have not been assessed. The aim was to determine whether cardiorespiratory fitness, as measured by CPET parameters—peak oxygen uptake (VO2 peak), ventilatory efficiency at anaerobic threshold (VE/VCO2 at AT), and anaerobic threshold (AT)—could predict overall survival (OS) and recurrence -free survival (RFS) in patients with all stages of ovarian cancer. Methods: This was a retrospective cohort study of patients who underwent CPET prior to surgery for suspected or confirmed ovarian cancer during 2019–2023 at the Northern Gynaecological Oncology Centre, United Kingdom. CPET outcomes were risk-stratified, with thresholds of AT ≥ 10 mL/min, VO2 peak ≥ 15 mL/kg/min, and VE/VCO2 at AT ≤ 34 indicating lower risk. Primary outcomes included OS and RFS. Results: A total of 303 patients were included, of whom 56 (18.5%) had a staging laparotomy, 130 (42.9%) underwent primary cytoreductive surgery, and 117 (38.6%) underwent interval cytoreductive surgery. Survival analysis showed that VO2 peak ≥ 15 was significantly associated with improved OS of the whole population (p = 0.032). VE/VCO2 at AT ≤ 34 was associated with improved survival in patients with advanced stage disease (p = 0.025) after ovarian cancer surgery. There was no association between CPET parameters and RFS. Conclusions: We found that peak VO2 ≥ 15 was associated with improvement of overall survival in patients with all stages of ovarian cancer. In addition, VE/VCO2 at AT ≤ 34 was associated with overall survival in patients with advanced-stage disease. Full article
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18 pages, 1880 KiB  
Article
Cardiopulmonary Exercise Testing Correlates with Quantitative Left Ventricular [99mTc]-DPD Uptake in Transthyretin Amyloid Cardiomyopathy
by Nikita Ermolaev, René Rettl, Robin Willixhofer, Christina Kronberger, Michael Poledniczek, Lena Marie Schmid, Franz Duca, Christina Binder, Mahshid Eslami, Dietrich Beitzke, Christian Loewe, Marcus Hacker, Andreas Kammerlander, Johannes Kastner, Jutta Bergler-Klein, Raffaella Calabretta and Roza Badr Eslam
J. Clin. Med. 2025, 14(9), 2999; https://doi.org/10.3390/jcm14092999 - 26 Apr 2025
Viewed by 305
Abstract
Background/Objectives: Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) often experience significantly reduced functional capacity due to myocardial involvement. Cardiopulmonary exercise testing (CPET) is the gold standard to quantify functional capacity, and 99mTc-DPD scintigraphy and SPECT/CT have proven to be highly effective tools [...] Read more.
Background/Objectives: Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) often experience significantly reduced functional capacity due to myocardial involvement. Cardiopulmonary exercise testing (CPET) is the gold standard to quantify functional capacity, and 99mTc-DPD scintigraphy and SPECT/CT have proven to be highly effective tools for diagnostic and disease monitoring. We aimed to investigate the complementary role and correlation between both methods, focusing on their combined potential as a strong prognostic framework for monitoring disease progression and evaluating treatment efficacy. Methods: A total of 44 patients with diagnosed ATTR-CM, who underwent 99mTc-DPD scintigraphy and SPECT/CT imaging as well as CPET, were included. All patients were divided into two groups based on the median DPD retention index (low DPD uptake: ≤5.0, n = 22; high DPD uptake: >5.0, n = 22). Results: The mean age was 78 years, with 82% of participants being male. Significant correlations were observed between peak VO2 and DPD retention index (r = −0.355, p = 0.018) as well as between peak VO2 at anaerobic threshold with DPD retention index (r = −0.391, p = 0.009). Interestingly, there was no strong correlation between VE/VCO2 slope and the retention index. A strong association was identified between cardiac biomarkers and peak VO2, specifically for NT-proBNP (r = −0.530, p < 0.001) and Troponin T (r = −0.431, p < 0.001). Conclusions: In ATTR-CM, significant correlations were observed between key CPET parameters and quantitative cardiac DPD uptake, which further reflects on disease severity and functional impairment. Our findings highlight the utility of integrating CPET and SPECT/CT for comprehensive patient assessment in ATTR-CM. Full article
(This article belongs to the Section Cardiovascular Medicine)
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17 pages, 7251 KiB  
Article
Use of a Silicon Microneedle Chip-Based Device for the Extraction and Subsequent Analysis of Dermal Interstitial Fluid in Heart Failure Patients
by Markus Renlund, Laurenz Kopp Fernandes, Pelle Rangsten, Mikael Hillmering, Sara Mosel, Ziad Issa, Volkmar Falk, Alexander Meyer and Felix Schoenrath
Diagnostics 2025, 15(8), 989; https://doi.org/10.3390/diagnostics15080989 - 13 Apr 2025
Viewed by 461
Abstract
Background/Objectives: Dermal interstitial fluid (dISF) is probably the most interesting biofluid for biomarker analysis as an alternative to blood, enabling higher patient comfort and closer or even continuous biomarker monitoring. The prerequisite for dISF-based analysis tools is having convenient access to dISF, as [...] Read more.
