In recent years, there has been a rise in the prevalence of autism spectrum disorder (ASD). The diagnosis of ASD requires behavioral observation and standardized testing completed by highly trained experts. Early intervention for ASD can begin as early as 1-2 years of age, but ASD diagnoses are not typically made until ages 2-5 years, thus delaying the start of intervention. There is an urgent need for non-invasive biomarkers to detect ASD in infancy. While previous research using physiological recordings has focused on brain-based biomarkers of ASD, this study investigated the potential of electrocardiogram (ECG) recordings as an ASD biomarker in 3-6-month-old infants. We recorded heart activity of infants at typical and elevated familial likelihood for ASD during naturalistic interactions with objects and caregivers. After obtaining the ECG signals, features such as heart rate variability (HRV) and sympathetic and parasympathetic activities were extracted from them. Then we evaluated the effectiveness of multiple machine learning classifiers for the classification of ASD likelihood. Our findings support our hypothesis that infant ECG signals contain a significant amount of information about ASD familial likelihood. Among the various machine learning algorithms tested, XGBoost performed best according to sensitivity (0.76±0.12), f1-score (0.75±0.12), precision (0.79±0. 12), classification accuracy (0.77±0.12, p-value = 0.01) and AUC (0.76±0.12, p-value = 0.02). These results suggest that ECG signals contains relevant information about the likelihood of an infant to develop ASD. Future studies should consider the potential of information contained in ECG, and other indices of autonomic control, for the development of biomarkers of ASD in infancy.

Heart failure (HF) diagnosis, phenotyping, prognosis, and treatment decisions are all based on the left ventricular ejection fraction (EF). Heart failure with mid-range EF (HFmrEF) is a third EF category for heart failure with an EF between 40 and 49 percent. Comparatively, heart failure with preserved EF or reduced EF has been largely unexplored. 10–25% of patients with HF have HFmrEF. Although HFmrEF has an intermediate clinical profile, it is more similar to HF with reduced EF, particularly because these patients have a high incidence of ischaemic heart disease. Heart failure with preserved EF has a lower risk of cardiovascular events than heart failure with reduced EF, which is milder. HFmrEF and HF with preserved EF patients have a similar or higher risk of non-cardiovascular adverse events than patients with HF with reduced EF. There is still a great deal of mystery surrounding HFmrEF. The purpose of this review is to describe the major pathophysiology of HFmrEF and its similarities and differences with the other two types of EF. It is the purpose of this paper to present a comprehensive overview of the currently available evidence in support of the pathophysiology of patients with HFmrEF. Further investigation of the pathophysiology, treatment, and prognosis of this condition will be needed in the future in order to better understand it.

Although renal denervation (RDN) protects against hypertension, hypertrophy, and heart failure (HF), it is not clear whether RDN preserves ejection fraction (EF) during heart failure (HFpEF). To test this hypothesis, we simulated chronic congestive cardiopulmonary heart failure (CHF) by creating aorta-vena cava fistula (AVF) in C57BL/6J wild type (WT) mice. There are four ways to create experimental CHF: (1) myocardial infarction (MI) which is basically ligating coronary by instrumenting and injuring the heart; (2) trans-aortic constriction (TAC), although it mimics systematic hypertension but TAC again constricts aorta on top of the heart and exposes the heart; (3) acquired CHF such as by dietary factors, diabetes/salt diets etc. but it is multifactorial, and finally (4) AVF, which is the only one wherein AVF is created ~1cm below the kidney where the aorta and vena cava share the common middle-wall. By creating fistula, the red blood enters vena cava without an injury to the heart. This model mimics CHF such as during aging where with age the preload keeps increasing than the aging heart can pump out due to the weakened cardiac myocytes. This also involves the right ventricle to lung to left ventricle flow, thus creating congestion. The heart in AVF goes to transition from preserved to reduced EF (i.e., HFpEF to HFrEF). In fact, there are more models of volume overload, such as the pacing-induced and mitral valve regurgitation but these are also injurious models. Our lab is one of the original labs in creating and studying the AVF phenotype. The RDN was created by treating the cleaned bilateral renal artery. After 6 weeks, blood, heart, and renal samples were analyzed for exosome, cardiac regeneration markers and renal cortex proteinases. Cardiac function was analyzed by echocardiogram (ECHO). Fibrosis was analyzed with trichrome staining. The results suggested that there was robust increase in exosomes’ level in AVF blood, suggesting compensatory systemic response during AVF-CHF. During AVF there was no change in cardiac eNOS, Wnt1 and β-catenin, however; during RDN there was robust increase in eNOS, Wnt1 and β-catenin compared to the sham group. As expected in HFpEF there was perivascular fibrosis, hypertrophy and pEF. Interestingly, increased levels of eNOS suggested that despite fibrosis, the NO generation was higher that most likely contributed to pEF during HF. The RDN intervention revealed an increase in renal cortical caspase 8 and a decrease in caspase 9. Since caspase 8 is protective and caspase 9 is apoptotic, we suggest that RDN protects against renal stresses, and apoptosis. Our findings also suggest that RDN is cardioprotective during HFpEF via the preservation of eNOS and accompanied endocardial-endothelial function.

Bright morning light (BML) entrains the body clock, modulates circadian rhythm, and improves sleep-wake disturbances. However, its impact on the autonomic nervous system (ANS) at night remains unclear. Hence, we investigated the effects of BML exposure on activities of the parasympathetic nervous system (PSNS) and sympathetic nervous system (SNS) at night. This non-randomized controlled pilot study included participants ≥60 years, diagnosed with a type of dementia or cognitive disorder. We excluded participants with pacemakers. The treatment group received 2500 lx BML, whereas the control group received approximately 200 lx of general lighting. We measured the heart rate variability to quantify ANS activity. The treatment group displayed significantly increased high-frequency (HF) power (Roy's largest root=2.44; P<.01) and insignificantly decreased normalized low-frequency (LF%) power. The corresponding low-frequency/high-frequency ratio (LF/HF), insignificant decrease, and cognitive function were correlated with PSNS activity (Roy's largest root=3.92; P<.01), which is effective for moderate dementia. BML exposure reduced SNS activity and enhanced PSNS activity at night, which consequently affected cognitive function. Furthermore, the light washout intervention markedly increased SNS activity at night. BML therapy may be a useful clinical tool for alleviating the deterioration of cognitive function.

Advancements in genomics, bioinformatics and genome editing have uncovered new dimensions in gene regulation. Post-transcriptional modifications by the alternative splicing of mRNA transcripts are critical regulatory mechanisms of mammalian gene expression. In the heart, there is an expanding interest in elucidating the role of alternative splicing in transcriptome regulation. Substantial efforts have been directed towards investigating this process in heart development and failure. However, few studies have shed light on alternative splicing products and their dysregulation in congenital heart defects (CHDs). While elegant reports have shown the crucial roles of RNA binding proteins (RBPs) in orchestrating splicing transitions during heart development and failure, the impact of RBPs dysregulation or genetic variation on CHDs has not been fully addressed. Herein, we review the current understanding of alternative splicing and RBPs’ roles in heart development and CHDs and discuss the impacts of perinatal splicing transition and its dysregulation in CHDs. We further summarize discoveries made of causal splicing variants in key transcription factors that have been implicated in CHDs. Improved understanding of the roles of alternative splicing in heart development and CHDs may potentially inform novel preventive and therapeutic advancements for newborn infants with CHDs.

Background: Congestive heart failure is the inability to pump blood throughout the body which causes the walls to be unable to pump adequately. Purpose: This study aimed to ascertain the effect of a contrast bath with a 30 º elevation on the reduction of edema in congestive heart failure patients at Ulin General Hospital, Banjarmasin. Methods: The design of this study was quasi-experimental with an unequal control group design. The population is patients with congestive heart failure, and the sample used is successive sampling. 34 respondents were divided into two groups, 17 respondents in the intervention group and 17 in the control group. Results: The Mann-Whitney result value P = 0.027 (P < 0.05) represented a significant reduction in Bath contrast edema with 30º feet elevation in the intervention group and control group patients with congestive heart failure. Conclusion: Based on the results of this study, it is expected to be able to apply contrast showers with an elevation of 30 º in nursing services to reduce the degree of edema in congestive heart failure patients.

This single-blind and cross-sectional study evaluated the role of Rho-kinase (ROCK) as a biomarker of the cardiovascular remodelling process assessed by echocardiography in competitive long-distance runners (LDR) during the training period before a marathon race. Thirty-six healthy male LDR (37.0±5.3 years; 174.0±7.0 height; BMI: 23.8±2.8; VO2-peak: 56.5±7.3 mL·kg-1·min-1) were separated into two groups according to previous training level: high-training (HT, n=16) ≥100 km·week-1 and low-training (LT, n=20) ≥70 and &lt;100 km·week-1. Also, twenty-one healthy nonactive subjects were included as a control group (CTR). A transthoracic echocardiography was performed and ROCK activity levels in circulating leukocytes were measured at rest (48-hr without exercising) the week before the race. HT group showed higher left ventricular mass index (LVMi) and left atrial volume index (LAVi) than other groups (p&lt;0.05, for both), also higher levels of ROCK activity were found in LDR (HT=6.17±1.41 vs CTR=1.64±0.66 (p&lt;0.01); vs LT=2.74±0.84; (p&lt;0.05)). In LDR a direct correlation between ROCK activity levels and LVMi (r=0.83; p&lt;0.001), and LAVi (r=0.70; p&lt;0.001) were found. In conclusion, in male competitive long-distance runners, the load of exercise implicated in marathon training is associated with ROCK activity levels and the left cardiac remodelling process assessed by echocardiography.

