ARTICLE | doi:10.20944/preprints202207.0131.v2
Subject: Computer Science And Mathematics, Mathematical And Computational Biology Keywords: fetal heart rate; maternal heart rate; cardiotocogram; gated recurrent unit; deep learning
Online: 22 July 2022 (03:08:59 CEST)
We have developed deep learning models for automatic identification of the maternal heart rate (MHR) and, more generally, false signals (FSs) on fetal heart rate (FHR) recordings. The models can be used to preprocess FHR data prior to automated analysis or as a clinical alert system to assist the practitioner. Three models were developed and used to detect (i) FSs on the MHR channel (the FSMHR model), (ii) the MHR and FSs on the Doppler FHR sensor (the FSDop model), and (iii) FSs on the scalp ECG channel (the FSScalp model). The FSDop model was the most useful because FSs are far more frequent on the Doppler FHR channel. All three models were based on a multilayer, symmetric, GRU and were trained on data recorded during the first and second stages of delivery. The FSMHR and FSDop models were also trained on antepartum recordings. The training dataset contained 1030 expert-annotated periods (mean duration: 36 min) from 635 recordings. In an initial evaluation of routine clinical practice, 30 fully annotated recordings for each sensor type (mean duration: 5 h for MHR and Doppler sensors, and 3 h for the scalp ECG sensor) were analyzed. The sensitivity, positive predictive value (PPV) and accuracy were respectively 62.20%, 87.1% and 99.90% for the FSMHR model, 93.1%, 95.6% and 99.68% for the FSDop model, and 44.6%, 87.2% and 99.93% for the FSScalp model. We built a second test dataset with a more solid ground truth by selecting 45 periods (lasting 20 min, on average) on which the Doppler FHR and scalp ECG signals were recorded simultaneously. Using scalp ECG data, the experts estimated the true FHR value more reliably and thus annotated the Doppler FHR channel more precisely. The models achieved a sensitivity of 53.3%, a PPV of 62.4%, and an accuracy of 97.29%. In comparison, two experts (blinded to the scalp ECG data) respectively achieved a sensitivity of 15.7%, a PPV of 74.3%, and an accuracy of 96.91% and a sensitivity of 60.7%, a PPV of 83.5% and an accuracy of 98.24%. Hence, the models performed at expert level (better than one expert and worse than the other), although a well-trained expert with good knowledge of FSs could probably do better in some cases. The models and datasets have been included in the Fetal Heart Rate Morphological Analysis open-source MATLAB toolbox and can be used freely for research purposes.
ARTICLE | doi:10.20944/preprints202212.0290.v2
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: heart rate variability; signal analysis
Online: 6 February 2023 (04:45:25 CET)
Heart rate variability (HRV) is commonly intended as the variation in the heart rate (HR) and it is evaluated in the time and frequency domains with various well known methods. In the present paper, we first consider an abstract model in which the HR is the instantaneous frequency of an otherwise periodic signal such as the electrocardiogram (ECG). Thus the ECG is assumed as a frequency modulated signal, or carrier signal, where HRV or HRVt is a supposed time-domain signal which is frequency modulating the carrier ECG signal around its average frequency. Hence we describe an algorithm able to frequency demodulate the ECG signal to extract a continuous signal HRVt with possibly enough time resolution to analyse fast time-domain variations in the instantaneous HR. After exhaustive testing of the method on simulated frequency modulated sinusoidal signals, we have applied the procedure on actual ECG tracings. The purpose of the work is to eventually use the heart as a kind of biological sensor of the fast activity of the autonomic nervous system (ANS) to study the ANS ultra-short-term event-evoked responses. A few preliminary, not clinical, real examples are also given.
ARTICLE | doi:10.20944/preprints201906.0139.v1
Subject: Computer Science And Mathematics, Other Keywords: fetal heart rate; baseline; acceleration; deceleration; MATLAB
Online: 15 June 2019 (03:39:37 CEST)
The fetal heart rate (FHR) is a screening signal for preventing fetal hypoxia during labor. When experts analyze this signal, they have to position a baseline and then identify decelerations and accelerations. These steps can potentially be automated and made more objective by signal processing analysis. Various methods have been described in the literature but there are no open-source programs for performing these steps. The MATLAB toolbox presented here comprises a standard signal pre-processing function, 11 re-coded literature methods for fetal heart rate analysis, a signal viewer (enabling annotation by an expert) and an evaluation procedure with various criteria measuring intrarater agreement.
ARTICLE | doi:10.20944/preprints202302.0415.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: reflectance PPG; reflectance photoplethysmography; heart rate estimation; video
Online: 24 February 2023 (02:52:59 CET)
Non-invasive heart rate (HR) monitoring is important in clinical settings as it plays a critical role in diagnosing a range of health conditions and assessing well-being. Presently, the gold standards for HR measurement are all based on sensors which require skin contact. Apart from inconvenience, contact sensors have proven problematic in certain scenarios – they cannot be used when mechanical isolation of the patient is imperative (burn victims, patients with shaky hands and feet), cause skin damage to premature babies in the ICU and increase the risk of spreading infections. Non-contact HR monitoring using a camera has been recently shown to be a viable alternative. It is now possible to record cardiac-synchronous blood volume variations from facial videos of human subjects under ambient lighting. These variations produce corresponding changes in skin reflectance which can be extracted as a raw reflectance photoplethysmography (rPPG) signal and processed to reveal HR. In this project, an algorithmic framework for webcam-based HR detection was successfully implemented in MATLAB. The investigation was based on 100 self-captured videos (dark-skinned subject) and 48 videos (from 12 subjects, all but one fair-skinned) obtained from COHFACE – an online database of facial videos and corresponding physiological signals. While the performance metrics (mean error, SNR) of the rPPG signals obtained from the self-captured videos were poor (best case mean error of 22%), they were good enough to demonstrate the success of the implementation. The poor results were primarily imputed to skin tone as rPPG SNR is known to be particularly low for dark tones. The results of the COHFACE videos were far superior, with mean error ranging from 3% to 15% (among 8 different rPPG signals) and 0% to 9% under ambient and dedicated lighting, respectively. This investigation sets the foundation for future research directed at optimizing rPPG performance metrics for dark-skinned subjects.
ARTICLE | doi:10.20944/preprints202306.1354.v1
Subject: Public Health And Healthcare, Other Keywords: 65%1RM bench press; Rest interval; Number of repetition (volume load); Heart rate recovery rate
Online: 19 June 2023 (12:36:16 CEST)
(1)Background:The purpose of the study was conducted to investigate the recovery of heart rate according to the performance level and rest interval conditions during 65%1RM bench press exercise;(2)Methods:The subjects of this study were eight healthy male college studentsin their 20 (years) attending University C. 1RM was measured before theexperiment, and the exercise sequence of six rest intervals (30sec, 1, 2, 3, 4,5min) was randomly selected and cross-distribution experiment. The experimental measurement was conducted a total of six times according to the rest interval condition (six conditions) once every 3 days to minimize the learning effect. The data was verified with repeated measures Two-way ANOVA and Contrast's repeated method was applied for post-comparison;(3)Results: First, the amount of exercise and the number of repetitions statistically substantially dropped (p<.001) as the number of sets rose, and a greater decline was shown when the rest periods got shorter. Second, the heart rate after exercise was increased significantly (p<.01) as the set progressed in the long rest interval conditions (4, 5min), and the heart rate after rest was increased statistically significantly (p<,05) as the set progressed in the short rest interval conditions (30sec, 1min). Third, the heart rate recovery rate (%) was able to perform more repetitions than in the short rest interval condition due to the relatively high physiological recovery of the neuromuscular and circulatory system under the long rest interval condition;(4)Conclusions: Therefore, according to the rest conditionduring the 65%1RM bench press exercise conducted in this study, the restinterval condition of 2~3min may be effective in improving muscular endurance,and the rest interval condition of 4~5min may be effective in improving muscular hypertrophy. As a result of this study, there was a significant difference in exercise performance (repetition) and physiological recovery depending on the rest interval condition according to the set progress during the same intensity resistance exercise. Through this, it is judged that it is possible to adjust the amount of exercise appropriate for the purpose of training by adjusting not only the intensity during resistance exercise but also the rest interval between sets.
CASE REPORT | doi:10.20944/preprints202005.0209.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: COVID-19 virus disease; Autonomic nervous system; Electrocardiography; Heart rate
Online: 12 May 2020 (12:22:06 CEST)
This case study investigates the heart rate (HR) and heart rate variability (HRV) in a patient with coronavirus disease 2019 (COVID-19). We report the case of a 58-year old male who contracted COVID-19. During his disease, 24-hour Holter electrocardiography (ECG) was performed continuously. For comparison, his 24-hour Holter ECGs from the previous 10 years were available. In this patient, COVID-19 was associated with a decrease in HR and a paradoxical decline in HRV. An abrupt decline in HRV and a decrease in HR may signal the onset of COVID-19 before common symptoms such as dry cough or fever appear. In addition, HRV and HR measurements may help to evaluate the course of the disease.
ARTICLE | doi:10.20944/preprints202306.0731.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: antispasmodic; heart rate variability; intestinal function; parasympathetic activity
Online: 9 June 2023 (15:50:58 CEST)
The impact of a non-anticholinergic spasmolytic drug (drotaverine hydrochloride) on 23 heart rate (HR), HR variability (HRV) and gastrointestinal tract (GIT) motility in the normal, resting 24 horses was determined. Ten adult riding horses had ECG recordings for 180 minutes after treat-25 ment with drotaverine (180 mg) or saline. Horses from the drotaverine group presented a de-26 creased of GIT contraction for two hours after treatment, but also showed drowsiness. Drotaverine 27 caused a reduction in cardiac vagal modulation of HR at T30 (P=0.050) and T60 (P=0.008) compared 28 to those receiving saline. RMSSD and high frequency (HF) recorded significantly low values after 29 drotaverine treatment by the end of the study, suggesting a decrease in parasympathetic activity. 30 HRV analysis indicated that drotaverine decreased both the low frequency (LF) and Lf/HF ratio 31 reflecting a decrease in sympathetic system. Non linear parameters registered low values after 32 drotaverine administration pointing a diminished in parasympathetic (for SD1) and sympathetic 33 (for SD2) activity. Decreased HRV was suggestive for a pervasive state of sympathetic hypervigi-34 lance of horses. The marked effect of drotaverine on HRV and GIT function in horses should be 35 taken into consideration when evaluating a clinical response to this drug in diseases associated 36 with smooth muscle spasm.
ARTICLE | doi:10.20944/preprints201907.0039.v1
Subject: Computer Science And Mathematics, Other Keywords: fetal heart rate, baseline, acceleration, deceleration, dataset
Online: 2 July 2019 (11:17:55 CEST)
The fetal heart rate (FHR) is a screening signal for preventing fetal hypoxia during labor. When experts analyze this signal, they have to position a baseline and identify decelerations and accelerations. These steps can potentially be automated and made more objective by data processing analysis, but training and evaluation datasets are required. Here, we describe a dataset of 155 FHR recordings in which a reference baseline, accelerations and decelerations have been annotated by expert consensus. 66 FHR recordings with a shared expert analysis have been included in a training dataset, and 90 other FHR recordings with a non-shared expert analysis have been included in an evaluation dataset. Researchers wishing to evaluate their automatic analysis method should submit their results for comparison with the expert consensus. The dataset also contains the results produced by 11 re-coded automatic analysis methods from the literature. All the data are available at http://utsb.univ-catholille.fr/fhr-review.
REVIEW | doi:10.20944/preprints202308.0732.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Heart rate variability, wearable device, autonomic nervous system, stress
Online: 9 August 2023 (08:13:01 CEST)
Heart rate variability (HRV) is a measurement of the fluctuation of time between each heartbeat and reflects the function of the autonomic nervous system. HRV is an important indicator for both physical and mental status and for broad-scope diseases. In this review, we discuss how wearable devices can be used to monitor HRV, and we compare the HRV monitoring function among different devices. In addition, we have reviewed the recent progress in HRV tracking with wearable devices and its value in health monitoring and disease diagnosis. Although many challenges remain, we believe HRV tracking with wearable devices is a promising tool that can be used to improve personal health.
ARTICLE | doi:10.20944/preprints202105.0440.v1
Subject: Social Sciences, Psychology Keywords: Heart rate variability (HRV); Conversation; Extraversion personality; Perceived social isolation
Online: 19 May 2021 (12:42:21 CEST)
Studies showed that introversion is the strongest personality trait related to perceived social isolation (loneliness), which can predict various complications beyond objective isolation such as living alone. Lonely individuals are more likely resort to social media for instantaneous comfort, but it is not a perpetual solution. Largely negative implications including poorer interpersonal relationship and depression were reported due to excessive social media usage. Conversational task is an established intervention to improve verbal communication, cognitive and behavioral adaptation among lonely individuals. Despite that behavioral benefits have been reported, it is unclear if they are accompanied by objective benefits underlying physiological changes. Here, we investigate the physiological signals from 28 healthy individuals during a conversational task. Participants were ranked by trait extraversion, where greater introversion is associated with increased susceptibility to perceived social isolation as compared to participants with greater extraversion as controls. We found that introverts had a greater tendency to be neurotic, and these participants also exhibited significant differences in task-related electrodermal activity (EDA), heart rate (HR) and HR variability (HRV) as compared to controls. Notably, resting state HRV among individuals susceptible to perceived loneliness was below the healthy thresholds established in literature. Conversational task with a stranger significantly increased HRV among individuals susceptible to isolation up to levels as seen in controls. Since HRV is also elevated by physical exercise and administration of oxytocin hormone (one form of therapy for behavioral isolation), conversational therapy among introverts could potentially confer physiological benefits to ameliorate social isolation and loneliness. Our findings also suggest that although the recent pandemic have changed how people are interacting typically, we should maintain a healthy dose of social interaction innovatively.
ARTICLE | doi:10.20944/preprints202304.0692.v1
Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: Emotion Recognition; smart bracelet; heart rate; wearable; Autism Spectrum Disorder (ASD)
Online: 21 April 2023 (08:38:45 CEST)
This paper presents a framework to recognize the affective state of children with Autism Spectrum Disorder (ASD) in an in-the-wild setting using Heart Rate (HR) information. Our algorithm classifies a child’s emotion into positive, negative, or neutral states by analyzing the heart rate signal. The HR signal is obtained from a smartwatch in real-time using our smartwatch application. The heart rate data is acquired when the child learns to code a robot while interacting with an avatar that assists the child in communications skills and programming the robot. In this paper, we also present a comparison of using HR data for the classification of emotions with classification based on features extracted from HR signals using Discrete Wavelet Transform (DWT). Our experimental results show that the proposed method produces a comparable performance with the state-of-the-art HR-based emotion recognition techniques, despite the fact that our experiments are performed in an uncontrolled setting as opposed to a lab environment. This work contributes to real-world affect analysis of children with ASD using HR information.
ARTICLE | doi:10.20944/preprints202008.0508.v1
Subject: Medicine And Pharmacology, Orthopedics And Sports Medicine Keywords: heart rate monitor; ECG; portable/wearable monitoring system; heart rate variability; long-term assessment; arrhythmia; QARDIO MD VSI system
Online: 24 August 2020 (07:45:40 CEST)
Heart Rate Monitors (HRMs) are an indispensable tool for controlling training parameters of healthy athletes. They became a source of information about stress heart rhythm disturbances, recognized as unexpected increases in heart rate (HR), which can be life-threatening for athletes. Most HRMs do not recognize the type of arrhythmia, confusing them with artifacts. The aim of the study was to assess the usefulness of ECG recording functions by sports HRMs among endurance athletes, coaches, and physicians in comparison with other basic and hypothetical functions. We conducted 3 surveys among endurance athletes (76 runners, 14 cyclists, and 10 triathletes), as well as 10 coaches and 10 sports doctors to obtain information on how important ECG recording is, and what functions of HRMs should be improved to meet their expectations in the future. The respondents were asked questions regarding use and hypothetical functions, as well as preference for HRM type (optical/strap). For athletes, the 4 most important functions were distance traveled, pace, instant heart rate, and information about reaching the oxygen threshold. ECG recording was the 8th and 9th most important for momentary and continuous, respectively. Coaches opined more importance to ECG recording. Doctors placed ECG recording as most important. All participants preferred optical HRMs to strap HRMs. Research on the improvement and implementation of HRM functions shows slightly different preferences of athletes compared to coaches and doctors. Suspected arrhythmia increases the value of the HRM’s ability to record ECGs during training by athletes and coaches. For doctors, this is the most desirable feature in any situation. Considering the expectations of all groups continuous ECG recording during training will significantly improve the safety of athletes.
ARTICLE | doi:10.20944/preprints202311.0576.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Obstructive sleep apnea; heart rate variability; continuous positive airway pressure
Online: 9 November 2023 (09:13:15 CET)
Autonomic dysregulation is associated with cardiovascular consequences in obstructive sleep apnea (OSA). This study aimed to investigate the effect of acute continuous positive airway pressure (CPAP) treatment on autonomic activity and to identify factors contributing to the heart rate variability (HRV) changes in OSA. Frequency domain HRV parameters were calculated and compared between the baseline polysomnography and during the CPAP titration in 402 patients with moderate to severe OSA. There were significant reductions in total power, very low-frequency band power, low-frequency band power, and high-frequency band power during the CPAP titration as compared to the baseline polysomnography. This tendency was more pronounced in men than in women, and in patients with severe OSA than those with moderate OSA. Multivariate analysis found that changes in apnea-hypopnea index and oxygen saturation were significantly associated with changes in sympathetic and parasympathetic activity, respectively. This study demonstrated that HRV parameters significantly changed during the CPAP titration, indicating a beneficial effect of CPAP in restoration of sympathetic and parasympathetic hyperactivity in OSA. Prospective longitudinal studies should determine whether long-term CPAP treatment aids in maintaining the long-lasting improvement of the autonomic functions, thereby contributing to the prevention of cardiovascular and cerebrovascular diseases in patients with OSA.
