Aerobic exercise training (AET) has been used in the management of heart disease. AET may, totally or partially, restore the activity and/or expression of proteins that regulate calcium (Ca2+) handling, optimize intracellular Ca2+ flow, and attenuate cardiac functional impairment in failing hearts. However, the literature presents conflicting data regarding the effects of AET on Ca2+ transit and cardiac function in rats with heart failure resulting from aortic stenosis. The objective of this study was to evaluate the effects of AET on calcium handling and cardiac function in rats with heart failure due to aortic stenosis. Wistar rats were distributed into two groups: control (Sham; n= 61) and aortic stenosis (AoS; n= 44). After 18 weeks, the groups were redistributed into: non-exposed to exercise training (Sham, n = 28 and AoS, n = 22) and trained (Sham-ET, n = 33 and AoS-ET, n = 22) for 10 weeks. Treadmill exercise training was performed with a velocity equivalent to the lactate threshold. Echocardiogram, isolated papillary muscle, and isolated cardiomyocyte analyzed cardiac function. During isolated papillary muscle assay and isolated cardimyocyte was evaluated Ca2+. The expression of regulatory proteins of diastolic Ca2+ was analyzed via Western Blot. AET attenuated the diastolic dysfunction and benefited the systolic function. AoS-ET animals presented better response to post-rest contraction, and SERCA2a and L-type Ca2+ channels blocked than the AoS. Furthermore, AET was able to improve aspects of the mechanical function and the responsiveness of the myofilaments to the Ca2+ of the AoS-ET animals. AoS animals presented alteration in the protein expression of the SERCA2a and NCX, and AET restored SERCA2a and NCX levels near normal values. Therefore, AET increased SERCA2a activity, improved the cellular Ca2+ influx mechanism, and increased myofilament responsiveness to Ca2+, attenuating cardiac dysfunction at cellular, tissue, and chamber levels in animals with aortic stenosis and heart failure.

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.

Abstract Objective: To review the relevant literature on the use of atrioventricular node ablation and pacing in patients with heart failure and atrial fibrillation. Methods: A PubMed/MEDLINE and SCOPUS search was performed in order to assess the clinical outcomes of atrioventricular node ablation and pacemaker implantation, as well as the complications that may occur. Results: Several clinical trials, observational analyses and meta-analyses have shown that “pace and ablate” strategy not only improves symptoms but also can enhance cardiac performance in patients with heart failure and atrial fibrillation. Although this procedure is effective and safe, some complications may occur including worsening of heart failure, permanent fibrillation, arrhythmias and sudden death. Regarding the implantation of pacemaker, cardiac resynchronization therapy is shown to be the optimal choice compared to right ventricle apical pacing. His bundle pacing is a promising alternative to cardiac resynchronization therapy and has shown beneficial effects, while left bundle brunch pacing is an innovative modality. Conclusions: Atrioventricular node ablation and implantation of pacemaker is shown to have beneficial effects on clinical outcomes of patients with atrial fibrillation ± heart failure who do not respond or are intolerant to medical treatment. Cardiac resynchronization therapy is the treatment of choice and His bundle pacing seems to be an effective alternative way of pacing in these patients.

Oxidative stress driven by several environmental and local airway factors associated with chronic obstructive bronchiolitis, a hallmark feature of COPD, plays a crucial role in the disease pathomechanism. Unbalance between oxidants and antioxidant defense mechanisms not only amplifies the local inflammatory processes, but it also worsens cardiovascular health and contribute to the COPD related cardiovascular dysfunctions and mortality. The current review summarizes recent developments in our understanding of different mechanisms contributing to oxidative stress and its countermeasures with special attention to those that link local and systemic processes. Major regulatory mechanisms orchestrating these pathways are also introduced together with some suggestions for further research on the field.

Transient Receptor Potential Vanilloid 4 (TRPV4) channel is a non-selective cation channel, mostly permeable to calcium (Ca2+), which participates to intracellular Ca2+ handling in cardiac cells. It is widely expressed through the body and is activated by a large spectrum of physico-chemical stimuli, conferring it a role in a variety of sensorial and physiological functions. With-in the cardiovascular system, TRPV4 expression was reported in cardiomyocytes, endothelial cells (ECs) and smooth muscle cells (SMCs) where it modulates mitochondrial activity, Ca2+ ho-meostasis, cardiomyocytes electrical activity and contractility, cardiac embryonic development, fibroblast proliferation but also vascular permeability, dilatation and constriction. On the other hand, TRPV4 channels participate in several cardiac pathological processes such as development of cardiac fibrosis, hypertrophy, ischemia-reperfusion injuries, heart failure, myocardial infarc-tion, and arrhythmia. In this manuscript, we provide an overview of TRPV4 channel implica-tions in cardiac physiology and discuss the potential of TRPV4 channel as therapeutic target against cardiovascular diseases.

Electrical impedance tomography (EIT) can monitor the real-time hemodynamic state of a conscious and spontaneously breathing patient noninvasively. However, cardiac volume signal (CVS) extracted from EIT images has a small amplitude and is sensitive to motion artifacts (MAs). This study aimed to develop a new algorithm to reduce MAs from the CVS for more accurate heart rate (HR) and cardiac output (CO) monitoring in patients undergoing hemodialysis based on the source consistency between the electrocardiogram (ECG) and the CVS of heartbeats. Two signals were measured at different locations on the body through independent instruments and electrodes, but the frequency and phase were matched when no MAs. As the number of motions per hour (MI) increased over 30, the proposed algorithm had a correlation of 0.83 and a precision of 1.65 beats per minute (BPM) compared to the conventional statical algorithm of a correlation of 0.56 and a precision of 4.04 BPM. For CO monitoring, the precision and upper limit of the mean ∆CO were 3.41 and 2.82 liters per minute (LPM), respectively, compared to 4.05 and 3.82 LPM of the statistical algorithm. The developed algorithm could reduce MAs and improve HR/CO monitoring accuracy and reliability, particularly in high-motion environments.

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.

Currently, old-style personal medicare techniques rely mostly on traditional methods, such as cumbersome tools and complicated processes, which can be time-consuming and inconvenient in some circumstances. Furthermore, such old methods need the use of heavy equipment, blood draws, and traditional bench-top testing procedures. Invasive ways of acquiring test samples can potentially cause patients discomfort and anguish. Wearable sensors, on the other hand, may be attached to numerous body areas to capture diverse biochemical and physiological characteristics as a developing analytical tool. Physical, chemical, and biological data transferred via the skin is used to monitor health in various circumstances. Wearable sensors can assess the aberrant conditions of the physical or chemical components of the human body in real-time, exposing the body state in time, thanks to unintrusive sampling and high accuracy. Most commercially available wearable gadgets are mechanically hard components attached to bands and worn on the wrist, with form factors ultimately constrained by the size and weight of the batteries required for the power supply. Wearable gadgets with “skin-like” qualities are a new type of automation that is only starting to make its way out of research labs and into pre-commercial prototypes. In this paper, we studied the recent advancement in battery-powered wearable sensors established on optical phenomena and skin-like battery-free sensors which brings a breakthrough in wearable sensing automation.

Wearable cardiac sensors pave the way to advanced cardiac monitoring applications based on heart rate variability (HRV). In real-life settings, heart rate (HR) measurements are subject to mo-tion artifacts that can be timely removed from the recordings. This leads to frequent data loss in the HR signal, especially for commercial devices based on photoplethysmography (PPG). The cur-rent study had two main goals: (i) to provide a white-box quality index that estimates the amount of missing samples in any piece of HR signal; and (ii) to quantify the impact of data loss on feature extraction in a PPG-based HR signal. This was done by comparing real-life recordings from com-mercial sensors featuring both PPG (Empatica E4) and ECG (Zephyr BioHarness 3). After an out-lier rejection process, our quality index was used to isolate portions of ECG-based HR signal that could be used as benchmark, to validate the output of Empatica E4 at the signal level and at the feature level. Our results showed high accuracy for estimating the mean HR, poor accuracy for short-term HRV features and moderate accuracy for longer-term HRV features. Levels of error could be substantially reduced by using our quality index to identify time windows with few or no missing data.

Artificial Intelligence are creating a paradigm shift in health care, being phenotyping patients through clustering techniques one of the areas of interest. Objective: To develop a predictive model to classify heart failure (HF) patients according to their left ventricular ejection fraction (LVEF), by using available data in Electronic Health Records (EHR). Subjects and methods: 2854 subjects more than 25 years old with diagnose of HF and LVEF measured by echocardiography were selected to develop an algorithm to predict patients with reduced EF using supervised analysis. Performance of the algorithm developed were tested in heart failure patients from Primary Care. To select the most influencing variables, LASSO algorithm setting was used and to tackle the issue of one class exceed the other one by a large proportion we used the Synthetic Minority Oversampling Technique (SMOTE). Finally, Random Forest (RF) and XGBoost models were constructed. Results: Full XGBoost model obtained the maximized accuracy, a high negative predictive value and the highest positive predictive value. Gender, age, unstable angina, atrial fibrillation and acute myocardial infarct are the variables that most influence FE value. Applied in the EHR data set with a total 25594 patients with an ICD-code of HF and no regular follow-up in Cardiology clinics, 6170 (21.1%) were identified as those pertaining to the reduced EF group. Conclusion: The algorithm obtained is able to rescue a number of HF patients with reduced ejection fraction that can be take benefit for a protocol with strong recommendation to succeed. Furthermore, the methodology can be used for studies with data extracted from the Electronic Health Records.

(1) Background: Most hemodialysis patients may experience physiological and psychological stress. Exposure to nature has been previously reported to reduce the measures of psychological and physiological stress, and immune function. This study aimed to investigate psychological and physiological effects of integrated indirect forest therapy on chronic renal failure patients undergoing hemodialysis. (2) Methods: As a quasi-experiment, this study employed a nonequivalent control group, repeated measurements, and a non-synchronized design. A total of 54 participants were included: 26 and 28 in the experimental and control groups, respectively. During hemodialysis, five types of forest therapy stimuli (visual, auditory, olfactory, tactile, and motor) were applied 3 times per week for 4 weeks during 15-minute sessions. (3) Results: Positive but not negative emotion measures differed between the groups after the intervention. Fatigue and physiological stress levels were significantly reduced in the experimental group, whereas no significant difference was found between the groups on the measures of psychological stress. Activation of both the parasympathetic and sympathetic nervous systems was similar in both groups, as was the number of natural killer cells. (4) Conclusion: Integrated indirect forest therapy may help increase positive emotions and reduce fatigue and stress levels during hemodialysis in patients with chronic renal failure.

This paper presents an effective heart disease prediction model through detecting the anomalies, also known as outliers, in healthcare data using the unsupervised K-means clustering algorithm. Most existing approaches for detecting anomalies are based on constructing profiles of normal instances. However, such techniques require an adequate number of normal profiles to justify those models. Our proposed model first evaluates an \textit{optimal} value of K using Silhouette method. Next, it intends to locate anomalies that are far from a certain threshold distance with respect to their clusters. Finally, the five most popular classification techniques such as K-Nearest Neighbor (KNN), Random Forest (RF), Support Vector Machines (SVM), Naive Bayes (NB), and Logistic Regression (LR) are applied to build the resultant prediction model. The effectiveness of the proposed methodology is justified using a benchmark dataset of heart disease.

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.

The physiological impact of walking in nature was quantified via continuous heart rate variabil-ity (HRV), pre- and post-walk saliva cortisol measures, and self-reported mood and mindfulness scores for N=17 participants who walked “The Green Road” at Walter Reed National Military Medical Center in Bethesda, Maryland. For N=15 of the participants, HRV analysis revealed two main groups: group 1 individuals who had a 104% increase (mean) in root mean square standard deviation (RMSSD) and 47% increase (mean) in standard deviation of NN values (SDNN) indi-cating an overall reduction in physiological stress from walking the Green Road, and group 2 in-dividuals who had a decrease (mean) of 42% and 31% in these respective HRV metrics signaling an increase in physiological stresses. Post-walk self-reported scores for vigor and mood disturb-ance were more robust for the Green Road than for a comparable urban road corridor and showed that higher HRV during the walk was associated with improved overall mood. Saliva cortisol was lower after taking a walk for all participants and showed that walking the Green Road elicited a significantly larger reduction in cortisol of 53% on average when compared with 37% of walking along an urban road. It is also observed that the order in which individuals walked the green road, and urban road also impacted their cortisol response with those walking the urban road before the green showing a substantial reduction in cortisol, suggesting a possible attenuation effect of walking the green road first. These findings provide quantitative data demonstrating the stress-reducing effects of being in nature, thus supporting the health benefit value of providing access to nature more broadly in many settings.

Cardiovascular disease (CVD) is a major global health concern. The number of people with CVD is expected to rise due to aging populations and increasing risk factors such as obesity and diabetes. Identifying new molecular markers is crucial for early diagnosis and treatment. Among these, plasma levels of some miRNAs specifically expressed in cardiac and skeletal muscle known as myomiRs, has gained attention for their roles in cardiovascular health. This study analyzed the plasma levels of myomiR-133a, -133b, and -206 in the pathogenesis of cardiovascular diseases. Exploiting of a case-control study design with patients recruited from several nursing homes form Calabria (Southern Italy) characterized by different types of CVD compared to non-CVD controls, we found downregulation of miR-133a in heart failure and miR-133b in stroke, along with the overall decreased expression of miR-133b and miR-206 in CVD patients. In silico functional characterization of their targets and signaling pathways revealed their involvement in critical cardiovascular processes. Although further research is necessary to fully elucidate their mechanisms and clinical utility, the results here reported support the idea that myomiRs could serve not only as biomarkers but also as therapeutic targets, offering new avenues for managing and potentially preventing CVD progression.