Patients with heart failure have difficulty in self-care management, as daily monitoring and recognizing symptoms do not readily triggers an action to avoid hospital admissions. The purpose of this study was to understand the impact of a nurse-led complex intervention on symptom recognition and fluid restriction. A latent growth model was designed to estimate self-care management and quality of life changes on patients with heart failure and assessed by a pilot study, for three months, to sixty-three patients (33 control, 30 intervention). Patients in the control group had a higher risk of hospitalisation (IRR 11.36; p<.001) and emergency admission (IRR 4.24; p<.001) at three-months follow-up. Analysis of the time scores demonstrated that the intervention group had a clear improvement in self-care behaviours (βSlope. Assignment_group=-.881; p<.001) and in the quality of life (βSlope. Assignment_group=1.739; p<.001). This study supports that a nurse-led program on symptom recognition and fluid restriction can have a positive impact on self-care behaviours and quality of life in patients with heart failure.

Alcohol consumption is now common practice worldwide, and functional brain networks are beginning to reveal the complex interactions observed with alcohol consumption and abstinence. The autonomic nervous system (ANS) has a well-documented relationship with alcohol use, and a growing body of research is finding links between the ANS and functional brain networks. This study recruited everyday drinkers in an effort to uncover the relationship between alcohol abstinence, ANS function, and whole brain functional brain networks. Participants (n=29), 24-60 years-of-age, consumed moderate levels of alcohol regularly (males 2.4 (±0.26) drinks/day, females 2.3 (±0.96) drinks/day). ANS function, specifically cardiac vagal tone, was assessed using the Porges-Bohrer method for calculating respiratory sinus arrhythmia (PBRSA). Functional brain networks were generated from resting-state MRI scans obtained following 3-day periods of typical consumption and abstinence. A multi-task mixed-effects regression model determined the influences of HRV and drinking state on functional network connectivity. Results showed differences in the relationship between the strength of network connections and clustering coefficients across drinking states, moderated by PBRSA. Increases in connection strength between highly clustered nodes during abstinence as PBRSA increases demonstrates a greater possible range of topological configurations at high PBRSA values. This novel finding begins to shed light on the complex interactions between typical alcohol abstinence and physiological responses of the central and autonomic nervous system.

Studies showed that introversion is the strongest personality trait related to perceived social isolation (loneliness), which can predict various complications beyond objective isolation such as living alone. Lonely individuals are more likely resort to social media for instantaneous comfort, but it is not a perpetual solution. Largely negative implications including poorer interpersonal relationship and depression were reported due to excessive social media usage. Conversational task is an established intervention to improve verbal communication, cognitive and behavioral adaptation among lonely individuals. Despite that behavioral benefits have been reported, it is unclear if they are accompanied by objective benefits underlying physiological changes. Here, we investigate the physiological signals from 28 healthy individuals during a conversational task. Participants were ranked by trait extraversion, where greater introversion is associated with increased susceptibility to perceived social isolation as compared to participants with greater extraversion as controls. We found that introverts had a greater tendency to be neurotic, and these participants also exhibited significant differences in task-related electrodermal activity (EDA), heart rate (HR) and HR variability (HRV) as compared to controls. Notably, resting state HRV among individuals susceptible to perceived loneliness was below the healthy thresholds established in literature. Conversational task with a stranger significantly increased HRV among individuals susceptible to isolation up to levels as seen in controls. Since HRV is also elevated by physical exercise and administration of oxytocin hormone (one form of therapy for behavioral isolation), conversational therapy among introverts could potentially confer physiological benefits to ameliorate social isolation and loneliness. Our findings also suggest that although the recent pandemic have changed how people are interacting typically, we should maintain a healthy dose of social interaction innovatively.

Patients with heart failure have difficulty in self-care management, as daily monitoring and recognizing symptoms do not readily trigger an action to avoid hospital admissions. The purpose of this study was to understand the impact of a nurse-led complex intervention on symptom recognition and fluid restriction. A latent growth model was designed to estimate self-care management and quality of life changes on patients with heart failure and assessed by a pilot study, for three months, to sixty-three patients (33 control, 30 intervention). Patients in the control group had a higher risk of hospitalisation (IRR 11.36; p<.001) and emergency admission (IRR 4.24; p<.001) at three-months follow-up. Analysis of the time scores demonstrated that the intervention group had a clear improvement in self-care behaviours (βSlope. Assign-ment_group=-.881; p<.001) and in the quality of life (βSlope. Assignment_group=1.739; p<.001). This study supports that a nurse-led program on symptom recognition and fluid restriction can have a positive impact on self-care behaviours and quality of life in patients with heart failure.

Background - Physiological helical flow in the ascending aorta has been well documented in the last two decades, accompanied by discussions on possible physiological benefits of such axial swirl. Recent 4D-MRI studies on healthy volunteers have shown indication of early generation of helical flow, early in the systole and already close to the valve plane. Objectives - Firstly, the aim of the study is to investigate the hypothesis of premature swirl existence in the ventricular outflow tract leading to already helical flow in the valve plane, and second to investigate the possible impact of two different mechanical valves design on the preservation of this early helical flow and its subsequent hemodynamic consequences. Methods - We use a pulse duplicator with an aortic arch and High Speed Particle Image Velocimetry to document the flow evolution in the systolic cycle. The pulse-duplicator is modified with a swirl-generating insert to generate early helical flow in the valve plane. Special focus is laid on the interaction of such helical flow with different designs of mechanical prosthetic heart valves, comparing a classical bileaflet mechanical heart valve, the St Jude Medical Regent valve (SJM Regent BMHV) with the Triflo trileaflet mechanical heart valve T2B version (Triflo TMHV). Results – When the swirl-generator is inserted, a vortex is generated in the core flow demonstrating early helical flow in the valve plane, similar as observed in the recent 4-D-MRI study taken for comparison. For the Triflo trileaflet valve, the early helical flow is not obstructed in the central orifice, similar as in the case of the natural valve. Conservation of angular momentum leads to radial expansion of the core flow and flattening of the axial flow profile downstream in the arch. Furthermore, the early helical flow helps to overcome separation at the outer and inner curvature. In contrast, the two parallel leaflets for the bileaflet valve impose a flow straightener effect, annihilating the angular momentum with negative impact on kinetic energy of the flow. Conclusion - The results imply better hemodynamics for the Triflo trileaflet valve based on hydrodynamic arguments under the discussed hypothesis. In addition, it makes the Triflo valve a better candidate for replacements in patients with pathological generation of nonaxial velocity in ventricle outflow tract.

In this paper, we aim to assess the electric current parameters and report the analysis of the associated degree of ventricular recovery during left ventricular assist device (LVAD) support. An assumption was made there is a linear relationship between ventricular recovery degree and the pump electric current pulsatility index (PI). The experimental study was carried out using the ViVitro Pulse Duplicator System with Sputnik 1 LVAD connected. Cardiac output (CO) and cardiac power output (CPO) were used as a measure of ventricular recovery degree. Different heart rates (HR) (59, 73, 86 bpm) and pump speeds (7600–8400 rpm in 200 rpm steps) were investigated. Ventricular stroke volumes in the range of 30–80 ml for each heart rate at certain pump speed were used. The obtained relationships of CO and CPO vs. PI was linear as the coefficients of determination for each regression curve were more than 0.8. CO vs. PI: R2=0.9218; 0.9271; 0.9172 and CPO vs. PI: R2=0.8517; 0.841; 0.8244 for HR=59 bpm; 73 bpm; 86 bpm, respectively. Study findings suggest that adequate interpretation of parameters could potentially serve as a valuable clinical tool to assess ventricular recovery based on LVAD infrastructure without requiring any special hemodynamic assessment.

Athletes are exposed to high-intensity loads to promote athletic performance, however without appropriate evaluation for its effects. This study investigates the effects of four types of exhaustion exercises on Heart Rate Variability (HRV) and Poincaré features as markers of central fatigue; Creatine Kinase (CK) and blood lactate concentrations ([LA-]b) as biomarkers of peripheral fatigue. To achieve this purpose, ten healthy volunteers were exposed to exhaustive exercise using isotonic-, isometric-, aerobic-, and anaerobic-fatigue protocols. HRV Poincaré features, standard deviation of instantaneous beat-to-beat R-R interval variability (SD1) and standard deviation of continuous long-term R-R interval variability (SD2) variables were collected. Central fatigue was tested through the sympathetic stress index (SS) and the sympathetic and parasympathetic index (SS/SD1). Blood samples were collected at the beginning and at the end of the exercises to determine CK and [LA-]b. The SD1 decreased in each exercise protocol, while the SS and SS/SD1 increased. [LA-]b and CK increased at the end of each protocol and correlated with SD1 and SS/SD1. HRV, CK, and [LA^-]_b are acute markers to detect, both central and peripheral fatigue; sensitive to the type, duration, and intensity of exercise, being HRV a novel noninvasive marker, simple and useful for sports coaches and athletes.