ARTICLE | doi:10.20944/preprints202305.1899.v1
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: newborn; heart rate variability; caffeine; apnoea; apnea; autonomic nervous system
Online: 26 May 2023 (09:36:15 CEST)
Neonatal apnoea has been treated with caffeine, affecting the central nervous and the cardiovascular system. Heart rate variability (HRV) reflects the activity of the autonomic nervous system (ANS) and might be used as a measure of ANS maturation in newborns. We aimed to establish the effect of caffeine on HRV in newborns and sought for a potential correlation between HRV and the postmenstrual age. In 25 newborns hospitalized due to apnoea and treated with caffeine (2.5 mg/kg), we assessed breathing frequency, arterial oxygen saturation, body temperature, and the heart rate, while they were sleeping. We assessed HRV by spectral analysis using fast Fourier transformation. The same protocol was reapplied 100 hours after caffeine withdrawal to assess control parameters. Caffeine increased breathing frequency (p=0.023) but did not affect any other parameter assessed including HRV. We established a positive correlation between postmenstrual age and HRV during treatment with caffeine as well as after caffeine had been withdrawn (total power: p=0.044; low-frequency band: p=0.039). Apparently, the maintenance dose of caffeine is too low to affect the heart rate and the HRV. A positive correlation between postmenstrual age and HRV might reflect maturation of ANS, irrespective of caffeine treatment.
ARTICLE | doi:10.20944/preprints201806.0325.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: heart rate variability, smoking, hypoxia, autonomic dysfunction
Online: 20 June 2018 (15:38:52 CEST)
Background and objectives: Smoking leads to autonomic dysfunction. However, the clinical methods for diagnosing this dysfunction are not sufficient. Since exogenous hypoxia leads to changes in the autonomic cardiac control, the aim of our study was to compare the activity of the autonomic nervous system via heart rate variability (HRV) in young “healthy” smokers and non-smokers before, during and after a short-term exogenous hypoxic exposure. Methods: Twenty-one healthy non-smoking males aged 28.0±7.4 (mean±SD) and fourteen healthy smoking males aged 28.1±4.3 with 9.2±5.6 pack-years were subjected to one-hour hypoxic exposure (FiО2=12.3±1.5%) via hypoxicator (AltiPro 8850 Summit+, Altitude Tech, Canada) with simultaneous recording of electrocardiography and pulse oximetry. HRV data was derived via specific software (Kubios HRV, Finland) by analyzing the pre-hypoxic, hypoxic and post-hypoxic periods. Results: Standard deviation of the intervals between normal beats (SDNN) was higher in non-smokers in the pre-hypoxic period (62.0±32.1 vs 40.3±16.2, p=0.013) but not in hypoxia (75.7±34.8 vs 57.9±18.3, p=0.167). When comparing intragroup HRV changes of shifting from hypoxic to post-hypoxic (normoxic) conditions we found that there is a significant increase in the root mean square of successive RR interval differences (RMSSD) (65.9±40.2 vs 75.1±45.9, p=0.011) and in the high frequency (lnHF) (6.8±1.4 vs 7.2±1.3, p=0.014) and a decrease in LF/HF (3.0±2.3 vs 1.9±1.5, p<0.001), but these changes were observed only in the group of non-smokers. Conclusions: Smoking likely impairs autonomic regulation in young healthy males and may lead to a decreased HRV even before subjective clinical signs and symptoms. Hypoxic exposure test could be applied in clinical practice for early detection of autonomic dysfunction in smokers, because their parasympathetic reactivation is blunted when shifting from hypoxic to normoxic ambient conditions measured by HRV.
ARTICLE | doi:10.20944/preprints202010.0278.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: sheep; gestation; hemodinamycs; heart rate variability; cardiac output
Online: 13 October 2020 (12:15:51 CEST)
This study aimed at evaluating changes in the clinical and echocardiographic parameters of pregnant sheep, as well as the HRV indexes due to the physiological alterations that happen at this stage implicating in high maternal metabolic demands. For this purpose, the study evaluated 10 Dorper sheep through their pregnancy, starting from the second month until the day before birth, conducting clinical, echocardiographic and electrocardiographic examinations focused on the HRV. The echocardiogram was conducted in a doppler ultrasound device with a multifrequency sectorial transducer in bidimensional mode. The HRV indexes were obtained through the Televet 100® system. There were increases in the thickness of the interventricular septum during diastole starting from the third month, and in the internal diameter of the left ventricle during systole and diastole at the second and third months, while the ejection fraction increased as the pregnancy progressed. The size of the left atrium increased starting at the second month. The SDNN, RMSSD and PNN50 HRV indexes were higher at the fifth month of pregnancy and after delivery. There were no significant differences in the frequency-domain HRV indexes during pregnancy. The gestation leads to alterations in the clinical parameters and the activity of the autonomic nervous system.
ARTICLE | doi:10.20944/preprints202105.0706.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: alcohol; brain networks; heart rate variability; abstinence; respiratory sinus arrhythmia
Online: 28 May 2021 (13:45:25 CEST)
Alcohol consumption is now common practice worldwide, and functional brain networks are beginning to reveal the complex interactions observed with alcohol consumption and abstinence. The autonomic nervous system (ANS) has a well-documented relationship with alcohol use, and a growing body of research is finding links between the ANS and functional brain networks. This study recruited everyday drinkers in an effort to uncover the relationship between alcohol abstinence, ANS function, and whole brain functional brain networks. Participants (n=29), 24-60 years-of-age, consumed moderate levels of alcohol regularly (males 2.4 (±0.26) drinks/day, females 2.3 (±0.96) drinks/day). ANS function, specifically cardiac vagal tone, was assessed using the Porges-Bohrer method for calculating respiratory sinus arrhythmia (PBRSA). Functional brain networks were generated from resting-state MRI scans obtained following 3-day periods of typical consumption and abstinence. A multi-task mixed-effects regression model determined the influences of HRV and drinking state on functional network connectivity. Results showed differences in the relationship between the strength of network connections and clustering coefficients across drinking states, moderated by PBRSA. Increases in connection strength between highly clustered nodes during abstinence as PBRSA increases demonstrates a greater possible range of topological configurations at high PBRSA values. This novel finding begins to shed light on the complex interactions between typical alcohol abstinence and physiological responses of the central and autonomic nervous system.
ARTICLE | doi:10.20944/preprints202007.0651.v1
Subject: Engineering, Bioengineering Keywords: Embryonic Heart Rate; Photoplethysmography (PPG); Continuous Wavelet Transform (CWT); Spectral Entropy
Online: 26 July 2020 (17:50:12 CEST)
The chicken embryo is a widely used experimental animal-model in many studies such as developmental biology and to study the physiological responses and adaptation to altered environments as well as for cancer and neurobiology research. Embryonic heart rate is an important physiological variable useful as an index reflecting the embryo's natural activity and is considered one of the most difficult parameters to measure. An acceptable measurement technique of embryonic heart rate should provide a reliable cardiac signal quality while maintaining adequate gas exchange through the eggshell along the incubation and embryonic developmental period. In this paper, we presented a detailed design and methodology for a non-invasive PPG-based prototype (Egg-PPG) for real-time and continuous monitoring of embryonic heart rate during incubation. An automatic embryonic cardiac wave detection algorithm, based on normalised spectral entropy, is described. The developed algorithm successfully estimated the embryonic heart rate with 98.7% accuracy. We believe that the developed overall system presented in this paper is showing a promising solution for non-invasion, real-time monitoring of embryonic cardiac signal, which can be used in both experimental studies (e.g., developmental embryology and cardiovascular research) and in industrial incubation applications.
ARTICLE | doi:10.20944/preprints202303.0400.v1
Subject: Computer Science And Mathematics, Computer Networks And Communications Keywords: maximal heart rate; endurance athletes; cardiopulmonary exercise test; HRmax; cardiac rehabilitation; running; cycling
Online: 22 March 2023 (14:26:11 CET)
Maximal heart rate (HRmax) is a widely used measure of cardiorespiratory fitness. Prediction of HRmax is an alternative to cardiopulmonary exercise testing (CPET), but its accuracy among endurance athletes (EA) requires evaluation. This study aimed to externally validate HRmax prediction models in the EA independently for running and cycling CPET. 4043 runners (age=33.58 (8.12) years; 83.53% males; BMI=23.66 (2.54) kg·m−2) and 1026 cyclists (age=36.88 (9.03) years; 89.67% males; BMI=24.04 (2.65) kg·m−2) underwent maximum CPET. Student t-test, mean absolute percentage error (MAPE), mean absolute error (MAE), and root mean square error (RMSE) were applied to externally validate 8 running and 5 cycling HRmax equations. HRmax was 184.60 (9.79) beats·min−1 and 182.66 (10.28) beats·min−1 respectively for running and cycling, p=0.001. Measured and predicted HRmax differed significantly (p=0.001) for 9 of 13 (69.23%) models. HRmax was overestimated by 8 (61.54%) and underestimated by 5 (38.46%) formulae. Overestimated HRmax ranged 0.08-4.94 beats·min−1 and underestimated HRmax ranged 0.03-4.90 beats·min−1. MAE and RMSE were 0.18-4.94 beats·min−1 and 9.13-10.47, respectively. MAPE ranged 3.95-4.69%. Prediction models do not allow for accurate estimation of HRmax. HRmax was more often underestimated than overestimated. Predicted HRmax can be implemented for EA as a supplemental method but CPET is the preferable approach.
ARTICLE | doi:10.20944/preprints201807.0488.v1
Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: heart rate variability; machine learning; abnormality detection; window shifting; high accuracy prediction
Online: 25 July 2018 (14:22:10 CEST)
The use of machine learning techniques in predictive health care is on the rise with minimal data used for training machine-learning models to derive high accuracy predictions. In this paper, we propose such a system, which utilizes Heart Rate Variability (HRV) as features for training machine learning models. This paper further benchmarks the usefulness of HRV as features calculated from basic heart-rate data using a window shifting method. The benchmarking has been conducted using different machine-learning classifiers such as artificial neural network, decision tree, k-nearest neighbour and naive bays classifier. Empirical results using MIT-BIH Arrhythmia database shows that the proposed system can be used for highly efficient predictability of abnormality in heartbeat data series.
ARTICLE | doi:10.20944/preprints202007.0652.v1
Subject: Engineering, Bioengineering Keywords: Pig’s Heart Rate; Photoplethysmography (PPG); Continuous Wavelet Transform (CWT); Motion Artefacts
Online: 26 July 2020 (17:58:26 CEST)
Animal welfare remains a very important issue in the livestock sector but monitoring animal welfare in an objective and continuous way remains a serious challenge. Monitoring animal welfare based upon physiological measurements instead of audio-visual scoring of behaviour would be a step forward. One of the obvious physiological signals related to welfare and stress is heart rate. The objective of this research was to measure heart rate (beat per minutes) on pigs with technology that soon will be affordable. Affordable heart rate monitoring is done today at large scale on humans using the Photo Plethysmography (PPG) technology. We used PPG sensors on pig’s body to test whether it allows getting reliable heart rate signal. A continuous wavelet transform (CWT)-based algorithm is developed to decouple the cardiac pulse waves from the pig. Three different wavelets, namely 2nd, 4th and 6th order Derivative of Gaussian (DOG, are tested. We show results of the developed PPG-based algorithm against electrocardiograms (ECG) as a reference measure for heart rate and this for an anesthetized versus a non-anesthetised animal. We tested three different anatomical body positions (ear, leg and tail) and give results for each body position of the sensor. In summary, it can be concluded that the agreement between PPG-based heart rate technique and reference sensor goes from 91 to 95 percentage. In this paper we showed the potential of using the PPG-based technology to assess pig’s hear rate.
ARTICLE | doi:10.20944/preprints202211.0361.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Heart Rate Variability; Inflammatory markers; Long-term Covid-19; Autonomic nervous system.
Online: 21 November 2022 (01:21:37 CET)
Background: Heart rate variability is a non-invasive, measurable, and established autonomic nervous system test. Long-term COVID-19 sequelae are unclear; however, acute symptoms have been studied. Objectives: To determine autonomic cardiac differences between long COVID-19 patients and heathy controls and evaluate associations among symptoms, comorbidities, and laboratory findings. Methods: This single-center study included long COVID-19 patients and healthy controls. The heart rate variability (HRV), a quantitative marker of autonomic activity, was monitored for 24 h using an ambulatory electrocardiogram system. HRV indices were compared between case and control groups. Symptom frequency and inflammatory markers were evaluated. The significance level of 5% (p-value 0.05) was adopted. Results: A total of 47 long COVID-19 patients were compared to 42 healthy controls. Patients averaged 43.8 (SD14.8) years old, and 60.3% were female. In total, 52.5% of patients had moderate illness. Post-exercise dyspnea was most common (71.6%), and 53.2% lacked comorbidities. COVID-19 patients had 4 times more dyslipidemia. CNP, D-dimer, and CRP levels were elevated (p-values of 0.0098, 0.0023, and 0.0015, respectively). The control group had greater SDNN24 and SDANNI (OR = 0.98 (0.97 to 0.99; p = 0.01)). Increased low-frequency (LF) indices in COVID-19 patients (OR = 1.002 (1.0001 to 1.004; p = 0.030)) and high-frequency (HF) indices in the control group (OR = 0.987 (0.98 to 0.995; p = 0.001)) were also associated. Conclusions: Patients with long COVID-19 had lower HF values than healthy individuals. These variations are associated with increased parasympathetic activity, which may be related to long COVID-19 symptoms and inflammatory laboratory findings.
REVIEW | doi:10.20944/preprints202305.2249.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: SARS-CoV-2; COVID-19; heart rate variability; cardiac; cardiovascular; parasympathetic; sympathetic; autonomic
Online: 31 May 2023 (12:55:32 CEST)
Cardiac damage has been attributed to SARS-Cov-2-related pathology contributing to increased risk of vascular events. Heart rate variability (HRV) is a parameter of functional neurocardiac integrity with low HRV constituting an independent predictor of cardiovascular mortality. Whether structural cardiac damage translates into neurocardiac dysfunction in patients infected with SARS-CoV-2 remains poorly understood. Hypothesized mechanisms of possible neurocardiac dysfunction in COVID-19 comprise direct systemic neuroinvasion of autonomic control centers, ascending virus propagation along cranial nerves and cardiac autonomic neuropathy. While the relationship between the autonomic nervous system and the cytokine cascade in general has been studied extensively, the interplay between the inflammatory response caused by SARS-CoV-2 and autonomic cardiovascular regulation remains largely unclear. We reviewed the current literature on the potential diagnostic and prognostic value of autonomic neurocardiac function assessment via analysis of HRV in patients with COVID-19. Furthermore, we discuss potential therapeutic targets of modulating neurocardiac function in this high-risk population.
ARTICLE | doi:10.20944/preprints202307.1259.v1
Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: real time; heart rate variability; psychological intervention program; complex posttraumatic stress disorder
Online: 19 July 2023 (09:42:40 CEST)
For a subject suffering from complex post-traumatic stress disorder, a psychological intervention program was designed, monitored in real-time during psychotherapy, and evaluated quantitatively and qualitatively after psychotherapy. One male subject participated in this program under consent. The proposed intervention program was designed using cognitive behavioral therapy and stabilization treatments for body-based sensory processes in four sessions of 90 min each. During psychotherapy, a wearable heart sensor and a communication application were utilized to determine the subject’s current psychological state. After the intervention, the effect of the proposed program was analyzed qualitatively and quantitatively using the Impact of Event Scale–Revised (IES-R-K), Athens insomnia scale (AIS), and heart rate variability (HRV). After the intervention program was conducted, the subject reconstructed his traumatic events and trained himself with certain psychological techniques to decrease his negative thoughts and emotions induced by his previous traumatic events. The IES-R-K and AIS ten months after the last session were changed positively by approximately 25% compared with the subject’s state before the first session. During psychotherapy, the HRV exhibited a significant correlation with the subject’s emotional state. The proposed intervention program induced a positive change in the subject. Although the HRV was well utilized in this investigation, more sophisticated statistical analysis will be required for clinical trials.
ARTICLE | doi:10.20944/preprints202007.0345.v1
Subject: Social Sciences, Psychology Keywords: foetus; music perception; tempo; heart rate variability; ultrasound exam; APIB scale; habituation; sensitization
Online: 16 July 2020 (07:49:50 CEST)
Music perception in foetuses has been explored under different theoretical paradigms such as habituation, categorical perception, sound preferences and recall. This study investigated the temporal dimension of music perception through the habituation and sensitization paradigm. Foetuses of 41 pregnant women, mean gestational age of 34.7 weeks (±2.4), were observed during ultrasound exams. Foetuses’ reaction to two different tempos (Allegro vs Adagio) and sources (internal vs external) of music stimuli was registered by heart rate variability (HR) and motor response according to the Assessment of Preterm Infants Behaviour scale (APIB) by its factors of movement (MOV) and organization (ORG). A folkloric lullaby, sung and played live with a stringed instrument by a musician, was presented in three stages that were compared to baseline: 1) slow tempo (Adagio), 2) fast tempo (Allegro); and 3) now sung by mother at slow tempo (Adagio). Exploratory analyses showed that all factors increased from baseline to first stage. HR and ORG varied significantly among stages, with HR being the strongest factor. MOV merely detected change from baseline to first stage. ORG decreased for Allegro but increased for maternal Adagio, while HR decreased to near baseline values. ANOVA-repeated measures with gestational age as covariate showed that all measures were sensitive to first music presentation (Adagio), although only HR and ORG differed among stages. Considering estimated marginal means, adjusted for gestational age, HR presented a sensitization pattern throughout stages, but ORG kept habituating to external source and increased to maternal Adagio, suggesting foetal discrimination by sound source. We conclude that foetuses showed different behavioural and physiological responses to external versus internal sound source and musical tempo. The combined use of a behavioural scale (APIB) and HR in foetuses proved to be a valid multidimensional instrument.
