In vivo optogenetics using a Utah Optrode Array with enhanced light output and spatial selectivity.

Optogenetics allows manipulation of neural circuits in vivo with high spatial and temporal precision. However, combining this precision with control over a significant portion of the brain is technologically challenging (especially in larger animal models). Here, we have developed, optimised, and tested in vivo, the Utah Optrode Array (UOA), an electrically addressable array of optical needles and interstitial sites illuminated by 181 µLEDs and used to optogenetically stimulate the brain. The device is specifically designed for non-human primate studies. Thinning the combined µLED and needle backplane of the device from 300 µm to 230 µm improved the efficiency of light delivery to tissue by 80%, allowing lower µLED drive currents, which improved power management and thermal performance. The spatial selectivity of each site was also improved by integrating an optical interposer to reduce stray light emission. These improvements were achieved using an innovative fabrication method to create an anodically bonded glass/silicon substrate with through-silicon vias etched, forming an optical interposer. Optical modelling was used to demonstrate that the tip structure of the device had a major influence on the illumination pattern. The thermal performance was evaluated through a combination of modelling and experiment, in order to ensure that cortical tissue temperatures did not rise by more than 1°C. The device was tested in vivo in the visual cortex of macaque expressing ChR2-tdTomato in cortical neurons. It was shown that the strongest optogenetic response occurred in the region surrounding the needle tips, and that the extent of the optogenetic response matched the predicted illumination profile based on optical modelling - demonstrating the improved spatial selectivity resulting from the optical interposer approach. Furthermore, different needle illumination sites generated different patterns of low-frequency potential (LFP) activity.

Primate V2 Receptive Fields Derived from Anatomically Identified Large-Scale V1 Inputs.

In the primate visual system, visual object recognition involves a series of cortical areas arranged hierarchically along the ventral visual pathway. As information flows through this hierarchy, neurons become progressively tuned to more complex image features. The circuit mechanisms and computations underlying the increasing complexity of these receptive fields (RFs) remain unidentified. To understand how this complexity emerges in the secondary visual area (V2), we investigated the functional organization of inputs from the primary visual cortex (V1) to V2 by combining retrograde anatomical tracing of these inputs with functional imaging of feature maps in macaque monkey V1 and V2. We found that V1 neurons sending inputs to single V2 orientation columns have a broad range of preferred orientations, but are strongly biased towards the orientation represented at the injected V2 site. For each V2 site, we then constructed a feedforward model based on the linear combination of its anatomically-identified large-scale V1 inputs, and studied the response proprieties of the generated V2 RFs. We found that V2 RFs derived from the linear feedforward model were either elongated versions of V1 filters or had spatially complex structures. These modeled RFs predicted V2 neuron responses to oriented grating stimuli with high accuracy. Remarkably, this simple model also explained the greater selectivity to naturalistic textures of V2 cells compared to their V1 input cells. Our results demonstrate that simple linear combinations of feedforward inputs can account for the orientation selectivity and texture sensitivity of V2 RFs.

An optrode array for spatiotemporally-precise large-scale optogenetic stimulation of deep cortical layers in non-human primates.

Optogenetics has transformed studies of neural circuit function, but remains challenging to apply to non-human primates (NHPs). A major challenge is delivering intense, spatiotemporally-precise, patterned photostimulation across large volumes in deep tissue. Such stimulation is critical, for example, to modulate selectively deep-layer corticocortical feedback circuits. To address this need, we have developed the Utah Optrode Array (UOA), a 10×10 glass needle waveguide array fabricated atop a novel opaque optical interposer, and bonded to an electrically addressable µLED array. In vivo experiments with the UOA demonstrated large-scale, spatiotemporally precise, activation of deep circuits in NHP cortex. Specifically, the UOA permitted both focal (confined to single layers/columns), and widespread (multiple layers/columns) optogenetic activation of deep layer neurons, as assessed with multi-channel laminar electrode arrays, simply by varying the number of activated µLEDs and/or the irradiance. Thus, the UOA represents a powerful optoelectronic device for targeted manipulation of deep-layer circuits in NHP models.