The chronic high fat dysbiosis diet (HFD) instigates cardiac remodeling, dysfunction and chronic heart failure (CHF). The therapeutic approaches focusing oxidative stress, inflammation and hyperlipidemia have not yielded significant positive clinical outcomes. Recent studies report that although mitochondrial ATP citrate lyase (ACLY) supports cardiac function, however, decreases more in human HFpEF than HFrEF. Interestingly, the ACLY synthesizes lipids and creates hyperlipidemia. Epigenetically, ACLY acetylates histone. The mechanism(s) are unknown. One hypothesis is that the HFD induces epigenetic folate 1-carbon metabolism (FOCM), heperhomocysteinemia (HHcy, a cause of abrogation of sleep-time dipping in blood pressure and hypertension) and heart failure. Interestingly, the probiotics utilizes the fat/lipids post-biotically, and increases the mitochondrial bioenergetics and attenuates the HFD induced heart failure. We suggest a novel and paradigm-shift epigenetic mitochondrial sulfur transsulfuration pathways that selectively target HFD-induced CHF. The HFD via transport and metabolomic pathways instigates cardiac remodeling and dyfunction. Previous studies from our laboratory, using a single cell analysis, revealed increase in transporter (SLC25A) of s-adenosine-methionine (SAM) during elevated levels of homocysteine (Hcy, i.e., hyperhomocysteinemia, HHcy), a consequence of impaired epigenetic recycling of Hcy back to methionine by increase in FOCM methylation of H3K4, K9, H4K20 and gene writer (DNMT) and decrease in eraser (TET/FTO). The Hcy transported to mitochondria by SLC7A for clearance via sulfur metabolomic transsulfuration by 3-mercaptopyruvate sulfur transferase (3MST). Interestingly, the HHcy decreases ATP, OCR, H₂S, PGC1α, TFAM, and increase in fission/fusion ratio, causing mitochondria dysfunction. We suggest that gut dysbiosis by HFD disrupts rhythmic epigenetic memory via FOCM and increase in DNMT1 and creates HHcy, leading to decrease mitochondrial transsulfuration and bioenergetics. The treatment with a probiotic, lactobacillus will eat the fat/lipids post-biotically and bi-directionally will produce folic acid and lactone-ketone body that will mitigate the HFD-induced mitochondrial remodeling and heart failure.

Background: Despite procedural advancements in the management of univentricular heart patients palliated with a Fontan-type circulation, their exercise capacity and quality of life remain limited. Postoperative exercise training programs offer potential benefits, yet practical implementation and adherence to guidelines are often inadequate. This systematic review and meta-analysis aimed to evaluate the safety, efficacy, and optimal exercise modalities for Fontan patients. Method: A systematic search was conducted on August 24, 2023, using PubMed, Scopus, Web of Science, and Cochrane Library. Studies were screened via Rayyan QCRI based on pre-set exclusion criteria, and their quality was assessed using the Cochrane RoB Tool 2 and the STROBE checklist. A meta-analysis employed a continuous random-effects model to assess the efficacy of cardiac rehabilitation interventions. Results: The study included twenty-six studies (7 RCTs, 19 cohorts) representing 22 individual cohorts. The key findings were that aerobic exercise, lower-extremity resistance training, and inspiratory muscle training significantly improved VO2, enhancing exercise capacity in Fontan patients. Conclusion: While the results are promising, it's crucial to remember that training programs varied widely. Exercise training shows promise for postoperative management, potentially improving exercise capacity, cardiac biomarkers, lung function, and lower limb strength. However, further research is not just a suggestion, but a necessity. It's necessary to refine protocols, assess long-term impacts, and investigate underlying mechanisms, especially for Fontan patients with severe clinical conditions. This emphasizes the importance and urgency of further research in this area.

Introduction: Carcinoid heart disease is a rare cause of right-sided valvular dysfunction, an important complication in patients with carcinoid syndrome. Objectives: We aim to present our own experience regarding early myocardial dysfunction in patients with carcinoid syndrome. Methods: 64 patients (35-90 year old, 62,5% female, 37,5% male patients) with carcinoid syndrome were evaluated be-tween October 2017 and June 2021. All patients underwent two-dimensional echocardiography with additional tissue Doppler and speckle-tracking techniques. For all patients there were measured urinary level of 5- hydroxyindolacetic acid, serotonin and NT-proBNP values. Results: The following echocardiographic features: global longitudinal strain of both ventricles, mean systolic velocity of the left ventricle, systolic velocity of the free wall of right ventricle, correlated with high values of specific biomarkers: serotonin, and urinary 5-hydroxyindolacetic acid, and also with the presence of hepatic metastases and poorly differentiated tumors. Discussion: In this study we identified several patients with early myocardial dysfunction due to carcinoid syndrome, representing a predictive model of poor prognosis, requiring further investigations. Conclusion: Echocardiographic assessment based on the measurement of systolic velocities, as well as the global longitudinal strain of both ventricles, together with specific biomarkers may contribute to better recognition of carcinoid heart disease in clinical practice, but this needs validation through further studies enrolling larger number of patients.

Introduction: Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common condition associated with high morbidity and mortality. Although patients with heart failure (HF) are known to have an increased risk of PE, there is limited evidence regarding its specific impact on patients with acute PE, both in presentation and outcomes, and its relationship with left ventricular ejection fraction (LVEF). Material and Methods: A prospective observational study was conducted at two tertiary hospitals, including patients with symptomatic acute PE between January 2012 and December 2022. The primary objective of the study was the development of a composite outcome (mortality, major bleeding, and recurrence) within the first 30 days. The secondary objective was the development of early complications in patients with HF and reduced LVEF. Results: Out of 1991 patients included with symptomatic acute PE, 7.13% had a history of HF. Patients with HF were older and had more comorbidities. The HF group showed higher mortality (11.27% vs. 4.33%, p<0.001) and major bleeding (9.86% vs. 4.54%, p=0.005). In multivariate analysis, HF was an independent risk factor for the development of the composite outcome (HR 1.93; 95% CI: 1.35-2.76). Reduced LVEF was independently associated with a higher risk of bleeding (HR 3.44; 95% CI: 1.34-8.81). Conclusion: In patients with symptomatic acute pulmonary embolism, heart failure is independently associated with a higher risk of early complications. Additionally, heart failure with reduced LVEF is an independent risk factor for major bleeding.

Right heart masses are usually suspected during a routine examination by transthoracic echocardiography or due to cardiac symptoms. Although very important, sometimes it may be a challenge to differentiate between normal structures (variants) and aberrant or pathologic masses regarding the right heart cardiac tumors. In the last entity, the majority of primary cardiac tumors in adults and children are benign; however, they may have a malignant counterpart. Right heart tumors might involve not only the walls (myocardium, endocardium and pericardium), but also valves and cardiac chambers. Cardiac tumors exhibit altered signal intensity and enhancement characteristics, requiring the use of several imaging methods following a multimodality-imaging algorithm that culminates in the excision or biopsy of the tumor formation. Therefore, various imaging modalities, including echocardiography, computer tomography, positron emission tomography, cardiac magnetic resonance imaging, scintigraphy or, even, invasive angiography, can be useful during their diagnosis. Echocardiography is the first-line non-invasive imaging modality used in the evaluation of the right heart tumors. Before the other diagnosis imaging modalities it is essential for defining morphology, assessing size, observing dynamic appearance, and evaluating functional abnormalities and hemodynamic consequences,. However, all imaging methods have frequently a complementary role; therefore, an integrated imaging approach is recommended.

Especially in the last two decades, due to the developments in durable mechanical circulatory support (MCS) technology and applications, left ventricular assist (LVAD) implantation has become used in more fragile end-stage heart failure patients with higher risk. Despite advances in technology and patient care processes, right heart failure remains the leading cause of morbidity and mortality after durable LVAD implantation. It is difficult to make decisions about the type and duration of MCS during preoperative evaluation, and many clinical, hemodynamic, biochemical and echocardiographic criteria must be taken into account when evaluating the right ventricle. Complex quantitative scoring systems, including measurements of different risk factors for postimplant right ventricular failure, and composite variables, including the anatomical and functional status of the right ventricle, have been used to decide between left or biventricular assist device implantation. The successful use of artificial intelligence (AI) and machine learning (ML) in various applications in the medical field has paved the way for the idea of using it to better predict possible conditions such as right heart failure after LVAD implantation. This review aims to evaluate the current situation of risk prediction models using AI and ML technology, which have become popular in recent years, and possible future developments in predicting right heart failure after the application of durable MCS systems.

Traditional diagnosis of patent foramen ovale (PFO) in the heart has involved the use of transcranial doppler (TCD). However, TCD is essentially a blind test that cannot directly visualize the location of blood vessels. Since TCD relies on qualitative assessments by examiners, there is room for errors, such as misalignment of the ultrasound's angle of incidence with the actual blood vessels. This limitation affects the reproducibility and consistency of the examination. In this study, we presented an alternative approach for assessing right-to-left shunt (RLS) associated with PFO using contrast transcranial color-coded doppler (C-TCCD) with bubble contrast. The patient under consideration had been diagnosed with an ischemic stroke through imaging, but the subsequent cardiac work-up failed to determine the cause. Employing C-TCCD for RLS screening revealed a confirmed RLS of Spencer’s three grades. Subsequently, transesophageal echocardiography (TEE) was conducted to evaluate PFO risk factors, confirming an 8 mm PFO size, a 21 mm tunnel length, a hypermobile interatrial septum, and persistent RLS. The calculated high-risk PFO score was 4 points, categorizing it as a very high-risk PFO. This case underscores the importance of C-TCCD screening in detecting RLS associated with PFO, especially in cryptogenic stroke patients when identifying the underlying cause of ischemic stroke becomes challenging.

Arrhythmia is a cardiac condition characterized by an irregular heart rhythm that hinders the proper circulation of blood, posing a severe risk to individuals’ lives. Globally, arrhythmias are recognized as a significant health concern, accounting for nearly 12 percent of all deaths. As a result, there has been a growing focus on utilizing artificial intelligence for the detection and classification of abnormal heartbeats. In recent years, self-operated heartbeat detection research has gained popularity due to its cost-effectiveness and potential for expediting therapy for individuals at risk of arrhythmias. However, building an efficient automatic heartbeat monitoring approach for arrhythmia identification and classification comes with several significant challenges. These challenges include addressing issues related to data quality, determining the range for heart rate segmentation, managing data imbalance difficulties, handling intra- and inter-patient variations, distinguishing supraventricular irregular heartbeats from regular heartbeats, and ensuring model interpretability. In this study, we propose the Reseek-Arrhythmia model, which leverages deep learning techniques to automatically detect and classify heart arrhythmia diseases. The model combines different convolutional blocks and identity blocks, along with essential components such as convolution layers, batch normalization layers, and activation layers. To train and evaluate the model, we utilized the MIT-BIH and PTB datasets. Remarkably, the proposed model achieves outstanding performance with an accuracy of 99.35% and 93.50% and an acceptable loss of 0.688 and 0.2564, respectively.

TomoBreast hypothesized that hypofractionated 15 fractions/3 weeks image-guided radiation therapy (H-IGRT) can reduce lung-heart toxicity, as compared with normofractionated 25-33 fractions/5-7 weeks conventional radiation therapy (CRT). 123 women with stage I-II operated breast cancer were randomized to receive CRT (N=64) or H-IGRT (N=59). The primary endpoint used a four-items measure of the time to 10% alteration in any of patient self-reported measure, physician clinical evaluation, echocardiography or lung function tests, analyzed by intention-to-treat without exclusion. Results found comparable survivals, but H-IGRT significantly reduced the toxicity measured by lung diffusion capacity and alveolar volume as compared with CRT, G1 in 53% (31/59) versus 72% (44/61) patients, P=0.006; G2, 29% versus 48%, P=0.020. H-IGRT significantly reduced the risk of composite cardio-pulmonary alteration at 5 years, 10.2% versus 26.7%, P=0.024. In conclusion, TomoBreast is a proof-of-concept that image-guided radiation-therapy can improve the overall balance of lung-heart outcomes in breast cancer adjuvant therapy. Furthermore, the significance of the findings supports the efficacy of a small trial size design, which can be critical when clinical research resources are limited.

Transcatheter aortic valve implantation (TAVI) has grown exponentially within the cardiology and cardiac surgical spheres. It has now become a routine approach for treating aortic stenosis. Several uncertainties have been raised about TAVI in comparison to conventional surgical aortic valve replacement (SAVR). The primary concerns are with regards to the longevity of the valves. Several factors have been identified that may predict poor outcomes following TAVI. These include the lesser-used finite element analysis (FEA) to quantify the properties of calcifications that affect TAVI valves. This can also be used in conjunction with other integrated software to ascertain the functionality of these valves. Other imaging modalities are now widely available such as Multi-detector row computed tomography(MDCT) which can accurately size the aortic valve annulus.. This may help reduce the incidence of paravalvular leaks and regurgitation which may necessitate further intervention. Structural valve degeneration (SVD) remains a key factor with varying results from current studies. The true incidence of SVD in TAVI compared to SAVR remains unclear with the lack of long term data. It is now widely accepted that both are part of the armamentarium and are not mutually exclusive. Decision-making for the appropriate intervention should be made via shared decision-making involving the heart team.

Obesity is linked to an inflammatory process, with adipocyte release triggering insulin resistance (IR) and autonomic imbalance. A cardiovagal trainning protocol has shown favorable results in autonomic balance and decrease of inflammatory markers. The aim of this study was to analyze the autonomic behavior related to inflammatory and metabolic parameters in obese people after a cardiovagal exercise protocol. Twenty people with obesity, were distributed by their HOMA-IR value: obese without IR (n/IR) (n=8) and obese with IR (y/IR) (n=12). The cardiovagal training program was carried out in both groups for 8 weeks at a frequency of 5 times per week. A blood sample was obtained to determine insulin, leptin, TNF alpha and IL6 levels, in addition to determining the HOMA-IR index and autonomic function was measured by heart rate variability. Changes were recorded in the OB-IR group, a decrease in inflammatory markers, glycemia and a reduction of sympathetic activity after the cardiovagal training intervention. In addition, significant differences between the y/IR and n/IR groups were shown in insulin, leptin, TNFa and IL6 values. It can be concluded that after 4 weeks of intervention with a cardiovagal trainning protocol, parasympathetic modulation increased and inflammatory markers decreased in obese subjects.