ARTICLE | doi:10.20944/preprints202304.0028.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: excessive Internet gaming; heart rate variability; high frequency; impulsivity, young male adults
Online: 3 April 2023 (13:46:36 CEST)
Several studies have reported a relationship between autonomic dysfunction during tasks and Internet addiction. Changes within 24 h regarding heart rate variability (HRV) may be a more sensitive indicator than short term observations. We evaluated the influence of excessive Internet usage on HRV using a 24 h electrocardiogram (ECG) and examined acute changes during computer game tasks. A total 13 high school students and 22 young adults were recruited, and divided into excessive Internet user and non- excessive user groups based on Internet addiction test scores. The ECG was recorded continuously for 24 h by a wearable sensor and during two computer games (the Iowa gambling task and each participant’s preferred game) using a standard type ECG system. Multiple psychometric tests were also conducted. The excessive Internet user group exhibited clinically significant depressive symptoms, and higher self-reported scores for anxiety, impulsivity, autistic tendencies, and sleep problems than the non- excessive internet user group. There were weak differences within the 24 h high-frequency (HF) band power between two groups. During the Iowa gambling task, younger participants exhibited a reduced HF response, which may be related to weaker top- down self- regulatory mechanisms.
ARTICLE | doi:10.20944/preprints202212.0410.v1
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: Heart rate variability; COVID-19; post-COVID-19 condition; long COVID; autonomic dysfunction; vagal nerve activity; symptomatology; lung function
Online: 22 December 2022 (03:13:53 CET)
Persistence of symptoms beyond three months after COVID-19 infection, often referred to as post-COVID-19 condition (PCC), is commonly experienced. It is hypothesized that PCC results from autonomic dysfunction with decreased vagal nerve activity, which can be indexed by low heart rate variability (HRV). The aim of this study was to assess the association of HRV upon admission with pulmonary function impairment and number of reported symptoms beyond three months after initial hospitalization for COVID-19 between February and December 2020. Follow-up took place three to five months after discharge and included pulmonary function tests and the assessment of persistent symptoms. HRV analysis was performed on one 10s electrocardiogram obtained upon admission. Analyses were performed using multivariable and multinomial logistic regression models. Among 171 patients who received follow-up, and with an electrocardiogram at admission, decreased diffusion capacity of the lung for carbon monoxide (DLCO) (41%) was most frequently found. After a median of 119 days (IQR 101-141), 81% of the participants reported at least one symptom. HRV was not associated with pulmonary function impairment or persistent symptoms three to five months after hospitalization for COVID-19.
ARTICLE | doi:10.20944/preprints202306.0179.v1
Subject: Engineering, Other Keywords: operator; forwarder; tractor with a timber trailer; ergonomics; heart rate; physical load
Online: 2 June 2023 (10:21:50 CEST)
This work deals with finding out whether the heart rate values of operators of forwarding machines during the work shift are influenced by the individual activities that the operator has to perform during timber skidding, or by the operators themselves. Furthermore, the work deals with determining the difficulty of individual activities in terms of physical load. For this purpose, the work shift of operators carrying out timber skidding was divided into individual activities: Driving, Maintenance, Forwarding, Break. During these work activities, the heart rate of each operator was taken for subsequent evaluation. The results show that the highest pulse rates of the operators were achieved during the Maintenance of the entrusted machine, while the highest pulse fluctuations in the operators were recorded during Forwarding. As part of this activity, the highest heart rate of the entire measurement process was recorded (132.0000 bpm), but also the lowest (42.0000 bpm). Furthermore, it was proven that both the operator and the activity he performs affect the pulse rate. The activities themselves did not differ from each other in only one of the six cases of comparison. Specifically, it was Driving and Forwarding.
ARTICLE | doi:10.20944/preprints202204.0088.v1
Subject: Engineering, Bioengineering Keywords: Lossy/ lossless compression; Huffman coding; real-time PPG measurement; heart rate estimate, Message Queueing Telemetry Transport (MQTT); healthcare system
Online: 11 April 2022 (04:21:00 CEST)
Nowadays, wearable devices for human health monitoring are increasingly become popular and widely used. Typically, the wearable device is small size and operates with batteries. Therefore, the wearable device acquires bio-signals and transfers to smartphones or personal computers (PC) via WiFi/ Bluetooth for processing data. To reduce power consumption is one of the most important challenges of designing wearable devices. To solve this problem, the proposed signal quality valuation (SQV) method can be select the high-quality signal and reduce the transfer time to other devices. In this paper, the proposed SQV and data compression method rely on real-time PPG signals analysis to retain important information of PPG signal, improve performance and power consumption of PPG devices. Besides, we also proposed Heuristic rules for heart rate (HR) estimation with compression data. The experimental results show that the highest compression ratio (CR) is 387.8 with BIDMC Physionet database (sampling frequencies of 125 Hz) and HR error as 1.43 bpm for averaging absolute error (avAE), the standard deviation absolute error (sdAE as 0.4) and relative error mean (avRE as 0.019). The proposed real-time PPG measurement system (sampling frequency as 100/ 200/ 400 Hz) reduce power consumption and open the new structure for healthcare application systems
ARTICLE | doi:10.20944/preprints202009.0575.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Amyloidosis; Right Heart; Cardiac involvement; heart ultrasound
Online: 24 September 2020 (08:26:32 CEST)
Amyloidosis is due to deposition of an excessive amount of protein in many parenchymal tissues, including myocardium. The onset of cardiac Amyloidosis (CA) is an inauspicious prognostic factor, that can lead to sudden death. We retrospectively analyzed 135 patients with systemic amyloidosis, admitted to our ward between 1981 and 2019. Among them, 54 patients (46.30% F / 53.70% M, age 63.95±12.82 years) presented CA at baseline. In 53 patients, there was associated with multiorgan involvement, while in one there was primary myocardial deposition. As control group, we enrolled 81 patients (49.30% F / 50.70% M, aged 58.33±15.65) who did not meet the criteria for CA. In 44/54 of patients CA was associated with AL, 5/54 with AA, 3/54 of patients with ATTR, in 1/54 AL was related to hemodialysis and 1/54 to Gel-Amyloidosis. The most common AL type was IgG (28/44); less frequent forms were either IgA (7/40) or IgD (2/40), while seven patients had a λ free light chain form. The 32 AL with complete Ig were 31 λ-chain and just one k-chain. CA patients presented normal BP (SBP 118.0±8.4 mmHg; DBP 73.8±4.9 mmHg), while those with nCA had increased proteinuria (p=0.02). TnI and NT-proBNP were significantly increased compared to nCA (p= 0.031 and p=0.047, respectively). In CA patients we found an increased LDH compared to nCA (p=0.0011). CA patients were also found to have an increased interventricular septum thickness compared to nCA (p=0.002), a decreased Ejection Fraction % (p=0.0018) and Doppler velocity E/e’ ratio (p=0.0095). Moreover, CA patients were seen to have an enhanced right atrium area (p=0.0179), right ventricle basal diameter (p= 0.0112) and wall thickness (p=0.0471) as compared to nCA, as well as an increased inferior cava vein diameter (p=0.0495). TAPSE was the method chosen to evaluate systolic function of the right heart. In CA subjects very poor TAPSE levels were found compared to nCA patients (p=0.0495). Additionally, we found a significant positive correlation between TAPSE and lymphocyte count (r=0.47; p=0.031) as well as Gamma globulins (r=0.43, p=0.033), Monoclonal component (r=0.72; p=0.047) and IgG values (r=0.62, p=0.018). On the contrary, a significant negative correlation with LDH (r=-0.57, p=0.005), IVS (r=-0.51, p=0.008) and diastolic function evaluated as E/e’ (r=-0.60, p=0.003) were verified. CA patients had very poor survival compared to controls (30 vs. 66 months in CA vs nCA, respectively, P=0.15). Mean survival of CA individuals was worse also when stratified according to NT-proBNP levels, using 2500 pg/mL as class boundary (174 vs. 5.5 months, for patients with lower vs higher values than the median, respectively p=0.013). In much the same way, decreased right heart systolic function was correlated with a worse prognosis (18.0 months median survival, not reached in subjects with lower values than 18mm, p=0.0186). Finally, our data highlight the potential prognostic and predictive value of right heart alterations characterizing amyloidosis, as a novel clinical parameter correlated to increased LDH and immunoglobulins levels. Overall, we confirm the clinical relevance of cardiac involvement and propose that right heart evaluation may be considered as a new marker for clinical risk stratification in patients with amyloidosis.
ARTICLE | doi:10.20944/preprints202309.0396.v1
Subject: Medicine And Pharmacology, Anatomy And Physiology Keywords: heterotaxy syndrome; atrial isomerism; heart surgery; congenital heart disease.
Online: 7 September 2023 (03:33:23 CEST)
Right atrial isomerism (RAI) is a complex entity whose treatment and outcome are heterogeneous. The aim of this study was to analyze the results obtained after cardiac surgery in patients with RAI. A retrospective study was conducted; it included patients diagnosed with RAI who underwent cardiac surgery; their follow-up was from January 1, 2010 to March 31, 2020. Demographic characteristics and perioperative conditions were described. Thirty-eight patients with RAI were included, the median age was 4 years (IQR 2-9.2), and 57.9% were men. The main diagnoses were atrioventricular canal (63.2%) and pulmonary stenosis (55.3%). The most common surgical procedures were modified Blalock‐Taussig shunt (65.8%) and total cavopulmonary connection with an extracardiac conduit fenestrated without cardiopulmonary bypass (15.9%). The use of inhaled nitric oxide was a marker of postoperative mortality in critically ill patients (OR: 10.33; 95% CI: 1.04 - 102.08; p = 0.02). The overall survival was 86.8%, with a better outcome in those who did not require reintubation (Log Rank, p < 0.01). The survival of RAI was similar to other centers of reference. Individuals with RAI should be evaluated rigorously to determine an adequate repair strategy, considering high morbidity and mortality.
ARTICLE | doi:10.20944/preprints202306.2009.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: heart failure; cardiomyopathy; ischemic heart disease; prognosis; women; men
Online: 29 June 2023 (07:27:12 CEST)
Background: Limited research has explored sex-specific differences in death predictors of HF pa-tients with ischemic (iCMP) and nonischemic (niCMP) cardiomyopathy. This study assessed sex differences in niCMP and iCMP prognosis. Methods: We studied 7,487 patients with HF between February 2017 and September 2020. Clini-cal features and echocardiographic findings were collected. We used Kaplan-Meier, Cox propor-tional hazards models, and score chi-square of Cox regression to determine death predictors in women and men. Results: mean age was 64.3±14.2 years, with 4,417 (59%) males. Women with iCMP and niCMP exhibited significantly higher mean age, higher mean left ventricular ejection fraction, and smaller left ventricular diastolic diameter than men. Over 2.26 years of follow-up, 325 (14.7%) women and 420 (15.7%) men, and 211 women (24.5%) and 519 men (29.8%) died in niCMP (p=NS) and iCMP (p=0.004), respectively. Cumulative incidence of death was higher in men with iCMP (log-rank p<0.0001) but similar in niCMP. Cox regression showed chronic kidney disease, dia-betes, stroke, atrial fibrillation, age, and myocardial infarction, as main predictors of death for iCMP in women and men. Conclusion: Women exhibited a better prognosis than men in iCMP, but similar for niCMP. Nevertheless, sex was not an independent predictor of death for both CMP.
ARTICLE | doi:10.20944/preprints202308.0895.v1
Online: 11 August 2023 (08:07:50 CEST)
This study investigated modifications in the ubiquitin proteasome system (UPS) in a mouse model of type 2 diabetes mellitus (T2DM) and their relationship to heart complications. db/db mice heart tissues were compared with WT mice tissues using RNA sequencing, qRT-PCR, and protein analysis to identify cardiac UPS modifications associated with diabetes. The findings unveiled a distinctive gene profile in the hearts of db/db mice with decreased levels of nppb mRNA and increased levels of Myh7, indicating potential cardiac dysfunction. mRNA levels of USP18 (deubiquitinating enzyme), psmb8, and psmb9 (proteasome β-subunits) were downregulated in db/db mice while mRNA levels of RNF167 (E3 ligase) were increased. Corresponding LMP2 and LMP7 proteins were downregulated in db/db mice, and RNF167 was elevated in Adult diabetic mice. Reduced expression of LMP2 and LMP7, along with increased RNF167 expression, may contribute to future cardiac deterioration commonly observed in diabetes. This study enhances our understanding of UPS imbalances in the hearts of diabetic mice and raises questions about the interplay between the UPS and other cellular processes, such as autophagy. Further exploration in this area could provide valuable insights into the mechanisms underlying diabetic heart complications and potential therapeutic targets.
REVIEW | doi:10.20944/preprints202308.1243.v1
Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: thyroid; heart; thyroid abnormalities; cardioprotection; heart failure; acute myocardial infarction
Online: 17 August 2023 (05:23:31 CEST)
The thyroid-heart relationship has a long and articulated history of its own, a history that en-compasses physiological and pathophysiological knowledge, the latter particularly in the context of cardiac diseases such as heart failure, arrhythmias and ischaemic heart disease. In recent years, molecular biology studies, in an experimental context, have highlighted the extraordinary dialogue that exists among the two systems in the field of cardioprotection, being an extremely important area for the treatment of cardiac diseases in both acute and chronic phases. In addi-tion, in the last few years, several studies have been carried out on the prognostic impact of al-terations in thyroid function, including subclinical ones, in heart disease, in particular in heart failure and acute myocardial infarction, with evidence of a negative prognostic impact of these and therefore with the suggestion to treat these alterations in order to prevent cardiac events, such as death. This review provides a comprehensive summary of the heart-thyroid relation-ship.
REVIEW | doi:10.20944/preprints202311.1143.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: coronary microvascular dysfunction; hypertension; hypertensive heart disease; myocardial fibrosis; heart failure
Online: 17 November 2023 (15:28:27 CET)
Coronary microvascular dysfunction (CMD) is a clinical entity linked with various risk factors that significantly affect cardiac morbidity and mortality. Hypertension, one of the most important, causes both functional and structural alterations in the microvasculature, promoting the occurrence and progression of microvascular angina. Endothelial dysfunction and capillary rarefaction play the most significant role in the development of CMD among patients with hypertension. CMD is also related to several hypertension-related morphological and functional changes in the myocardium in the subclinical and early clinical stages, including left ventricular hypertrophy, interstitial myocardial fibrosis, and diastolic dysfunction. This indicates the fact that CMD, especially if associated with hypertension, is a subclinical marker of end-organ damage and heart failure, particularly the one with preserved ejection fraction. This is why it is important to search for microvascular angina in every patient with hypertension and chest pain not associated with obstructive coronary artery disease. Several highly sensitive and specific non-invasive and invasive diagnostic modalities have been developed to evaluate the presence and severity of CMD, but also to investigate additional complications that can affect further prognosis, especially among those with hypertensive heart disease. Although various pharmacological and interventional treatments demonstrated certain clinical effects, integrated diagnostic and therapeutic algorithms are necessary to reduce the burden of this emerging condition.
REVIEW | doi:10.20944/preprints202105.0432.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: myofibroblasts; fibrosis; heart failure
Online: 19 May 2021 (07:55:59 CEST)
Fibroblasts are differentiated to myofibroblasts and produce collagen and other extracellular matrix when the heart is exposed to stresses. Myocardial infarction and pressure overload-induced hypertrophy are major stresses to induce differentiation of fibroblasts. Since collagen can compensate the missing tissue due to injury, appropriate production of collagen is beneficial for the injured heart against rupture. However, excessive deposition of collagen is called fibrosis and causes cardiac dysfunction. After fibroblasts are differentiated to myofibroblasts, myofibroblasts can further change their phenotypes. In addition, myofibroblasts are found to have a new function other than collagen production. Myofibroblasts have macrophage-like functions that engulf dead cells and secrete anti-inflammatory cytokines. So far, research on fibroblasts has been delayed due to the lack of available markers for selective isolation of fibroblasts. In recent years, it has become possible to genetically label fibroblasts, sequence the cells at single cell levels, and manipulate function or the number of cells. Based on new technologies, the origin of fibroblasts and myofibroblasts, time-dependent changes of fibroblast states after injury, and heterogeneity have been demonstrated. Here, I will introduce recent advances in fibroblasts and myofibroblasts.
COMMUNICATION | doi:10.20944/preprints202309.1187.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: galectin-3; cardiac hypertrophy; immunohistochemical expression; heart transplantation; heart disease; cardiorenal syndrome
Online: 19 September 2023 (03:42:54 CEST)
Background: Galectin-3 (Gal-3) overexpression is associated with fibroblastic proliferation and the production of collagen, resulting in increased cardiac fibrosis and remodelling. Aim of the study was to investigate on the expression of Gal-3 in hypertrophic hearts. We examined 19 surgical specimens taken from interventricular septum of 8 patients with Tetralogy of Fallot, 4 patients with aortic valve stenosis, 1 cardiac explant affected from dilated cardiomyopathy, and 6 myocardial biopsies of patients submitted to heart transplantation. Methods: All the samples were routinely processed, stained with Hematoxylin-Eosin, Trichromic stain and elastic fiber stain and selected by having the morphological features of myocardial hy-pertrophy: myocytolysis, nuclear pleomorphism, interstitial fibrosis. Results: At immunohistochemistry, myocardial fibers showed cytoplasmic expression of Gal-3 in the 4 patients with aortic valve stenosis (diffuse in 3 and mild in 1), in the 1 patient with cardiac explant (mild) and in the 4/6 transplanted hearts (mild and focal in 3 and diffuse in 1). The 8 patients affected from Tetralogy of Fallot and 2 patients with transplanted hearts resulted negative. Conclusions: The results agreed with the hypothesis that Gal-3 may play a role in cardiac hyper-trophy; its expression in myocardial fibers is not related with the morphological aspects as suggested by the absence in pediatric cases. The presence in myocardial biopsies taken from transplanted hearts would suggest a possible role in predicting clinical outcome of such patients.