Background/Objectives: Dermal interstitial fluid (dISF) is probably the most interesting biofluid for biomarker analysis as an alternative to blood, enabling higher patient comfort and closer or even continuous biomarker monitoring. The prerequisite for dISF-based analysis tools is having convenient access to dISF, as well as a better knowledge of the presence, concentration, and dynamics of biomarkers in dISF. Hollow microneedles represent one of the most promising platforms for access to pure dISF, enabling the mining of biomarker information. Methods and Results: Here, a microneedle-based method for dISF sampling is presented, where a combination of hollow microneedles and sub-pressure is used to optimize both penetration depth in skin and dermal interstitial fluid sampling volumes, and the design of an open, prospective, exploratory, and interventional study to examine the detectability of inflammatory and cardiocirculatory biomarkers in the dISF of heart failure patients, the relationship between dISF-derived and blood-derived biomarker levels, and their kinetics during a cardiopulmonary exercise test (CPET) is introduced. Conclusions: The dISF sampling method and study presented here will foster research on biomarkers in dISF in general and in heart failure patients in particular. The study is part of the European project DIGIPREDICT—Digital Edge AI-deployed DIGItal Twins for PREDICTing disease progression and the need for early intervention in infectious and cardiovascular diseases beyond COVID-19. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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13 pages, 593 KiB  
Article
Ventilatory Response to Exercise in HFrEF-COPD: Importance of Exercise Modality
by Marta Íscar Urrutia, Julia Herrero Huertas, Marina Acebo Castro, Ramón Fernández Álvarez, Beatriz Díaz Molina and Marta García Clemente
J. Clin. Med. 2025, 14(8), 2538; https://doi.org/10.3390/jcm14082538 - 8 Apr 2025
Viewed by 374
Abstract
Background: Heart failure with reduced ejection fraction (HFrEF) frequently coexists with chronic obstructive pulmonary disease (COPD), and both conditions share symptoms such as exertional dyspnea. The cardiopulmonary exercise test (CPET) is an essential tool for assessing ventilatory and cardiovascular function and plays a [...] Read more.
Background: Heart failure with reduced ejection fraction (HFrEF) frequently coexists with chronic obstructive pulmonary disease (COPD), and both conditions share symptoms such as exertional dyspnea. The cardiopulmonary exercise test (CPET) is an essential tool for assessing ventilatory and cardiovascular function and plays a key role in the differential diagnosis of dyspnea. However, the impact of exercise modality on the ventilatory and cardiovascular parameters obtained remains unclear in these groups. Our aim is to compare the oxygen consumption (V·O2) and breathing reserve (BR) values obtained from CPET on a treadmill and a cycle ergometer in patients with HFrEF-COPD and those with HFrEF alone. Methods: A prospective observational study included 65 patients with HFrEF (LVEF ≤ 40%), 18 of whom had COPD. Two CPETs were performed, the first on a treadmill and the second 48–72 h later on a cycle ergometer. Results: In the group with HFrEF-COPD, peak oxygen consumption (VO2/kg) and maximum ventilation (VE) values were significantly higher on the treadmill (20 ± 5 vs. 17 ± 4 mL/kg/min, p < 0.001 and 55 ± 19 vs. 45 ± 11 L/min, p < 0.001, respectively), while breathing reserve (BR%) was lower on the treadmill (16 ± 21 vs. 33 ± 20, p < 0.001). Compared to the HFrEF group, patients with HFrEF-COPD had a lower BR in both exercise modalities (p = 0.01). Conclusions: Treadmill CPET demonstrates greater oxygen consumption and a more pronounced ventilatory response. BR is consolidated as a differential parameter in ventilatory limitation. The choice of exercise modality should be considered based on the underlying pathologies and the objective of the test. Full article
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15 pages, 2793 KiB  
Review
Geometric Analyses of the Expiratory Flow–Volume Curve to Identify Expiratory Flow Limitation During Exercise
by Hans Haverkamp, Gregory Petrics and Yannick Molgat-Seon
Fluids 2025, 10(4), 94; https://doi.org/10.3390/fluids10040094 - 3 Apr 2025
Viewed by 451
Abstract
An important purpose of cardiopulmonary exercise testing (CPET) is to query the mechanisms for unexplained shortness of breath or exaggerated exertional dyspnea. Expiratory flow limitation (EFL) is an important indicator of ventilatory constraint that can negatively influence both dyspnea and exercise capacity. Unfortunately, [...] Read more.