Integration of a body sensor network of wearable devices for cardio-respiratory monitoring.

Wearable devices represent a non-invasive tool to monitor cardio-respiratory parameters. This paper presents a telemedicine platform constituted of four wireless units. Three wearable inertial measurement units monitor the respiratory-related excursions of the thorax and of the abdomen with respect to a reference unit (positioned on the lower back), through which respiratory rate and normalized tidal volume are extracted. The fourth unit is a reflectance wrist-worn pulse oximeter. To validate the system, 20 healthy volunteers (12 men) participated in a protocol designed to induce desaturation conditions and subsequent changes in the respiratory pattern by means of rebreathing. The results were evaluated against two different gold standards (SenTec for pulse oximetry and Cardiopulmonary Exercise Testing machine for all units) with Bland-Altman analyses. The resulting biases for the oxygen saturation comparison between the device to be validated and the SenTec and CPET systems are -0.90% and -2.68% respectively, with agreement intervals equal to [-6.37, 4.57] and [-9.00, 3.63]. Regarding the respiratory rate comparison with respect to the CPET system, the bias is -0.01 bpm with a [-11.36, 11.35] agreement interval.Clinical Relevance-This paper provides a validation of an integrated non-invasive wearable system for cardio-respiratory monitoring to be used outside of clinical settings and during the daily life of patients.

A participatory process to design an app to improve adherence to anti-osteoporotic therapies: A development and usability study.

Objective: The aim of the study was to develop an app to improve patients' adherence to therapy for osteoporosis and to test its usability. Methods: In Phase I, the app functions needed to improve medication adherence were identified through a focus group with six patients with osteoporosis and a joint interview with two bone specialists. The app prototype was then developed (Phase II) and refined after its feasibility testing (Phase III) for 13-25 days by eight patients. Finally, the app underwent usability testing (Phase IV) for 6 months by nine other patients. The mHealth App Usability Questionnaire (MAUQ) was used to collect the assessment of the app by the 17 patients. Results: The final version of the app provided information on osteoporosis, allowed patients to contact the bone specialist for an additional consultation, and generated a reminder for taking medications accompanied by feedback on adherence. The assessment of the app was positive but evaluations differed between the feasibility and usability testing, with the former displaying a significantly (p ≤ .05) better assessment across all MAUQ items. Conclusions: In this study, we tested an app for improving adherence to medical therapies in patients with osteoporosis. The usability testing revealed a lower "patient-centered" performance of the app as compared to that observed during the feasibility phase. Future developments of the study include increasing the testing cohort and adding a technical support during the usability testing.

Digital technologies for step counting: between promises of reliability and risks of reductionism.

Step counting is among the fundamental features of wearable technology, as it grounds several uses of wearables in biomedical research and clinical care, is at the center of emerging public health interventions and recommendations, and is gaining increasing scientific and political importance. This paper provides a perspective of step counting in wearable technology, identifying some limitations to the ways in which wearable technology measures steps and indicating caution in current uses of step counting as a proxy for physical activity. Based on an overview of the current state of the art of technologies and approaches to step counting in digital wearable technologies, we discuss limitations that are methodological as well as epistemic and ethical-limitations to the use of step counting as a basis to build scientific knowledge on physical activity (epistemic limitations) as well as limitations to the accessibility and representativity of these tools (ethical limitations). As such, using step counting as a proxy for physical activity should be considered a form of reductionism. This is not per se problematic, but there is a need for critical appreciation and awareness of the limitations of reductionistic approaches. Perspective research should focus on holistic approaches for better representation of physical activity levels and inclusivity of different user populations.

Dysregulation of ventilation at day and night time in heart failure.