Atrial fibrillation (AF) is a form of sustained cardiac arrhythmia and microRNAs (miRs) play crucial roles in pathophysiology of AF. To identify novel miR-mRNA pairs, we performed RNAseq from atrial biopsies of AF and non-AF patients. Differentially expressed miRs (11-down and 9-up) and mRNAs (95-up and 82-down) were identified and hierarchically clustered in a heat-map. Subsequently, GO, KEGG, and GSEA analyses were run to identify deregulated pathways. Then, miR targets were predicted in miRDB database, and a regulatory network of negatively correlated miR-mRNA pairs was constructed using Cytoscape. To select potential candidate genes from GSEA analysis, top-50 enriched genes in GSEA were overlaid with predicted targets of differentially deregulated miRs. Besides, protein-protein-interaction (PPI) network of enriched genes in GSEA was constructed, and subsequently GO and canonical pathway analyses were run for genes in PPI network. Our analyses showed that TNF-α, p53, EMT, and SYDECAN1 signaling were among the highly affected pathways in AF samples. SDC-1 (syndecan-1) was the top-enriched gene in p53, EMT, and SYDECAN1 signaling. Consistently, SDC-1 mRNA and protein levels were significantly higher in atrial samples of AF patients. Among negatively correlated miRs, miR-302b-3p was experimentally validated to suppress SDC-1 transcript levels. Overall, our results suggested that miR-302b-3p/SDC-1 axis may involve in pathogenesis of AF.

Aims: Heart failure (HF) is frequently accompanied by atrial fibrillation (AF), a combination that worsens the outcomes of both diseases. Despite advances in the treatment of AF, it remains a serious and unsolved problem for clinicians and researchers. The aim of this study was to examine risk factors for incidents of paroxysmal and persistent AF in patients having heart failure with mid-range ejection fraction (HFmrEF). Methods. Overall, 71 patients with HFmrEF and non-valvular AF, including paroxysmal and persistent types, were enrolled in this study. As a control group, 42 HFmrEF patients without AF were also enrolled. All patients underwent detailed physical examination, including resting electrocardiography, echocardiography, and 24-hour ambulatory Holter monitoring. Levels of the inflammation markers high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) and the fibrotic marker transforming growth factor-β1 (TGF-β1) were measured by ELISA and expressed as odds ratios. Results: We show that paroxysmal AF was associated with higher diastolic blood pressure, whereas both paroxysmal and persistent forms of AF were associated with more frequent occurrence of hypertensive crisis episodes and greater body mass index. Progression from paroxysmal to persistent AF was associated with significant ventricular remodeling. Persistent and paroxysmal AF were associated with higher levels of inflammatory markers when compared to HFmrEF patients having no AF. In addition, TGF-1 was significantly increased in HFmrEF patients having persistent but not paroxysmal AF. Conclusions: Occurrence of AF, first paroxysmal and then persistent, in HFmrEF patients is associated with left ventricular remodeling and the appearance of systemic inflammatory and fibrotic markers. Changes in those parameters may be indicators by which to identify patients at increased risk of atrial fibrillation. Further studies are needed to determine the prognostic validity of these markers.

Phosphodiesterases (PDEs) are the principal superfamily of enzymes responsible for degrading the secondary messengers 3’,5’-cyclic nucleotides cAMP and cGMP. Their refined subcellular localization and substrate specificity contribute to finely regulate cAMP/cGMP gradients in various cellular microdomains. Redistribution of multiple signal compartmentalization components is often perceived under pathological conditions. Thereby PDEs have long been pursued as therapeutic targets in diverse disease conditions including neurological, metabolic, cancer and autoimmune disorders in addition to numerous cardiovascular diseases. PDE2 is a unique member of the broad family of PDEs. In addition to its capability to hydrolyze both cAMP and cGMP, PDE2 is the sole isoform that may be allosterically activated by cGMP increasing its cAMP hydrolyzing activity. Within the cardiovascular system, PDE2 serves as an integral regulator for the crosstalk between cAMP/cGMP pathways and thereby may couple chronically adverse augmented cAMP signalling with cardioprotective cGMP signalling. This review provides a comprehensive overview of PDE2 regulatory functions in multiple cellular components within the cardiovascular system and also within various subcellular microdomains. Implications for PDE2 mediated crosstalk mechanisms in diverse cardiovascular pathologies are discussed highlighting the prospective use of PDE2 as a potential therapeutic target in cardiovascular disorders.

Congenital heart disease (CHD) is among the 4 more common causes of infant mortality in Latin America. Pulse oximetry screening (POS) is useful for early diagnosis and improved outcomes of critical CHD. We describe POS implementation efforts in Latin American countries guided and/or coordinated by the Ibero American Society of Neonatology (SIBEN) as well as the unique challenges that are faced for universal implementation. SIBEN collaborates to improve neonatal quality of care and outcomes. A few years ago, a Clinical Consensus on POS was finalized. Since then, we participated in 12 Latin American countries to educate neonatal nurses and neonatologists on POS and to help with its implementation. The findings reveal that despite wide disparities in care that exist between and within countries, and the difficulties and challenges for implementing POS, significant progress was made. We conclude that universal POS is not easy to implement in Latin America but, when executed, not only it has been of significant value for babies with CHD but also for many with other hypoxemic conditions. The successful and universal implementation of POS in the future is essential to reduce the mortality associated with CHD and other hypoxemic conditions and will ultimately lead to the survival of many more Latin American babies. POS saves newborns’ lives in Latin America.

Comorbidities can have a cumulative effect on hospital outcomes of care, such as the length of stay (LOS), and hospital mortality. This study examines patients hospitalized with Congestive Heart Failure (CHF), a life-threatening condition, which, when it coexists with a burdened disease profile, the risk for negative hospital outcomes increases. Since coexisting conditions co-interact, with a variable effect on outcomes, clinicians should be able to recognize these joint effects. In order to study CHF comorbidities, we used medical claims data from CMS. After extracting the most frequent cluster of CHF comorbidities, we: (i) Calculated, step-by-step, the conditional probabilities for each disease combination inside this cluster (ii) Estimated the cumulative effect of each comorbidity combination on the LOS and hospital mortality (iii) Constructed (a) Bayesian, scenario-based graphs and (b) Bayes-networks to visualize results. Results show that, for CHF patients, different comorbidity constructs have variable effect on the LOS and hospital mortality. Therefore, dynamic comorbidity risk assessment methods should be implemented for informed clinical decision making in any ongoing effort for quality of care improvements.

The enhancement of health-beneficial omega-3 long chain polyunsaturated fatty acid (n-3 LC-PUFA) contents in the muscle, liver, heart and kidney of Australian prime lambs through pasture grazing and supplementation with oil infused pellets was investigated. Forty-eight first-cross prime lambs were randomly assigned into a split-plot design with pasture type as the main plot effect and pellet supplementation as a sub-plot effect in a feeding trial that lasted for nine weeks. The n-3 LC-PUFA content in Longissimus dorsi muscle of all lambs was well above the 30 mg threshold for “omega-3 source” nutrition claim under the Australian Food Standards and Guidelines. Pasture type impacted the fatty acid contents in muscle, heart and kidney of prime lambs. Lambs grazing cocksfoot only had the highest 18:3n-3 (ALA) and n-3 LC-PUFA contents (67.1 mg/100g and 55.2 mg/100 g, respectively). Supplementation of pellets with or without oil infusion to grazing lambs decreased the ALA and n-3 LC-PUFA contents and increased n-6/n-3 ratio in Longissimus dorsi muscle. The fatty acid content in internal organs of grazing lambs was also affected by pellet supplementation. The liver and kidney of grazing lambs were both “good sources” (60 mg/100 g) of omega-3. The cocksfoot grass showed considerable potential for producing healthy, premium quality meat with high contents of n-3 and n-3 LC-PUFA which may consequently enhance the omega-3 intake of Australian lamb consumers.

Myxomatous mitral valve disease (MMVD) is a leading cause of cardiac morbidity and mortality in dogs, requiring targeted intervention at various stages of disease progression. MMVD is characterized by thickening of the mitral valve leaflets, leading to mitral regurgitation and cardiac remodeling. This progressive disease impairs valve function, causing volume overload in the left atrium and ventricle, which can eventually lead to congestive heart failure. MMVD involves complex mechanisms, including genetic predisposition, neurohormonal activation, and mechanical stress on the valve. Thickened valve leaflets fail to seal properly during systole, resulting in mitral regurgitation and increased left atrial pressure. This triggers compensatory mechanisms like activation of the renin-angiotensin-aldosterone system (RAAS), contributing to further cardiac remodeling. Chronic RAAS activation results in fluid retention, vasoconstriction, and fibrosis, all of which can worsen heart failure. This mini-review provides an overview of current therapeutic strategies for the management of MMVD and discusses preliminary findings from our consortium regarding the preclinical and clinical efficacy of the sodium-glucose co-transporter type-2 (SGLT-2) inhibitor, dapagliflozin, in dogs.

This paper intoduces a non-standard research technique to clarify how complex phenomena, such as those that are abundantly present in human physiology, can be faithfully described using fractal dynamical models with and without stochastic forces. This method for conducting research involves tracing the his- torical evolution of understaning an empirical medical process faciltated by the fractal calculus perspective. Herein we trace the analysis of the time series for heart rate varability (HRV) developed for diagnosing the cardiovascular health of a patient. This is done herein by introducing four (one empirical which en- tails three theoretical fractal models) distinct but related fractal models each one introduced to solve a particular problem arising from a fundamental defect in the previous model but in generalizing a model at one stage to resolve the problem associated with the defect another is invariably introduced by the re- placement model. It is through the utilization of the fractional calculus that the necessity for rethinking how to systematically incorporate additonal layers of complexity are revealed ultimately resulting in a 'complete' description of its empirical dynamics in fractal terms.

Global stress is widespread in todays post-pandemic world of political and economic uncertainty. Vibroacoustic technology is a vibrotactile intervention with multiple uses, and its impact on stress lacks interpretation. This research assessed if the vibroacoustic technology of a Vibroacoustic Sound Massage (VSM) can reduce psychological, physiological and cognitive stress. The Perceived Stress Scale (PSS-10), and electrocardiogram (ECG) and electroencephalogram (EEG) biosignals were used to quantify results. Participants were divided into Low Stress and High Stress groups. ECG results show VSM increased parasympathetic activity for all participants, with the Low Stress group more effected. EEG results indicate increased concentration (TBR), reduced arousal and increased relaxation (BAR), and non-significant effects on participant well-being (FAA), though variability in this metric was homogenised after VSM. Together, these results validate VSM as an effective support tool for stress management and further research is required.

Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. In particular, the modRNA-based COVID-19 vaccines have proven that modRNA is a safe and effective therapeutic tool. Moreover, modRNA has the potential to treat various human diseases including cardiac dysfunction. Acute myocardial infarction (MI) is a major cardiac disorder that currently lacks curative treatment options. MI is commonly accompanied by fibrosis and impaired cardiac function. Our group previously demonstrated that the matricellular protein CCN5 inhibits cardiac fibrosis (CF) and improves cardiac dysfunction. However, it remains elusive whether the early intervention of CF under stress conditions is beneficial or more detrimental due to potential adverse effects such as left ventricular (LV) rupture. To obtain acute CCN5 expression, we used modRNA-mediated gene transfer in a mouse MI model. To evaluate CCN5 activity, we established two independent experimental schemes: 1) preventive intervention and 2) therapeutic intervention. Cardiac function and structural changes were measured by echocardiography and magnetic resonance imaging. Finally, fibrosis and the underlying molecular pathway were analyzed by western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry. The modRNA-CCN5 gene transfer successfully ameliorated CF and enhanced cardiac function in both preventive and therapeutic interventions without LV rupture or any adverse cardiac remodeling. Conclusively, early intervention in CF by modRNA-CCN5 gene transfer is an efficient and safe therapeutic modality for treating MI-induced heart failure without adverse structural remodeling.

Elevated blood glucose levels, known as glycemia, play a significant role in sudden cardiac arrest, often resulting in sudden cardiac death, particularly among those with diabetes. Understanding this link has been a challenge for healthcare professionals, leading many research groups to investigate the relationship between blood glucose levels and cardiac electrical activity. Our hypothesis suggests that glucose-sensing mechanisms in cardiac tissue could clarify this connection. To explore this, we adapted a single-compartment, in-silico model of the human atrial node's action potential. We incorporated glucose-sensing mechanisms with voltage-gated sodium ion channels using ordinary differential equations. Parameters for the model were based on existing experimental studies to mimic the impact of glucose levels on atrial node action potential firing. Simulations using voltage clamp and current clamp techniques showed that elevated glucose levels decreased sodium ion channel currents, leading to a reduction in the sinoatrial node action potential frequency. In summary, our model provides a cellular-level understanding of how high glucose levels can lead to bradycardia and sudden cardiac death.

Heart failure is associated with a significant mortality rate, and an elevated prevalence of this condition has been noted among hypertensive patients. The identification of predictive factors for heart failure progression in hypertensive individuals is crucial for early intervention and improved patient outcomes. In this study, we aimed to identify these predictive factors utilizing medical history data for hypertension patients. Specifically, we focused solely on utilizing medical data preceding the diagnosis of hypertension to enable patients to anticipate the onset of potential heart failure at the time of hypertension diagnosis. Age-specific and ICD system-specific predictive factors were identified utilizing the MIMIC-IV database through the application of two analytical approaches: chi-square tests and XGBoost modeling. Our findings reveal 21 overall predictive factors, encompassing conditions such as atrial fibrillation, the use of anticoagulants, kidney failure, obstructive pulmonary disease, and anemia. These factors were assessed through a comprehensive review of the existing literature. We anticipate that the results will offer valuable insights for the risk assessment of heart failure in hypertensive patients.

This study aimed to investigate the relationship between sleep duration, dementia severity, age, and ANS regulation. This cross-sectional pilot study included 27 older patients with probable Alzheimer’s disease, hospitalized at a psychiatric center. We measured heart rate variability to assess ANS regulation at night, evaluated dementia severity using the Clinical Dementia Rating scale, and obtained sleep duration data from sleep diaries maintained by psychiatric nurses. The data were analyzed using repeated-measures generalized linear models with age, sex, dementia severity, and medication (antipsychotics) as covariates. A sleep duration of 7–8 h per night was associated with better ANS regulation than other sleep durations, as indicated by sympathovagal balance (p = 0.005). ANS dysregulation was characterized by a 20.7% increase in sympathetic nervous system activity and a 14.8% decrease in parasympathetic nervous system (PSNS) activity. We found a significant correlation between dementia severity and PSNS activity (p = 0.04) and observed an inverted U-shaped association between sleep duration and ANS regulation. This pilot study demonstrated that a sleep duration of 7–8 h per night may be critical in maintaining optimal ANS regulation. Bidirectional associations between sleep duration, inadequate sleep duration, aging, and ANS regulation warrant further investigation.