Rapid diagnosis of acute myocardial infarction is critical for intervention and treatment to decrease morbidity and mortality. For this reasons, this study aimed to design a sensitive biosensor for cardiac troponin I (cTnI) for early prediction and intervention. The sensor was designed from golden plate immobilized with anti- cTnI antibody conjugated with horseradish peroxidase (HRP) enzyme. The rate of degradation of H2O2 is directly related to serum cTnI level. Serum cTnI level was quantified from 3 studied groups including; healthy subjects and patients with ischemic heart (IHD) diseases and myocardial infarction (MI) by ELISA and biosensor techniques to achieve the improved sensitivity of the biosensor. It was found that cTnI levels in healthy subjects ranged from 8-13 ng/dl and in patients with IHD ranged from 20 - 41 ng/dl and MI range from 57- 180 ng/dl. The sensitivity of biosensor was ranged from 85-95% compared with ELISA technique. The developed biosensor is promising in ICU hospitals for early diagnosis and prevent complications of the stroke. It is recommended to apply this biosensor in the large scale of patients with different stages of the cardiac disease.

Objectives: 1) To describe the cardiovascular health of the construction workers in Hong Kong, 2) to examine the demographic differences in cardiovascular health, and 3) to examine the association between modifiable lifestyle behaviors and cardiovascular conditions. Methods: 626 registered construction workers were included in the analysis. Blood chemistry, blood pressure, weight and height were measured. Face-to-face questionnaire interview was conducted. T-tests and One-way ANOVAs were used to compare the cardiovascular health score, cardiovascular outcomes, and lifestyle behaviors by demographic characteristics. Logistic regressions were performed to assess the cardiovascular outcomes by lifestyle behaviors. Results: Two-thirds of the construction workers failed to achieve three out of the seven “ideal” cardiovascular health indicators. The younger, more educated, and female subjects had better cardiovascular health scores than their counterparts. The ideal fish and seafood consumption was associated with 1) ideal weight status and 2) ideal cholesterol level, whereas less soft drink consumption was associated with ideal cholesterol level. Conclusions: The findings highlighted the importance of promoting cardiovascular health in the construction industry. This study provided insights for future interventions, which should include increasing fish and seafood intake, decreasing soft drink consumption, and enhancing the health literacy amongst older, less educated, and male construction workers.

The purpose of the present study was to determine the relationship between healthy lifestyle behaviors, physical fitness and coronary risk factors in university students. 320 male and female (n_m:171; n_f:149) students from a university participated in this study voluntarily. For the determination of body composition and Body Mass Indexes (BMI), subjects’ height, body weight, and skinfold thickness were taken and body fat percentage (%Fat) was determined. Healthy lifestyle behaviors were determined using the healthy lifestyle behaviors questionnaire. Indicators of physical fitness included flexibility (sit-up) (F), muscle strength and endurance (isometric knee (KS), back strength (BS) and a total of shuttle (TS), sprint performance, BMI, and body fat percentage (%fat). Coronary heart disease risk factors included mean arterial blood pressure (systolic (SBP) and diastolic (DBP)), fasting blood levels of triglycerides (TG), total cholesterol (TC), hematocrit (HT), and hemoglobin (HM). Results indicated subjects have normal body mass index, body fat percentage, SBP, DBP, TG, TCF, BS, KS. The results of the Pearson Product Moment Correlation Analysis, indicated that SBP, DBP, TG, TCF, BS, KS for male and female was significantly correlated with flexibility (sit-up) (F), muscle strength and endurance (isometric knee (KS), back strength (BS) and total of shuttle (TS)), sprint performance. (p<0.01; p<0.05), In conclusion, the findings of the present study indicated that physical fitness and healthy lifestyle behaviors play a determinant role in coronary heart disease risk factors for male and female students from a university.

Heart failure with preserved ejection fraction (HFpEF) is a multifariousness syndrome, account-ing for over half of heart failure (HF) patients receiving clinical treatment. The prevalence of HFpEF is rapidly increasing in the coming decades as the global population ages. It is becoming clearer that HFpEF has a lot of different causes, which makes it challenging to find effective treatments. Currently, there are no proven treatments for people with deteriorating HF, or HFpEF. Although the pathophysiologic foundations of HFpEF are complex, excessive reactive oxygen species (ROS) generation and increased oxidative stress caused by mitochondrial dys-function seem to play a critical role in the pathogenesis of HFpEF. Emerging evidence from an-imal models and human myocardial tissues from failed hearts shows that mitochondrial aberra-tions cause a marked increase in mitochondrial ROS (mtROS) production and oxidative stress. Furthermore, studies have reported that common HF medications like beta blockers, angioten-sin receptor blockers, angiotensin-converting enzyme inhibitors, and mineralocorticoid receptor antagonists indirectly reduce the production of mtROS. Despite the harmful effects of ROS on cardiac remodelling, maintaining mitochondrial homeostasis and cardiac functions requires small amounts of ROS. In this review, we will provide an overview and discussion of recent findings on mtROS production, its threshold for imbalance, and the subsequent dysfunction that leads to related cardiac and systemic phenotypes in the context of HFpEF. We will also focus on newly discovered cellular and molecular mechanisms underlying ROS dysregulation, current therapeutic options, and future perspectives for treating HFpEF by targeting mtROS and associ-ated signal molecules.

The purpose of this paper is to review the involvement of mitochondria in the actions of nitroglycerin (glycerol trinitrate -GTN) and the redox disturbances underlying diseases it treats. The paper begins by explaining complex I as the initial site of formation of superoxide and the process whereby it leads to the development of glutathione dependent tolerance. Next, the paper describes new formulations for preventing tolerance. The paper ends by illustrating diseases that may benefit from treatment with novel glutathione based GTN formulations and treatment approaches.

Background: Chronic heart failure (CHF) often necessitates the use of high doses of diuretics, which can lead to side effects such as worsening renal function and electrolyte imbalances. Methods: A total of 102 patients (median age 75 years) were included in the study and divided into two groups based on the level of diuretic therapy. The diuretic group received the following average doses: furosemide — 39.1 ± 22.1 mg, torasemide — 7.4 ± 3 mg, and spironolactone — 42 ± 12.4 mg. Biochemical analyses were performed on days 1 and 7 of hospitalization, with measure-ments of sodium, potassium, glucose, urea, and plasma osmolality (eOSM). Results: By day 7, the plasma osmolality in the diuretic group increased from 300 [297; 304] to 302.2 [298.3; 305.8] mOsm/L (p = 0.039). Urea levels in the diuretic group rose to 7.95 [5.65; 9.90] mmol/L by day 7, while remaining stable in the non-diuretic group at 5.90 [5.05; 7.50] mmol/L (p = 0.012). The proportion of urea to plasma osmolality (PropUrea/eOSM) in the diuretic group in-creased to 2.63% [1.89; 3.28] compared to 2.00% [1.70; 2.50] in the non-diuretic group (p = 0.011). The proportion of sodium to plasma osmolality (PropNa/eOSM) in the diuretic group decreased to 46.46% [46.02; 46.74], compared to 46.68% [46.33; 46.89] in the non-diuretic group (p = 0.050). Analysis of PropNa/eOSM and PropUrea/eOSM on day 7 without considering salt intake yielded statistically significant results, though they were less robust compared to models including salt intake. For example, in the PropUrea/eOSM model, the odds ratio (OR) was 3.01 (95% CI 1.74, 5.89; p < 0.001), and in the PropNa/eOSM model, the OR was 0.19 (95% CI 0.07, 0.43; p < 0.001). Conclusion: The study confirmed that high salt intake and active diuretic therapy significantly influence the biochemical parameters of patients with chronic heart failure (CHF), contributing to the develop-ment of the aestivation phenomenon. This is characterized by an increase in nonionic osmolytes such as urea, which may represent a physiological adaptation to stress. Patients receiving diuret-ics and following a high-salt diet exhibited significant changes in plasma osmolality and urea levels, indicating a physiological adaptation that may worsen prognosis by increasing the risk of sarcopenia and cachexia. Further research is needed to better understand these mechanisms and develop strategies to mitigate the negative effects.

Introduction: Antenatal diagnosis of cardiac abnormalities and counselling parents about postnatal care requires a multidisciplinary team which includes a paediatric cardiologist a neonatologist and a fetal medicine physician. Some of this expertise is not available in all centres with fetal medicine expertise, however with modern technology, this could be provided remotely. Our objective was to assess the feasibility and outcomes of a pre-natal multidisciplinary tele-echocardiography diagnostic and counselling services Materials and Methods: Two centres based in separate countries provided a joint diagnostic and counselling service over a period of 14 months. The primary centre undertook the fetal echocardiography with a Voluson E10 machine and images transmitted live using Zoom OPS system with video-consultation and counselling. The fetal echo was performed using the ISUOG Guidelines check list. Results: There was an initial feasibility period of 2 months during which 10 women whose fetuses had normal hearts were scanned to test the workability of the system. Over a period of 12 months, 513 high risk fetuses were then scanned and out of these 27 had congenital malformations. The most common were hypoplastic left heart syndrome (HHLS) and atrio-ventricular septal defect. Tele-echocardiography and counselling was successful in all the cases. Satisfaction with the service was 3.8/4 with the main limitation being the need for further referral to a tertiary centre for delivery. Conclusion: Tele-echocardiography is reliable and when combined with live counselling and support from a paediatric cardiologist, is an option acceptable to patients. The greatest benefit was from being counselled by a team of experts at a single consultation rather than having to travel to another centre for consultation. With rapidly evolving technology, making video transmission easier and less expensive, we feel that consideration should be given not only to the development of tele-echocardiography but extended to other aspects of fetal medicine.