Heart failure (HF) is characterized by an increase in ventilatory response to exercise of multifactorial aetiology and by a dysregulation in the ventilatory control during sleep with the occurrence of both central and obstructive apnoeas. In this setting, the study of the ventilatory behaviour during exercise, by cardiopulmonary exercise testing, or during sleep, by complete polysomnography or simplified nocturnal cardiorespiratory monitoring, is of paramount importance because of its prognostic value and of the possible effects of sleep-disordered breathing on the progression of the disease. Moreover, several therapeutic interventions can significantly influence ventilatory control in HF. Also, rest daytime monitoring of cardiac, metabolic, and respiratory activities through specific wearable devices could provide useful information for HF management. The aim of the review is to summarize the main studies conducted at Centro Cardiologico Monzino on these topics.

A smart tablet application to quantitatively assess the dominant hand dexterity.

BACKGROUND AND OBJECTIVE: The Nine-Hole Peg Test (NHPT) is the most used test to assess hand dexterity in clinical practice and is considered the gold standard but only evaluates the time needed to complete the task. The aim of this work is to describe a graphic test on a smart tablet to assess in a quantitative as well qualitative way the dominant hand dexterity and to validate it in a cohort of neurological subjects and healthy controls. METHODS: The task consists in asking the subject to connect with a graphic line the start and the end point of a pre-defined path, with two different widths, in the most precise and fastest way possible. The path is constituted by a 'meander' and a 'spiral' part. The subjects perform the task on a smart tablet with a capacitive pen four times. The three parameters of interest considered at each trial are the execution time, length path, and number of interactions with the border. The app automatically computes these three parameters and stores the completed test files. The results of the digital graphic test are compared to the NHPT results. Healthy and pathological subjects are compared to each other, and performances obtained in different repetitions are compared to assess the learning effect in each population. RESULTS: 53 subjects with a definitive diagnosis of neurodegenerative/genetic neurological disorders (34 men, mean age 59.1 ± 16.1) and 78 healthy controls (33 men, mean age 42.5 ± 16.3) were recruited. Among the pathological subjects, 31 also performed the NHPT. The graphic test clearly distinguish between the two populations for all parameters of interest. Moreover, compared to the gold standard NHPT, time has a moderate positive correlation (r = 0.57, p ≤ 0.001), whereas interactions and length have a strong positive correlation (r = 0.81, p ≤ 0.001) and (r = 0.69, p ≤ 0.001), respectively. CONCLUSIONS: The proposed digital test can measure in an accurate, quantitative and qualitative way dominant hand disability and can result more informative with respect to the gold standard NHPT. In homogeneous cohort of subjects (for example affected by multiple sclerosis or Parkinson disease), the digital test can be used as an outcome measure in clinical trials as well as a tool for monitoring disease progression at the dominant hand level.

Fitbit Data to Assess Functional Capacity in Patients Before Elective Surgery: Pilot Prospective Observational Study.

BACKGROUND: Preoperative assessment is crucial to prevent the risk of complications of surgical operations and is usually focused on functional capacity. The increasing availability of wearable devices (smartwatches, trackers, rings, etc) can provide less intrusive assessment methods, reduce costs, and improve accuracy. OBJECTIVE: The aim of this study was to present and evaluate the possibility of using commercial smartwatch data, such as those retrieved from the Fitbit Inspire 2 device, to assess functional capacity before elective surgery and correlate such data with the current gold standard measure, the 6-Minute Walk Test (6MWT) distance. METHODS: During the hospital visit, patients were evaluated in terms of functional capacity using the 6MWT. Patients were asked to wear the Fitbit Inspire 2 for 7 days (with flexibility of -2 to +2 days) after the hospital visit, before their surgical operation. Resting heart rate and daily steps data were retrieved directly from the smartwatch. Feature engineering techniques allowed the extraction of heart rate over steps (HROS) and a modified version of Non-Exercise Testing Cardiorespiratory Fitness. All measures were correlated with 6MWT. RESULTS: In total, 31 patients were enrolled in the study (n=22, 71% men; n=9, 29% women; mean age 76.06, SD 4.75 years). Data were collected between June 2021 and May 2022. The parameter that correlated best with the 6MWT was the Non-Exercise Testing Cardiorespiratory Fitness index (r=0.68; P<.001). The average resting heart rate over the whole acquisition period for each participant had r=-0.39 (P=.03), even if some patients did not wear the device at night. The correlation of the 6MWT distance with the HROS evaluated at 1% quantile was significant, with Pearson coefficient of -0.39 (P=.04). Fitbit step count had a fair correlation of 0.59 with 6MWT (P<.001). CONCLUSIONS: Our study is a promising starting point for the adoption of wearable technology in the evaluation of functional capacity of patients, which was strongly correlated with the gold standard. The study also identified limitations in the availability of metrics, variability of devices, accuracy and quality of data, and accessibility as crucial areas of focus for future studies.