ARTICLE | doi:10.20944/preprints202311.1913.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Congestive heart failure; echocardiography; hand-held echocardiogram; heart failure; images, advanced practice providers
Online: 29 November 2023 (23:04:44 CET)
Objectives: Evaluate hand-held echocardiography (HHE) performed and interpreted by trained Advanced Practice Providers (APPs) on hospitalized CHF patients for image quality and interpretation, by comparing against expert echocardiographer and SE findings. Background: Congestive heart failure (CHF) is associated with increased hospital admissions and mortality. While standard echocardiogram (SE) is the gold standard for cardiac assessment, it is not readily available. Hospitalized CHF patients require rapid assessment for expedited treatment. Methods: Over 6 months, five trained APPs performed HHE on hospitalized CHF patients and interpreted: a) Left ventricular (LV) size, b) LV ejection fraction (LVEF), and c) right atrial pressure (RAP). The study echocardiographer reviewed and blindly interpreted HHE images and compared with APPs and SE findings. Kappa-statistics determined the degree of agreement between APPs and study echocardiographer interpretation of HHE images and SE. Results: 80 CHF patients [age 73±14 years, 58% males; LVEF (by SE) 45±19%; 36.3% body mass indexes ≥30 kg/m2] were enrolled. HHE interpretation by APPs had good agreement for LVEF (kappa 0.79) with study echocardiographer and SE (kappa 0.74), and good agreement for RAP (kappa 0.67) with study echocardiographer. Correlation between absolute LVEF interpretation by study echocardiographer on HHE and SE was r=0.88 (p<0.0001). Conclusions: Trained APPs obtained diagnostic-quality HHE images and interpreted LV function and RAP in CHF patients, with good agreement with the study echocardiographer. LVEF by HHE correlated with LVEF by SE. Our study suggests trained APPs can use HHE to evaluate LVEF and RAP in CHF patients leading to expedited and optimized treatment.
ARTICLE | doi:10.20944/preprints202311.1198.v1
Subject: Biology And Life Sciences, Parasitology Keywords: Heart fibrosis; Chagas disease; Pirfenidone
Online: 20 November 2023 (07:34:46 CET)
Cardiac fibrosis is a severe outcome of Chagas disease (CD), caused by the protozoan Trypanosoma cruzi. Clinical evidence revealed a correlation between fibrosis levels with impaired cardiac performance in CD patients. Therefore, we sought to analyze the effect of inhibitors of TGF- (pirfenidone), p38-MAPK (losmapimod) and c-Jun (SP600125) on the modulation of collagen deposition in cardiac fibroblasts (CF) and in vivo models of T. cruzi chronic infection. Sirius Red/Fast green dye was used to quantify both collagen expression and total protein amount, assessing cytotoxicity. The compounds were also used to treat C57/Bl6 mice chronically infected with T. cruzi, Brazil strain. We identified an anti-fibrotic effect in vitro for pirfenidone (TGF-β inhibitor, IC50 114.3 μM), losmapimod (p38 inhibitor, IC50 17.6 μM) and SP600125 (c-Jun inhibitor, IC50 3.9 μM). This effect is independent of CF proliferation since these compounds do not affect T. cruzi-induced host cell multiplication as measured by BrdU incorporation. Assays of chronic infection of mice with T. cruzi have shown a reduction in heart collagen by pirfenidone. These results propose a novel approach to fibrosis therapy in CD, with the prospect of repurposing pirfenidone to prevent the onset of ECM accumulation in the heart of the patients.
ARTICLE | doi:10.20944/preprints202310.0466.v1
Subject: Biology And Life Sciences, Parasitology Keywords: Sarcocystis; chamois; heart; diaphragm; Germany
Online: 9 October 2023 (07:36:37 CEST)
Chamois are mountain ungulates (Subfamily Caprinae) which inhabit several medium and high altitude mountain ranges from southern Europe to the Near East. The first findings of Sarcocystis cysts in the musculature of chamois were reported in the 1970s. However, only limited work on the epidemiology of sarcocystosis and identification of the species of Sarcocystis in chamois has been done in the past. The present work was part of a comprehensive study on the parasites of chamois in Germany aiming to provide, for the first time, data on the prevalence and intensity of Sarcocystis infection in native Alpine chamois using histology examination of heart and/or diaphragm tissue samples collected from 216 chamois (40 kids and 176 chamois ranging of one up to 18 years of age). Sarcocysts were detected in either heart or diaphragm of 167/216 chamois (77.3%) with 131 of 183 heart samples and 127 of 215 diaphragm samples testing sarcocyst positive. Of the 181 chamois with both heart and diaphragm available (34 kids and animals up to 18 years of age), sarcocysts were detected in heart and/or diaphragm of 142 animals translating in an overall 78.5% prevalence of Sarcocystis infection (95%CI 72.5% - 84.4%). Sarcocysts were more frequently recorded in heart vs. diaphragm (72.4% vs. 56.4%; p=0.0021), and diaphragm positivity was associated with heart positivity (p=0.0001). Sarcocyst positivity (heart and/or diaphragm) was significantly (p<0.001) lower in kids than in the older chamois (27.1% vs. 88.6%, respectively) but prevalence did not differ between the sexes, regardless of the chamois’ age (p>0.3). Intensity of infection was generally low (<10 sarcocysts per cm² muscle cut) in both heart positive and diaphragm positive animals (94.7% and 93.7%, respectively) with heart yielding higher sarcocyst counts than diaphragm (p<0.001). Both heart and diaphragm sarcocyst counts were significantly (p<0.001) lower in kids than in the older chamois. Sarcocystis infection was demonstrated to be prevalent in chamois in Germany but intensity is apparently low. Further studies are desired to identify the species of Sarcocystis parasitizing the chamois using both phenotypic and molecular characteristics.
REVIEW | doi:10.20944/preprints202308.0192.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: heart failure; gut; microbiome; relationship
Online: 2 August 2023 (10:05:19 CEST)
There is a bidirectional relationship between the heart and the gut. Gut microbiome is an excellent gut-homeostasis keeper since controls the growth of potentially harmful bacteria and protects the microbiota environment. There is evidence suggesting that diet rich in fatty acid can be metabolized and converted by gut microbiome and hepatic enzymes to trimethyl-amine N-oxide (TMAO) a product that is associated with atherogenesis, platelet dysfunction, thrombotic events, coronary artery disease, stroke, heart failure and ultimately death. Heart failure, by inducing gut ischemia and congestion and consequently gut barrier dysfunction promote an intestinal leak of microbes or even of their products, facilitating their entrance into the circulation and thus stimulating the low-grade inflammation and hence the immune response. Drugs used for heart failure may alter the gut microbiome, and conversely gut microbiome may modify the pharmacokinetic properties of the drugs. Modification of lifestyle based mainly on exercise and Mediterranean diet along with the use of pre- or probiotics may be beneficial to some extent for the gut microbiome environment. The potential role of gut microbiome in heart failure development and outcomes is a fruitful area of future research.
ARTICLE | doi:10.20944/preprints202306.0800.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: hypertrophic cardiomyopathy; cardiomyopathies; heart failure
Online: 12 June 2023 (08:41:43 CEST)
Background: Hypertrophic Cardiomyopathy (HCM) is the most common inherited Cardiomyopathy. The hallmark of HCM is myocardial fibrosis which contributes to heart failure, arrhythmias, and sudden cardiac death (SCD). Objective: To identify the factors implicated in heart failure symptoms and functional capacity of patients with HCM. Methods: In this cohort study, 43 patients with HCM were recruited. According to functional capacity and symptoms presentation, patients were categorized according to NYHA classification, and echocardiographic measurements of left ventricle systolic and diastolic function have been conducted. The echocardiographic assessment of right vetriculo-arterial coupling (RVAC) has been made by calculating the tricuspid annular peak systolic tissue Doppler velocity (TASV)/estimated RV systolic pressure (RVSP) ratio. Results: Almost half, 22 (51%) of our study population present symptoms of heart failure and were categorized as the symptomatic group - NYHA 2 or higher. Maximum LVOT gradient, RVSP, and the ratio of E/e’ were higher in the “symptomatic” compared to the “asymptomatic” group. TASV was lower in the “symptomatic” compared to the asymptomatic group (11±1cm/sex vs. 13±2cm/sec, p=0.04). However, there was no difference in other potentially influential factors, such as heart rate or systemic blood pressure. The SCD risk score does not differ between the two studied groups. The RVAC (estimated with the TASV/RVSP ratio) was lower in the “symptomatic” compared with the “asymptomatic” group (0.32±0.09 vs. 0.46±0.11, p<0.001). Conclusion: A low RVAC (as TASV/RVSP ratio) value could represent an echocardiographic marker of right ventricular-arterial uncoupling in patients with HCM and may impaired functional status.
REVIEW | doi:10.20944/preprints202203.0301.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Heart Failure; Gravity; Ischemia; Brain
Online: 22 March 2022 (12:38:29 CET)
During the 90 days following hospitalization for acute heart failure, ejection fraction and type of discharge medications have been shown in clinical trials to have little effect on mortality. We examined the recent literature addressing brain-related etiologies of sudden death following heart failure. Two mechanisms of sudden unexpected death have been suggested to possibly result from 4 significant influences on pathophysiology in the brain. The two causes of death are severe cardiac arrhythmia, and neurogenic pulmonary edema. They are both mediated through the brainstem autonomic nuclei generally, and executed specifically through the dorsal motor nucleus of the vagus nerve. The four significant influences on pathophysiology in the brainstem autonomic nuclei are: 1) Hyper-stimulation of neurons in the solitary tract nucleus, increasing their metabolic requirements; 2) Inadequate blood flow at a vascular watershed terminus; 3) Additionally decreased blood flow following vasoconstriction related to relative hyperventilation and decreased pCO2 levels; 4) Gravitational ischemia in the brain—caused by the weight of the brain mass sitting above the brainstem. Changes in head tilt release gravitational ischemia in the brain. There is no specific head position (relative to gravity) that is considered favorable or unfavorable for an extended period of time (i.e. more than 24 hours). Even a small degree of head elevation, used in managing pulmonary congestion, may increase gravitational ischemia in the posterior fossa and brainstem. In this paper we suggest a new and important research avenue for intervening in cardiac arrhythmias, and preventing their occurrence, through the non-invasive use of head-tilting, and other head repositioning maneuvers. This could potentially help many geriatric patients with heart failure, who have decreased mobility in bed, and who tend to stay in one position longer, thereby increasing gravitational ischemia in the brain.
ARTICLE | doi:10.20944/preprints202010.0625.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: heart failure; cardiovascular; comparative; evolution
Online: 30 October 2020 (08:06:24 CET)
Heart failure with preserved ejection fraction (HFpEF) is a leading form of human cardiovascular disease and commonly associated with systemic hypertension. Unique evolved adaptations in giraffe myocardia may be a natural animal model of resistance to HFpEF. In humans, pressure-overload induced left ventricular thickening (PLVT) impairs diastolic relaxation, elevates left atrial pressures and may progress to heart failure with symptoms including exercise intolerance. In healthy giraffe, the left ventricle thickens as developmental neck lengthening widens the vertical distance between the heart and head increasing pressures needed to maintain constant brain perfusion. Yet, diastolic relaxation and exercise capacity are unimpaired, a critical adaptation for prey species such as giraffe. The proximate mechanisms underlying this unique cardiovascular physiology are not yet characterized. Developmental PLVT in giraffe emerges as a species-specific evolved adaptation which offers a roadmap for identifying innovations in therapeutic and prevention strategies for HFpEF.
REVIEW | doi:10.20944/preprints201910.0040.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: diabetes; exercise; cardiomyopathy; heart failure
Online: 3 October 2019 (13:59:22 CEST)
Diabetes mellitus is associated with cardiovascular, ophthalmic, and renal comorbidities. Among these, diabetic cardiomyopathy (DCM) causes the most severe symptoms and is considered to be a major health problem worldwide. Exercise is widely known as an effective strategy for the prevention and treatment of many chronic diseases. Importantly, the onset of complications arising from diabetes can be delayed or even prevented by exercise. Regular exercise is reported to have positive effects on diabetes mellitus and the development of DCM. The protective effects of exercise include the prevention of cardiac apoptosis, fibrosis, oxidative stress, and microvascular diseases, as well as improvement in cardiac mitochondrial function, and calcium regulation. The present review summarizes the recent findings to describe the potential mechanisms by which exercise may prevent DCM and heart failure.
REVIEW | doi:10.20944/preprints201810.0235.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: heart; ursodeoxycholic acid; cardioprotection; signaling
Online: 11 October 2018 (08:35:28 CEST)
Bile acids (BA) are classically known as an agent important in lipid absorption and cholesterol metabolism. Nowadays, BAs have been found to be involved in various cellular signaling pathways such as protein kinase cascades, cyclic AMP (cAMP) synthesis and calcium mobilization. In addition, they have also been shown to regulate glucose and energy homeostasis. Bile acids are ligands for several nuclear hormone receptors, including FXR. Recently, muscarinic receptor and TGR5, G-protein-coupled receptor (GPCR), have been suggested to play a role in bile acid activity which is independent of nuclear hormone receptors. Moreover, BAs have also been studied in other GPCR associated pathways, namely sphingosine-1-posphate and glucagon receptor. Hydrophobic bile acids have been proven to affect heart rate and its contraction. Elevated bile acids are associated with arrhythmias in adults and fetal heart. Altered ratios of primary and secondary bile acid are reported in chronic heart failure patients. Meanwhile in patients with liver cirrhosis, cardiac dysfunction has been strongly linked to the increase of serum bile acid concentrations. In contrast, the most hydrophilic BA known as ursodeoxycholic acid has been found beneficial in improving peripheral blood flow in chronic heart failure patients and protecting heart against reperfusion injury.
ARTICLE | doi:10.20944/preprints201711.0062.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: sacubitril valsartan; heart failure; treatment
Online: 9 November 2017 (09:17:37 CET)
Introduction In sacubitril-valsartan (sacub/v), the effects of an angiotensin II receptor blocker (ARB) exerted by valsartan are strengthened by the addition of sacubitril, an inhibitor of neutral endopeptidases. PARADIGM - HF study proved this association to be superior to enalapril in reducing both all-cause death and cardiovascular mortality, as well as heart failure (HF) hospitalizations in patients with cardiac insufficiency and reduced left ventricular ejection fraction( HFREF) belonging to NYHA class II-IV. To test whether even in our experience sacub/v is associated with favorable outcomes concerning mortality and morbidity, an outpatient small population of HFREF patients was retrospectively studied, of whom one third was treated with sacub/v instead of conventional therapy with ACE -inhibitors or ARBs. Methods A retrospective cohort study was carried out to assess the effects of sacub/v in addition to beta-blocker and mineral receptor antagonist (MRA) in a group of HFREF patients in NYHA classes II-III compared with conventional therapy (comprising ACE inhibitor or ARB added to beta-blocker plus a MRA) administered in a second group of HFREF patients with comparable clinical features retrospectively enrolled as controls. In the two groups, the therapeutic regimen was established in accordance with the preferences of the treating physician. Additionally, in both groups, evidence-based drug therapy was supplemented by the adjunct of a loop diuretic, usually furosemide, at variable doses. The primary outcomes of interest were all-cause death and HF hospitalizations. Safety outcomes were symptomatic hypotension, angioedema, hyperkalemia and worsening renal function. Results Mortality at six months was 6.8% in patients under therapy with sacub/v versus 34% in those treated with conventional therapy (odds ratio[OR] = 0.14; 95% CI: 0.04-0.49). Moreover, HF hospitalizations in the observation period considered were 4.5% in sacub/v group versus 59% in the conventional therapy group (OR = 0.03; 95% CI: 0.01–0.14). Safety outcomes included in our study (angioedema, hyperkalemia, hypotension and worsening renal function) showed a comparable profile in the two groups, with evidence of good tolerability of sacub/v , except for the side - effect " hypotension" (PAS < 100 mm Hg) , found in 15.9% of patients under sacub/v versus 5.7% reported in controls (OR = 3.14; 95% CI: 0.94–10.55). Conclusions In our experience, sacub/v has yielded a strong protection against both all-cause death and HF hospitalizations at six months , in the absence of significant noxious side effects. Nevertheless, considering the retrospective character of the study and the relatively exiguous sample size, further post marketing observational studies would be desirable . In particular, studies aiming at exploring safety of the new pharmacologic principle, namely mainly focusing on hypotension and angioedema, are warranted, in order to validate further this very efficacious molecule for therapy of chronic HF, especially stable HFREF in NYHA classes II-III.
CASE REPORT | doi:10.20944/preprints202307.0438.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: heart rate monitor; endurance running; arrhythmia, tachycardia; artifacts; exertion rhythm disorders; Munchhausen syndrome; athlete's heart
Online: 7 July 2023 (07:41:51 CEST)
A 36-year-old professional marathon runner reported sudden heart palpitations occurring during competitions, with heart rates (HR) of 230 bpm recorded on sports HR monitor (HRM) over 4 years. These episodes subsided upon the cessation of exercise. Electrocardiograms, echocardiography, and cardiac magnetic resonance imaging results were borderline for athlete's heart. Because an electrophysiology study and standard exercise tests provoked no arrhythmia, doctors suspected Munchhausen syndrome. Ultimately, an exercise test that simulated the physical effort during a competition provoked tachyarrhythmia consistent with the HRM readings. This case demonstrates the diagnostic difficulties related to exercise-induced arrhythmia and the diagnostic usefulness of sports HRMs.