An important purpose of cardiopulmonary exercise testing (CPET) is to query the mechanisms for unexplained shortness of breath or exaggerated exertional dyspnea. Expiratory flow limitation (EFL) is an important indicator of ventilatory constraint that can negatively influence both dyspnea and exercise capacity. Unfortunately, due to logistical challenges and lack of sufficient clinical training, EFL is rarely measured during CPET. The conventional method for identifying exercise EFL is limited because it requires patient cooperation and it is also dependent on the maximal expiratory flow–volume curve, which underestimates actual maximal expiratory flow during exercise. Simplified methods for identifying EFL that are based on the shape of the exercise tidal flow–volume curve would improve the accessibility of measuring EFL during exercise. The overall aim of this review is to critically review the approaches and methods used to measure EFL in exercising adults. We review the physiology underlying EFL and the conventional methods for determining exercise EFL. We then provide critical analyses of more recent methods for identifying exercise EFL that are based on the geometry of the exercise tidal expiratory flow–volume curve. Finally, we highlight recent work designed to assess exercise EFL using a type of deep machine learning known as a convolutional neural network. Full article
(This article belongs to the Special Issue Respiratory Flows)
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10 pages, 2831 KiB  
Article
The Actual Role of CPET in Predicting Postoperative Morbidity and Mortality of Patients Undergoing Pneumonectomy
by Antonio Mazzella, Riccardo Orlandi, Patrick Maisonneuve, Clarissa Uslenghi, Matteo Chiari, Monica Casiraghi, Luca Bertolaccini, Giovanni Caffarena and Lorenzo Spaggiari
J. Pers. Med. 2025, 15(4), 136; https://doi.org/10.3390/jpm15040136 - 31 Mar 2025
Viewed by 349
Abstract
This study aims to determine whether maximal oxygen consumption (VO2max) or predicted postoperative (ppo)-VO2max could still reliably predict postoperative complications and deaths in lung cancer patients undergoing pneumonectomy and which values could be more reliably considered as the optimal threshold. Methods: We [...] Read more.
This study aims to determine whether maximal oxygen consumption (VO2max) or predicted postoperative (ppo)-VO2max could still reliably predict postoperative complications and deaths in lung cancer patients undergoing pneumonectomy and which values could be more reliably considered as the optimal threshold. Methods: We retrospectively collected data of consecutive patients undergoing pneumonectomy for primary lung cancer at the European Oncological Institute (April 2019–April 2023). Routine preoperative assessment included cardiopulmonary exercise testing (CPET) and a lung perfusion scan. We evaluated the morbidity and mortality rates; associations between morbidity, mortality, VO2max, and ppoVO2max values were investigated through ANOVA or Fisher’s exact test as appropriate. Receiver operating characteristic (ROC) curves were applied to further explore the relation between VO2max, ppoVO2max values, and 90-day mortality. Results: The cardiopulmonary morbidity rate was 32.2%; the 30-day and 90-day mortality rates were 2.2% and 6.7%. The PpoVO2max values were significantly lower in patients experiencing cardiopulmonary complications or deaths compared to the whole cohort, whereas VO2max, though showing a trend towards lower values, did not reach statistical significance. A VO2max value threshold of 15 mL/kg/min correlated significantly with 90-day mortality, while a ppoVO2max cut-off of 10 mL/kg/min was significantly associated with cardiopulmonary complications and 30-day and 90-day mortality rates. ROC curve analysis revealed ppoVO2max as a better predictor of 90-day mortality compared to VO2max. Conclusions: CPET and a lung perfusion scan are two key elements for the preoperative evaluation of patients undergoing pneumonectomy, since it provides a holistic assessment of cardiopulmonary functionality. We recommend the routine calculation of ppoVO2max, particularly when adopting a 10 mL/kg/min threshold. Full article
(This article belongs to the Special Issue Novel Challenges and Advances in Thoracic Surgery)
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20 pages, 238 KiB  
Article
The Effects of Consuming Mineral Water from the “Topla Voda” Spring on the Body Composition and Functional and Biochemical Parameters of Professional Male Handball Athletes: A Pilot Study
by Djordje Batinic, Andrija Djuranovic, Milos Maletic, Sanja Stankovic, Vladimir Zivkovic, Dejan Stanojevic, Sergey Bolevich, Milan Savic and Vladimir Jakovljevic
Sports 2025, 13(4), 100; https://doi.org/10.3390/sports13040100 - 26 Mar 2025
Viewed by 363
Abstract
Adequate hydration is crucial to an athlete’s health and performance. There is some evidence that the different compositions of various mineral water types may improve exercise performance and affect different biomarkers. The aim was to investigate the consumption of mineral water from the [...] Read more.