An Optrode Array for Spatiotemporally Precise Large-Scale Optogenetic Stimulation of Deep Cortical Layers in Non-human Primates.

Optogenetics has transformed studies of neural circuit function, but remains challenging to apply in non-human primates (NHPs). A major challenge is delivering intense and spatially precise patterned photostimulation across large volumes in deep tissue. Here, we have developed and validated the Utah Optrode Array (UOA) to meet this critical need. The UOA is a 10×10 glass waveguide array bonded to an electrically-addressable µLED array. In vivo electrophysiology and immediate early gene (c-fos) immunohistochemistry demonstrated the UOA allows for large-scale spatiotemporally precise neuromodulation of deep tissue in macaque primary visual cortex. Specifically, the UOA permits both focal (single layers or columns), and large-scale (across multiple layers or columns) photostimulation of deep cortical layers, simply by varying the number of simultaneously activated µLEDs and/or the light irradiance. These results establish the UOA as a powerful tool for studying targeted neural populations within single or across multiple deep layers in complex NHP circuits.

Patient characteristics associated with the acceptability of teleconsultation: a retrospective study of osteoporotic patients post-COVID-19.

BACKGROUND: Due to the COVID-19 pandemic, teleconsultations (TCs) have become common practice for many chronic conditions, including osteoporosis. While satisfaction with TCs among patients increases in times of emergency, we have little knowledge of whether the acceptability of TCs persists once in-person visits return to being a feasible and safe option. In this study, we assess the acceptability of TCs across five dimensions for osteoporosis care among patients who started or continued with TCs after the COVID-19 pandemic had waned. We then explore the patient characteristics associated with these perceptions. METHODS: Between January and April 2022, 80 osteoporotic patients treated at the Humanitas Hospital in Milan, Italy, were recruited to answer an online questionnaire about the acceptability of TCs for their care. The acceptability of TCs was measured using a modified version of the Service User Technology Acceptability Questionnaire (SUTAQ), which identifies five domains of acceptability: perceived benefits, satisfaction, substitution, privacy and discomfort, and care personnel concerns. Multivariable ordinary least squares (OLS) linear regression analysis was performed to assess which patient characteristics in terms of demographics, socio-economic conditions, digital skills, social support, clinical characteristics and pattern of TC use were correlated with the five domains of acceptability measured through the SUTAQ. RESULTS: The degree of acceptability of TCs was overall good across the 80 respondents and the five domains. Some heterogeneity in perceptions emerged with respect to TCs substituting for in-person visits, negatively impacting continuity of care and reducing the length of consultations. For the most part, acceptability was not affected by patient characteristics with a few exceptions related to treatment time and familiarity with the TC service modality (i.e., length of osteoporosis treatment and number of TCs experienced by the patient). CONCLUSIONS: TCs appear to be an acceptable option for osteoporosis care in the aftermath of the COVID-19 pandemic. This study suggests that other characteristics besides age, digital skills and social support, which are traditionally relevant to TC acceptability, should be taken into account in order to better target this care delivery modality.

Diagnosing acute kidney injury ahead of time in critically ill septic patients using kinetic estimated glomerular filtration rate.