ARTICLE | doi:10.20944/preprints202202.0017.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: protein-protein interactions; interactome; congenital heart disease; developmental disorder; hypoplastic left heart syndrome; web application
Online: 1 February 2022 (16:00:59 CET)
Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) affecting 1 in 5,000 newborns. We constructed the interactome of 74 HLHS-associated genes identified from a large-scale mouse mutagenesis screen, augmenting it with 408 novel protein-protein interactions (PPIs) using our High-precision Protein-Protein Interaction Prediction (HiPPIP) model. The interactome is available on a webserver with advanced search capabilities (http://severus.dbmi.pitt.edu/wiki-HLHS). 364 genes including 73 novel interactors were differentially regulated in tissues/iPSC-derived cardiomyocytes of HLHS patients. Novel PPIs facilitated the identification of TOR signaling and endoplasmic reticulum stress modules. 60.5% of the interactome consisted of housekeeping genes that may harbor large-effect mutations and drive HLHS etiology but show limited transmission. Network proximity of diabetes, Alzheimer’s disease, and liver carcinoma-associated genes to HLHS genes suggested a mechanistic basis for their comorbidity with HLHS. Interactome genes showed tissue-specificity for sites of extracardiac anomalies (placenta, liver and brain). The HLHS interactome shared significant overlaps with the interactomes of ciliopathy and microcephaly-associated genes, with the shared genes respectively enriched for genes involved in intellectual disability and/or developmental delay, and neuronal death pathways. This supported the increased burden of ciliopathy variants and prevalence of neurological abnormalities observed among HLHS patients with developmental delay and microcephaly respectively.
REVIEW | doi:10.20944/preprints202004.0346.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: coronavirus; heart; prognosis; COVID-19; ICU
Online: 19 April 2020 (13:15:27 CEST)
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging infectious disease with currently a pandemic state. Cardiac function can be involved, affecting prognosis, in addition with lung feature severity, particularly in patients with comorbidities. Since the renin angiotensin aldosterone (RAA) system may interact with SARS-Cov-2, researches are still ongoing to assess the prognostic value of RAA blockers in cardiology.
ARTICLE | doi:10.20944/preprints201903.0082.v1
Subject: Medicine And Pharmacology, Veterinary Medicine Keywords: RAAS; Canine Congestive Heart Failure; Therapeutics
Online: 6 March 2019 (13:33:08 CET)
Congestive heart failure (CHF) is a major cause of morbidity and mortality with an increasing prevalence in human and canine populations. Similar to humans, overactivation of the renin-angiotensin aldosterone system is involved in the pathophysiology of CHF in dogs. Current therapeutic strategies for the management of canine CHF include the use of RAAS inhibitors, diuretics and inodilators. The present review summarizes data from our own research on the modulation of the renin-angiotensin cascade in dogs in dogs, together with new findings (including novel therapeutic targets) from the veterinary and the human literature.
REVIEW | doi:10.20944/preprints201902.0030.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: biomarkers; miRNAs; heart failure; system biology
Online: 4 February 2019 (11:44:17 CET)
Heart failure (HF) has several etiologies including myocardial infarction (MI) and left ventricular remodeling (LVR), but its progression remains difficult to predict in clinical practice. Systems biology analyses of LVR after MI predict molecular insights of this event such as modulation of microRNA (miRNA) that could be used as a signature of HF progression. To define a miRNA signature of LVR after MI, we use 2 systems biology approaches integrating either proteomic data generated from LV of post-MI rat induced by left coronary artery ligation or multi-omics data (proteins and non-coding RNAs) generated from plasma of post-MI patients from the REVE-2 study. The first approach predicts 13 miRNAs and 3 of these miRNAs were validated to be associated with LVR in vivo: miR-21-5p, miR-23a-3p and miR-222-3p. The second approach predicts 24 miRNAs among 1310 molecules and 6 of these miRNAs were selected to be associated with LVR in silico: miR-17-5p, miR-21-5p, miR-26b-5p, miR-222-3p, miR-335-5p and miR-375. We identified a signature of 7 microRNAs associated with LVR after MI that support the interest of integrative systems biology analyses to define a miRNA signature of HF progression.
REVIEW | doi:10.20944/preprints201808.0027.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Hedgehog; Ischemia; Heart; Brain; Skeletal muscle
Online: 1 August 2018 (16:31:01 CEST)
Hedgehog (Hh) proteins are prototypical morphogens known to regulate epithelial/mesenchymal interactions during embryonic development. In addition to its pivotal role in embryogenesis, the Hh signaling pathway may be recapitulated in post-natal life in a number of physiological and pathological conditions, including ischemia. This review highlights the involvement of Hh signaling in ischemic tissue regeneration and angiogenesis, with particular attention to the heart, the brain, and the skeletal muscle. Updated information on the potential role of the Hh pathway as a therapeutic target in ischemic condition is also presented.
ARTICLE | doi:10.20944/preprints201608.0100.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Cardiac troponin I; Ischemic heart disease
Online: 9 August 2016 (14:31:47 CEST)
Background and objectives: The correlation of cardiac troponin I with early in-hospital outcomes in acute myocardial infarction is not well established. This study aims to assess the role of troponin I in predicting in-hospital outcomes and early left ventricular systolic dysfunction in patients with ST-segment elevation myocardial infarction (STEMI). Patients and methods: In a prospective study, 116 patients (74males and 42 females), with STEMI who had been admitted to the Coronary CareUnit from March 2015 to September 2015 were enrolled. Patients were divided according to the level of troponin I on admission into 3 groups (low, medium and high elevation). Results: The mean age (+ SD) of the patients was 60+11.4 years. The troponin level of 66.2% of males was high compared with 52.4% of females (p=0.002). The incidence of acute pulmonary edema (21.1%), cardiogenic shock (7%) and early left ventricular systolic dysfunction (49.3%) was significantly higher among patients with high troponin level compared with (0%, 0% and 16%, respectively) among patients with low troponin level. All deaths and cardiac arrest were of high troponin level. Conclusions: High admission troponin I in STEMI permits early identification of patients at increased risk of major cardiac complications and death.
ARTICLE | doi:10.20944/preprints201608.0087.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: natriuretic peptides; heart failure; congestion; outcome
Online: 9 August 2016 (11:33:03 CEST)
Background According to some authors, a single isolated measurement of serum BNP executed on hospital admission would not be a sufficiently accurate method to predict the outcome of patients with ADHF. Aims For verifying this assumption, a retrospective study was conducted on patients hospitalized for ADHF. Our main objective was to ascertain whether there was any difference in midterm mortality among patients with rising BNP at discharge as compared to those with decreasing BNP at discharge. Methods Medical records were examined so as to make a partition of the ADHF patient population into two groups, the former characterized by a rise in BNP during hospitalization, and the latter exhibiting a decrease in BNP in the measurement taken at hospital discharge. Results 177 patients were enrolled in a retrospective study. Among them, 53 patients (29.94%) had increased BNPs at the time of discharge, whereas 124 (70.06%) showed decreases in serum BNP during their hospital stay. The group with patients who exhibited BNP increases at the time of discharge had higher degree of congestion evident in the higher frequency of persistent jugular venous distention and persistent orthopnea at discharge. Moreover, patients with increased BNP at the time of discharge had a lower reduction in inferior vena cava maximum diameter [1.58 ± 2.2 mm vs. 6.32 ± 1.82 mm; p (one-way ANOVA)=0.001]. In contrast, there was no significant difference in weight loss when patients with increased BNP at discharge were compared to those with no such increase. A total of 14 patients (7.9%) died during the six-month follow-up period. Cox proportional hazard analysis revealed that BNP increase at the time of discharge was an independent predictor of six-month all-cause mortality after adjustment for age, sodium at discharge, creatinine at discharge and New York Heart Association (NYHA) class at discharge (hazard ratio 34.49; 95% confidence intervals: 4.55–261.06; P =0.001). Conclusions Among patients with history of ADHF, more elevated BNP levels at the time of discharge from the hospital compared to those detected at admission identify a patient subset with higher grade of congestion and higher six-month mortality.
ARTICLE | doi:10.20944/preprints202311.0661.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: endocarditis; aortic valve replacement; prosthetic heart valve.
Online: 9 November 2023 (15:01:57 CET)
Background: Infective endocarditis(IE) is a serious disease and in many cases surgery is necessary. Whether the type of prosthesis implanted for aortic valve replacement(AVR) for IE impacts patient survival is a matter of debate. The aim of the present study is to quantify differences in long-term survival, recurrence of endocarditis AVR for IE according to prosthesis type among patients aged 40 to 65 years. Methods: This was an analysis of the INFECT-REGISTRY. Overall, 4365 patients were diagnosed and operated on for IE from 2000 to 2021. Of these, 549 aged between 40 and 65 years underwent AVR. 268(48.8%) received mechanical prostheses, and 281(51.2%) biological ones. Confounders were adjusted using optimal full matching propensity score. Results: A significant trend in reduction of implantation of mechanical vs biological prostheses was observed during the study period(p<0.0001). Long-term survival was significantly higher among patients receiving a mechanical prosthesis than those receiving a biological prosthesis (hazard ratio [HR] 0.546,95%CI: 0.322-0.926, p=0.025). Mechanical prostheses were significantly associated with less recurrent endocarditis after AVR (HR 0.268,95%CI:0.077-0.933,p=0.039).Conclusions: The present analysis of the INFECT-REGISTRY shows increased survival and reduced recurrence of endocarditis after mechanical aortic valve prosthesis implant for IE in middle-aged patients.
ARTICLE | doi:10.20944/preprints202309.1483.v1
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: radiology; computed tomography; coronary angiography; phantom; heart
Online: 22 September 2023 (05:16:02 CEST)
Abstract: Background: Coronary angiography CT scans play a pivotal role in diagnosing cardiovascular diseases, providing crucial information for treatment planning. However, concerns regarding radiation exposure have prompted the need for establishing region-specific diagnostic reference levels (DRLs) to ensure patient safety. This study aims to assess radiation exposure during coronary angiography CT scans in the Northeast Assam population and establish DRLs tailored to this demographic. Methods: A total of 380 patients were referred to the Primus Diagnostic Centre and Heath City Hospital, Guwahati Assam, during the study with coronary artery disturbances. Data on the technical parameters used in CT procedures were taken in 2021-2022. The aim and study's objective was Organ and surface dose to specific radiosensitive organs (Chest) estimation using software imPACT 1.0.4 from National Radiological Protection Board (NRPB) SR250 Monte Carlo dataset. Results: The study population (n = 380) comprised 190 men and 190 women with an average age of 29 to 75 years. The Mean ± SD of BMI and ED are 22.42±1.06 and 21.57±4.27 respectively. The mean DLP is 854.67, and the mean ED is 21.57. The effective doses for males (13- 27) mSv were in females (13-29) mSv. The DRL for Male population was found to be 24.26mSv.cm2 whereas for female population it was 24.69mSv.cm2. Conclusions: This study highlights the necessity of establishing tailored diagnostic reference levels for coronary angiography CT scans in the Northeast Assam population. By doing so, healthcare providers can ensure optimal image quality while minimizing radiation exposure, ultimately enhancing patient safety and quality of care. These findings have implications for radiological practice in the region and contribute to the ongoing efforts to standardize radiation doses in medical imaging procedures.
ARTICLE | doi:10.20944/preprints202306.1359.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: left atrial function, heart failure; stepwise exercise
Online: 19 June 2023 (12:59:37 CEST)
Background: the aim of this study was to assess acute changes on left atrial (LA) function a during a progressive exercise in patients with heart failure with mid-range ejection fraction (HFmrEF) in comparison to healthy controls (HS). Methods: twenty patients with established HFmrEF were compared with 10 HS, age-matched controls. All subiects performed a stepwise exercise test on cyclette. Echocardiography was performed at baseline, during submaximal effort, at peak of exercise, and after 5 minutes of recovery. Results: HS obtained an higher value of METs at peak exercise than HFmrEF (7.4 vs 5.6; between group p 0.002). Heart rate and systolic blood pressure presented a greater increase in the HS group than in HFmrEF (between-groups p 0.006 and p 0.003 respectively). In the HFmrEF group peak atrial longitudinal strain (PALS), and conduit strain were both increased at submaximal exercise (p<0.05 for both versus baseline) and remained constant at peak exercise. Peak atrial contraction strain (PACS) did not show significant changes during the exercise. In the control group PALS and PACS increased significantly at submaximal level (p<0.05 for both versus baseline) but PALS returned near baseline values at peak exercise; conduit strain decreased progressively during the exercise in HS. Stroke volume (SV) increased in both groups at submaximal exercise; at peak exercise SV remained constant in the HFmrEF while it decreased in controls (between-groups p 0.002). Conclusions: Patient with HFmrEF, show a proper increase of LA reservoir function during incremental exercise that contributes to maintain SV throughout the exercise.
ARTICLE | doi:10.20944/preprints202306.0014.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: SGLT2 inhibition; empagliflozin; heart failure; interleukin 6
Online: 1 June 2023 (03:33:38 CEST)
Background: Inhibition of sodium-glucose co-transporter 2 (SGLT-2) has been shown to be beneficial in the treatment of diabetic and non-diabetic patients with heart failure with reduced ejection fraction (HFrEF). The underlying mechanisms are incompletely understood. The present prospective study investigates for the first time the effect of empagliflozin on various soluble markers of inflammation in HFrEF. Methods: We included 50 inpatients with HFrEF and diabetes mellitus type 2. Half of the patients received a therapy with the SGLT-2-inhibitor empagliflozin in addition to standard medication, the other half of the patients did not receive empagliflozin and were considered as control group. Quality of life, functional status and soluble immunological parameters in serum were assessed at baseline and after 3 months. Results: Baseline characteristics of both groups revealed no significant differences. Patients on empagliflozin demonstrated a significant improvement in the Minnesota living with heart failure questionnaire (baseline 44.2 ± 20.2 vs. 24 ± 17.7; p<0.001), in distance in the 6-minute walk test (baseline 343 ± 145 m vs. 450 ± 115 m; p<0.001) and in soluble interleukin-6 level (baseline 21.7 ± 21.8 pg/ml vs. 13.7 ± 15.8 pg/ml; p=0.008). There was no significant change of these or other parameters in the control group (p>0.05 each). Conclusions: The empagliflozin-induced improvement of quality of life and functional capacity in patients with HFrEF and type 2 diabetes mellitus is accompanied by a substantial reduction of interleukin-6 levels. Thus, antiinflammatory effects may contribute to the benefits of SGLT2-inhibitors in heart failure.
ARTICLE | doi:10.20944/preprints202305.1473.v1
Subject: Engineering, Bioengineering Keywords: Decellularization; heart valve; tissue engineering; xenograft; biomaterial
Online: 22 May 2023 (08:26:48 CEST)
In order to overcome the disadvantages of existing treatments in heart valve tissue engineering, decellularization studies are carried out. The main purpose of decellularization is to eliminate the immunogenicity of biologically derived grafts and to obtain a scaffold that allows recellularization while preserving the natural tissue architecture. SD and SDS are detergent derivatives frequently used in decellularization studies. The aim of our study is to decellularize the pulmonary heart valves of young Merino sheep by using low-density SDS and SD detergents together, and then to perform their detailed characterization to determine whether they are suitable for clinical studies. Pulmonary heart valves of 4-6 month old sheep were decellularized in detergent solution for 24 hours. The amount of residual DNA was measured to determine the efficiency of decellularization. Then, the effect of decellularization on the ECM by histological staining was examined. In addition, the samples were visualized by SEM to determine the surface morphologies of the scaffolds. Uniaxial tensile test was performed to examine the effect of decellularization on biomechanical properties. The results showed DNA removal of 94% and 98% from the decellularized leaflet and artery portions after decellularization relative to the control group. No cell nuclei were found in histological staining and it was observed that the 3-layer leaflet structure was preserved. As a result of the tensile test, it was determined that there was no statistically significant difference between the control and decellularized groups in the UTS and elasticity modulus, and the biomechanical properties did not change. In conclusion, we suggest that the pulmonary valves of decellularized young Merino sheep can be used as a initial matrix in heart valve tissue engineering studies.
ARTICLE | doi:10.20944/preprints202305.1056.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: heart failure; hospitalization; cardiovascular outcomes; electronic consultation
Online: 15 May 2023 (15:30:16 CEST)
(1) Objectives. Patients with heart failure (HF) who experience hospitalizations for worsening HF (HFH) are at high risk of subsequent events. We aimed to evaluate the impact of an outpatient care management program that includes a clinician-to-clinician e-consultation using an integrated electronic medical record in a healthcare area with a widely dispersed population on delay time in care, hospital admissions, and mortality in a high-risk group of patients with HF and previous episodes of HFH. (2) Methods. We selected 6,444 HF patients who visited the cardiology service at least once between 2010 and 2021. Of these, 4,851 were attended in e-consult, and 2,008 in one-time in-person consultations. In 2,230 HF patients, there was documentation of a previous episode of HFH. Using an interrupted time series regression model, we analysed the impact of incorporating e-consult into the health care model in the group of patients with HFH and evaluated the elapsed time to cardiology care, heart failure (HF), cardiovascular (CV), and all-cause hospital admissions and mortality, calculating the incidence relative risk (iRR). (3) Results. In the group of patients with previous HF hospitalizations, the introduction of e-consult substantially decreased waiting times to cardiology care. The time elapsed to care after e-consult implementation was significantly reduced compared with the previous in-person period (8.6 [8.7] vs 55.4 [79.9] days, p<0.001). In that group of patients, after e-consult implantation, hospital admissions for HF were reduced (iRR [CI95%]: 0,837 [0,840-0,833]), 0,900 [0,862-0,949] for CV and 0,699 [0,678-0,726] for all-cause hospitalizations. There was also lower mortality (iRR [CI95%]: 0.715 [0.657-0.798] due to HF, 0,737 [0.764-0.706] for CV and 0,687 [0.652-0,718] for all-cause). The improved outcomes after e-consultation implementation were significantly higher in the group of patients with previous HFH and were independent of the patient’s clinical characteristics managed during the in-person or e-consultation periods. (4) Conclusions. In HF patients with previous HFH, an outpatient care program that includes an e-consult significantly reduced waiting times to cardiology care and was safe, with a lower rate of hospital admissions and mortality in the first year.