Children and adolescents (C&A) with congenital heart defects (CHD) have decreased functional capacity and executive functioning (EF) due to brain abnormalities and decreased oxygen saturation. Exercise may improve EF via increased cognitive demands and cerebral blood supply. The purpose of this review was to identify current evidence describing the impact of physical activity (PA) interventions on EF in C&A with CHD. The following databases were searched from 2014-present: MEDLINE, EMBASE, CINAHL, Scopus, CENTRAL, and PsycInfo. Article inclusion criteria consisted of participants from birth to 18 years with CHD, interventions related to PA, and EF as an outcome. Articles were excluded if: adults were included, translation to English was impossible, and full access was unavailable. As a result of the review, 431 studies were screened. Three articles underwent full analyzation and only one met all criteria and this study found that with exercise there were significant improvements on self-reported cognitive functioning and parent-reported social functioning. Despite theoretical benefits, only one published study has investigated the role that PA interventions have on EF in C&A with CHD. Further investigation of the effect PA interventions have on EF in C&A with CHD is needed.

Background: Pleural effusion (PE) is often classified as either a transudative or an exudative process. The aim of the study was to examine the causes of pleural effusions and the short- and long-term survival in the older patients hospitalized in the acute geriatric and internal medicine wards. Methods: Patients aged ≥ 65 years, who underwent thoracentesis, were included in this retrospective study. To distinguish between exudate and transudate PE, the Light’s criteria were applied. We compared medical indices and mortality in patients with exudate PE to those with transudate effusion according two age groups (65 - 85 vs. > 85 years). Results: The rates of the main etiologies of PE were congestive heart failure (CHF), 46%, lung infections, 25%, and malignancy, 12%, of the whole study population. Lung infections accounted for 53% of the exudate PE patients, with a higher presence among the >85 group of patients. The etiology of transudate PE was primarily CHF, more common among the patients of the >85 group. In malignancy, CHF and lung infections patients, the chances of dying within one year were 80.3%, 63.2%, and 45.5%, respectively. In transudate PE patients, ten-year survival of the 65-85 group of patients was significantly higher. In the exudate PE patients, there was no difference in survival between the two age groups. Right-sided and bilateral pleural effusions were associated with worse prognosis. Conclusion: Clinicians encountering patients with PE should be aware of their heightened mortality risks, and should carefully monitor their underlying etiology and employ appropriate optimal management.

Systemic inflammation and coronary microvascular endothelial dysfunction are essential pathophysiological factors in heart failure with preserved ejection fraction (HFpEF) that support the use of statins. The pleiotropic properties of statins, such as anti-inflammatory, antihypertrophic, antifibrotic, and antioxidant effects, are generally accepted and may be beneficial in HF, especially in HFpEF. Numerous observational clinical trials have consistently shown a beneficial prognostic effect of statins in patients with HFpEF, while the results of two larger trials in patients with HFrEF have been controversial. Such differences may be related to a more pronounced impact of the pleiotropic properties of statins on the pathophysiology of HFpEF and pro-inflammatory comorbidities (arterial hypertension, diabetes mellitus, obesity, chronic kidney disease) that are more common in HFpEF. This review discusses the potential mechanisms of statin action that may be beneficial for patients with HFpEF, as well as clinical trials that have evaluated the statin effects on left ventricular diastolic function and clinical outcomes in patients with HFpEF.

Regulatory T cells are key immune cells to initiate tolerable immune responses. TGFβ is the key cytokine of regulatory T cells. TGFβ is also the master cytokine to stimulate tissue fibrosis. Systemic sclerosis is an autoimmune disease related to overt organ fibrosis. Thus, systemic sclerosis is a disease related to regulatory T cell over-representation. Besides, many end stage organ failures including heart failure, liver cirrhosis, uremia, and pulmonary fibrosis also related to tissue fibrosis. Thus, TGFβ producing regulatory T cells are also involved in the pathogenesis of these end stage organ failure. Once we know the significance of TGFβ and it induced tolerable immune reactions in the pathophysiology of end organ failure, we can develop better prevention or therapeutic strategies to combat these detrimental disorders.

In this study, we propose the Signal Integration Reconstruction Peak Detection (SIRPD) algorithm for reliable Cardiac Beat Interval (CBI) measurement using functional Near-Infrared Spectroscopy (fNIRS) signals. This algorithm enhances reliability by identifying a regular waveform in cerebral blood flow associated with heartbeats. The SIRPD algorithm assesses the Signal Quality Index (SQI) per channel, discards signals from unavailable channels, and interpolates oxygenated and total hemoglobin concentration signals, thereby boosting resolution and integrating the signal into a single channel. The integrated and smoothed signal is transformed to identify the most significant periodic waveform, from which the CBI is extracted. Validated with data from 20 healthy subjects who simultaneously recorded fNIRS and ECG signals, our findings confirm the equivalence of the CBI derived from ECG and calculated through the SIRPD algorithm from fNIRS (R^2 = .98, RMSE = .011, ICC = .991). We also extracted heart rate variability (HRV) features, confirming no significant difference in all features between ECG and fNIRS devices. Uniquely, this study regards the fNIRS heart signal not as an artifact source but as a valuable bio signal. The proposed method, which allows for the detection of cardiac beat intervals from cerebral blood flow oscillations, suggests the potential clinical applicability of fNIRS as an auxiliary indicator for various cardiovascular factors.

(1) Background: Cardiorespiratory fitness (CRF) is a prognostic factor regarding long time morbidity and mortality. To assess CRF the well-known gold standard is cardiopulmonary exercise testing (CPET), which is a time consuming and expensive test. Therefore, alternative methods for routine evaluation of CRF are needed for the general population as well as for specific patient groups such as children and young adults with congenital heart disease. The Stair Climbing Test (SCT) is a simple and resource saving test reported in the current literature. This test is used in various settings to assess different health associated risk factors including cardiorespiratory fitness, muscular resilience, therapy effectiveness or pre- and postoperative morbidity and mortality.

Researchers have asserted that, as patients rely on external powerful sources to control their disorders, in addition to their own internal powers and virtues, examining their coping mechanisms can lead to a better understanding of the initiation and progression of chronic diseases and uncover potential opportunities to balance and enhance their psycho-spiritual well-being and possibly their treatment and recovery. This review serves as a user’s manual for investigators who choose to use the CSI-SF to conduct their research on coping behaviors. The CSI-SF that measures four coping strategies based on 16 items was first assessed using the Jackson Heart Study (JHS) cohort in 2007. The reliability and construct validity of the CSI-SF was also later assessed among hemodialysis patients across 13 countries. In this study, the CSI-SF was assessed to be a reliable and valid instrument for measuring coping strategies. The CSI-SF serves the purpose of developing an inner voice that can assist with understanding how people cope with everyday life. The information gathered from administration of the CSI-SF can inform investigators about environmental cues and triggers that can also impact individual health.

This study aimed to determine the correlation of colour M-mode velocity propagation in the assessment of left ventricular diastolic function among acute decompensated heart failure patients with preserved ejection fraction (HFpEF). This research is an observational analytical study using a cross–sectional study design conducted from April to June 2022. The subjects of this study were patients diagnosed with acute HFpEF and treated at Dr. Soetomo General Academic Hospital, Surabaya. Patients with heart rhythm disturbances, moderate to severe valvular heart disease, and congenital heart defects were excluded from this study. Patients were measured for diastolic function including mitral valve early mitral inflow velocity (MV E Velocity), mitral peak velocity of early filling (E’) (E' Septal and E' Lateral), left atrial volume index (LAVI), The maximal tricuspid regurgitation velocity (TR V Max), Vp, the ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/E'), the ratio between early and late ventricular filling velocity (E/A) and E/Vp Ratio. N-terminal-pro hormone B-type natriuretic peptide (NT–ProBNP) examination was also performed on study subjects as an additional diagnosis of acute heart failure. There were 33 patients who met the inclusion and exclusion criteria and were included in our study. There were 26 patients (78.8%) with grade I diastolic dysfunction, 4 patients (12.1%) with grade II diastolic dysfunction, and 3 patients (9.1%) with grade III diastolic dysfunction. There is a strong positive correlation between Vp with parameters E' Septal (p = &lt; 0.001; r = 0.636) and E' Lateral (p = &lt; 0.001; r = 0.650). Vp is negatively correlated with the ratio E/E' (p = 0.029; r = –0.37). The PCWP estimate with E/Vp ratio had a strong correlation with the NT–Pro BNP value &gt; 300 pg/ml in acute HFpEF patients (p = &lt; 0.001; r = 0.726) compared to the PCWP estimate with E/E' (p = &lt; 0.001; r = 0.549). There is no correlation between Vp value and degree of diastolic dysfunction in patients with acute HFpEF.