INTRODUCTION: Accurate and actionable diagnosis of Acute Kidney Injury (AKI) ahead of time is important to prevent or mitigate renal insufficiency. The purpose of this study was to evaluate the performance of Kinetic estimated Glomerular Filtration Rate (KeGFR) in timely predicting AKI in critically ill septic patients. METHODS: We conducted a retrospective analysis on septic ICU patients who developed AKI in AmsterdamUMCdb, the first freely available European ICU database. The reference standard for AKI was the Kidney Disease: Improving Global Outcomes (KDIGO) classification based on serum creatinine and urine output (UO). Prediction of AKI was based on stages defined by KeGFR and UO. Classifications were compared by length of ICU stay (LOS), need for renal replacement therapy and 28-day mortality. Predictive performance and time between prediction and diagnosis were calculated. RESULTS: Of 2492 patients in the cohort, 1560 (62.0%) were diagnosed with AKI by KDIGO and 1706 (68.5%) by KeGFR criteria. Disease stages had agreement of kappa = 0.77, with KeGFR sensitivity 93.2%, specificity 73.0% and accuracy 85.7%. Median time to recognition of AKI Stage 1 was 13.2 h faster for KeGFR, and 7.5 h and 5.0 h for Stages 2 and 3. Outcomes revealed a slight difference in LOS and 28-day mortality for Stage 1. CONCLUSIONS: Predictive performance of KeGFR combined with UO criteria for diagnosing AKI is excellent. Compared to KDIGO, deterioration of renal function was identified earlier, most prominently for lower stages of AKI. This may shift the actionable window for preventing and mitigating renal insufficiency.

Wearable Health Technology for Preoperative Risk Assessment in Elderly Patients: The WELCOME Study.

Preoperative identification of high-risk groups has been extensively studied to improve patients' outcomes. Wearable devices, which can track heart rate and physical activity data, are starting to be evaluated for patients' management. We hypothesized that commercial wearable devices (WD) may provide data associated with preoperative evaluation scales and tests, to identify patients with poor functional capacity at increased risk for complications. We conducted a prospective observational study including seventy-year-old patients undergoing two-hour surgeries under general anesthesia. Patients were asked to wear a WD for 7 days before surgery. WD data were compared to preoperatory clinical evaluation scales and with a 6-min walking test (6MWT). We enrolled 31 patients, with a mean age of 76.1 (SD ± 4.9) years. There were 11 (35%) ASA 3-4 patients. 6MWT results averaged 328.9 (SD ± 99.5) m. Daily steps and 𝑉𝑂2𝑚𝑎𝑥 as recorded using WD and were associated with 6MWT performance (R = 0.56, p = 0.001 and r = 0.58, p = 0.006, respectively) and clinical evaluation scales. This is the first study to evaluate WD as preoperative evaluation tools; we found a strong association between 6MWT, preoperative scales, and WD data. Low-cost wearable devices are a promising tool for the evaluation of cardiopulmonary fitness. Further research is needed to validate WD in this setting.

Electrical Impedance Tomography: From the Traditional Design to the Novel Frontier of Wearables.

Electrical impedance tomography (EIT) is a medical imaging technique based on the injection of a current or voltage pattern through electrodes on the skin of the patient, and on the reconstruction of the internal conductivity distribution from the voltages collected by the electrodes. Compared to other imaging techniques, EIT shows significant advantages: it does not use ionizing radiation, is non-invasive and is characterized by high temporal resolution. Moreover, its low cost and high portability make it suitable for real-time, bedside monitoring. However, EIT is also characterized by some technical limitations that cause poor spatial resolution. The possibility to design wearable devices based on EIT has recently given a boost to this technology. In this paper we reviewed EIT physical principles, hardware design and major clinical applications, from the classical to a wearable setup. A wireless and wearable EIT system seems a promising frontier of this technology, as it can both facilitate making clinical measurements and open novel scenarios to EIT systems, such as home monitoring.