ARTICLE | doi:10.20944/preprints202305.0387.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: concurrent training; heart failure; left atrial dysfunction
Online: 6 May 2023 (07:51:04 CEST)
Left atrial dysfunction is associated with exercise intolerance and poor prognosis in heart failure (HF). The effects of exercise training on atrial function in patients with HF with mid-range ejection fraction (HFmrEF) are unknown. The purpose of the present study was to assess the effects of a 12-weeks supervised concurrent, aerobic continuous plus resistance, exercise training (SCT) pro-gram on left atrial function of patients with HFmrEF. The study included 70 stable patients, who were randomly assigned into two groups: SCT with (three session/week) or a control (CON) group directed to follow contemporary exercise preventive guidelines at home. Before starting the training program and at 12-weeks, all patients performed: ergometric test, 6-minute walk test and echocardiography. At 12-weeks, exercise duration at ergometric test and distance walked at 6-minute walk test presented a significant greater increase in the SCT compared to control (be-tween-groups p 0.0001 and p 0.004 respectively). Peak atrial longitudinal strain and conduit strain presented an increase of 29% and 34% respectively in the SCT and were unchanged in the CON (between-groups p 0.008 and p 0.001 respectively). Peak atrial contraction strain increased of 21% in the SCT with no changes in the CON (between-groups p 0.002). Left ventricular global longi-tudinal strain increased significantly SCT compared to control (between-groups p 0.03). In con-clusions SCT improved left atrial and left ventricular function in HFmrEF
ARTICLE | doi:10.20944/preprints202209.0185.v1
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: congenital heart disease; chest radiograph; electrocardiogram; echocardiography
Online: 14 September 2022 (02:55:41 CEST)
This study aimed to evaluate the role of chest radiographs and electrocardiograms in predicting the hemodynamics of congenital heart disease (CHD). This retrospective study included 50 patients with a diagnosis of CHD who had undergone any form of cardiac intervention, either surgical or nonsurgical between September 2019 and September 2020. Chest radiographs and electrocardiograms were evaluated and compared with the diagnostic gold standard echocardiography. Chest radiographs had the highest sensitivity, specificity, and accuracy, with all being 100%, in detecting situs and cardiac position. There was a very good agreement between chest radiographs and echocardiography in the detection of both situs and cardiac position (κ = 1.00, p < 0.001), while moderate agreement was observed for the detection of cardiomegaly, position of aortic knuckle, main pulmonary artery dilation, and right pulmonary artery dilation. Electrocardiograms had a high sensitivity (100.00%), but modest specificity and accuracy for the detection of left ventricle pressure overload. For the detection of left atrial enlargement and left ventricle volume overload, electrocardiograms had high specificity (94.12% and 94.29%, respectively) but low sensitivity and modest accuracy. There was a moderate agreement between electrocardiograms and echocardiography in the detection of right ventricle pressure overload (κ = 0.43, p = 0.002) and left ventricle volume overload (κ = 0.46, p < 0.001). The study findings indicate that chest radiographs and electrocardiograms alone are not adequate for the assessment of hemodynamics of CHD and reinstates the recommendation that in addition to routine chest radiographs and electrocardiograms, echocardiography should be performed.
COMMUNICATION | doi:10.20944/preprints202206.0258.v1
Subject: Medicine And Pharmacology, Anesthesiology And Pain Medicine Keywords: desflurane; cardiac surgery; halogenated; kidney; heart; preconditioning
Online: 20 June 2022 (04:52:02 CEST)
Introduction: The effect of halogenated drugs as cardioprotectors in cardiac surgery has been evaluated in several studies. However, the possibility that there is a protective role at renal level, triggered by their use, is currently under study. Aortic valve replacement and coronary revascularization are the most frequent surgeries in cardiac surgery. Our research evaluates the effect of desflurane compared to propofol in aortic valve replacement surgery at renal level; including its administration during extracorporeal circulation. Method: Quasi-experimental prospective study performed on 60 patients, divided into 2 groups according to the drug used in intraoperative aortic valve replacement surgery. In group 1 propofol was used as a hypnotic during surgery, in group 2 desflurane was used. Differences in kidney damage measured through the urinary NGAL marker were evaluated. Other markers of renal function and myocardial damage and the need for inotropic support during the first 48 hours were also measured. Results: There were significant variations in the values of urinary NGAL and creatinine regarding to basal values in the propofol group, but not in the desflurane group, in which there were no differences in the hemodynamic parameters and myocardial damage. Conclusion: the use of desflurane during aortic valve replacement surgery produced better renal preservation than propofol.
ARTICLE | doi:10.20944/preprints202201.0116.v1
Subject: Medicine And Pharmacology, Anesthesiology And Pain Medicine Keywords: Ischaemia/reperfusion injury; Development; Mitochondria; Immature Heart
Online: 10 January 2022 (13:38:07 CET)
Metabolic and ionic changes during ischaemia predispose the heart to the damaging effects of reperfusion. Such changes and the resulting injury differ between immature and adult heart. Therefore, cardioprotective strategies for adults need to be tested in immature heart. We have recently shown that simultaneous activation of PKA and EPAC confers marked cardioprotection in adult hearts. The aim of this study is to investigate the efficacy of this intervention in immature hearts and determine whether the mitochondrial permeability transition pore (MPTP) is involved. Isolated perfused Langendorff hearts from both adult and immature rats were exposed to global ischaemia and reperfusion injury (I/R) following control perfusion or perfusion after an equilibra-tion period with activators of PKA and/or EPAC. Functional outcome and reperfusion injury were measured and in parallel, mitochondria were isolated following 5 min reperfusion to determine whether cardioprotective interventions involved changes in MPTP opening behaviour. Perfusion for 5 minutes preceding ischaemia of injury- matched adult and immature hearts with 5 µM 8-Br (8-Br-cAMP-AM), an activator of both PKA and EPAC, led to significant reduction in post-reperfusion CK release and infarct size. Perfusion with this agent also led to a reduction in MPTP opening propensity in both adult and immature hearts. These data show that immature hearts are innately more resistant to I/R injury than adults, and that this is due to a reduced ten-dency to MPTP opening following reperfusion. Further, simultaneous stimulation of PKA & EPAC causes cardioprotection which is additive to the innate resistance.
REVIEW | doi:10.20944/preprints202112.0172.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: monocyte subset; heart failure; inflammation; cytokine; macrophage
Online: 10 December 2021 (11:54:31 CET)
Chronic heart failure (CHF) results when heart cannot constantly supply the body tissues with oxygen and required nutrients, and it can be categorized as heart failure (HF) with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF). There are different causes and mechanisms of the HF pathogenesis; however, the inflammation can be regarded as one of the factors promoting both HFrEF and HFpEF. Monocytes, a subgroup of leucocytes, are known as cellular mediators in response to cardiovascular injury and are closely related to inflammatory reactions. These cells are a vital component of the immune system and are the source of macrophages, which participate in cardiac tissue repair after injury. However, the monocytes are not homogenous as thought, and thus can present different functions under different cardiovascular disease conditions. In addition, there is still an open question whether the functions of monocytes and macrophages should be regarded as a cause or a consequence in CHF development. Therefore, our aim was to summarize the current studies on the function of various monocyte subsets in CHF with a focus on the role of a certain monocyte subset in HFpEF and HFrEF patients, and the relation to inflammatory markers.
ARTICLE | doi:10.20944/preprints202011.0185.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: heart failure; 6-minute walk test; prognosis
Online: 4 November 2020 (10:08:38 CET)
Background: The 6-minute walk test (6MWT) is a simple and low-cost method that allows assessment of functional capacity in patients with heart failure (HF). However, the prognostic role of 6MWT in HF remains uncertain. Objectives: We aimed to evaluate the 6MWT as a predictor of mid-term adverse outcomes in patients with HF with mid-range and reduced ejection fraction. Methods: Prospective single-center cohort study that included patients with HF with an ejection fraction under 50% at a specialized outpatient HF service. Patients underwent the 6MWT on admission and were compared according to the distance walked: Group I walked ≥350 meters and group II <350 meters. The primary outcome was a composite of death from any cause or hospitalization for HF decompensation in one-year follow-up. Secondary outcomes were the components of the primary outcome in an isolated analysis. Results: Sixty patients were included, 43.3% male, with a mean age of 61.1 ± 12.9 years and ejection fraction 34.3 ± 10.1%. 52 patients (86.7%) were on guideline-directed triple therapy for HF. The average distance walked in the 6MWT was 395.1 ± 98.8 meters, with 40 patients (66.7%) in group I and 20 (33.3%) in group II. The primary outcome in groups I and II were, respectively, 15,0% and 35,0% (p=0.05). One-year mortality was 5.0% vs 15.0% (p=0.18) and the hospitalization rate was 10.0% vs 20.0% (p=0.28). Conclusions: There was no association of distance <350 meters in the 6MWT with the primary outcome in patients with HF. Despite the higher occurrence of outcomes in group II, the difference was not statistically significant in this analysis. On a selective basis, the 6MWT may be a useful tool for prognostic stratification in HF, if combined with other methods.
ARTICLE | doi:10.20944/preprints202011.0003.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Heart Failure; Acute Kidney Injury; Prognosis; Mortality.
Online: 2 November 2020 (08:09:49 CET)
Introduction: Decompensated heart failure (HF) is a complex and debilitating syndrome, which constitutes a severe emergency condition with high morbidity and mortality. The kidneys play fundamental roles in the pathophysiology of HF and, in the context of decompensations, acute kidney injury (AKI) has a bilateral cause-and-effect relationship, which can significantly worsen prognosis. However, the interaction between AKI and decompensated HF is poorly understood. Objective: This study aimed to assess the occurrence of AKI in patients hospitalized due to decompensated HF and to analyze its prognostic impact during hospitalization. Methods: Prospective single-center observational study that included patients hospitalized due to decompensated HF in a tertiary-level teaching hospital, conducted between July 2017 and January 2020. Patients who developed AKI during hospitalization were compared with those who did not develop it, until hospital discharge or death. AKI was defined as a serum creatinine increase greater than or equal to 0.3 mg/dl in 48 hours, a 1.5-fold increase in baseline creatinine in seven days or urinary volume <0.5 ml/kg/h during six hours, according to the Acute Kidney Injury Network (AKIN) criteria. The endpoints analyzed were death, need for invasive mechanical ventilation (IMV) and length of hospital stay. The Wilcoxon, Mann-Whitney and unpaired student t tests were used. Results: Ninety-nine patients were included, with a mean age of 65.4 ± 14 years, of which 47 (47.5%) were male and 52 (52.5%) were female. Reduced ejection fraction was observed in 77.8% of patients, whilst 22.2% had a diagnosis of HF with preserved EF. The decompensation clinical classifications were: dry and warm = 7 (7.1%), wet and warm = 72 (72.7%), wet and cold = 15 (15.1%) and dry and cold = 5 (5.1%). The average left ventricular ejection fraction was 38.3% ± 15. AKI ocurred in 22 patients (22.2%). Comparison between patients who evolved with and without AKI showed higher mortality (36.4% vs 10.4%, p = 0.004) and the need for IMV (54.5% vs 13%, p = 0.0001) in the first group. There was no significant difference regarding the length of in-hospital stay (22.9 ± 19 vs 18.8 ± 16 days, p = 0.26). Conclusions: The occurrence of AKI was frequent in patients with decompensated HF requiring hospitalization, affecting approximately one out of five patients. This complication was significantly associated with increased mortality and the need for IMV during hospitalization.
REVIEW | doi:10.20944/preprints202010.0493.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: COVID-19; Obesity; BMI; heart; lung; severity
Online: 23 October 2020 (13:28:04 CEST)
Obesity is a significant public health concern with higher morbidity. Obesity patients are at risk of severe COVID-19 infection and obesity is a higher risk factor for intensive Care Unit admission in COVID-19 infection. Obesity status affects lung volumes, cardiac structure and hemodynamics. Obesity is associated with a low inflammation state, endothelial dysfunction, hyperinsulinaemia and metabolic disorders. The authors review cardio-respiratory pathophysiological aspects involved in obesity and propose clinical management in obese patients infected by COVD-19.
ARTICLE | doi:10.20944/preprints202008.0034.v1
Subject: Medicine And Pharmacology, Orthopedics And Sports Medicine Keywords: Acupuncture; lactate; heart rate; physical performance; sustainability
Online: 2 August 2020 (14:46:22 CEST)
Studies have demonstrated the positive effects of acupuncture on athletic performance. The aim of this study was to determine the acute effects of acupuncture on heart rate, the perceived exertion scale and lactate levels in recreational athletes. Fifteen competitive males engaged in HIIT. The characteristic was 29.86±2.51 years old, heart rate reserve 59.00±3.33, lactate 3.17±0.50 mM/DL. The subjects were submitted to two exercise sessions. Both training sessions consisted of 10 burpees, 12 thrusters and 14 box jumps (75 cm high) for 12 minutes. Activity intensity was between 85 and 95% of maximum heart rate. Acupuncture points: ST36, L3, LI11. The student’s t-test was adopted, Shapiro-Wilk test was applied for normality, and Pearson correlation. There was a positive correlation of r = 0.69 between lactate levels and heart rate. Lactate: Lac1 15.00±1.18 – Lac2 19.59± 1.46 p= 0.0001*; Heart 1rate: HRF 163.71±7.27 – HRF2 177.60±6.99 p=0.0001*; Blood pressure: SBP1 174.86±1.57 – SBP2 180.86±1.77 p= 0.0001*; PES1: 19.4±1.14; PES2 16.8±0.84 p= 0.0001*; weight1 – 182,57±12,05; weight 2 206,43±11,39 p=0.0325*. Acupuncture increased lactate accumulation, heart rate and blood pressure, suggesting that the exertion reached after acupuncture is higher than without acupuncture. The acupuncture technics improved the athlete performance.
ARTICLE | doi:10.20944/preprints202308.0249.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: heart; ischemia; reperfusion; electrocardiography; ultra-high resolution electrocardiography; power spectral density; ischemic heart disease; subclinical atherosclerosis; sensitivity; risk stratification
Online: 3 August 2023 (05:17:42 CEST)
The sensitivity of exercise ECG is marginally sufficient for detection of mild reduction of coronary blood flow in patients with early coronary atherosclerosis. Here we describe the application of new technique of ECG registration/analysis – ultrahigh resolution ECG (UHR ECG) – for early detection of myocardial ischemia (MIS). The utility of UHR ECG vs. conventional ECG (C ECG) was tested in anesthetized rats and pigs. Transmural MIS was induced in rats by the ligation of the left coronary artery (CA). In pigs, subendocardial ischemia of variable extent was produced by stepwise inflation of balloon within the right CA causing 25-100% reduction of its lumen. In rats, a reduction in power spectral density (PSD) in high-frequency (HF) channel of UHR ECG was registered at 60 s after ischemia (power 0.81±0.14 vs. 1.25±0.12 mW at baseline, p<0.01). This was not accompanied by any ST segment elevation on C ECG. In pigs, PSD in HF channel of UHR ECG was significantly decreased at 25% reduction of CA lumen, while ST segment on C ECG remained unchanged. In conclusion, UHR ECG enabled earlier detection of transmural MIS compared to C ECG. PSD in HF-channel of UHR ECG demonstrated greater sensitivity in the settings of subendocardial ischemia.
CASE REPORT | doi:10.20944/preprints202311.1692.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: mavacamten; cardiac myosin inhibitor; hypertrophic cardiomyopathy; heart failure
Online: 27 November 2023 (11:50:17 CET)
We describe real-world use of mavacamten in 50 patients with oHCM. Consistent with EXPLORER-HCM and VALOR-HCM, we report significant improvement in wall thickness, mitral regurgitation, left ventricular outflow tract obstruction and NYHA class. Moreover, in our center’s experience, neither arrhythmia burden, nor contractility have worsened in the vast majority of patients: We note a clinically insignificant mean decrease in left ventricular ejection fraction (LVEF), with only two patients requiring temporary mavacamten discontinuance for LVEF < 50%. Adverse events were rare, unrelated to mavacamten itself, and seen solely in patients with disease too advanced to have been represented in clinical trials. Our multidisciplinary pathway enabled us to provide a large number of patients with a novel closely-monitored therapeutic within just a few months of commercial availability. These data lead us to conclude that mavacamten, as a first-in-class cardiac myosin inhibitor, is safe and efficacious in real-world settings.
ARTICLE | doi:10.20944/preprints202311.0159.v1
Subject: Medicine And Pharmacology, Emergency Medicine Keywords: Heart Failure; older adults; ultrasound; outcomes; pleural effusion
Online: 2 November 2023 (10:31:43 CET)
The decompensation trajectory check is a basic step to assess the clinical course and to plan future therapy in hospitalized patients with acute heart failure (ADHF). Due to the atypical presentation and clinical complexity, trajectory checks can be challenging in the oldest old patients with acute HF. Point of care ultrasound (POCUS) proved to be helpful in the clinical decision-making of patients with dyspnea, but no study has attempted to verify its effectiveness in predicting determinants of HF in-hospital worsening. In this single-center prospective study, we consecutively enrolled patients aged 75 or older hospitalized with acutely decompensated HF in a tertiary care hospital. All the patients underwent complete clinical examination, blood tests, and POCUS including Lung Ultrasound, Focused Cardiac Ultrasound, Pleural Effusion score (PEFs), and Inferior Vena Cava (IVC) assessment. Out of 184 patients hospitalized with ADHF enrolled in the study, sixty experienced HF in-hospital worsening. No differences were found among patients with HF worsening and controls in terms of age, gender, frailty, and left ventricular ejection fraction. By multivariable logistic analysis, total PEFs [aOR: 1.15 (CI95% 1.02– 1.33), p = 0.043], and IVC collapsibility [aOR: 0.90 (CI95% 0.83 – 0.95), p = 0.039] emerged as independent predictors of acute HF worsening after extensive adjustment for potential confounders.