Redox balance is increasingly identified as a major player in cellular signaling. A fundamentally simple reaction of oxidation and reduction of cysteine residues in cellular proteins is the central concept in this complex mode of protein function regulation. Oxidation of key cysteine residues occurs at the physiological levels of reactive oxygen species (ROS) but are reduced by a supply of thiol antioxidant molecules including glutathione, glutaredoxin and thioredoxin. While these molecules show complex compensatory roles in experimental conditions, transgenic animal models provide a comprehensive picture to pinpoint the role of each antioxidant. In this review we have specifically focused on the available literature on Thioredoxin-1 system transgenic models that includes Thioredoxin and Thioredoxin reductase proteins. As identification of Thioredoxin protein targets is technically challenging the true contribution of this system in maintaining cellular balance remains unidentified, including the role of this system in the brain.

Investigations are currently in progress to assess the potential of elevated FABP3 levels as biomarkers for assessing cardiac and cerebral injury post-stroke. Ongoing research endeavors are concentrated on elucidating the specific mechanisms by which FABPs, particularly FABP3, contribute to the complex processes involved in ischemic stroke. This study employs molecular docking techniques within a Virtual Screening framework to examine the interaction between various natural substances and the active site of human heart fatty acid-binding protein (PDB Code 4TKH). Utilizing Pyrx and Autodock Vina, the research aims to pinpoint compounds demonstrating robust binding interactions, characterized by high binding energy scores (kcal/mol) and the formation of multiple chemical bonds. The anticipated outcomes have the potential to yield valuable insights into the molecular interactions influencing human heart fatty acid-binding protein, suggesting possible implications for therapeutic interventions using these natural substances.From the docking and predicted toxicity results, Resistomycin has demonstrated superior characteristics compared to Morusin.

Infant electrocardiograms (ECG) and heart rates (HR) are very useful biosignals for psychological research and clinical work, but can be hard to analyze properly, particularly long form (≥5 minutes) recordings taken in naturalistic environments. Infant HRs are typically much faster than adult HRs, and so some of the underlying frequency assumptions made about adult ECGs may not hold for infants. However, the bulk of publicly available ECG approaches focus on adult data. Here, existing open-source ECG approaches are tested on infant datasets. The best performing open-source method is then modified to maximize its performance on infant data (e.g., including a 15Hz high pass filter, adding local peak correction). The HR signal is then subsequently analyzed, developing an approach for cleaning data with separate sets of parameters for the analysis of cleaner and noisier HR. A Signal Quality Index (SQI) for HR is also developed, providing insight into where a signal is recoverable and where it is not, allowing for more confidence in analysis performed on naturalistic recordings. The tools developed and reported in this paper provide a base for future analysis of infant ECG and related biophysical characteristics. Of particular importance, the proposed solutions outlined here can be efficiently applied to real-world large datasets.

In patients with prior Takotsubo syndrome (TTS), long lasting functional cardiac limitations were described as compared with normal subjects. Emotions-triggered Takotsubo syndrome (E-TTS) has more favorable outcomes than TTS preceded by a physical trigger or by no identifiable fac-tors. The aim of the present study was to assess long-term cardiac functional limitations in a co-hort of asymptomatic E-TTS patients. We enrolled n=39 asymptomatic patients with a diagnosis of E-TTS. Cardiopulmonary exercise tests (CPET) were performed at 30 [12-40] months median fol-low-up from the acute event. A cohort of n=39 individuals matched for age, sex, body mass index and comorbidities served as control. Despite recovery of left ventricular ejection fraction, patients with prior E-TTS had lower peak VO2 and percentage of predicted peak VO2 (17.8 ± 3.6 vs 22.5 ± 6.5; P < 0.001 and 75.2 ± 14.1 % vs 100.6 ± 17.1%, P <0.001), VO2 at anaerobic threshold (AT) (11.1 [10.1-12.9] vs 14.4 [12.5-18.7]; P <0.001), peak O2 pulse (9.7 ± 2.5 vs 13.1 ± 3.5; P <0.001) and higher VE/VCO2 slope (30.4 ± 3.7 vs 27.2 ± 3.5; P <0.001) compared with matched controls. We found no statistically significant differences in heart rate reserve (HRR), respiratory equivalent ratio (RER), mean blood pressure and peak PetCO2 between patients and controls. Despite its favorable out-come, patients with E-TTS in our population were found to have subclinical long-term functional cardiac limitations as compared with a control cohort.

Aims: The objective of this study was to assess the cost-effectiveness of the CardioMEMS HF system in a HF Clinic in Spain by evaluating the real-time remote monitoring of pulmonary artery pressures, which has shown to reduce heart failure (HF) related hospitalizations and improve the quality of life for selected HF patients. Particularly, the study aimed to determine the value of CardioMEMS in Southern Europe, where healthcare costs are significantly lower and its effectiveness remains uncertain. Methods: This single-centre study enrolled all consecutive HF patients who had been implanted with a pulmonary artery pressure sensor (CardioMEMS-HF system, Abbott Laboratories, Abbott Park, IL, USA). The number of HF hospitalizations in the year before and the year after the sensor implantation was compared and quality-adjusted life years (QALY) gained based on a literature review of previous studies was calculated. Results: The rate of HF hospitalisations was significantly lower at 1 year compared with the year before CardioMEMS implantation (0.25 versus 1.10 events/patient-years, HR 0.22, p=0.001). At the end of first year, the usual management outperformed the CardioMEMS HF system, resulting in a net monetary value difference of 2,540€ per patient and a benefit-cost ratio of 0.38. However, by the end of the second year, the CardioMEMS system is estimated to reduce costs compared to usual management. Conclusions: Based on the results, we suggest that remote monitoring of pulmonary artery pressure with the CardioMEMS HF system represents a long-term cost-effective strategy in a healthcare setting in Southern Europe.

Due to the complex and variable anatomy of the left atrial appendage, percutaneous left atrial appendage closure (LAAC) can be challenging. In this study, we investigated the impact of fusion imaging (FI) on the LAAC learning curve of 2 interventionalists. The first interventionalist (IC 1) was initially trained without FI and continued his training with FI. The second interventionalist (IC 2) performed all procedures with FI. We compared the first 36 procedures without FI of IC 1 (group 1) with his next 36 interventions with FI (group 2). Furthermore, group 1 was compared to 36 procedures of IC 2 who directly started his training with FI (group 3). Group 1 demonstrated that the learning curve without FI has a flat course with weak correlations for fluoroscopy time, contrast volume, and procedure time, but not for dose area product. Group 2 with FI showed improvement with a steep course and strong correlations for all 4 parameters. In group 3 we also saw a steep progression with strong correlations. Furthermore, the mean measurements of the procedural parameters in the groups with FI decreased significantly as indicator for procedural efficacy. We demonstrated that FI may improve the learning curve of experienced and non-experienced ICs.

Background: Long QT syndrome (LQTS) can lead to ventricular arrhythmia and sudden cardiac death. The most common congenital cause of LQTS is mutations in the channel subunits generating the cardiac potassium current IKs. Zebrafish (Danio rerio) have been proposed as a powerful system to model human cardiac diseases due to the similar electrical properties of the zebrafish heart and the human heart. Methods: We used high resolution all-optical electrophysiology on ex-vivo zebrafish hearts to assess the effects of IKs analogues on the cardiac action potential. Findings: We found that chromanol 293B (an IKs inhibitor) prolonged the action potential duration (APD) in the presence of E4031 (an IKr inhibitor applied to drug-induced LQT2) and to a lesser extent in the absence of E4031. Moreover, we show that PUFA analogues slightly shorten the APD of the zebrafish heart. However, PUFA analogues failed to reverse the APD prolongation in drug-induced LQT2. However, a more potent IKs activator, ML-277, partially reversed the APD prolongation in drug-induced LQT2 zebrafish hearts. Interpretation: Our results suggest that IKs plays a limited role in ventricular repolarizations in the zebrafish heart under resting conditions but plays a more important role when IKr is compromised, as if IKs in zebrafish serves as a repolarization reserve as in human hearts. This study shows that potent IKs activators can restore the action potential duration in drug-induced LQT2 in zebrafish heart.

Repeated desaturation of oxyhemoglobin, micro-arousals, which are typical in obstructive sleep apnea syndrome (OSAS), have negative effects on the health of patients, leading to a wide range of complications such as cardiovascular (arterial hypertension, pulmonary hypertension, chronic heart failure, arrhythmias, myocardial infarction) cerebrovascular (strokes), metabolic (insulin resistance, obesity, diabetes mellitus, metabolic syndrome), gastrointestinal (non-alcoholic liver disease), urinary (chronic renal failure), neuropsychiatric complications and a wide range of malignancies. This in turn has a multilateral effect on familial, occupational and social life, as well as increasing the risk of road traffic accidents or accidents at workplace. Awareness, timely screening and prevention of complications play an important role in the diagnosis and treatment of comorbid conditions. This review focuses on comorbidities in OSAS and the effect of CPAP therapy on their prognosis.