Sheep’s milk is a significant source of nucleotides monophosphate (NMPs) but can also contain undesirable residues from veterinary drugs, posing a potential human health risk. This study introduces a novel application of 2D-LC, in heart-cutting mode, for the simultaneous determination of nucleotides and veterinary drug residues in sheep’s milk. Two-dimensional liquid chromatography (2D-LC) allows for the separation of these compounds in a single chromatographic run despite their differing physicochemical properties. The proposed method separates six veterinary drug residues and five NMPs in a single injection. The compounds were separated using a C18 reversed-phase column in the first dimension and a Primesep SB analytical column in the second dimension. The method performance was evaluated in terms of linearity range, detection and quantification limits, matrix effects, precision, and accuracy. The results demonstrated good linearity and sensitivity, with quantification limits allowing for the quantification of veterinary drugs at the maximum residue level and nucleotides at typical levels found in milk samples. The method has been successfully applied to the analysis of sheep’s milk samples acquired from local supermarkets, with recoveries within a range of 70-119 % and 82-117 % for veterinary residues and NMPs, respectively.

Synchronous electrical cardioversion is a relatively common procedure in the emergency department (ED), often performed for unstable supraventricular tachycardia (SVT) or unstable ventricular tachycardia (VT). However, it is also used for stable cases resistant to drug therapy, which carry a risk of deterioration. In addition to the inherent risks linked with procedural sedation, there is a possibility of malignant arrhythmias or bradycardia, which could potentially result in cardiac arrest following this procedure. Here, we present a case of complete heart block unresponsive to transcutaneous pacing and positive inotropic and chronotropic drugs for 90 minutes, resulting in multiple cardiac arrests. The repositioning of the transcutaneous cardio-stimulation electrodes, one of them placed in the left latero-sternal position and the other at the level of the apex, led to immediate stabilization of the patient. Extubation of the patient was performed the following day, while full recovery and discharge within 7 days, after insertion of a permanent pacemaker.

(1) Background: Sudden Infant Death Syndrome (SIDS) represents unexplained and sudden deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for prolonged QTc or Long QT Syndrome (LQTS) should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiogram (ECG) could identify congenital heart defects (CHD) early, especially those not detected at birth. Infants with prolonged QT intervals typically undergo genetic analysis for Long QT Syndrome; (2) Methods: The study involved infants aged 20-40 days, born clinically healthy, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHD identified immediately after birth, as well as those who underwent ECG or echocardiogram for other clinical or historical indications, were excluded from the study. The data were analyzed using SPSS version 22.0; (3) Results: Of the 42,200 infants involved, 2,245 were enrolled, with 39.9% being males. Subsequently, 164 children (37.8% males) with prolonged QT intervals underwent further diagnostic investigations. Genetic mutations were identified in 11 out of 18 tested children. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Medications used included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%; (4) Conclusions: The screening has proven effective in early diagnosing Long QT Syndrome and other cardiac rhythm anomalies, with additional benefits in detecting mutations and/or QTc prolongations in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening.

Background: Heart failure is a major cause of morbidity and mortality worldwide; left ventricular diastolic dysfunction plays a leading role in this clinical context. Diastolic dysfunction may be predisposed by increased abdominal fat and, consequently, increased pericardial and epicardial adiposity. This study aimed to determine whether pericardial and epicardial fat are associated with left ventricular diastolic function. Methods: 82 patients had their abdominal circumference measured and underwent transthoracic echocardiography to measure the thickness of pericardial and epicardial fat and assess the left ventricular diastolic function. Two groups were created based on mean pericardial fat thickness (4.644 mm) and were related to abdominal circumference and echocardiographic parameters. Results: Subjects in the PF High group showed a significant decrease in septal e' (p&lt;0.0001), lateral e' (p&lt;0.0001) and E/A ratio (p=0.003) and a significant increase in E/e' ratio (p&lt;0. 0001), E wave deceleration time (p=0. 013), left atrial volume (p&lt;0.0001), LV mass (p=0.003), tricuspid regurgitant jet velocity (p&lt;0.0001) and LV diameter (p=0.014) compared to the PF Low group. Conclusions: Measurement of abdominal circumference, pericardial and epicardial fat is an early indicator of diastolic changes with transthoracic echocardiography being the gold standard exam.

BACKGROUNDː The so-called Low Cardiac Output Syndrome (LCOS) is one of the most common complications in pediatric patients with congenital heart disease undergoing corrective surgery. LCOS requires high concentrations of inotropes to support cardiac contractility and improve cardiac output, allowing for a better systemic perfusion. To date, serum lactate concentrations and central venous oxygen saturation (ScVO2) are the most commonly used perfusion markers, but they are not completely reliable to identify a state of global tissue hypoxia. The study aims to evaluate whether the venoarterial carbon dioxide difference/arterial-venous oxygen difference ratio [P(v-a)CO2/C(a-v)O2] can be a good index to predict the development of LCOS in the aforemen-tioned patients, so as to treat it promptly. METHODSː This study followed a population of 98 children undergoing corrective cardiac surgery from June 2018 to October 2020 at the Department of Cardiac Surgery of University Hospital Inte-grated Trust and their subsequent admission at the Postoperative Cardiothoracic Surgery Intensive Care Unit. During the study, central arterial and venous blood gas analysis were carried out before and after cardiopulmonary bypass (CPB) (pre-CPB and post-CPB), at admission to intensive care unit, before and after extubation and at any time of instability or modification of the patient’s clinical and therapeutic conditions. RESULTSː The data analysis shows that 46.9% of the children developed a LCOS (in line with the current literature) but that there is no statistically significant association between the P(v-a)CO2/C(a-v)O2 ratio and LCOS onset. Despite the limits of statistical significance, however, a 31% increase in the ratio emerged from the pre-CPB phase to the post-CPB phase when LCOS is present. CONCLUSIONSː This study confirms a statistically significant association between the most used markers in adult patients (serum lactate concentration, ScVO2 and oxygen extraction ratio-ERO2) measured in the pre-CPB phase and the incidence of LCOS onset, especially in patients with he-modynamic instability before surgery.

(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&lt;.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&lt;.01) as the set progressed in the long rest interval conditions (4, 5min), and the heart rate after rest was increased statistically significantly (p&lt;,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.

The use of active video games or exergames has been booming recently, as they are motivating and promote exercise and healthy lifestyle habits for their users, and these immersive virtual reality (IVR) exercise programs could be compared to traditional physical exercise programs. A starting point for this would be to explore the physiological responses that can be generated by its use. Therefore, the main objective of this study was to evaluate the response across certain physiological parameters (heart rate, blood pressure and stress) after an IVR exergame exposure in a sample of healthy adults, and secondarily to explore its feasibility and usefulness as a tool to facilitate physical exercise. 37 healthy adults (22-54 years, 54.1% women) participated in the study. They carried out one exergaming session with the HTC Vive ProTM hardware. The primary outcome was evaluated using the concentration of cortisol, heart rate and blood pressure. Secondary outcomes were evaluated with safety using the Simulator Sickness Questionnaire (SSQ); usability evaluated with the System Usability Scale (SUS); personal experiences evaluated with Game Experience Questionnaire (GEQ) and perceived exertion through the Borg perceived effort scale. All participants completed the IVR session without significant adverse effects, and all physiological parameters analysed increased significantly in relation to pre-intervention levels. Perceived exertion corresponded to a moderate to intense exercise (6.30±0.50/10 on the modified Borg scale). All the sample considered the experience as good or very good and would recommend it. These findings support that our IVR session can be compared to a moderate to intense physical activity, as it involved similar perceived exertion with significant increases in heart rate, blood pressure and salivary cortisol levels.

Cardiogenic shock (CS) is part of a clinical syndrome consisting of acute left ventricular failure causing severe hypotension leading to inadequate organ and tissue perfusion. The most com-monly used devices to support patients affected by CS are Intra-Aortic Balloon Pump (IABP), Impella 2.5 pump and Extracorporeal Membrane Oxygenation. The aim of this study is the com-parison between Impella and IABP using CARDIOSIM© software simulator of the cardiovascular system. The results of the simulations included baseline conditions from a virtual patient in CS followed by IABP assistance in synchronized mode with different driving and vacuum pressures. Subsequently, the same baseline conditions were supported by the Impella 2.5 with different ro-tational speeds. The percentage variation with respect to baseline conditions was calculated for hemodynamic and energetic variables during IABP and Impella assistance. Impella pump driven with a rotational speed of 50000 rpm increased the total flow by 4.36% with a reduction in left ventricular end diastolic volume (LVEDV) by ≅15% to ≅30%. A reduction in left ventricular end systolic volume (LVESV) by ≅10% to ≅18% (≅12% to ≅33%) was observed with IABP (Impella) as-sistance. Taking into account the limitations of a simulation setting, this study highlights that assistance with the Impella device leads to higher reduction in LVESV, LVEDV, left ventricular external work and left atrial pressure-volume loop area compared to IABP support.

This article presents raw data of biaxial tensile measurements of rat heart passive myocardium conducted in lab scale environment. The passive myocardium of the rat was divided into three regions, namely: left ventricle, mid-wall and right ventricle. The biaxial dataset of passive rat myocardia is presented as stress vs strain of the passive rat myocardium in various regions. The determination of valid material properties of the heart plays an important role in the development computational models. These computational models are useful in studying various scenarios and mechanisms of heart diseases. In addition, valid and accurate materials are critical in the development of new therapies. The dataset presented here is useful in the area of soft tissue mechanics including studying the mechanisms of heart diseases such as myocardial infarction. Accordingly, the evaluation of stress and strain in left ventricle, mid-wall and right ventricle was performed.

(1) Background: New sensor technologies in wearables and other consumer health devices open up promising opportunities to collect real-world data. As cardiovascular diseases remain reason number one for disease and mortality worldwide, cardiology offers potent monitoring use-cases with patients in their out-of-hospital daily routine. Therefore, the aim of this systematic review is to investigate the status quo of studies monitoring patients with cardiovascular risks and patients suffering from cardiovascular diseases in a telemedical setting using not only a smartphone-based app, but also consumer health devices such as wearables and other sensor-based devices. (2) Methods: A literature search was conducted across five databases and the results were examined according to the study protocols, technical approaches and qualitative and quantitative parameters measured. (3) Results: Out of 166 articles, 8 studies were included in this systematic review. These cover interventional and observational monitoring approaches in the area of cardiovascular diseases, heart failure and atrial fibrillation using various app, wearable and health device combination. (4) Conclusions: Depending on the researcher’s motivation a fusion of apps, patient reported outcome measures and non-invasive sensors can be orchestrated in a meaningful way adding major contributions to monitoring concepts for both, individual patients and larger cohorts.

Background: Sacubitril/valsartan has been shown to be superior to enalapril in reducing the risks of death and hospitalization for heart failure (HF). However the effect on cardiac performance remains unknown. We sought to evaluate the effects of sacubitril/valsartan on clinical, bioumoral and echocardiographic parameters in patients with HFrEF. Methods: Sacubitril/valsartan was administered to 205 HFrEF patients. Results: Among 230 patients (mean age 59 ± 10 years, 46% with ischemic heart disease) 205 (89%) completed the study. After a follow–up of 10.49 (2.93±18.44) months, the percentage of patients in NYHA class III changed from 40% to 17% (p<0.001). Median N–Type natriuretic peptide (Nt-proBNP) decreased from 1865 ± 2318 to 1514 ± 2205 pg/mL, (p=0.01). Furosemide dose reduced from 131.3 ± 154.5 to 120 ± 142.5 (p=0.047). Ejection fraction (from 27± 5.9% to 30 ± 7.7% (p<0.001) and E/A ratio (from 1.67 ± 1.21 to 1.42 ± 1.12 (p=0.002)) improved. Moderate to severe mitral regurgitation (from 30.1% to 17.4%; p=0.002) and tricuspid velocity decreased from 2.8 ± 0.55 m/sec to 2.64 ± 0.59 m/sec (p<0.014). CONCLUSIONS: Sacubitril/valsartan induce “hemodynamic reverse remodeling” and in association with Nt-proBNP concentrations lowering improve NYHA class despite a diuretic dose reduction.

Background: Several preventive strategies to reduce dyslipidaemia, have been suggested of which dietary modification features as an important one. Addition of almonds in our daily diets has been proposed to beneficially impact the lipid profile. This review critically examines the available evidence assessing the effect of almonds on dyslipidaemia in the South Asian (particularly Indian) context. Methods: An extensive review comprising of epidemiological studies, clinical trials, meta-analyses and systematic reviews was conducted from published literature from across the world. Studies examining the effect of almonds on different aspects of dyslipidaemia viz. high LDL-C, low HDL-C, triglyceridaemia, high total cholesterol levels have been included. Results: Dyslipidaemia is a major risk factor for coronary heart disease and strategies to manage dyslipidaemia have been shown to reduce the incidence of CVD. Although there are proven pharmacological therapies to help manage this condition, there are not many nutritional interventions which can impact dyslipidaemia. Almonds have been shown to reduce LDL-C which is a known risk factor for CHD, in several studies and the effect of almonds has been well documented in systematic reviews and meta-analysis of clinical trials. Conclusions: Addition of almonds in the diet has been shown to not only to reduce LDL-C levels, but also to maintain HDL-C levels. This review informs about the use of this simple nutritional strategy which may help manage known major risk factors for heart disease such as high LDL-C and low HDL-C levels especially in the context of South Asians.