REVIEW | doi:10.20944/preprints202310.0293.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: personalized; individualized; open heart surgery; implantation; systematic review
Online: 5 October 2023 (13:45:08 CEST)
Personalized surgery is not just a new trend but rather a patient-specific approach to therapy that makes it possible to adopt a targeted approach for a specific patient and closely mirrors the approach of personalized medicine. However, the application of tailored surgery in the context of cardiovascular replacement surgery was not systematically reviewed. The ability to customize a device is highly dependent on the collection of radiological image data for precise prosthesis modelling. These facts are essential to "tailor-made" device design for precise prosthesis implantation. According to this study, computed tomography (CT) was the most prominent imaging modality; however, transoesophageal echocardiography and echocardiography were also found to be helpful. Additionally, a dynamic finite element simulation is also an attractive alternative to the finite element analysis for an in-silico experiment. Nonetheless, there is a paucity of relevant publications and sporadic evidence. More clinical studies have been warranted, notwithstanding that the derived data and results from the insight into the use of therapeutic interventions may be of multiple directives in clinical practices and beyond. This study may help the integration of personalized devices for better comprehending predicted clinical outcomes, thus leading towards enhanced performance gains.
ARTICLE | doi:10.20944/preprints202308.1262.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: atrial fibrillation; gender; electrical cardioversion; heart failure; mortality
Online: 17 August 2023 (07:15:22 CEST)
Background: There is limited data on gender-based differences in atrial fibrillation (AF) treatment and prognosis. Our aim was to examine gender-related differences in medical attention in emergency department (ED) and follow-up (FU) among patients diagnosed with an AF episode and to determine whether there are gender-related differences in clinical characteristics, therapeutic strategies and long-term adverse events in this population. Methods: We performed a retrospective observational study of patients who presented to a tertiary hospital ER for AF from 2010-2015, with a minimum FU of one year. Data on medical attention received, mortality and other adverse outcomes were collected and analyzed. Results: Among the 2 013 patients selected, 1232 (60%) was female. Women were less likely than men to be evaluated by a cardiologist during the ED visit (11.5% vs. 16.6%, p=0.001) and were less likely to be admitted (5.9% vs. 9.5%, p<0.05). Electrical cardioversion was performed more frequently in men, both during the first episode (3.4% vs. 1.2%, p=0.001) and during FU (15.9% vs. 10.6%, p<0.001), in spite of a lower AF recurrence rate in women (9.9% vs 18.1%). During FU, women had more hospitalizations for heart failure (26.2% vs. 16.1%, p<0.001). Conclusions: In patients with AF, although no gender differences in mortality, there were significant differences in clinical outcomes, medical attention received, and therapeutic strategies. Women underwent fewer attempts at cardioversion, had a lower probability of being evaluated by cardiologists and showed a higher probability of hospitalization for heart failure. Being alert to these iniquities should facilitate to adopt measures to correct them.
REVIEW | doi:10.20944/preprints202307.1285.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Extracellular vesicles; MicroRNAs; Sorting mechanism; Biomarkers; Heart failure
Online: 20 July 2023 (02:49:03 CEST)
Extracellular vesicles (EVs) are emerging mediators of intracellular and inter-organ communications in cardiovascular diseases (CVDs), especially in the pathogenesis of heart failure through the transference of EV-containing bioactive substances. microRNAs (miRNAs) are contained in EV cargo and are involved in the progression of heart failure. Over the past several years, a growing body of evidence has suggested that the biogenesis of miRNAs and EVs are tightly regulated, and the sorting of miRNAs into EVs is highly selective and tightly controlled. Extracellular miRNAs, in particular circulating EV-miRNAs, have shown promising potential as prognostic and diagnostic biomarkers for heart failure and as therapeutic targets. In this review, we summarize the latest progress concerning the role of EV-miRNAs in HF and their application in a therapeutic strategy development for heart failure.
ARTICLE | doi:10.20944/preprints202306.1254.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Parkinson’s disease; cardiac metabolism; heart; 6-hydroxydopamine; metabolites
Online: 16 June 2023 (14:16:00 CEST)
Parkinson’s-disease (PD) is an incurable age-related neurodegenerative disease and its global prevalence of disability and death has increased exponentially. Although motor symptoms are the characteristic manifestations of PD, the clinical spectrum also contains a wide variety of non-motor symptoms, which are the main cause of disability and determinants of the decrease in a patient's quality of life. Noteworthy in this regard is the stress on the cardiac system that is often observed in the course of PD, however its effects have not yet been adequately researched. Here, an untargeted metabolomics approach was used to assess changes in cardiac metabolism in the 6-hydroxydopamine model of PD. Beta-sitosterol, campesterol, cholesterol, monoacylglycerol, α-tocopherol, stearic acid, beta-glycerophosphoric acid, o-phosphoethanolamine, myo-inositol-1-phosphate, alanine, valine and allothreonine, are the metabolites that significantly discriminate Parkinsonian rats from sham counterparts. Upon analysis of the metabolic pathways with the aim of uncovering the main biological pathways involved in concentration patterns of cardiac metabolites, biosynthesis of both phosphatidylethanolamine and phosphatidylcholine, glucose-alanine cycle, the glutathione metabolism and plasmalogen synthesis most adequately differentiated sham and Parkinsonian rats. Our results reveal that both lipid and energy metabolism are particularly involved in changes in cardiac metabolism in PD. These results provide insight into cardiac metabolic signatures in PD and indicate potential targets for further investigation.
REVIEW | doi:10.20944/preprints202306.0991.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: exercise; diabetes; obesity; hypertension; ventricular remodeling; heart failure
Online: 14 June 2023 (05:34:21 CEST)
Left ventricular (LV) remodeling is a dynamic process which is characterized by abnormal LV wall thickness and altered myocardial geometry, and it is considered as a negative prognostic factor in both heart failure with reduced eject fraction (HFrEF) and heart failure with preserved eject fraction (HFpEF). Hypertension, type 2 diabetes (T2D) and obesity are strongly correlated with the development and the progression of LV remodeling, LV hypertrophy and LV systolic and/or diastolic dysfunction. Indeed, the beneficial impact of exercise training on primary and secondary prevention of cardiovascular disease (CVD) has been well-established. Recent studies highlight that exercise training enhances functional capacity, muscle strength and endurance, cardiac function and cardiac-related biomarkers, among patients with established coronary artery disease (CAD) or HF, thus improving substantially their cardiovascular prognosis, survival rates and needs for rehospitalization. Therefore, in this review article, we discuss the evidence of LV remodeling in patients with cardiometabolic risk factors, such as hypertension, T2D, obesity, and also highlight the current studies evaluating the effect of exercise training on LV remodeling in these patients.
ARTICLE | doi:10.20944/preprints202304.0797.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Heart failure; Malnutrition; Exercise; Amino-acids; mTOR; Deptor
Online: 23 April 2023 (08:45:26 CEST)
Malnutrition, clinically evident primarily with sarcopenia, is present in more than 50% of CHF patients and is an independent factor of morbidity and mortality. Several pathophysiological mechanisms, such as reduced appetite, metabolic imbalance and altered protein synthesis/degradation rate, due to the blood increase of hypercatabolic molecules, have been proposed to explain this phenomenon. Nutritional supplementation with proteins, amino acids and vitamins have all been used to treat malnutrition, acting through mTOR stimulation. However, the success and efficacy of these procedures are often contradictory and not conclusive. Interestingly, data on exercise training show that exercise reduces mortality and increase functional capacity, although it also increases energy expenditure and nitrogen providing substrate needs. Therefore, this paper discusses the molecular mechanisms of integrated nutritional approaches that would stimulate metabolic anabolic pathways. Pivotal in our opinion, is the relationship between exercise and Deptor, a subunit of the mTOR complex. Consequently, we propose a combination of personalized and integrate nutritional supplementation as well as exercise to treat malnutrition and related anthropometric and functional CHF-related disorders.
REVIEW | doi:10.20944/preprints202304.0422.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: heart failure; kidney disease; multidisciplinary assessment; personalized treatment
Online: 17 April 2023 (07:27:32 CEST)
CKD in HF patients is very common condition, their dysfunction is closely linked and influence each other, so their management required multidisciplinary and personalized approaches. The diagnosis of HF and CDK relies on signs and symptoms. Several tools, such as blood-based biomarkers and echography help us to clarify and discriminate the main characteristics of these patients. Evidence in improving survival due to new drug-employment in HF, has increasingly challenged physicians to manage patients with multiple diseases, especially in patients with CKD. The difficulty is in the safe administration of these drugs in patients with HF and CKD. Knowing up to which values of creatinine or renal clearance any drug can be administered is fundamental. We wanted to summarize, on this sizable and complex topic, the experiences of various prior study to get clearer ideas and a more precise reference about the assessment and management of HF and CKD.
ARTICLE | doi:10.20944/preprints202212.0376.v2
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Sport; Heart Rate; Breathe Rate; Monitoring; Functional Athlete Readiness; Impedance; Rheography
Online: 6 January 2023 (02:04:00 CET)
Background/Objectives: The purpose of the proposed study is disclosure of correlations between the dynamics of the Breathe Rate (BR) and Heart Rate (HR) when performing the intermittent physical operation at maximum power on a cycle ergometer.Methods: The stage on the study of the General functional athlete readiness (GFAR) performed using the sports standard “Red Engine” and the cycle ergometer in 16 volunteers (10 men, 6 women) whose average age was 21±1.17 years. To determine the sports potential of the volunteers in this study, we used own Coefficient of Anaerobic Capacity (CANAC Q, beats). Continuous recording of the heart rate and respiratory rate of volunteers in the maximum power sports test was carried out by the “RheoCardioMonitor” device with an athlete functional readiness module based on the method of Transthoracic electrical impedance rheography (TEIRG).Results: The degree of correlation of functional indicators (M, HRM, GFAR) with CANAC Q for the group in full (n=80) occurred at a very high level, which confirmed the effectiveness of using the Coefficient of Anaerobic Capacity (CANAC Q) in assessing the general functional athlete readiness of the volunteers. Conclusions: CANAC Q measured in “beats” of the heart and recorded very accurately using the method of transthoracic electrical impedance rheography (TEIRG). For this reason as promising sports PSM-system, CANAC Q can replace the methods for determining the functional athlete readiness by blood lactate concentration and maximum oxygen consumption.
ARTICLE | doi:10.20944/preprints202109.0250.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: mthfr; folic acid; heart development; zebrafish; CRISPR/Cas9
Online: 15 September 2021 (09:16:39 CEST)
Folic acid, one of the 13 essential vitamins, plays an important role in cardiovascular development. Mutations in folic acid synthesis gene 5,10-methylenetetrahydrofolate reductase (MTHFR) is significantly associated with the occurrence of congenital heart disease. However, the mechanisms underlying the regulation of cardiac development by mthfr gene are poorly understood. Here, we exposed zebrafish embryos to excessive folate or folate metabolism inhibitors. And we established a knock-out mutant of mthfr gene in zebrafish by using CRISPR/Cas9. The zebrafish embryos of insufficient or excessive folic acid, and mthfr-/- mutant all gave rise to early pericardial edema and cardiac defect at 3 days after fertilization(dpf). Furthermore, the folic acid treated embryos showed abnormal movement at 5dpf. The expression levels of cardiac marker genes hand2, gata4 and nppa changed in the abnormality of folate metabolism embryos and mthfr-/- mutant, and there is evidence that they are related to the change of methylation level caused by the change of folate metabolism. In conclusion, our study provides a novel model for the in-depth study of MTHFR gene and folate metabolism. And our results reveal that folic acid has a dose-dependent biphasic effect on early cardiac development.
ARTICLE | doi:10.20944/preprints202109.0110.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: cardiac fibroblasts; sex-specific; estrogen; fibrosis; heart failure
Online: 6 September 2021 (17:24:51 CEST)
Several studies have demonstrated estrogen’s cardioprotective abilities in decreasing the fibrotic response of cardiac fibroblasts (CFs). However, the majority of these studies are not sex-specific, and those at the cellular level utilize tissue culture plastic, a substrate that has a stiffness much higher than physiological conditions. Understanding the intrinsic differences between male and female CFs under more physiologically “healthy” conditions will help to elucidate the divergences in their complex signaling networks. We aimed to do this by conducting sex-disaggregated analysis of changes in cellular morphology and relative concentrations of profibrotic signaling proteins in CFs cultured on 8kPa stiffness plates with and without 17-β estradiol (E2). Cyclic immunofluorescent analysis indicated that there is a negligible change in cellular morphology due to sex and E2 treatment and that the differences between male and female CFs are occurring at a biochemical rather than structural level. Several proteins corresponding to profibrotic activity had various sex-specific responses with and without E2 treatment. Single-cell correlation analysis exhibited varied protein-protein interaction across experimental conditions. These findings demonstrate the need for further research into the dimorphisms of male and female CFs to develop better tailored, sex-informed prevention and treatment interventions of cardiac fibrosis.
ARTICLE | doi:10.20944/preprints202103.0655.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: mitochondria; Ca2+ handling; heart failure; CaMKII; cardiomyocyte hypertrophy
Online: 26 March 2021 (10:41:00 CET)
Background : ATPase inhibitor factor-1 (IF1) preserves cellular ATP under conditions of respiratory collapse, yet the function of IF1 under normal respiring conditions is unresolved. We tested the hypothesis that IF1 promotes mitochondrial dysfunction and pathological cardiomyocyte hypertrophy in the context of heart failure (HF). Methods and results Cardiac expression of IF1 was increased in mice and in humans with HF, downstream of neurohumoral signaling pathways and in patterns that resembled the fetal-like gene program. Adenoviral expression of wild type IF1 in primary cardiomyocytes resulted in pathological hypertrophy and metabolic remodeling as evidenced by enhanced mitochondrial oxidative stress, reduced mitochondrial respiratory capacity, and the augmentation of extra-mitochondrial glycolysis. Similar perturbations were observed with an IF1 mutant incapable of binding to ATP-synthase (E55A mutation), indication that these effects occurred independent of binding to ATP synthase. Instead, IF1 promoted mitochondrial fragmentation and compromised mitochondrial Ca2+ handling, which resulted in sarcoplasmic reticulum Ca2+ overloading. The effects of IF1 on Ca2+ handling were associated with the cytosolic activation of CaMKII and inhibition of CaMKII or co-expression of catalytically dead CaMKIIδC was sufficient to prevent IF-1 induced pathological hypertrophy. Conclusions IF1 represents a novel member of the fetal-like gene program that contributes to mitochondrial dysfunction and pathological cardiac remodeling in HF. Furthermore, we present evidence for a novel, ATP-synthase independent, role for IF1 in mitochondrial Ca2+ handling and mitochondrial- to nuclear crosstalk involving CaMKII.
ARTICLE | doi:10.20944/preprints202101.0291.v1
Subject: Computer Science And Mathematics, Algebra And Number Theory Keywords: Heart diseases; Auscultation; Machine learning; Telemedicine; Digital Stethoscope
Online: 15 January 2021 (12:45:45 CET)
One of the oldest and common methods of diagnosing heart abnormalities is auscultation. Even for experienced medical doctors, it is not an easy task to detect abnormal patterns in the heart sounds. Most of the digital stethoscopes are now capable of recording and transferring the heart sounds. Moreover, it is proven that auscultation records can be classified as healthy or unhealthy via artificial intelligence techniques. In this work, an artificial intelligence-powered mobile application that works in a connectionless fashion is presented. According to the clinical experiments, the mobile application can detect heart abnormalities with approximately 92% accuracy which is comparable if not better than humans since only a small number of well-trained cardiologists can analyze auscultation records better than artificial intelligence. Using the diagnostic ability of artificial intelligence in a mobile application would change the classical way of auscultation for heart disease diagnosis.
ARTICLE | doi:10.20944/preprints202005.0483.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Lung CT; imaging; COVID-19; Pneumonia; Heart Failure
Online: 31 May 2020 (16:49:04 CEST)
Background: Lung CT provides an effective modality to evaluate patients with suspected COVID-19. However, overlapping imaging findings with cardiogenic pulmonary oedema have been reported. Reports comparing lung CT features of these diseases have not been elaborated. Thus, we aimed to investigate these gaps in the knowledge regarding low-dose lung CT features of patients with COVID-19 pneumonia with those with acute heart failure (HF). Methods: This retrospective analysis enrolled hospitalized patients with COVID-19 (n=10) and acute heart failure (n=9) that exclusively underwent low-dose lung CT scans within 24-hours of admission. Clinical and lung CT characteristics were collected and analysed. Results: Ground-glass-opacities (GGO) appearance has been recorded in all subjects in HF and COVID-19 group. There was no significant statistical difference between the two groups for rounded morphology, consolidation, crazy paving pattern, lesion distribution, parenchymal band (P> 0.05). However, diffuse lesions were more frequent in HF cases (55.6% vs. 0%) than in COVID-19 pneumonia, which had predominantly multifocal pattern. Notably, CT images in HF patients were more likely to have signs of interstitial tissue thickening such as the interlobular septums, fissures and peribronchovascular interstitium (55.6% vs 0%, 88.9% vs 20% and 44.4% vs 0%,respectively), as well as cardiomegaly (77.8% vs 0%), increased artery to bronchus ratio (55.6% vs 0%), and pleural effusions (77.8% vs 0%). Conclusions: Major overlaps of lung CT imaging features existed between COVID-19 pneumonia and acute HF cases. However, signs of fluid redistribution are clues that favour HF over COVID-19 pneumonia.
ARTICLE | doi:10.20944/preprints201911.0174.v1
Subject: Social Sciences, Behavior Sciences Keywords: heart rate variability; dyads; physiological synchrony; relationship; emotion
Online: 15 November 2019 (06:09:04 CET)
The mere co-presence of another person synchronizes physiological signals, but no study has systematically investigated effects of type of emotional context and type of relationship in eliciting dyadic physiological synchrony. In this study, we investigated the synchrony of pairs of strangers, companions, and romantic partners while watching a series of video clips designed to elicit different emotions. Maximal cross-correlation of heart rate variability (HRV) was used to quantify dyadic synchrony. The findings suggest that an existing social relationship might reduce the predisposition to conform one's autonomic responses to a friend or romantic partner during social situations that do not require direct interaction.