The kidney and the heart work together in balancing the body circulation and although their physiology is based on strict inter dependence, their performance fulfills different aims. While the heart can rapidly increase its own oxygen consumption to comply with the wide changes in metabolic demand linked to body function, the kidney physiology is primarily designed to maintain a stable metabolic rate and has limited capacity to cope with any steep increase in renal metabolism. In the kidneys the glomerular population filters a large amount of blood and the tubular system has been programmed to reabsorb 99% of filtrate by reabsorbing sodium together with other filtered substances including all glucose molecules. Glucose reabsorption involves the sodium-glucose cotransporters SGLT2 and SGLT1 on the apical membrane in the proximal tubular section; it also enhances bicarbonate formation so as to preserve the acid-base balance. The complex work of reabsorption in the kidney is the main factor in renal oxygen consumption; analysis of renal glucose transport in disease states is providing better understanding of the renal physiology changes that occur when clinical conditions alter the neurohormonal response leading to an increase in glomerular filtration pressure. In this circumstance glomerular hyperfiltration occurs, imposing a higher metabolic demand on kidney physiology and causing progressive renal impairment. Albumin urination is the warning signal of renal engagement over-exertion and most frequently heralds heart failure development, regardless of disease etiology. The review analyzes the mechanisms linked to renal oxygen consumption, focusing on sodium-glucose management.

This paper presents a framework to recognize the affective state of children with Autism Spectrum Disorder (ASD) in an in-the-wild setting using Heart Rate (HR) information. Our algorithm classifies a child’s emotion into positive, negative, or neutral states by analyzing the heart rate signal. The HR signal is obtained from a smartwatch in real-time using our smartwatch application. The heart rate data is acquired when the child learns to code a robot while interacting with an avatar that assists the child in communications skills and programming the robot. In this paper, we also present a comparison of using HR data for the classification of emotions with classification based on features extracted from HR signals using Discrete Wavelet Transform (DWT). Our experimental results show that the proposed method produces a comparable performance with the state-of-the-art HR-based emotion recognition techniques, despite the fact that our experiments are performed in an uncontrolled setting as opposed to a lab environment. This work contributes to real-world affect analysis of children with ASD using HR information.

Biomarkers have become an important tool in the diagnosis and management of cardio renal syndromes (CRS), a complex condition characterized by dysfunction in both the cardiovascular and renal systems. These biomarkers can help identify the presence and severity of CRS, predict its progression and outcomes, and facilitate personalized treatment options. Several biomarkers, including natriuretic peptides, troponins, and inflammatory markers, have been extensively studied in CRS and have shown promising results in improving diagnosis and prognosis. In addition, emerging biomarkers such as kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin offer potential for early detection and intervention of CRS. However, the use of biomarkers in CRS is still in its infancy, and further research is needed to establish their utility in routine clinical practice. This review highlights the role of biomarkers in the diagnosis, prognosis, and management of CRS and discusses their potential as valuable clinical tools for personalized medicine in the future.

The onset of embryonic heart beating may be regarded as the defining feature for the beginning of personal human life. Clarifying the timing of the 1^st human heartbeat, therefore, has religious, philosophical, ethical, and medicolegal implications. This article reviews the historical and contemporary sources of knowledge on the beginning of human heart activity. Special attention is given to the problem of the determination of the true age of human embryos and to the problem of visualization of the human embryonic heart activity. It is shown that historical and current textbook statements about the onset of blood circulation in man do not derive from observations on living human embryos but derive from the extrapolation of observations on animal embryos to the human species. This fact does not preclude the existence of documented observations on human embryonic heart activity: Modern diagnostic (ultrasound) and therapeutic (IVF) procedures facilitate the visualization of early embryonic heart activity in precisely dated pregnancies. Such studies showed that the human heart started its pumping action during the 4^th post-fertilization week. A small number of direct observations on the heart activity of aborted human embryos were reported since the 19^th century but did not receive much recognition by embryologists.

The combination of statistical learning technologies with large databases of psychophysiological data has appropriately generated enthusiastic interest in future clinical applicability. It is argued here that this enthusiasm should be tempered with the understanding that significant obstacles must be overcome before the systematic introduction of psychophysiological measures into neuropsychiatric practice becomes possible. The nonspecificity of psychophysiological measures complicates their use in diagnosis. Low test-retest reliability complicates use in longitudinal assessment, and quantitative psychophysiological measures can normalize in response to placebo intervention. Ten cautionary observations are introduced and, in some instances, possible directions for remediation are suggested.

Background A decline in cardiovascular hospitalizations was observed during the initial phases of the COVID-19 pandemic. We examine the continued effect of the pandemic on cardiovascular hospitalizations and the associated mortality rates during the first year of the pandemic in Israel. Methods We conduct a retrospective cohort study using the data of Clalit Health Services, the largest healthcare organization in Israel. We divide the Corona year into six periods (three lockdowns and three post-lockdowns) and compare the incidence rates of cardiovascular hospitalizations and their 30-day mortality during each period to the previous three years. Results The number of non-STEMI hospitalizations during the first year of the pandemic was 13.7% lower than the average of the previous three years (95% CI 11%-17%); STEMI hospitalizations were 15.7% lower (95% CI 13%-19%); and CHF hospitalizations were 23.9% lower (95%, CI 21%-27%). No significant differences in 30-day mortality rates were observed for AMI patients during most of the periods, whereas the annual 30-day all-cause mortality rate of CHF was 23% higher. Conclusions Hospitalizations for AMI and CHF were significantly lower during the first year of the pandemic relative to 2017–9. Mortality rates were higher in the case of CHF patients but not in the case of AMI patients, possibly due a change in the clinical acuity of patients arriving at the hospitals. We conclude that targeted public health messaging should be implemented, together with proactive monitoring in order to identify residual disability in patients that may have received non-optimal treatment during the pandemic.

Heart attacks and strokes are one of the leading causes of death in the world today, and heart attacks caused by clogged arteries that carry blood to the heart muscle are a significant part of these strokes. These are caused by the accumulation of fat particles in the walls of the arteries and the reduction of blood flow through it over a long process. The process of fat penetration in the underlying layers of the Artery wall has been the focus of many researchers, and various researches and Simulations have been done on it, in each of them, the effect of specific parameters has been considered. In the present study, the effect of blood flow rate on the flow pattern in a bifurcate artery with two ducts has been investigated using FLUENT software with Computation fluid dynamic Method. The effect of the angle between the two ducts of the Artery on the flow pattern has been investigated.

Direct cardiac reprogramming of fibroblasts into induced cardiomyocytes (iCMs) is a promising approach but remains a challenging technology of regenerative medicine for damaged myocardium. Efforts have been focused on improving the efficiency by understanding fundamental mechanisms. One of the major challenges is that the plasticity of cultured fibroblast varies batch to batch with unknown mechanisms. Here, we noticed that a portion of in vitro cultured fibroblasts have been activated to differentiate into myofibroblasts, marked by the expression of αSMA, even in the primary cell culture of tissues. Both forskolin, which activates adenylyl cyclase and increases cAMP concentration, and TGFbeta inhibitor SB431542 can efficiently suppress myofibroblast differentiation of cultured fibroblasts. However, SB431542 improved but forskolin blocked iCM reprogramming of fibroblasts that were infected with retroviruses of Gata4, Mef2c and Tbx5 (GMT). Moreover, inhibitors of cAMP downstream signaling pathways, PKA or CREB-CBP, significantly improved the efficiency of iCM reprogramming. Consistently, inhibition of p38/MAPK, another upstream regulator of CREB-CBP, also improved reprogramming efficiency. We then investigated if inhibition of these signaling pathways in primary cultured fibroblast could improve their plasticity for reprogramming, and found that preconditioning of cultured fibroblasts with CREB-CBP inhibitor significantly improved the cellular plasticity of fibroblasts to be reprogrammed, yielding ~2-fold amount of reprogrammed iCMs compared to that of untreated control cells. In conclusion, suppression of cAMP/PKA/CREB signaling axis improves fibroblast plasticity for direct cardiac reprogramming.

Stress has been identified as one of the major causes of automobile crashes which then lead to high rates of fatalities and injuries each year. Stress can be measured via physiological measurements and in this study the focus will be based on the features that can be extracted by common wearable devices. Hence the study will be mainly focusing on the heart rate variability (HRV). This study is aimed to develop a good predictive model that can accurately classify stress levels from ECG-derived HRV features, obtained from automobile drivers, testing different machine learning methodologies such as K-Nearest Neighbor (KNN), Support Vector Machines (SVM), Multilayer Perceptron (MLP), Random Forest (RF) and Gradient Boosting (GB). Moreover, the models obtained with highest predictive power will be used as reference for the development of a machine learning model that would be used to classify stress from HRV features derived from HRV measurements obtained from wearable devices. We demonstrate that MLP was the ideal stress classifier by achieving a Recall of 80%. The proposed method can be also used on all applications in which is important to monitor the stress level e. g. in physical rehabilitation, anxiety relief or mental wellbeing.