An IMU-Based Wearable System for Respiratory Rate Estimation in Static and Dynamic Conditions.

PURPOSE: Breathing parameters change with activity and posture, but currently available solutions can perform measurements only during static conditions. METHODS: This article presents an innovative wearable sensor system constituted by three inertial measurement units to simultaneously estimate respiratory rate (RR) in static and dynamic conditions and perform human activity recognition (HAR) with the same sensing principle. Two units are aimed at detecting chest wall breathing-related movements (one on the thorax, one on the abdomen); the third is on the lower back. All units compute the quaternions describing the subject's movement and send data continuously with the ANT transmission protocol to an app. The 20 healthy subjects involved in the research (9 men, 11 women) were between 23 and 54 years old, with mean age 26.8, mean height 172.5 cm and mean weight 66.9 kg. Data from these subjects during different postures or activities were collected and analyzed to extract RR. RESULTS: Statistically significant differences between dynamic activities ("walking slow", "walking fast", "running" and "cycling") and static postures were detected (p < 0.05), confirming the obtained measurements are in line with physiology even during dynamic activities. Data from the reference unit only and from all three units were used as inputs to artificial intelligence methods for HAR. When the data from the reference unit were used, the Gated Recurrent Unit was the best performing method (97% accuracy). With three units, a 1D Convolutional Neural Network was the best performing (99% accuracy). CONCLUSION: Overall, the proposed solution shows it is possible to perform simultaneous HAR and RR measurements in static and dynamic conditions with the same sensor system.

Size tuning of neural response variability in laminar circuits of macaque primary visual cortex.

A defining feature of the cortex is its laminar organization, which is likely critical for cortical information processing. For example, visual stimuli of different size evoke distinct patterns of laminar activity. Visual information processing is also influenced by the response variability of individual neurons and the degree to which this variability is correlated among neurons. To elucidate laminar processing, we studied how neural response variability across the layers of macaque primary visual cortex is modulated by visual stimulus size. Our laminar recordings revealed that single neuron response variability and the shared variability among neurons are tuned for stimulus size, and this size-tuning is layer-dependent. In all layers, stimulation of the receptive field (RF) reduced single neuron variability, and the shared variability among neurons, relative to their pre-stimulus values. As the stimulus was enlarged beyond the RF, both single neuron and shared variability increased in supragranular layers, but either did not change or decreased in other layers. Surprisingly, we also found that small visual stimuli could increase variability relative to baseline values. Our results suggest multiple circuits and mechanisms as the source of variability in different layers and call for the development of new models of neural response variability.

The paradox of the artificial intelligence system development process: the use case of corporate wellness programs using smart wearables.

Artificial intelligence (AI) systems have been widely applied to various contexts, including high-stake decision processes in healthcare, banking, and judicial systems. Some developed AI models fail to offer a fair output for specific minority groups, sparking comprehensive discussions about AI fairness. We argue that the development of AI systems is marked by a central paradox: the less participation one stakeholder has within the AI system's life cycle, the more influence they have over the way the system will function. This means that the impact on the fairness of the system is in the hands of those who are less impacted by it. However, most of the existing works ignore how different aspects of AI fairness are dynamically and adaptively affected by different stages of AI system development. To this end, we present a use case to discuss fairness in the development of corporate wellness programs using smart wearables and AI algorithms to analyze data. The four key stakeholders throughout this type of AI system development process are presented. These stakeholders are called service designer, algorithm designer, system deployer, and end-user. We identify three core aspects of AI fairness, namely, contextual fairness, model fairness, and device fairness. We propose a relative contribution of the four stakeholders to the three aspects of fairness. Furthermore, we propose the boundaries and interactions between the four roles, from which we make our conclusion about the possible unfairness in such an AI developing process.

Validation of a graphic test to quantitatively assess the dominant hand dexterity.