REVIEW | doi:10.20944/preprints201901.0312.v1
Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: embryonic heart tube; extracellular matrix; cardiac jelly; hydraulic skeleton; heart skeleton; valveless pumping; blood flow; non-circular cross sections; ballooning; trabeculation
Online: 30 January 2019 (11:16:14 CET)
The early embryonic heart is a multi-layered tube consisting of (1) an outer myocardial tube; (2) an inner endocardial tube; and (3) an extracellular matrix layer interposed between myocardium and endocardium, called “cardiac jelly” (CJ). During the past decades, research on CJ has mainly focused on its molecular and cell biological aspects. This review focuses on the morphological and biomechanical aspects of CJ. Special attention is given to (1) the spatial distribution and fiber architecture of CJ; (2) the morphological dynamics of CJ during the cardiac cycle; and (3) the removal/remodeling of CJ during advanced heart looping stages, which leads to the formation of ventricular trabeculations and endocardial cushions. CJ acts as a hydraulic skeleton displaying striking structural and functional similarities with the mesoglea of jellyfish. CJ not only represents a filler substance, facilitating end-systolic occlusion of the embryonic heart lumen. Its elastic components antagonize the systolic deformations of the heart wall and thereby power the refilling phase of the ventricular tube. Non-uniform spatial distribution of CJ generates non-circular cross sections of the opened endocardial tube (initially elliptic, later deltoid), which seem to be advantageous for valveless pumping. Endocardial cushions arise from non-removed remnants of the original CJ.
ARTICLE | doi:10.20944/preprints202310.1359.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: organ recipient; heart transplantation; primary graft dysfunction; interleukin; apolipoprotein
Online: 20 October 2023 (13:40:14 CEST)
End-stage heart failure (ESHF) leads to hypoperfusion and edema formation in the whole body and is accompanied by neurohormonal and immunological alterations. Orthotopic heart transplantation (HTX) has been used as a beneficial option for ESHF. Due to the shortage of donor hearts, the ideal matching and timing of donors and recipients has become more important. Our aim was to explore the relationship between the clinical outcome of HTX and the cytokine and apolipoprotein profiles of the recipient pericardial fluid obtained at transplantation after opening the pericardial sac. The clinical data and the interleukin, adipokine and lipoprotein levels in the pericardial fluid of twenty recipients were investigated. Outcome variables included primer graft dysfunction (PGD), need for posttransplantation mechanical cardiac support (MCS), International Society for Heart and Lung Transplantation grade ≥ 2R rejection and mortality. Recipient risk scores were also investigated. Leptin levels were significantly lower in patients with PGD than in those without PGD (median: 6.36 [IQR: 5.55-6.62]; versus 7.54 [IQR=6.71-10.44]; p = 0.029). Higher ApoCII levels (median: 14.91 [IQR: 11.55-21.30] versus 10.31 [IQR=10.02-13.07]; p = 0.042) and ApoCIII levels (median: 60.32 [IQR: 43.00-81.66] versus 22.84 [IQR=15.84-33.39]; p=0.005) were found in patients (n=5) who died in the first 5 years after HTX. In patients who had rejection (n=4) in the first month after transplantation, the levels of adiponectin (median: 74.48 [IQR: 35.51-131.70] versus 29.96 [IQR: 19.86-42.28]; p=0.039), ApoCII (median: 20.11 [IQR: 13.06-23.54] versus 10.32 [IQR: 10.02-12.84]; p=0.007) and ApoCIII (median: 70.97 [IQR: 34.72-82.22] versus 26.33 [IQR: 17.18-40.17; p=0.029) were higher than those in the nonrejection group. Moreover, the pericardial thyroxine (T4) levels (median: 3.96 [IQR: 3.49-4.46] versus 4.69 [IQR: 4.23-5.77]; p=0.022) were lower in patients with rejection than in patients who did not develop rejection. Our results indicate that apolipoproteins can facilitate the monitoring of rejection and could be a useful tool in the forecast of early and late complications.
ARTICLE | doi:10.20944/preprints202309.1894.v1
Subject: Medicine And Pharmacology, Transplantation Keywords: Personality change; organ transplant; heart transplant; temperament; emotions; preferences
Online: 27 September 2023 (11:08:09 CEST)
Personality changes have been reported to occur following organ transplantation, and most commonly among heart transplant recipients. We set out to examine whether personality changes do occur following transplantation, and specifically, what types of changes occur among heart transplant recipients compared to other organ recipients. A cross-sectional study was conducted in 2022, in which 47 participants (23 heart recipients and 24 other organ recipients) completed an online survey. In this study, 89% of all transplant recipients reported experiencing personality changes after receiving their organ transplant, which was similar for heart and other organ recipients. With the exception of physical attributes, the types of personality changes reported were similar between the two groups. These finding indicate that heart transplant recipients are not unique in their reported experience of personality changes following organ transplantation. Further studies are needed to deepen our understanding of what causes these personality changes following organ transplantation.
ARTICLE | doi:10.20944/preprints202308.1669.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: atrial fibrillation; heart failure; rhythm strategy; catheter ablation; snapshot
Online: 25 August 2023 (02:48:47 CEST)
Background and Objectives: Proper use of oral anticoagulants is crucial in the management of non-valvular atrial fibrillation (AF) patients. Left atrial appendage closure (LAAC) may be considered for stroke prevention in patients with AF and contraindications for long-term anticoagulant treatment. We aimed to assess the anticoagulation status and LAAC indications in patients with AF from HECMOS (Hellenic Cardiorenal Morbidity Snapshot) survey. Materials and Methods: HECMOS was a nationwide snapshot survey of cardiorenal morbidity in hospitalized cardiology patients. HECMOS used an electronic platform to collect demographic and clinically relevant information from all patients hospitalized on March 3, 2022, in 55 different cardiology departments. In this substudy, we included patients with known AF without mechanical prosthetic valves and moderate to severe mitral valve stenosis. Patients with prior stroke, previous major bleeding, poor adherence to anticoagulants, and end-stage renal disease were considered candidates for LAAC. Results: Two hundred fifty-six patients (mean age 76.6±11.7, 148 males) were included in our analysis. Most of them (n=159; 62%) suffered from persistent AF. Mean CHA2DS2-VASc score was 4.28±1.7, while mean HAS-BLED score was 1.47±0.9. Three out of 3 patients with a CHA2DS2-VASc 0 or 1 (female) received improperly anticoagulants. Sixteen out of 18 patients with a CHA2DS2-VASc 1 or 2 (female) received anticoagulants. Thirty-three out of 235 patients with a CHA2DS2-VASc > 1 or 2 (for female) did not receive improperly anticoagulants. Among 221 under anticoagulant therapy, 191 (86.4%) received non-vitamin K antagonist oral anticoagulants (NOACs) and 30 (13.6%) received vitamin K antagonists. Relative indications for LAAC were present in 64 patients with NVAF (60 had only one risk factor and 2 had two concurrent risk factors). In detail, 36 had a prior stroke, 17 patients had a history of major bleeding, 15 patients reported poor or no adherence to the anticoagulant therapy and 5 had eGFR< 15 ml/min/1.73m2. Moreover, 33 had a HAS-BLED score ≥3. No LAAC treatment was recorded. Conclusions: Anticoagulation status was nearly optimal in a high thromboembolic risk population of cardiology patients, mainly treated with NOACs. One out of four AF patients should be screened for LAAC.
REVIEW | doi:10.20944/preprints202308.1645.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: dilated cardiomyopathy; heart failure; cardiac device therapy; genetic analysis
Online: 23 August 2023 (09:20:43 CEST)
Dilated cardiomyopathy (DCM) is a common form of cardiomyopathy, characterized by ventricular chamber dilatation and systolic dysfunction, in the absence of coronary artery disease, arterial hypertension, valvular or congenital diseases. DCM is a heterogeneous group of disorders of the myocardium caused by genetic factors, environmental factors, or a combination of both. DCM affects mainly men aged between 20 and 50 years, being considered one of the main causes of heart failure (HF) and the main indication for heart transplantation. Guideline-based HF treatment is the mainstay of management for patients with DCM. In recent years, gene therapy and induced pluripotent stem cells have become promising strategies. In this review, we summarize the relevant clinical issues, and current treatment of DCM patients, including the role of genetic evaluation.
REVIEW | doi:10.20944/preprints202307.1283.v2
Subject: Biology And Life Sciences, Life Sciences Keywords: smartwatch; stress; wearable device; heart rate variability; comparative analysis
Online: 25 July 2023 (09:28:26 CEST)
In the modern world, stress has become a pervasive concern that affects individuals' physical and mental well-being. To address this issue, many wearable devices have emerged as potential tools for stress detection and management, by measuring heart rate, heart rate variability (HRV), and various matrices related to it. This literature review aims to provide a comprehensive analysis of existing research on HRV tracking and Biofeedback using smartwatches and finger monitor/sensor pairing with reliable 3rd party mobile apps like Elite HRV, Welltory, and HRV4Training specifically designed for stress detection and management. we apply various algorithms and methodologies employed for HRV analysis and stress detection is discussed, including time-domain, frequency-domain, and non-linear analysis techniques. Prominent smartwatches, such as Apple Watch, Garmin, Fitbit, Polar, and Samsung Galaxy Watch, are evaluated based on their HRV measurement accuracy, data quality, sensor technology, and integration with stress management features. We describe the efficacy of smartwatches in providing real-time stress feedback, personalized stress management interventions, and promoting overall well-being. To assist researchers, doctors, and developers use smartwatch technology to address stress and promote holistic well-being, we discuss the data's advantages and limitations, future developments, and the significance of user-centered design and personalized interventions. Keywords: smartwatch; stress; wearable device; heart rate variability; comparative analysis
ARTICLE | doi:10.20944/preprints202307.0511.v1
Subject: Public Health And Healthcare, Public, Environmental And Occupational Health Keywords: tree processing; ergonomic evaluation; workload; heart rate; wearable technology
Online: 7 July 2023 (13:09:19 CEST)
The aim of the work was to carry out an ergonomic assessment of the workload when working with a chainsaw during motor-manual tree processing. Wearable technology was used, namely Garmin, Biostrap and Whoop devices, which are generally available. The dependence of the heart rate (HR) on physical workload was examined to calculate Heart Rate Index. The case study was done with one worker, three variations of chainsaw devices cutting the poplar wood. It was proved that the use of a heavier work tool, MS 500i /90 cm 9,3 kg, significantly contributes both to the creation of a non-physiological working position and to an increase in the energy required to perform work, which was represented by an increase in heart rate. With a lighter work tool and a shorter cutting blade, both a decrease in heart rate and a reduction in the working time were performed in a non-physiological position. The results can be used in common practice for workers´ self-assessment to increase safety and health protection at work or work productivity not only in motor-manual processing in forestry related professions.
REVIEW | doi:10.20944/preprints202307.0090.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: Sacubitril-valsartan; heart failure; ejection fraction and cardiovascular disease
Online: 3 July 2023 (13:25:11 CEST)
Background: The 2021 “Universal Definition of Heart Failure (HF)” Proposed the following left ventricle ejection (LVEF) phenotype classification: ≤40%; HF with intermediate LVEF: between 41-49% and HF with preserved LVEF: ≥50%. LVEF represents the percentage of left ventricular ejected volume in each cardiac cycle and Cut-points considered statistically normal are: ≥52% in men and ≥54% in women. The prevalence HFpEF is of 35-60% among the HF phenotypes, with a facing to increase rates in relation to HFrEF and is associated with mortality rates similar to those of HFrEF. The pathophysiology of HFpEF is based on vascular and metabolic dysfunction, therefore, there is less neurohumoral stimulation compared to HFrEF. Methodology: A systematic review was performed to report of information related to Sacubitril-valsartan and the treatment of HFrEF. Terms related to “treatment” and “brazil” were used in the databases PubMed (MEDLINE) and Scientific Electronic Library Online (SCIELO). Results: Clinical trials testing drugs that modulate the neurohumoral system in patients with HFpEF failed to demonstrate benefit in the combined endpoint of reduced mortality/hospitalization due to HF compared to placebo to date. Sacubitril-valsartan is a drug with a mechanism of action surrogate the pathophysiological concept of HFpEF, it is safe and decreased endpoints of natriuretic peptides and left atrial structure in a phase II clinical study. Conclusions: The PARAGON-HF trial demonstrated that sacubitril-valsartan reduced the primary endpoint of the study when assessed the pre-specified subgroup of LVEF≤57% and improved the secondary endpoints of performance status and renal function in the population.
ARTICLE | doi:10.20944/preprints202306.2247.v1
Subject: Arts And Humanities, Archaeology Keywords: hominins; chopper; human evolution; heart rate; piano playing; technome
Online: 30 June 2023 (11:47:16 CEST)
The length of time it takes to experimentally make one-sided choppers, as found in the fossil record, bears a linear relationship to the knapping process of fabricating them. In addition, this temporal frame appears to be related to human heart rates measured as beats per minute, which act as a physiological metronome. We achieved these observations assuming that any paleolithic one-sided chopper has the information needed to estimate quantitatively the number of strikes on it. The experimental data allow us to establish the total timing needed for the standard fabricating of any one-sided chopper. We discuss issues derived from these experimental results, showing the evolution of human neurological abilities from 2.4 million years ago to the Modern period through the duration of time needed for making one chopper to that needed to play a 19th-century music score on a piano. Given that the neuronal and physiological distance between both actions differs by a factor of 6, we propose the concept of “technome” to measure human evolution by using methodological homogeneous metrics applied to these two human technologic objects, the chopper and the piano.
REVIEW | doi:10.20944/preprints202306.0876.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Transseptal puncture; TSP; left atrium catheterization; left heart catheterization
Online: 13 June 2023 (04:33:32 CEST)
Transseptal puncture is an established technique for achieving left atrium access during cardiac procedures. It is associated with low overall complication rate and high success rates. Although being almost a century old technique, recent years brought a substantial development in the field, allowing for faster and safer left atrium catheterization. In this paper we discuss its history, complications, available techniques and current state of the art.
REVIEW | doi:10.20944/preprints202304.0738.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Heart failure; Sodium-glucose co-transporter; diabetes; cardiovascular outcomes.
Online: 23 April 2023 (03:13:59 CEST)
Sodium-glucose co-transporter 2 (SGLT2) inhibitors, originally used for diabetes mellitus, are gaining more popularity for other indications owing to their positive cardiovascular and renal effects. Initially, SGLT2 inhibitors were shown to reduce heart failure (HF) hospitalization and improve cardiovascular outcomes in patients with type 2 diabetes. Later, SGLT2 inhibitors were evaluated in patients with HF with reduced ejection fraction (HFREF) and had beneficial effects independent of the presence of diabetes. Recently, reduction in cardiovascular outcomes were also observed in patients with HF with preserved ejection fraction (HFPEF). SGLT2 inhibitors also reduced renal outcomes in patients with chronic kidney disease. Overall, these drugs have an excellent safety profile with a negligible risk of genitourinary tract infections and ketoacidosis. In this review, we discuss the current data regarding SGLT2 inhibitors in special populations including acute myocardial infarction, acute HF, right ventricular (RV) failure, patients with left ventricular assist device (LVAD), and patients with type1 diabetes. We also discuss the potential mechanisms behind the cardiovascular benefits of these drugs.
REVIEW | doi:10.20944/preprints202211.0551.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: biomarkers; Heart failure with preserved ejection fraction; Metabolomic; microRNA
Online: 29 November 2022 (11:58:09 CET)
Heart failure with preserved ejection fraction (HFpEF) remains a poorly characterized syndrome with many dark aspects related to different patients profile, various associated risk factors and wide aetiologies. It comprises several pathophysiological pathways related to endothelial dysfunction, myocardial fibrosis, extracellular matrix deposition and high inflammatory response. Up to now, it has been described only for clinical appearance and most common associated risk factors without an effective characterization of biological processes responsible for cardiovascular deteriorations. Recent advances in laboratory and metabolomic researches showed that HFpEF appears strictly related to specific cells and molecular mechanisms dysregulation. Some biomarkers are capable to early identify these processes adding new insights into diagnosis and risk stratification. Additionally recent advances on intermediate metabolites reflecting provide relevant information on intrinsic cellular and energetic substrate alterations. The systematic combination of clinical imaging and laboratory data may lead to a precision medicine approach providing prognostic and therapeutic advantages. Current review reports traditional and emerging biomarkers recently investigated in HFpEF setting, and it purpose a new diagnostic approach based on integrative information achieved from risk factors burden, hemodynamic dysfunction and biomarkers signature partnership.
ARTICLE | doi:10.20944/preprints202205.0346.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: β-adrenoceptor; diabetes; empagliflozin; heart; pressure-volume loop analysis
Online: 25 May 2022 (09:59:26 CEST)
Diabetes mellitus leads to cardiovascular complications including impaired cardiac β-adrenoceptor (β-AR) function. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, such as empagliflozin (EMPA) improve outcomes in heart failure patients and animal models thereof. Therefore, we have investigated the effects of EMPA on in vivo cardiac function (pressure-volume loop analysis) and β-AR-mediated contractile responses (papillary strips) in streptozotocin (STZ; 40 mg/kg, i.p.)-induced diabes in male Sprague Dawley rats (control, EMPA-treated control, diabetic, EMPA-treated diabetic) in a design reflecting late-onset treatment. 13-16 weeks after STZ injection treatment with a low dose of EMPA (10 mg/kg/day, daily oral gavage) or vehicle was administered for another 8 weeks. EMPA did not change cardiac function in control rats. Diabetic rats had a reduced heart rate, cardiac output, stroke work, rate of contration and rate of relaxation and increased isovolumic relaxation, whereas in vitro responses were not markedly attenuated. Treatment with EMPA showed a trend for improvement of some but not all parameters. Our results indicate that low dose EMPA treatment had limited effects on cardiac impairment despite reducing blood glucose when initiated after diabetes is manifest. Future studies with a higher dose and greater sample sizes could help to clarify the possible benefits of EMPA on the diabetic heart.