Introduction: Left atrial hypertension is one of the pathophysiologies of heart failure with preserved ejection fraction. We hypothesized that left atrial pressure response (LAPR) to incremental pacing is higher in patients with atrial fibrillation (AF) and can predict left ventricular diastolic dysfunction. Methods: Patients requiring left atrial access as a part of a therapeutic procedure for AF (n=204, AF group) or supraventricular tachycardia (n=34, control group) were analyzed (male n=183, 54±12 years old). LAPR was measured during incremental pacing. Results: Baseline left atrial pressure and LAPR at all pacing rates were not different between the AF and control groups. They were higher in patients with a high E/e’ (≥ 8) than in those with a low E/e’ (&lt; 8). LAPR at a pacing interval of 400ms and E/e' were positively correlated (r=0.373, p&lt;0.001). Body mass index and a high E/e' were independent predictors of pacing-induced left atrial hypertension. Conclusions: The LAPR to incremental pacing was constant regardless of AF. The non-invasive echocardiographic marker E/e' reflected pacing-induced left atrial hypertension.

Animal welfare remains a very important issue in the livestock sector but monitoring animal welfare in an objective and continuous way remains a serious challenge. Monitoring animal welfare based upon physiological measurements instead of audio-visual scoring of behaviour would be a step forward. One of the obvious physiological signals related to welfare and stress is heart rate. The objective of this research was to measure heart rate (beat per minutes) on pigs with technology that soon will be affordable. Affordable heart rate monitoring is done today at large scale on humans using the Photo Plethysmography (PPG) technology. We used PPG sensors on pig’s body to test whether it allows getting reliable heart rate signal. A continuous wavelet transform (CWT)-based algorithm is developed to decouple the cardiac pulse waves from the pig. Three different wavelets, namely 2^nd, 4^th and 6^th order Derivative of Gaussian (DOG, are tested. We show results of the developed PPG-based algorithm against electrocardiograms (ECG) as a reference measure for heart rate and this for an anesthetized versus a non-anesthetised animal. We tested three different anatomical body positions (ear, leg and tail) and give results for each body position of the sensor. In summary, it can be concluded that the agreement between PPG-based heart rate technique and reference sensor goes from 91 to 95 percentage. In this paper we showed the potential of using the PPG-based technology to assess pig’s hear rate.

The chicken embryo is a widely used experimental animal-model in many studies such as developmental biology and to study the physiological responses and adaptation to altered environments as well as for cancer and neurobiology research. Embryonic heart rate is an important physiological variable useful as an index reflecting the embryo's natural activity and is considered one of the most difficult parameters to measure. An acceptable measurement technique of embryonic heart rate should provide a reliable cardiac signal quality while maintaining adequate gas exchange through the eggshell along the incubation and embryonic developmental period. In this paper, we presented a detailed design and methodology for a non-invasive PPG-based prototype (Egg-PPG) for real-time and continuous monitoring of embryonic heart rate during incubation. An automatic embryonic cardiac wave detection algorithm, based on normalised spectral entropy, is described. The developed algorithm successfully estimated the embryonic heart rate with 98.7% accuracy. We believe that the developed overall system presented in this paper is showing a promising solution for non-invasion, real-time monitoring of embryonic cardiac signal, which can be used in both experimental studies (e.g., developmental embryology and cardiovascular research) and in industrial incubation applications.

Body acceleration due the heartbeat-induced reaction forces can be measured as smartphone accelerometer (m-ACC) signals. Our aim was to test the feasibility of using m-ACC to detect changes induced by stress by ultra-short heart rate variability (USV) indices (SDNN and RMSSD). Sixteen healthy volunteers were recruited; m-ACC was recorded while in supine position, during spontaneous breathing (REST) and during one minute of mental stress (MS) induced by arithmetic serial subtraction task, simultaneous with conventional ECG. Beat occurrences were extracted from both ECG and m-ACC and used to compute USV indices using 60, 30 and 10s durations, both for REST and MS. A feasibility of 93.8% in the beat-to-beat m-ACC heart rate series extraction was reached. In both ECG and m-ACC series, compared to REST, in MS the mean beat duration was reduced by 15% and RMSSD decreased by 38%. These results show that short term recordings (up to 10 sec) of cardiac activity using smartphone’s accelerometers are able to capture the decrease in parasympathetic tone, in agreement with the induced stimulus.

Automated Electrocardiogram (ECG) processing is an important technique which helps in identifying abnormalities in the heart before any formal diagnosis. This research presents a real-time and lightweight R-assisted feature extraction algorithm and a heartbeat classification scheme which achieves highly accurate abnormality detection. In the proposed algorithm, we extract fifteen features from each heartbeat taken from raw Lead-II ECG signals. The features carry medically valuable information such as locations, amplitude and energy of ECG waves (P, Q, R, S, T waves) which are then used for detection of any abnormality that might be present in the heartbeat using various classification algorithms. We have used four popular databases from Physionet and extracted ten thousand ECG signals from each for training the models and benchmarking results. Four classification models i.e. Naïve Bays, k-Nearest Neighbor, Neural Network, Decision Tree were used for abnormality detection validating the efficiency of the system.

-529391451442Citation: To be added by editorial staff during production. Academic Editor: Firstname Lastname Received: date Revised: date Accepted: date Published: date Copyright: © 2023 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).0Citation: To be added by editorial staff during production. Academic Editor: Firstname Lastname Received: date Revised: date Accepted: date Published: date Copyright: © 2023 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Abstract: SARS-CoV-2 vaccination offered the opportunity to get out of the pandemic and thereby worldwide health, social, and economic disasters. However, in addition to efficacy, safety is an important issue for any vaccine. The mRNA-based vaccine platform is considered to be safe but side effects are being reported more frequently as more and more people around the world become treated. Myo-pericarditis is the major, but not the only cardiovascular complication of this vaccine, hence it is important not to underestimate other side effects. We report a case series of patients affected by cardiac arrhythmias post mRNA vaccine from our clinical practice and the literature. Reviewing the official vigilance database emerged that heart rhythm disorders after Covid vaccination are not uncommon and deserve more clinical and scientific attention. Since Covid vaccine is the only vaccination to have been related to this side effect questions arose about whether these vaccines could affect heart conduction. Although the risk-benefit is clearly in favor of vaccination heart rhythm disorders are not a negligible issue and there are red flags in the literature about the risk of post-vaccination malignant arrhythmias in some predisposed patients. In light of these findings, we investigated the potential mechanism for the Covid vaccine to impact on cardiac electrophysiology and cause heart rhythm disorders.

Diuretic resistance is a servomechanism involving superoxide that results from the use of escalating doses of diuretics in the treatment of heart failure. Without intervention this may lead to increased heart failure mortality. Recent heart failure studies involving the use of SGLT2 inhibitors and GLP-1 agonists have shown reductions in the need for loop diuretics along with reductions in hospitalizations for heart failure and cardiovascular mortality. Multiple mechanisms have been proposed to explain the benefits of both these drug classes but this paper is the first to explain and propose superoxide induced diuretic resistance as a therapeutic target for the treatment of heart failure.

Background: Despite tremendous advances in medicine, infective endocarditis (IE) continues to be a challenge for physicians due to increasing morbidity and unchanged high mortality. Objectives: Our aim was to evaluate clinical outcomes in patients with IE and to identify predictors of in-hospital mortality. Material and methods: The study was retrospective, single-centered, and included 270 patients diagnosed with IE, for the period 2005-2021 (median age 65 (51–74), man 177 (65.6%). Results: Native IE (NVIE) was found in 180 (66.7%), prosthetic IE (PVIE) in 88 (33.6%) and cardiac device-related IE (CDRIE) in 2 (0.7%), significantly more in the non-survivors group. Healthcare associated IE (HAIE) was 72 (26.7%), the most common pathogen were Staphylococci and the proportion of Gram-negative bacteria (GNB) non-HACEK were significantly higher in non-survivor’s vs survivors (11 (15%) vs 9 (4.5%), p=0.004). Overall, early surgery was performed in 54 (20%) patients, with a significant difference between deceased/alive (3 (4.5%) vs 51 (25.1%, p=0.000). The all-cause in-hospital mortality rate was 24.8% (67). The risk factors identified that increased the risk of death were septic shock (OR – 83 1; 95% CI (17.0-405.2), p=0.000) and acute heart failure (OR –24.6; 95% CI (9.2-65.0), p=0.000). Early surgery (OR – 0.03, 95% CI (0.01-0.16), p=0.000) and low Charlson comorbidity index (OR – 0.85, 95% CI (0.74-0.98, p=0.026) in turn reduce this risk. Conclusion: We found that acute heart failure and septic shock are independent predictors of in-hospital mortality. Low Charlson comorbidity index and early surgery increased survival. Knowing the predictors of death would change the therapeutic approach to a more aggressive one and improve the near and long-term prognosis of patients with IE.

Bioimpedance analysis (BIA) is a validated non-invasive technique already proven to be useful for the diagnosis, prognosis, and management of body fluids in subjects with heart failure (HF) and chronic kidney disease (CKD). Although BIA has been widely employed for research purposes, its clinical application is still not fully widespread. The aim of this review is to provide a comprehensive overview of the state of art of BIA utilization by analysing the clinical benefits, limitations, and the potential future developments in this clinically unexplored field.