Early diagnosis of paroxysmal atrial fibrillation (PAF) could suggest patients to receive timely interventions in clinical practice. Various PAF onset prediction algorithms might benefit from accurate heart rate variability (HRV) analysis and machine learning classification but to be challenged in real-time monitoring scenarios. The aim of this study is to present an end-to-end deep learning based PAFNet model that integrates a sliding window technique on raw R-R interval of electrocardiogram (ECG) segments to achieve a real-time prediction of PAF onsets. This integration enable the deep convolutional neural network (CNN) to be customized as a light-weight architecture that accommodates the size of sliding windows simply by altering the input layer, specifically its effectiveness in making a new prediction with each new heartbeat. Catering to potential influence of input sizes, three CNN models were trained using 50, 100, and 200 R-R intervals, respectively. For each model, the performance of automated algorithms was evaluated for PAF prediction using a ten-fold cross-validation. As a results, a total of 56,381 PAFN-type and 56,900 N-type R-R interval segments was collected from publicly accessible ECG databases, and a promising prediction performance of the automated algorithm with a 100 R-R intervals was achieved in terms of the sensitivity of 97.12%, the specificity of 97.77%, and the accuracy of 97.45%, respectively. Importantly, the automated algorithm with a sliding windows step of 1 could process one sample in only 23.1 milliseconds and identify the onset of PAF at least 45 minutes in advance. The present results suggest that the sliding window technique on raw R-R interval sequences along by deep learning based algorithms may offers the possibility of providing an accurate, real-time, and end-to-end clinical tool for mass monitoring of PAF.

Congenital heart disease (CHD) is a prevalent congenital disorder diagnosed with high frequency, affecting approximately 0.8% to 1.2% of all live births. Research has demonstrated that the use of pulse oximetry and clinical examination as a screening tool for CHD diagnosis has proven extremely valuable. We conducted a retrospective longitudinal study over a 3-year period that involved screening 1188 newborns admitted to the NICU during the first 72 hours of life within this timeframe. 201 newborns were diagnosed with CHD. Almost all (n=198) had a positive screening test during the 72-hour period, while 3 had a negative screening test, but were later diagnosed using echocardiography. The prevalence rate was 16.67%. A confusion matrix was constructed with 198 true positives (TP), 3 false negatives (FN), no false positives (FP), and 987 true negatives (TN). The sensitivity of the screening test was 98.51%, while the specificity 100%, with no false positives. In our study, a total of 9 deaths occurred. Using the Kaplan-Meier method, the survival probability appeared to be slightly above 0.9 (95.5%), indicating that almost all patients survived past 72 hours after being diagnosed with CHD. Pulse oximetry is an effective, low cost and easy-to-use method and a useful tool to assess and lead to the diagnosis of CHD.

Cardiovascular diseases (CVDs) represent the leading cause of global mortality with 1,7 million deaths a year. One of the alternative systems to drug therapy to minimize the risk of CVDs is represented by alpha-linolenic acid (ALA), an essential fatty acid of the Omega-3 series, known for its cholesterol-lowering effect. The main purpose of this review is to analyze the effects of ALA and investigate the relevant n-6/n-3 ratio in order to maintain functionally beneficial effects. Concerning the lipid-lowering preventive effects, ALA may favorably affect the values of LDL-C and triglycerides in either adult and pediatric populations and it has a positive and protective effect against hypertension, suggesting that ALA is an useful diet-related antihypertensive compound. According to the 2009 EFSA statement, dietary ALA may contribute to reducing the risk of CVDs, thanks to anti-hypertensive, anti-atherosclerotic and cardio-protective effects.

In this work, we developed a highly sensitive multiplexed immunosensor for direct simultaneous detection of both N-terminal Natriuretic Peptide (NT-proBNP) and Cortisol in human artificial saliva (AS). The developed biosensor platform based on silicon nitride was composed from four gold working microelectrodes (WEs) and an integrated counter and reference electrode. Gold WEs were biofunctionalized through carboxyl diazonium (4-APA) to immobilize both anti- NT-proBNP and anti-Cortisol antibodies for simultaneous detection. The electroaddressing of the 4-APA onto the gold WE surfaces was realized by cyclic voltammetry (CV), while the interaction between antibodies and antigens in PBS was monitored by electrochemical impedance spectroscopy (EIS). The antigen detection in human AS was realized by EIS combined with the standard addition method. The immunesensor was highly sensitive and selective toward the corresponding biomarkers in both PBS and artificial human saliva as well as in the presence of other potential interfering biomarkers such as tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10). The limit of detection (LOD) was at 0.2pg/mL for NT-proBNP within the range 0.03 to 0.9pg/mL, while the LOD for Cortisol was 0.06 ng/mL within the range 0.02 to 0.6 ng/mL for Cortisol in artificial saliva. The developed immunosensor is very promising for significant detection time reducing as it allows the simultaneous detection of various biomarkers.

Systemic lupus erythematosus (SLE) myocarditis is presumed to be rare but associated with ad-verse outcomes. If SLE diagnosis has not previously been established, its clinical presentation is often unspecific and difficult to recognize. Furthermore, there is a lack of data in the scientific literature regarding myocarditis and its treatment in systemic immune-mediated diseases, leading to its late recognition and undertreatment. We present the case of a young woman whose first lupus manifestations included acute perimyocarditis, among other symptoms and signs that provided clues to the diagnosis of SLE. Transthoracic and speckle tracking echocardiography were helpful in detecting early abnormalities in myocardial wall thickness and contractility while waiting for cardiac magnetic resonance (CMR). Since the patient presented with acute decompensated heart failure (HF), HF treatment was promptly started in parallel with immunosuppressive therapy, with a good response. In the treatment of myocarditis with heart failure, we were guided by the echocardiographic findings, biomarkers for myocardial injury N-terminal pro b-type natriuretic peptide (NT-proBNP) and hs-troponin I, biomarkers for systemic inflammation erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and biomarkers for SLE disease activity (Complement C)3, C4, and anti-dsDNA levels.

Background and Objectives: Acute Heart Failure (AHF) is a common disease and a cause of high morbidity and mortality, constituting a major health problem. The main purpose of this study was to determine the impact of multiorgan ultrasound in identifying the pulmonary hypertension (PH) in patients admitted due to AHF, predict the evolution of the disease during hospitalization and identify areas of improvement in the care of patients with AHF. Materials and Methods: Patients were evaluated with a standard exam of lung ultrasound, echocardiography, inferior vena cava (IVC) and femoral, renal, hepatic, portal venous Doppler flow patterns at admission and on the day of discharge. Results: Thirty patients were enrolled during November 2021. The mean age was seventy-nine years (Standard Deviation – SD 13,4). Seven patients (23.3%) had a renal function worsening. Regarding ultrasound findings, venous excess ultrasonography score (VExUS) score was calculated at admission and at discharge, surprisingly remaining unchanged or even worsened in most of them (21 patients, 70.0%). The area under the curve for the Lung Score was 83.9% (p = 0.008), obtaining a cutoff value of 10 that showed a sensitivity of 82.6% and a specificity of 71.4% in the identification of intermediate and high PH. It was possible to monitor significant changes between both exams on the lung score (p &lt;0.001), hepatic vein Doppler (p &lt;0.001), portal vein Doppler (p = 0.030), intra-renal vein Doppler (p = 0.025) and VExUS score (p = 0.023), remaining similar the femoral vein Doppler (p = 0.177) and IVC (p = 0.132). Conclusions: Our study results suggest that performing serial multiorgan Point-of-Care ultrasound can help us to better identify high and intermediate probability of PH patients with AHF. Currently proposed multi-organ, venous Doppler scanning protocols, such as the VExUS score, should be further studied in different populations before expanding its use in AHF patients.

Cardiovascular diseases (CVD) are the leading cause of premature death and disability in humans. Increasing data suggest that CVD is closely related to lipid metabolism and signaling. This study aimed to assess whether circulating lysophospholipids (LPL), lysophosphatidic acids (LPA) and monoacylglycerols (MAG) may be considered as biomarkers of CVD. For this objective, the evolution of the plasma levels of 22 compounds (13 LPL, 6 LPA and 3 MAG) was monitored by liquid chromatography coupled with tandem mass spectrometry (HPLC/MS²) in different rat models of CVD, i.e. angiotensin-II-induced hypertension (HTN), ischemic chronic heart failure (CHF) and sugen/hypoxia(SuHx)-induced pulmonary hypertension (PH). On one hand, there was modest changes on the monitored compounds in HTN (LPA 16:0, 18:1 and 20:4), LPC 16:1) and CHF (LPA 16:0, LPC 18:1 and LPE 16:0 and 18:0) models compared to control rats but these changes were no longer significant after correction for multiple testing. On the other hand, PH was associated with important changes in plasma LPA with a significant increase in the 16:0, 18:1, 18:2, 20:4 and 22:6 species. A deleterious impact of LPA was confirmed on isolated human pulmonary smooth muscle cells with an increase in their proliferation. This study demonstrates that circulating LPA species are increased in rats with PH and may contribute to the pathophysiology of this disease. Additional experiments are needed to assess whether the modulation of LPA signaling in PH may be of interest.

Dictyostelium discoideum is gaining increasing attention as a model organism for the study of calcium binding and calmodulin function in basic biological events as well as human diseases. After a short overview of calcium-binding proteins, the structure of Dictyostelium calmodulin and the conformational changes effected by calcium ion binding to its four EF hands is compared to its human counterpart, emphasizing the highly conserved nature of this central regulatory protein. The calcium-dependent and -independent motifs involved in calmodulin binding to target proteins are discussed with examples of the diversity of calmodulin binding proteins that have been studied in this amoebozoan. The methods used to identify and characterize calmodulin binding proteins is covered followed by the ways Dictyostelium is currently being used as a system to study several neurodegenerative diseases and how it could serve as a model for studying calmodulinopathies such as those associated with specific types of heart arrythmia. Because of its rapid developmental cycles, its genetic tractability, and a richly endowed stock center, Dictyostelium is in a position to become a leader in the field of calmodulin research.

Transforming growth factor beta (TGF-β) is a determinant for inflammation and fibrosis in cardiac and skeletal muscle in Chagas disease. To determine its regulatory mechanisms, we investigated the response of T. cruzi-infected cardiomyocytes (CM), cardiac fibroblasts (CF) and L6E9 skeletal myoblasts to TGF-β. Cultures of CM, CF and L6E9 were infected with T. cruzi (Y strain) and treated with TGF-β (1–10 ng/mL, 1h or 48 h). Fibronectin (FN) distribution was analyzed by immunofluorescence and Western blot (WB). Phosphorylated SMAD2 (PS2), phospho-p38 (p-p38), and phospho-c-Jun (p-c-Jun) signaling were evaluated by WB. CF and L6E9 showed an increase in FN from 1 ng/mL of TGF-β, while CM displayed FN modulation only after 10 ng/mL treatment. CF and L6E9 showed higher PS2 levels than CM, while p38 is less stimulated in CF than CM and L6E9. After T. cruzi infection, localized FN disorganization was observed in infected CF and L6E9. T. cruzi induced an increase in FN in CF cultures, mainly in uninfected cells. Infected CF cultures treated with TGF-β showed a reduction in PS2 and an increase in p-p38 and p-c-Jun levels. Our data suggest that p38 and c-Jun pathways may be participating in the fibrosis regulatory process mediated by TGF-β after T. cruzi infection.

Reduced autonomic responses have been reported in horses of advanced age, predisposing them to compromised well-being. Maintained physical exertion tends to preserve autonomic function in geriatric horses. However, the impact of structured exercise regimens on autonomic modulation in geriatric horses has yet to be elucidated. A study was conducted to compare the autonomic modulation in geriatric horses with different activity levels: living sedentarily (SEL), retaining unstructured activities (RAT) and practising a structured exercise regimen (SER). The study observed heart rate variability (HRV) and found that the minimum and mean heart rate decreased in SER horses at 10–12 weeks, with no changes in SEL or RAT horses over the study period. Beat-to-beat (RR) intervals showed no differences in SEL horses, temporal fluctuation at 8–10 weeks in RAT horses and an increase at 10–12 weeks in SER horses. HRV was higher in SER than in RAT horses, as well as in SER horses to a lesser extent. Geriatric horses engaging in a structured exercise regimen demonstrated better autonomic regulation, reflecting lower stress than those retaining unstructured activities or living sedentarily. These results carry welfare implications for developing health management in geriatric horses.

There is an increasing understanding that some mitral valve pathologies have developmental origins. The time course of valvulogenesis varies by animal model, where in cattle, the branched chordae tendineae architecture becomes fully developed at full term. The mechanism by which chordae tendineae bifurcate during fetal development remains unknown. The current study presents a detailed description of bovine chordae tendineae formation and bifurcation during fetal development. Analysis of Movat Pentachrome-stained histological sections of the developing mitral valve apparatus were accompanied by micro-CT imaging. TEM imaging of chordae branches and common trunks allowed measurement of collagen fibril diameter distributions. We observed a proteoglycan-rich “transition zone” at the junction between the fetal mitral valve anterior leaflet and chordae tendineae with “perforations” lined by MMP1/2 and Ki-67 expressing endothelial cells. This region also contained clusters of proliferating endothelial within the bulk of the tissue. We hypothesize this zone marks a region where chordae tendineae bifurcate during fetal development. In particular, perforations, created by localized MMP activity serve as a site for the initiation of a “split” of a single chordae attachment into two. This is supported by TEM results that suggest a similar population of collagen fibrils runs from the branches into a common trunk. A clear understanding of normal mitral valvulogenesis and it’s signaling mechanisms will be crucial in developing therapeutics and/or tissue-engineered valve replacements.

High-flow oscillatory ventilation (HFOV) is a common rescue treatment in infants and children with respiratory failure. This type of ventilation is an effective technique in numerous diseases that affect a child in the postnatal period, such as ARDS, meconium aspiration syndrome (MIS), postnatal pulmonary bleeding and idiopathic pulmonary hypertension (IPH). Although this ventilation technique is commonly recognized as a valuable therapeutic option in the general pediatric population, this is not the same for children with congenital cardiovascular diseases. The key mechanism of oscillatory ventilation is continuous positive pressure administered within the airways via a small tidal volume at high frequency. Tidal volumes are between 1 and 3 ml/kg delivered at 5 – 15 Hz equivalent to 300 – 900 breaths per minute. Few older studies conducted on humans and animals highlight that HFOV may be dangerous for congenital heart patients. According to these evidences, hemodynamic parameters such as blood pressure, wedge pressure, central venous pressure, heart rate and inotrope level can be dangerously changed for patients with congenital heart disease, therefore oscillatory ventilation should be avoided. Numerous retrospective studies have pointed out how oscillatory ventilation constitutes a valid therapeutic option in children with congenital heart disease. Recently, new evidences have highlighted how hemodynamic parameters are modified in a non-significant way by this type of ventilation, remaining beneficial as in the normal pediatric population. This narrative review aims to describe the mechanisms of oscillatory ventilation and collect all the available evidences to support its use in pediatric patients with congenital heart problems.