Dexterity dysfunction is a key feature of disability in many neurological and non-neurological diseases. The Nine-Hole Peg Test (NHPT) is the most used test to assess hand dexterity in clinical practice but presents limitations. A new graphic test to enhance objective evaluation of the of the dominant hand dexterity is proposed. The task consists in drawing a continuous line in paths composed by a part with multiple orthogonal changes of direction ('meander'), and a second part derived from the Archimedean spiral ('spiral'). The test was validated in 200 healthy controls and 93 neurological patients. 48 patients performed also the NHPT. Several parameters were analyzed, among which total time, total length, number of touches and number of crossings. Healthy subjects display statistically significant differences with respect to pathological subjects in the case of total time, number of touches, and number of crossings (p<0.001), but not in the case of total length (p = 0.27) needed to complete the second sheet. Moreover, healthy controls display a learning effect, the time needed to complete the second sheet was significantly lower than for the first sheet (p<0.001), and an inverse correlation with age was observed (r = 0.56, p<0.001). The comparison between the NHPT and the new test showed a strong positive correlation (r = 0.71, p<0.001) whereas touches and crossing a weak positive one (r = 0.35, p = 0.01). The new test distinguishes between a slow but precise performance and a fast but imprecise performance, thus providing additional information with respect to NHPT.

A Scoping Review on Wearable Devices for Environmental Monitoring and Their Application for Health and Wellness.

This scoping review is focused on wearable devices for environmental monitoring. First, the main pollutants are presented, followed by sensing technologies that are used for the parameters of interest. Selected examples of wearables and portables are divided into commercially available and research-level projects. While many commercial products are in fact portable, there is an increasing interest in using a completely wearable technology. This allows us to correlate the pollution level to other personal information (performed activity, position, and respiratory parameters) and thus to estimate personal exposure to given pollutants. The fact that there are no univocal indices to estimate outdoor or indoor air quality is also an open problem. Finally, applications of wearables for environmental monitoring are discussed. Combining environmental monitoring with other devices would permit better choices of where to perform sports activities, especially in highly polluted areas, and provide detailed information on the living conditions of individuals.

Comparison between PtCO2 and PaCO2 and Derived Parameters in Heart Failure Patients during Exercise: A Preliminary Study.

Evaluation of arterial carbon dioxide pressure (PaCO2) and dead space to tidal volume ratio (VD/VT) during exercise is important for the identification of exercise limitation causes in heart failure (HF). However, repeated sampling of arterial or arterialized ear lobe capillary blood may be clumsy. The aim of our study was to estimate PaCO2 by means of a non-invasive technique, transcutaneous PCO2 (PtCO2), and to verify the correlation between PtCO2 and PaCO2 and between their derived parameters, such as VD/VT, during exercise in HF patients. 29 cardiopulmonary exercise tests (CPET) performed on a bike with a ramp protocol aimed at achieving maximal effort in ≈10 min were analyzed. PaCO2 and PtCO2 values were collected at rest and every 2 min during active pedaling. The uncertainty of PCO2 and VD/VT measurements were determined by analyzing the error between the two methods. The accuracy of PtCO2 measurements vs. PaCO2 decreases towards the end of exercise. Therefore, a correction to PtCO2 that keeps into account the time of the measurement was implemented with a multiple regression model. PtCO2 and VD/VT changes at 6, 8 and 10 min vs. 2 min data were evaluated before and after PtCO2 correction. PtCO2 overestimates PaCO2 for high timestamps (median error 2.45, IQR -0.635-5.405, at 10 min vs. 2 min, p-value = 0.011), while the error is negligible after correction (median error 0.50, IQR = -2.21-3.19, p-value > 0.05). The correction allows removing differences also in PCO2 and VD/VT changes. In HF patients PtCO2 is a reliable PaCO2 estimation at rest and at low exercise intensity. At high exercise intensity the overall response appears delayed but reproducible and the error can be overcome by mathematical modeling allowing an accurate estimation by PtCO2 of PaCO2 and VD/VT.