Adequate hydration is crucial to an athlete’s health and performance. There is some evidence that the different compositions of various mineral water types may improve exercise performance and affect different biomarkers. The aim was to investigate the consumption of mineral water from the “Topla voda” spring in terms of its safety profile and its effect on body composition and functional and biochemical parameters in professional athletes. During the preparation phase of their mesocycle, 14 male professional handball players underwent a complete sports medical screening exam with a cardiopulmonary exercise test (CPET), blood gas analysis, and oxidative stress marker dynamics taken at four points during the CPET. The athletes were then randomized into two equal groups; the first group consumed mineral water, and the second group consumed tap water. After four weeks, the biochemical analysis and CPET were repeated. Routine analyses showed that the “mineral water” group had increased their mean corpuscular hemoglobin (ANCOVA = 0.050) and mean corpuscular hemoglobin concentration (ANCOVA = 0.001) and had a greater metabolic equivalent of task (MET) value at the end of the test (ANCOVA = 0.049), with no significant changes in the other measured parameters. Consuming “mineral water” appears to be safe, with some potential positive effects compared with tap water, mostly in terms of hemoglobin parameters and exercise tolerance. Full article
14 pages, 1411 KiB  
Article
Cardiac Involvement and Heart Failure Staging in Patients with Systemic Sclerosis Without Pulmonary Arterial Hypertension
by Maria Isilda Oliveira, Bruno Bragança, José Rodrigues Gomes and Mário Santos
J. Clin. Med. 2025, 14(7), 2211; https://doi.org/10.3390/jcm14072211 - 24 Mar 2025
Viewed by 466
Abstract
Background/Objectives: Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by fibrosis and vascular damage, significantly increasing the risk of heart failure (HF). Methods: This cross-sectional study included 61 SSc patients (92% female, mean age 63 ± 13 years), excluding [...] Read more.
Background/Objectives: Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by fibrosis and vascular damage, significantly increasing the risk of heart failure (HF). Methods: This cross-sectional study included 61 SSc patients (92% female, mean age 63 ± 13 years), excluding those with pulmonary arterial hypertension, referred to a tertiary pulmonary hypertension center. HF stages were classified according to updated guidelines. Clinical, echocardiographic, hemodynamic, and functional capacity data were analyzed in relation to HF stages. Results: A total of 48% of patients had pre-symptomatic HF (5% stage A, 43% stage B), while 38% had symptomatic HF (stage C). Advanced HF stages were significantly associated with older age (p = 0.02) and multiorgan involvement (p = 0.045) but not with SSc subtype or autoantibodies. Structural and functional echocardiographic abnormalities were prevalent (77% and 10%, respectively). Markers of elevated ventricular filling pressure such as left atrial volume (p = 0.011) and E/e’ ratio (p = 0.03) correlated with HF severity. Functional impairment was observed with lower 6 min walk test (6MWT) distance (p = 0.017), reduced VO2 peak (p = 0.015), and increased VE/VCO2 slope (p = 0.002). Resting pulmonary artery wedge pressure did not correlate with HF stage (p = 0.93). VE/VCO2 slope and 6MWT were independently associated with HF severity. Conclusions: Preclinical and symptomatic HF are highly prevalent in SSc patients. HF staging was linked to disease severity, age, and cardiovascular risk factors. Functional capacity tests (6MWT and CPET) serve as valuable tools for HF risk stratification. These findings highlight the critical need for comprehensive cardiovascular assessment and targeted management strategies to mitigate HF progression in SSc patients. Full article
(This article belongs to the Special Issue Clinical Advances in Autoimmune Disorders)
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