Predicting heart disease is crucial for early diagnosis and intervention, significantly improving patient outcomes and reducing mortality rates. This study compares various machine learning models, including Logistic Regression, Random Forest, Gradient Boosting, XGBoost, and Long Short-Term Memory (LSTM) networks, using the Cleveland Heart Disease dataset. Comprehensive preprocessing steps were undertaken, such as handling missing values, converting categorical variables to numeric forms, and binarizing the target variable for binary classification. Each model was rigorously evaluated using performance metrics, including accuracy, precision, recall, F1-score, and the area under the receiver operating characteristic curve (AUC-ROC). SHapley Additive exPlanations (SHAP) values were employed to provide insights into feature importance, ensuring model transparency and interpretability. The results indicate that XGBoost outperformed all other models, achieving an accuracy of 90% and an AUC-ROC of 0.94, demonstrating its superior ability to capture complex patterns in the data through advanced optimization techniques and regularization. This study highlights the significant potential of advanced machine learning techniques, particularly ensemble methods like Gradient Boosting and XGBoost, in enhancing heart disease prediction. These models offer higher accuracy and valuable interpretability, making them practical tools for early diagnosis in clinical settings. Future research should focus on integrating these models into healthcare systems and exploring hybrid approaches to further improve predictive performance and clinical applicability.

Single-confinement housing can pose welfare risks to domestic horses. This study investigated horses’ stress responses when confined to single stalls in different stable designs in a tropical savanna region to address a literature gap. In total, 23 horses were assigned to a stable with a central corridor and solid external walls (A) (N = 8), a stable with one side corridor and solid external walls (B) (N = 6) or a stable with a central corridor and no solid external walls (C) (N = 9). Air velocity, relative humidity, air temperature and noxious gases were measured inside the stables, and the heart rate and HRV of the horses were also determined. The relative humidity was lower in stable C than in stable A (p &lt; 0.05), while the air temperature was higher in stable C than in stable B (p &lt; 0.05) during the day. The airflow and ammonia levels were higher in stable C than in stables B and A (p &lt; 0.01–0.0001). Overall, horses’ HRV in stable A was lower than in those in stables B and C (p &lt; 0.05-0.01). Horses in stable A tended to experience more stress than those in other stables.

fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF). Join us on a journey that unravels the mysteries of molecular intricacies, delves into advanced imaging techniques, and sheds light on therapeutic pathways. Unveiling the role of cardiac amyloidosis, particularly sub-clinical isolated cardiac amyloidosis (ICA), the narrative unfolds the heightened risk of AF in the elderly. State-of-the-art imaging techniques like cardiac magnetic resonance (CMR) and molecular imaging step into the spotlight, unraveling diagnostic and prognostic nuances of AF and HFpEF. Embarking on the molecular voyage, the article navigates through next-generation sequencing and comprehensive genomic profiling, shedding light on genetic alterations shaping the AF-HFpEF landscape. This molecular compass lays the groundwork for personalized medicine, illuminating pathways to identify therapeutic bullseyes and biomarkers. In the realm of medical strategies, the discussion homes in on the promising notes struck by SGLT2 inhibitors, particularly dapagliflozin, orchestrating a reduction in AF burden. Characters like spironolactone and dronedarone make appearances, each weaving a distinct tale, revealing their potential roles in steering the ship for AF- HFpEF patients. The subplot involving obesity in HFpEF unfolds, with the LEGACY study portraying the benefits of weight reduction. The pivotal intervention of catheter ablation emerges as the hero, boasting positive outcomes in reducing hospitalization rates and overall mortality for AF-HFpEF patients. However, cautionary tales echo about its impact on left atrial function, adding layers of complexity that beckon careful consideration and monitoring. Amidst the narrative, critical discussions unfold about the limitations of current research, echoing the need to define acute heart failure, refine imaging techniques, and tailor management strategies. The narrative passionately advocates for a personalized touch in addressing AF-HFpEF, recognizing the unique blend of clinical and molecular personas. In essence, this review paints a vivid mural of AF-HFpEF, skillfully bridging the realms of molecular intricacies and the artistry of clinical management.

The single set of electron transporters of the cardiac mitochondrial respiratory chain is organized into three separate supercomplexes. Two of them contain complex I, a dimer of complex III, and two dimers of complex IV. The third supercomplex contains a dimer of complex III and two dimers of complex IV. We also considered two important discoveries. First, the enzymes of β-oxidation of fatty acids are physically associated with respirasome. Second, β-oxidation of fatty acids creates the highest level of QH2 and reverses the flow of electrons from QH2 through complex II, reducing fumarate to succinate. We argue that the respirasome is uniquely adapted for the β-oxidation of fatty acids. The acyl-CoA dehydrogenase complex reduces the membrane’s pool of ubiquinone to QH2, which is instantly oxidized by the 2complex III-4complex IV supercomplex, generating high energization of mitochondria and reversing the electrons flow through the complex II, which reverses the electrons flow through the complex I increasing the NADH/NAD+ ratio in the matrix. The mitochondrial nicotinamide nucleotide transhydrogenase catalyzes a hydride (H-, a proton plus two electrons) transfer across the inner mitochondrial membrane, reducing the cytosolic pool of NADP(H), thus providing the heart with ATP for muscle contraction and energy and reducing equivalents for the housekeeping processes.

This review paper presents a flashback on the evolution of the disease throughout the centuries, describes in summary pathophysiologic mechanisms, discusses briefly the mechanism of action of the diuretics, presents their role in decongesting heart failure patients and unfolds the data behind ultrafiltration in the management of acutely or chronically decompensated heart failure (ADHF), focusing on all the available data and advancements in this field. Acutely decompensated heart failure (ADHF) presents a critical clinical condition characterized by worsening symptoms and signs of heart failure, necessitating prompt intervention to alleviate congestion and improve cardiac function. Diuretics have traditionally been the mainstay for managing fluid overload in ADHF. Mounting evidence suggests that due to numerous causes, such as coexisting renal failure or chronic use of the loop diuretics, an increasing rate of diuretic resistance is noticed and needs to be addressed. There has been a series of trials that combined diuretics of different categories, without the expected results. Emerging evidence suggests that ultrafiltration may offer an alternative or adjunctive approach.

Heart disease is a global health concern of paramount importance, causing a significant number of fatalities and disabilities. Precise and timely diagnosis of heart disease is pivotal in pre-venting adverse outcomes and improving patient well-being, thereby creating a growing demand for intelligent approaches to predict heart disease effectively. This paper introduces an Ensemble Heuristic-Metaheuristic Feature Fusion Learning (EHMFFL) algorithm for heart disease diagnosis. Within the EHMFFL algorithm, a diverse ensemble learning model is crafted, featuring different feature subsets for each heterogeneous base learner, including support vector machine, K-nearest neighbors, logistic regression, random forest, naive bayes, decision tree, and XGBoost. The primary objective is to identify the most pertinent features for each base learner, leveraging a combined heuristic-metaheuristic approach that integrates the heuristic knowledge of Pearson correlation coefficient with the metaheuristic-driven grey wolf optimizer. The second objective is to aggregate the decision outcomes of the various base learners through ensemble learning, aimed at constructing a robust prediction model. The performance of the EHMFFL algorithm is rigorously assessed using the Cleveland and Statlog datasets yielding remarkable results with an accuracy of 91.8% and 88.9%, respectively, surpassing state-of-the-art machine learning, ensemble learning, and feature selection techniques in heart disease diagnosis. These findings underscore the potential of the EHMFFL algorithm in enhancing diagnostic accuracy for heart disease and providing valuable support to clinicians in making more informed decisions regarding patient care.

Individuals diagnosed with systemic arterial hypertension (SAH) are considered risk groups for COVID-19 severity. This study assessed differences in cardiac autonomic function (CAF) and functional capacity (CF) in SAH individuals without COVID-19 infection compared to SAH individuals post-COVID-19. Participants comprised 40 SAH individuals aged 31 to 80 years old, grouped as SAH with COVID-19 (G1; n=21) and SAH without COVID-19 (G2; n=19). CAF was assessed via heart rate variability (HRV), measuring R-R intervals during a 10-minute supine period. Four HRV indices were analyzed through symbolic analysis: 0V%, 1V%, 2LV%, and 2UV%. FC assessment was performed by a 6-minute walk test (6MWT). G1 and G2 showed no difference between significant age, anthropometric, clinical and medication. G2 exhibited superior 6MWT performance, covering more distance (522±78 vs. 465±59 meters, p&lt;0.05). Specifically, G2 demonstrated a moderate, positive correlation between 6MWT and the 2LV% index (r=0.58; p&lt;0.05). Shorter walking distances were observed during 6MWT in SAH individuals post-COVID-19. However, the study did not find impaired cardiac autonomic function in SAH individuals post-COVID-19 compared to those without. This suggests that while COVID-19 impacted FC, CAF remained relatively stable in this population.

Despite the efforts to deliver the best evidence-based care, in-hospital death is an inevitable event among some patients hospitalized in cardiology departments. We retrospectively evaluated mortality events from inpatient admissions to Cardiology Department between 2010-2019. Data were collected from morbidity &amp; mortality meeting presentations which evaluated comorbidities, medical history, treatments, and causes of death for the overall cohort and according to age group and sex. There were 1,182 registered deaths. The most common causes of death among patients were acute myocardial infarction (AMI) (53.0%), heart failure (HF, 11.7%), cardiac arrest (CA, 6.6%), HF with complication/defined cardiomyopathy (6.3%) and sepsis (4.4%). We observed a decline in deaths from AMI from 61.9% in 2010 to 46.7% in 2019 while there was an apparent increase in deaths from HF (11.1% in 2010 to 25.9% in 2019). Compared to patients ≥65 years, younger patients were more likely to have died from CA (15.7% vs. 4.3%, p&lt;0.001) and other cardiac reasons (3.0% vs. 0.4%, p&lt;0.001). The majority of deaths were due to AMI, HF, and CA. We observed a significant decline in the proportion of deaths due to AMI in recent years with an increase in deaths due to HF.

Pathological aseptic calcification is the most common form of structural valvular degeneration (SVD), leading to premature failure of heart valve bioprostheses (BHVs). The processing methods used to obtain GA-fixed pericardium-based biomaterials determine the hemodynamic characteristics and durability of BHVs. This article presents a comparative study of the effects of several processing methods on the degree of damage to the ECM of GA-fixed pericardium-based biomaterials as well as on their biostability, biocompatibility, and resistance to calcification. Based on the assumption that preservation of the native ECM structure will enable the creation of calcinosis-resistant materials, this study provides a soft biomimetic approach for the manufacture of GA-fixed biomaterials using gentle decellularization and washing methods. It has been shown that the use of soft methods for preimplantation processing of materials, ensuring maximum preservation of the intactness of the pericardial ECM, radically increases the resistance of biomaterials to calcification. The data obtained are of interest for the development of new calcinosis-resistant biomaterials for the manufacture of BHVs.

Circulating extracellular microvesicles (cEVs) are characterised by presenting surface antigens of parental cells. Since their biogenesis involves the translocation of phosphatidylserine (PS) from the inner to the outer-leaflet of the plasma membrane, exposed PS has been considered as a recognition hallmark of cEVs. However, not all cEVs externalise PS. In this study we have phenotypically and quantitatively characterised cEVs by flow cytometry with special attention to the proportions of PS in chronic heart failure patients (cHF; n=119) and reference non-HF group (n=21). PS─-cEVs were predominantly found in both groups. Parental markers showed differential pattern depending on PS exposure. Endothelium-derived and connexin 43-rich cEVs were mainly PS─-cEVs and significantly increased in cHF. On the contrary, platelet-derived cEVs were mostly PS+ and were increased in non-HF. We observed similar levels of PS+- and PS─-cEVs in non-HF subjects when analysing immune cell-derived EVs, but there was a subset-specific difference in cHF patients. Indeed, those cEVs carrying CD45+, CD29+, CD11b+ and CD15+ were mainly PS+-cEVs, while those carrying CD14+, CD3+ and CD56+ were mainly PS─-cEVs. In conclusion, endothelial and red blood cells are stressed in cHF patients as detected by a high shedding of cEVs. Despite PS+-cEVs and PS─-cEVs represent two distinct cEV populations, their release and potential function as both biomarkers and shuttles for cell communication seem unrelated to PS content.

The wavelet spectral characteristics of three respiratory muscle signals (Scalenus (SC), Parasternal intercostal (IC) and Rectus abdominis (RA)) and one locomotor muscle Brachioradialis (BR) were analyzed in the time-frequency (T-F) domain during breath-holding (BH). Study was performed for an end-expiratory BH maneuver on twelve healthy, physically active, naive apneists (6 professional athletes; 6 recreational athletes, two in the post-COVID-19 period) using surface electromyography (sEMG). We observe individual effects dependent on muscle oxygenation and person’s fitness, consistent with the mechanism of motor unit (MU) recruitment and the transition of slow-twitch oxidative (type 1) to fast-twitch (oxidative) glycolytic (type 2) muscle fibers. Professional athletes had longer BH duration (BHD) and strong hypercapnic response on expiratory RA, which is activated abruptly at higher BHDs in a person-specific range below 250 Hz and dependent on BHD. This is in contrast with recreational athletes, who had strong hypoxic response on inspiratory IC, which is activated faster and gradually in the frequency range of 250-450 Hz (independent of the apneist and BHD). This pilot study preliminarily indicates that it is possible to non-invasively assess the physiological characteristics of skeletal muscles, especially oxygenation, and improve physical fitness tests by determining T-F features of elevated myoelectric IC and RA activity during BH.

The 22q11.2 deletion syndrome is a multisystemic disorder characterized by a marked variability of phenotypic features making the diagnosis challenging for clinicians. The wide spectrum of clinical manifestations includes congenital heart defects, most frequently conotruncal cardiac anomalies, thymic hypoplasia and predominating cellular immune deficiency, laryngeal developmental defects, midline anomalies with cleft palate and velar insufficiency, structural airway defects, facial dysmorphism, parathyroid and thyroid gland hormonal dysfunctions, speech delay, developmental delay, neurocognitive and psychiatric disorders. Significant progress has been made in understanding the complex molecular genetic etiology of the 22q11.2 deletion syndrome underpinning the heterogeneity of clinical manifestations. The deletion is caused by chromosomal rearrangements in meiosis and is mediated by non-allelic homologous recombination events between low copy repeats or segmental duplications in the 22q11.2 region. A range of genetic modifiers, environmental factors as well as the impact of hemizygosity on the remaining allele contribute to the intricate genotype-phenotype relationships. This comprehensive review has been aimed at highlighting the molecular genetic background of 22q11.2 deletion syndrome in correlation with a clinical multidisciplinary approach.

A critical aspect of coronary heart disease (CHD) care and secondary prevention is ensuring patients have access to evidence-based information. The purpose of this review is to summarise the guiding principles, content, context and timing of information and education that is beneficial for supporting people with CHD and potential communication strategies including digital interventions. We conducted a scoping review involving searching four databases (Web of Science, PubMed, CINAHL, Medline) for articles published from January 2000 to August 2022. Literature was identified through title and abstract screening by expert reviewers. Evidence was synthesised according to the review aims. Results demonstrated that information-sharing, decision-making, goal-setting, positivity and practicality are important aspects of secondary prevention and should be patient-centred and evidenced based with consideration of patient need and preference. Initiation and duration of education is highly variable between and within people, but hence communication and support should be regular and ongoing. In conclusion, text messaging programs, smartphone applications and wearable devices are examples of digital health strategies that facilitate education and support for patients with heart disease. There is no one size fits all approach that suits all patients at all stages and hence flexibility and a suite of resources and strategies is optimal.

Covid-19 pandemic affected outcome in ST-elevation myocardial infarction (STEMI) patients in majority of countries. We aimed to assess retrospectively admissions, treatments, complications and mortality of STEMI patients in the northeast of Slovenia in the first (March-May 2020) and the second wave (October-December 2020) of Covid-19 pandemic and compare them with the data from 2019 (March-October). Comparing 2019 and both waves of Covid-19 pandemic we observed nonsignificant differences in the number of STEMI admissions, in baseline characteristics, in the use of primary percutaneous coronary intervention (PCI), either within the first 3 (40.5%* vs 30.2% vs 25%*, *p = 0.074) and 6 hours, nonsignificant differences in TIMI III flow after primary PCI and in hospital complications, except for significant increase in hospital heart failure (23.3% vs 42%, p = 0.015) and mitral regurgitation in the second wave (10% vs 26.9%, p = 0.008) of the pandemic with nonsignificant increase in hospital mortality (8.9% vs 9.4% vs 13.6%) in both waves of the pandemic. We conclude, that with increased severity of Covid-19 pandemic in the second wave there was a longer delay to primary PCI in STEMI patients, resulting in significantly increased hospital heart failure and nonsignificantly increased hospital mortality

Decades of research identified numerous gene biomarkers of cardiac diseases whose restored sequence or/and expression level was hoped to recover the normal cardiac function. However, each human has unique and dynamic pathophysiological characteristics resulting from the unrepeatable combination of favoring factors such are: race, sex, age, medical history, diet, stress, exposure to toxins, habits etc. As such, no treatment fits everybody and finding personalized solutions is a top priority for medicine of 21st century. The Genomic Fabric Paradigm (GFP) provides the most theoretically possible comprehensive characterization of the transcriptome, its alterations in disease and recovery following a treatment. By attaching to each gene the independent average expression level, expression variation and expression coordination with each other gene, GFP delivers thousands times more information than the traditional analysis. This report presents the theoretical bases of the GFP and some applications to our microarray data from mouse models of post ischemic, and constant and intermittent hypoxia-induced heart failure. The GFP analyses revealed novel transcriptomic aspects of the gene expression control and networking under ischemic conditions. Through all-inclusive characterization of the transcriptome and the unrepeatable gene hierarchy in each condition, GFP is an essential avenue towards development of a truly personalized cardiogenomic therapy.

Turner syndrome (TS) is a chromosomal disorder that is caused by a missing or structurally ab-normal second sex chromosome. Subjects with TS are at an increased risk of developing intrauterine growth retardation, low birth weight, short stature, congenital heart diseases, infertility, obesity, dyslipidemia, hypertension, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular diseases (stroke and myocardial infarction). The underlying pathogenetic mechanism of TS is unknown. The assumption that X chromosome-linked gene haploinsufficiency is associated with the TS phenotype is questioned since such genes have not been identified. Thus, other pathogenic mechanisms have been suggested to explain this phenotype. Morphogenesis encompasses a series of events that includes cell division, the production of migratory precursors and their progeny, differentiation, programmed cell death, and integration into organs and systems. The precise control of the growth and differentiation of cells is essential for normal development. The cell cycle frequency and the number of proliferating cells are essential in cell growth. 45,X cells have a failure to proliferate at a normal rate, leading to a decreased cell number in a given tissue during organogenesis. A convergence of data indicates an association between a prolonged cell cycle and the phenotypical features in Turner syndrome. This review aims to examine old and new findings concerning the relationship between a prolonged cell cycle and TS phenotype. These studies reveal a diversity of phenotypic features in TS that could be explained by reduced cell proliferation. The implications of this hypothesis for our understanding of the TS phenotype and its pathogenesis are discussed. It is not surprising that 45,X monosomy leads to cellular growth pathway dysregulation with profound deleterious effects on both embryonic and later stages of development. The prolonged cell cycle could represent the beginning of the pathogenesis of TS, leading to a series of phenotypic consequences in embryonic/fetal, neonatal, pediatric, adolescence, and adulthood life.

miRNAs have recently attracted investigators' interest as regulators of valvular diseases pathogenesis, diagnostic biomarkers, and therapeutical targets. Evidence from in-vivo and in-vitro studies demonstrated stimulatory or inhibitory roles in mitral valve prolapse development, aortic leaflet fusion, and calcification pathways, specifically osteoblastic differentiation and transcription factors modulation. Tissue expression assessment and comparison between physiological and pathological phenotypes of different disease entities, including mitral valve prolapse and mitral chordae tendineae rupture, emerged as the best strategies to address miRNAs over or under-representation and thus, their impact on pathogeneses. In this review, we discuss the fundamental intra- and intercellular signals regulated by miRNAs leading to defects in mitral and aortic valves, congenital heart diseases, and the possible therapeutic strategies targeting them. These miRNAs inhibitors comprise of antisense oligonucleotides and sponge vectors. The miRNA mimics, miRNA expression vectors, and small molecules are instead possible practical strategies to increase specific miRNA activity. Advantages and technical limitations of these new drugs, including instability and complex pharmacokinetics, are also presented. Novel delivery strategies, such as nanoparticles and liposomes, are described to improve knowledge on future personalized treatment directions.

Heart disease is one of the most common diseases in middle-aged citizens. Among the vast number of heart diseases, coronary artery disease (CAD) is considered a common cardiovascular disease with a high death rate. The most popular tool for diagnosing CAD is the use of medical imaging, e.g., angiography. However, angiography is known for being costly and also associated with a number of side effects. Hence, the purpose of this study is to increase the accuracy of coronary heart disease diagnosis by selecting significant predictive features in order of their ranking. In this study, we propose an integrated method using machine learning. The machine learning methods of random trees (RTs), the decision tree of C5.0, support vector machine (SVM), the decision tree of Chi-squared automatic interaction detection (CHAID) are used in this study. The proposed method shows promising results and the study confirms that the RTs model outperforms other models.

SIRT6 is a NAD+ dependent enzyme and stress response protein that has sparked the curiosity of a plethora of researchers in different branches of the biomedical sciences. A unique member of the known Sirtuin family, SIRT6 has several different functions in several different molecular pathways related to DNA repair, glycolysis, gluconeogenesis, tumorigenesis, neurodegeneration, cardiac hypertrophic responses and so on. Only in recent times however did the potential usefulness of SIRT6 come to light as we learned more about its biochemical activity, regulation, biological roles and structure [1]. Even until very recently, SIRT6 was known more for chromatin signaling but being a nascent topic of study, more information has been ascertained and its potential involvement in major human diseases namely, diabetes, cancer, neurodegenerative diseases and heart disease has been demonstrated. It is pivotal to explore the mechanistic workings of SIRT6 since future research may hold the key to engendering strategies, involving SIRT6, that may have significant implications for human health and expand upon possible treatment options. In this review, we are primarily concerned with exploring the latest understanding of SIRT6 and how it can alter the course of several life-threatening diseases that cripple today’s society such as processes related to aging, cancer, neurodegenerative diseases, heart disease and diabetes. In addition, SIRT6 has shown to be involved in liver disease, inflammation and bone related issues but more emphasis is given to the former. Lastly, any recent promising pharmacological investigations and study of potential therapeutic targets are also delineated in this review.

Cardiac dynamics are traditionally linked to a left ventricle, right ventricle and septum morphology, a topography that differs from the heart’s 5-century-old anatomic description of containing a helix and circumferential wrap architectural configuration. Torrent Guasp’s helical ventricular myocardial band (HVMB) defines this anatomy and its structure, explains why the heart’s 6 dynamic actions of narrowing, shortening, lengthening, widening, twisting and uncoiling happen. This database raises questions about deductions behind “accepted cardiac mechanics”, and its functional aspects will challenge and overturn them. These suppositions include the LV, RV, and septum description, timing of mitral valve opening, isovolumic relaxation period, reasons for torsion/twisting, untwisting, reasons for longitudinal and circumferential strain, echocardiographic sub segmentation, resynchronization, RV function dynamics, and diastolic dysfunction’s cause and unrecognized septum impairment. Torrent Guasp’s revolutionary contributions may alter future understanding of the diagnosis and treatment of cardiac disease.

Many children on the autism spectrum engage in challenging behaviors, like aggression, due to difficulties communicating and regulating their stress. Identifying effective intervention strategies is often subjective and time-consuming. Utilizing unobservable internal physiological data to predict strategy effectiveness may help simplify this process for teachers and parents. This study examined whether heart rate data can predict strategy effectiveness. Teachers and coders from the research team recorded behavioral and heart rate data over three months for each participating student on the autism spectrum using the KeepCalm app, a platform that provides in-the-moment strategy suggestions based on heart rate and past behavioral data, across 226 instances of strategy interventions. A binary logistic regression was performed to assess whether heart rate reduction, time to return to heart rate baseline, and documented skills and challenging behaviors predicted strategy effectiveness. Results suggested that heart rate reduction may be a significant predictor, and supported the existing practice of using behavioral patterns as proxies for strategy effectiveness. Additional analyses indicate proactive strategies are more effective and are associated with greater reduction in heart rate, relative to reactive strategies. Further exploration of how internal physiological data can complement observable behaviors in assessing intervention strategy effectiveness is warranted given the novelty of our findings.

Background/Objectives: Prospective cohort studies are useful for studying how biomolecular status affects risk of adverse health outcomes. Less well known is that the longer the follow-up time, the lower the apparent effect due to “regression dilution.” Here we evaluate how follow-up time affects the relationship between serum 25-hydroxyvitamin D [25(OH)D] concen-tration and incidence of stroke and major cardiovascular events (MCEs). Methods: Findings re-garding the relative risk (RR) of stroke and MCEs with respect to serum 25(OH)D concentrations at baseline from prospective cohort studies were plotted against mean follow-up time. Fifteen studies from mainly European countries and the United States were used for stroke, with nine studies for MCEs. Linear regression analyses were performed for follow-up periods of up to 10 years. Results: For stroke, the linear regression fit for 1–10 years is RR = 0.34 + (0.065 × follow-up [years]), r = 0.84, adjusted r2 = 0.67, p <0.001. No significant change was evident for studies with follow-up periods of 10–20 years. For MCEs, the linear fir for 1–8.1 years is RR = 1.61 ‒ (0.074 × follow-up [years]), r = 0.75, adjusted r2 = 0.49, p = 0.03. Discussion: The shorter the follow-up period, the greater the apparent effect of vitamin D in reducing risk of stroke and MCEs. In addition, the apparent effect of higher 25(OH)D concentration found for the shortest follow-up time is more than twice as high as the estimate based on averaging the results for all studies without considering follow-up time. Mechanisms have been found to explain how higher serum 25(OH)D concentrations could reduce risk of stroke and MCEs. Randomized controlled trials have not shown that vitamin D supplementation significantly reduces risk of either stroke or MCE, probably because risk of both outcomes increases rapidly below 15 ng/mL (38 nmol/L) and it is difficult in Western developed countries to enroll enough participants with concentrations that low. Nonetheless, vitamin D’s role in reducing risk of stroke and MCE can be considered causal on the basis of an evaluation of the evidence with respect to Hill’s criteria for causality in a biological system. Conclusions: Serum 25(OH)D concentrations above 20 ng/mL are associated with significantly reduced risk of stroke and MCEs in an apparent causal manner. Raising serum 25(OH)D concentrations to >20 ng/mL should be recommended for everyone likely to be at risk for stroke or MCE and indeed in the general population.

Background: Systemic-to pulmonary collaterals (SPC) are common in congenital heart disease (CHD). Particularly in single ventricle anatomy and Fontan circulation, SPC can both complicate the postoperative course and lead to clinical deterioration in the long term. Treatment of SPC is controversial. The aim of our study was (1) to analyze retrospectively patients who underwent SPC embolization using Concerto™ Helix nylon-fibred microcoils (CHM) and (2) to describe the interventional technique. Methods: In this a single-center retrospective observational cohort study, we analyzed clinical and imaging data of all patients who underwent transcatheter embolization of SPC using CHM from January 2016 to December 2023. Results: In 38 consecutive patients (65.8 % male, median age 41 months, range 2 – 490), a total number of 141 CHM had been implanted into 64 SPC in 49 procedures. The majority were arterial SPC (n = 59/64) originating from the thoracic aorta or its branches; 5/64 were veno-venous SPC. Primary closure succeeded in all procedures. The CHM diameters ranged from 3 to 8 mm, with 5 mm being the most commonly used diameter. The mean coil / SPC ratio was 2.6 (range 1.3 – 5.3). CHM implantation was performed via 4 French sheaths. Both detachment and stable positioning was simple and safe. Neither non-target embolization nor coil migration occurred. One complication occurred with a minor vascular injury without clinical relevance. Conclusion: CHM are easy to use and appropriate for SPC embolization in all age groups, including infants, with a low complication rate. The coils are particularly suitable for closure of collaterals with small diameter or tortuous course.

Bicuspid Aortic valve Stenosis (BCAS) with an incidence of 3% of the world's population constitutes the most frequent Congenital Heart Disease whereas all other subtypes collectively constitute 1% of all life births. Most and the extreme severity spectrum of valvular Aortic Stenosis (VAS) in adulthood are cases of congenital bicuspid aortic valve. It seems that the congenital occurrence of the bicuspid aortic valve is a major prerequisite of the pathological calcifications and fibrosis seen in adults. Those progressive changes can't be explained by sole hemodynamic destructive forces but other factors inherent to the bicuspid valve tissue are also contributing. Therapeutic options of (VAS) are relatively stagnant and have been limited to invasive and surgical options. Prudent observation of the risk factors of some CHDs including BCAS was the epigenetic effect of planetary electromagnetic field on the delicate process of endothelial mesenchymal transformation (EndoMT). The incidence of BCAS is progressively increasing as we depart north from the equator to the north pole. A deeper understanding of the cellular and molecular mechanisms underlying EndoMT in congenital as well as acquired heart diseases is expected to open a new era in reversing heart disease in the human species. The potential to manipulate EndoMT and its signaling pathways or to reverse it with external electromagnetic power is an exciting therapeutic option for a wide array of congenital and acquired heart diseases including bicuspid aortic stenosis (BCAS) in the human species.

Bioactive peptides are sequences of amino acids, cut from the parent protein with en-zymes or high pressure processing that can impart a tertiary health benefit to the con-sumer that goes beyond basic human nutrition. This study explores mesopelagic fish in-cluding Maurolicus muelleri and Benthosema glaciale as sources of peptides with an-ti-inflammatory, heart health beneficial, antioxidant and other bioactivities. Bioactive peptides were generated post-catch using different enzymatic hydrolysis processes ap-plied to mesopelagic species caught from experimental cruises targeting these fish. Maurolicus muelleri and Benthosema glaciale were the dominant species processed. Bi-oactive hydrolysates included a Maurolicus muelleri Alcalase hydrolysate and a Maurolicus muelleri autolysis. Hundreds of peptide sequences were identified using mass spectrome-try from active hydrolysates. In silico analysis was used to rank identified peptide se-quences in terms of overall bioactivity using Peptide Ranker, anti-inflammatory activity using PrepAIP, ability to impart Umami flavours with Umami-MRNN and dipeptidyl peptidase IV inhibitory potential using AntiDMPpred . Thirty peptides were selected fol-lowing in silico analysis. Several of the selected peptides had sequence homology with peptides derived from other fish proteins including Atlantic salmon (peptide QCPLHR-PWAL) and thin-lipped mullet (peptide FDAFLPM). Seven peptides predicted to have an-ti-inflammatory, anti-type 2 diabetes or Umami potential using in silico strategies were chemically synthesized and their anti-inflammatory activities confirmed using in vitro bioassays with COX-1 and COX-2 enzymes. The peptide QCPLHRPWAL inhibited COX-1 and COX-2 by 82.90% (+/-0.54) and 53.84% respectively and had a selectivity index greater than 10. This peptide warrant further research as a novel anti-inflammatory/pain relief peptide. Other bioactivities associated with DPP-IV inhibition and Umami flavours de-velopment are discussed. Identified peptides offer potential for use in functional foods or topical agents to prevent pain and inflammation associated with diseases like psoriasis, arthritis and inflammatory bowel disease, however further research in vivo is required.

(1) Background: The proportion of fully mechanized harvesting systems in Austria is constantly increasing especially because of the technological development of the machines, which allows them to drive on increasingly steep terrain. This leads to additional challenges and potential hazards for the operators, which may also cause higher stress levels. The purpose of this study is to develop and debate a new set of methodologies for determining time and space resolved psychophysiology data to analyze stressful and non-stressful work situations for harvester and forwarder operators; (2) Methods: we suggest a study protocol to analyze a) tasks performed by the driver, b) environmental factors, like slope gradient, c) the psychophysiological response of experts during these tasks, and d) evaluate the worker´s subjective stress and fatigue before and after a harvest operation. (3) Results: Within this manuscript we present a study protocol based on quantitative and qualitative methods, like time and space resolved psychophysiology, questionnaires, qualitative interviews, as well as video and sensor-based analysis of environmental and machine data. The first results from real measurements of a forwarder driver are presented; (4) Conclusions: This multimodal research protocol serves to explore the relationship between stress, fatigue, and performed tasks. Through our quantitative and qualitative methodology, researchers can improve the health and safety of forest workers at work, improve their productivity and reduce damage to remaining trees.

Overhydration (OH) is a prevalent medical problem occuring in patients with kidney failure, but a specific marker has still not been found. Currently, clinicians employ techniques such as bioimpedance spectroscopy (BIS), ultrasound (US) markers of fluid overload or markers of heart and kidney function such as NT-pro-BNP, GFR or creatinine levels. New serum markers, including but not limited to Ca-125, Galectin-3 (Gal-3), Adrenomedullin (AMD) and Urocortin-2 (UCN-2), are presently under research, displaying promising results. The necessity to ascertain a more precise marker of overhydration is urgent mainly because physical examination is exceptionally imprecise. Signs and symptoms of fluid overload, like edema or gradual increase of body mass, are not always present, notably in patients with chronic kidney disease. This review paper summarizes actual knowledge of a patient's hydration status estimation, focusing specifically on kidney diseases.

Heart failure with reduced ejection fraction (HFrEF) is considered a major healthcare problem with frequent decompensations, high hospitalization and mortality rates. In severe heart failure (HF), the symptoms are refractory to medical treatment and require advanced therapeutic strategies. Early recognition of HF sub- and decompensation is the cornerstone of the timely treatment intensification and, therefore, improvement of the prognosis. Echocardiography is the gold standard for the assessment of systolic and diastolic functions. It allows to obtain accurate and non-invasive measurements of the ventricular function in HF. In severely compromised HF patients, advanced cardiovascular ultrasound modalities may provide a better assessment of intracardiac hemodynamic changes and subclinical congestion. Particularly, cardiovascular and lung ultrasound allow to make a more accurate diagnosis of subclinical congestion in HFrEF. The aim of this review is to summarize the advantages and limitations of currently available ultrasound modalities in the ambulatory monitoring of patients with HFrEF.

This review is devoted to present the history of CARDIOSIM© software simulator platform, which was developed in Italy to simulate the human cardiovascular and respiratory system. The first version of CARDIOSIM© was developed at the Institute of Biomedical Technologies of the National Research Council in Rome. The first platform version published in 1991 ran on PC with disk operating system (MS-DOS) and was developed using the Turbo Basic language. The last version runs on PC with Microsoft Windows 10 operating system; it is implemented in Visual Basic and C++ languages. The platform has a modular structure consisting of seven different general sections, which can be assembled to reproduce different pathophysiological conditions. The software simulator can reproduce the most important circulatory phenomena in terms of pressure and volume relationships. It represents the whole circulation using a lumped-parameter model and enables the simulation of different cardiovascular conditions according to Starling’s law of the heart and a modified time-varying elastance model. Different mechanical ventilatory and circulatory devices have been implemented in the platform including thoracic artificial lung, ECMO, IABP, pulsatile and continuous right and left ventricular assist devices, biventricular pacemaker and biventricular assist devices. CARDIOSIM© is used in clinical and educational environment.

A large body of evidence reports about the positive effects of physical activity in pathophysiological conditions associated with aging. Physical exercise, alone or in combination with other medical therapies, unquestionably causes reduction of symptoms in chronic non-transmissible diseases often leading to significant amelioration or complete healing. The molecular basis of this exciting outcome, however, remain largely obscure. Epigenetics, exploring at the interface between environmental signals and the remodelling of chromatin structure, promises to shed light on this intriguing matter possibly contributing to the identification of novel therapeutic targets. In this review, we shall focalize on the role of sirtuins (Sirts) a class III histone deacetylases (HDACs) which function has been frequently associated, often with a controversial role, to the pathogenesis of aging-associated pathophysiological conditions including cancer, cardiovascular, muscular, neurodegenerative, bones and respiratory diseases. Numerous studies, in fact, demonstrate that Sirt-dependent pathways are activated upon physical and cognitive exercises linking mitochondrial function, DNA structure remodelling and gene expression regulation to designed medical therapies leading to tangible beneficial outcomes. However, in similar conditions, other studies assign to sirtuins a negative pathophysiological role. In spite of this controversial effect, it is doubtless that studying sirtuins in chronic diseases might lead to an unprecedented improvement of life quality in the elderly.

Myocardial infarction, more commonly known as heart attack, is a huge health problem around the world. It is a result of inadequate blood supply to certain parts of the heart and death of heart muscle cells in that region. Although it has been around for a long time, newer and newer ways of probing myocardial infarction is being followed. Bioinformatics and Systems Biology are relatively recent fields to try to give new insights into myocardial infarction. Following the footsteps of others, this in silico study has tried to chime in on the investigation into myocardial infarction. The study began with the gene expression omnibus dataset uploaded to the NCBI from a whole-genome gene expression analysis carried out at Mayo Clinic in Rochester, Minnesota. From the dataset, differentially expressed genes following first-time myocardial infarction were identified and classified into up-regulated and down-regulated ones. Gene Set Enrichment Analysis (GSEA) was carried out on the up-regulated genes which were statistically significant and corresponded with the NCBI generated annotations. Protein-Protein Interaction Network for these genes was constructed. GSEA revealed 5 transcription factors, 5 microRNAs and 3 pathways significantly associated with them. From the Protein-Protein Interaction Network, 6 key proteins (hub nodes) have been identified. These 6 proteins may open a new window of opportunity for the discovery/design of new drugs for mitigating the damage caused by myocardial infarction.

Depression is the commonest mental disorder worldwide. Both antidepressants and psychotherapy are effective in treating depression, but response to these treatments is often incomplete. Yoga-based interventions (YBIs) have emerged as a promising adjunctive treatment for depression. Recent research has attempted to identify the biological mechanisms associated with the antidepressant actions of YBIs. In this scoping review, conducted according to the PRISMA-ScR guidelines, the PubMed and Scopus databases were searched to retrieve research on biomarkers of response to YBIs in patients with depression. Eleven studies were included in the review. Based on these studies, YBIs may improve depression through beneficial effects on systemic inflammation, stress axis regulation, cardiac autonomic functioning, and possibly reductions in oxidative stress-related cellular damage. Increases in brain-derived neurotrophic factor (BDNF) may represent a final common pathway upon which these processes converge. Though these results are theoretically plausible, they should be interpreted with caution due to certain methodological limitations in the existing research. Replication of these results and improvements in study methodology, and the evaluation of other biomarkers relevant to the pathophysiology of depression, could further elucidate the mechanism of action of YBIs in this disorder, and identify which patients would benefit most from this treatment approach.

Many countries are facing the advent of super-aging societies, where sarcopenia and frailty will become emerging problems. Elderly people suffer from various diseases, such as diabetes, heart failure, chronic kidney disease and dementia. The prevalence of comorbidities is a major problem in countries with aged populations. Underlying diseases, such as diabetes, heart failure, chronic kidney disease and also dementia are associated with sarcopenia and frailty, and they are frequent causes of falls, fractures, and a decline in activities of daily living. Fractures in the elderly people are associated with bone fragility, which is influenced by diabetes and chronic kidney disease. Nutritional support for chronic disease patients and sarcopenic individuals with adequate energy and protein intake, vitamin D supplementation, blood-glucose-level management for individuals with diabetes, obesity prevention, nutritional education for healthy individuals, and the enlightenment of society could be crucial to solving the problems in super-aging societies.

Many countries are facing the advent of super-aging societies, where sarcopenia and frailty will become emerging problems. Elderly people suffer from various diseases, such as diabetes, heart failure, chronic kidney disease and dementia. The prevalence of comorbidities is a major problem in countries with aged populations. Underlying diseases, such as diabetes, heart failure, chronic kidney disease and also dementia are associated with sarcopenia and frailty, and they are frequent causes of falls, fractures, and a decline in ADL. Fractures in the elderly people are associated with bone fragility. Diabetes and chronic kidney disease are associated with bone fragility. Nutritional support for chronic disease patients and sarcopenic individuals with adequate energy and protein intake, vitamin D supplementation, blood-glucose-level management for individuals with diabetes, obesity prevention, nutritional education for healthy individuals, and the enlightenment of society could be crucial to solving the problems in super-aging societies.

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.

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

Background: our purpose is to assess the effectiveness and safety of sacubitril/valsartan (SV) in “real-world” patients with heart failure and reduced ejection fraction (HFrEF), including a broader spectrum of patients than those in clinical trials and evaluating variables not previously described in the literature. Methods: real-world study in HFrEF patients (N:204), both in and out-patients, who started SV between October 2017 and December 2018. We performed a prospective analysis with a 12-month follow-up. The study outcomes were effectiveness and safety, measured by individual parameters and combined endpoints, comparing the pre and post practice periods. Results: at the end of follow-up, an improvement of left ventricle ejection fraction (LVEF): 29.8% vs 33.7; p<0.0001, a decrease in NT-proBNP levels (3928 pg/mL vs 2902 pg/mL; p=0.012), number of hospital admissions (141 vs 35; p<0.0001) and percentage of patients with implantable cardioverter defibrillator (ICD) indication (79.9% vs 49.5%; p<0.0001) were observed. Of our population, 81.3% met a combined efficacy endpoint (defined by increase of LVEF, reduction of hospital admission or improvement in functional class). No differences were observed in parameters regarding safety. Conclusions: Sacubitril/valsartan has brought about a revolution in the therapeutic management of HFrEF patients and its use may raise questions about what is considered "optimal medical therapy" prior to implantation of cardiac devices.