Heart failure (HF) is a global health concern with rising incidence and poor prognosis. While the essential role of nutritional and dietary strategies in HF patients is acknowledged in the existing scientific guidelines and clinical practice, there are no comprehensive nutritional recommendations for optimal dietary management of HF. In this review, we discuss results from recent studies on the obesity paradox and the effects of calorie restriction and weight loss, intermittent fasting, the Western diet, the Mediterranean diet, the ketogenic diet, and the DASH diet on HF progression. Many of these strategies remain under clinical and basic investigation for their safety and efficacy, and there is considerable heterogeneity in the observed response, presumably because of heterogeneity in the pathogenesis of different types of HF. In addition, while specific aspects of cardiac metabolism, such as changes in ketone body utilization, might underlie the effects of certain dietary strategies on the heart, there is a critical divide between supplement strategies (i.e. with ketones) and dietary strategies that impact ketogenesis. This review aims to highlight this gap by exploring emerging evidence supporting the importance of personalized dietary strategies to prevent progression and improve outcomes in the context of HF.

(1) Background: Heart rate variability (HRV) has emerged as a potential prognostic tool in cardiovascular diseases, offering individualized insights into autonomic nervous system activity. However, real-time HRV data during the acute phase of STEMI, particularly during percutaneous coronary intervention (PCI), was not previously explored. (2) Methods: This single-center, observational cohort study included 104 STEMI patients undergoing primary percutaneous coronary intervention (PCI). HRV parameters were measured using a wearable device (CE marked) during PCI, capturing dynamic responses. The association between HRV parameters and adverse outcomes, including in-hospital mortality and major adverse cardiovascular events (MACE), were assessed. (3) Results: HRV parameters significantly decreased after myocardial revascularization, particularly SDNN, RMSSD, pNN50, HF, SD1, and SD2/SD1 ratio. Significant associations were found between reduced SD2/SD1 ratio, approximate entropy, and adverse outcomes, including increased in-hospital mortality and MACE. The SD2/SD1 ratio was significantly lower in patients who died during the hospital stay (p = 0.008) compared to survivors. Approximate entropy was also significantly lower in deceased patients (p = 0.019). (4) Conclusions: Real-time HRV monitoring using wearable technology offers valuable data regarding dynamic physiological changes during primary PCI. The integration of HRV into routine clinical practice, facilitated by wearable devices, could improve the risk stratification and event prediction in STEMI patients.

Sick sinus syndrome (SSS) is a disease of sinus rhythm abnormalities. This study aimed to establish an SSS model by injecting 3% NaOH into the jugular vein(JV). Sprague-Dawley rats were randomly divided into sham, 3% NaOH, and 10% NaOH groups. Anesthetized rats underwent electrocardiogram recording before right JV exposure. Rats in the experimental groups received NaOH injections at 0.01 ml/s, while the sham group did not. Model success was evaluated after one hour. Heart rate(HR) and rhythm were documented at 1 hour, 1 week, and 2 weeks post-molding, including HE staining, membrane ion transcription and expression, and calcium ion content test. In the 3% NaOH group, the model establishment rate was 87%, and the mortality rate was 13%, whereas in the 10% NaOH group, they were 57% and 43% respectively (P < 0.01). The HR of the 3% NaOH group decreased at multiple time points post-molding (P < 0.001), presenting as arrhythmias such as sinus bradycardia. The JV sustained less damage, with necrosis of P cells, changes in membrane ion channels, and reduced calcium ion distribution. In conclusion, JV injection of 3% NaOH can establish the SSS model and benefit animals.

Background: Heart failure (HF) remains a challenging healthcare issue, necessitating innovative therapies like cardiac resynchronization-defibrillation therapy (CRT-D). However, defining CRT-D responders lacks uniformity, impeding effective clinical evaluation. This study explores diverse CRT-D responder definitions, encompassing functional, echocardiographic, and laboratory criteria. Materials & Methods: A single-center study involving 132 CRT-D patients scrutinized responder criteria, including NYHA stage, LVEF increase, and proBNP decrease. Statistical analyses, such as Kaplan–Meier curves and Cox hazard regression, were employed to evaluate responder characteristics and survival outcomes. Results: Responder rates varied across criteria, revealing nuanced patient profiles. CRT-D responders, defined by NYHA decrease, LVEF increase, or proBNP decrease, exhibit improved survival rates after 2 and 3 years (p < 0.050). Young age, absence of recent myocardial infarction, and normal right ventricular, echocardiographic parameters emerge as predictors for positive response. In part, drug-based HF therapy correlates with increased responder rates. Cox regression identified LVEF ≥ 5% and proBNP decrease ≥ 25% as independent predictors of extended survival. Conclusions: CRT-D responder definitions exhibit considerable variability, emphasizing the need for a nuanced, patient-centered approach. Factors like right ventricular function, drug therapy, atrial fibrillation, and renal function influence responses. The study enriches our understanding of CRT-D response, contributing to the foundation for personalized HF management.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome characterized by multiple risk factors and associated conditions. HFpEF prevalence is rising, and its prognosis remains poor after the first hospitalization. Using a two-hit HFpEF murine model, we aimed at studying cardiac reverse remodelling after stopping the causing stress (Angiotensin II [AngII]) and a high-fat diet [HFD]; MHS) and introducing voluntary exercise. We studied in young male and female C57Bl6/J mice fed or not with an HFD (60% calories from fat) the cardiac response to AngII (1.5 mg/kg/day for 28 days). Then, MHS was stopped, and VE was started for another four weeks (RR). We studied the effects of MHS and RR on the circulatory microRNA (miR) profile (miRNome) and the myocardial miRNome to characterize the cardiac and non-cardiac response of small RNAs. AngII alone and MHS but not the HFD caused cardiac hypertrophy (CH), left ventricular (LV) concentric remodelling and left atrial enlargement in male mice. HFD-induced CH and LV concentric remodelling only in female mice. Four weeks after RR, CH, LV concentric remodelling and atrial enlargement were reversed. We performed bulk circulatory and LV miR sequencing. We did not observe differences linked to biological sex. RR restored normality for circulatory miRNome, whereas LV miRNome remained relatively similar to the one after MHS. Among the 25 most abundant circulatory miRs, ten were modulated by MHS (9 upregulated). In the LV, 8 of the 25 most abundant miR were upregulated by MHS, and 10 were downregulated. MiRNomes from AngII, HFD or MHS shared many common modulated miRs (32), suggesting that the overall response of organs producing the bulk of circulatory small non-coding RNA was similar even for seemingly different stress.

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 the internal mechanisms 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 biophysics mechanisms in cardiac tissue could clarify this connection. To explore this, we adapted a single-compartment, computational 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 mathematical model provides a cellular-level understanding of how high glucose levels can lead to bradycardia and sudden cardiac death.

This report elucidates the first surgical correction of an infundibular muscular ventricular septal defect (VSD) in a one-year-old Ragdoll cat via cardiac arrest using cardiopulmonary bypass, a method that is rarely used in feline cardiac surgery. VSDs can lead to congestive heart failure and pulmonary hypertension, particularly in patients with large shunts. This case involved a VSD that was atypically located and classified under the Soto classification instead of the standard Kirklin classification. Detailed echocardiography revealed that the defect required intervention owing to left heart and main pulmonary artery enlargement. Despite the VSD being located on the contralateral side, as anticipated in the preoperative examinations, the choice of median sternotomy allowed for successful closure of the defect. Conversely, the insertion of two cannulas into the ascending aorta resulted in damage to the adjacent thoracic duct, causing transient chylothorax, which resolved with conservative treatment. Cardiac arrest induced by a cardioplegic solution facilitated the surgical procedure, although it has led to anemia in cats. However, on postoperative day 490, the patient exhibited only minor residual shunting with normalized heart size, and remained healthy. This technique appears to be a viable treatment option for congenital heart disease in cats.

Heart failure (HF) is a life-threatening disorder and is treated by drug therapies and surgical interventions such as heart transplantation and left ventricular assist device (LVAD). However, these treatments can lack effectiveness in the long term and are associated with issues such as donor shortage in heart transplantation, and infection, stroke, or gastrointestinal bleeding in LVADs. Therefore, alternative therapeutic strategies are still needed. In this respect, stem cell therapy has been introduced for the treatment of HF and numerous preclinical and clinical studies using various types of stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been shown to improve cardiac function and attenuate left ventricular remodeling. IPSCs, which have a capacity of unlimited proliferation and differentiation to cardiomyocytes, are a promising cell source for myocardial regeneration therapy. This review discusses the current status of cardiac regenerative therapy using iPSCs.

Cardiovascular diseases (CVDs) remain the leading cause of mortality. Traditional approaches to diagnosing and treating CVDs often involve interpretation, which can lead to errors. The emergence of Artificial Intelligence (AI) and Machine Learning aids the management of CVDs. AI examines amounts of data and identifies patterns offering solutions for disease detection, risk prediction, and patient care. The American Heart Association's 2023 Scientific Sessions (AHA23) showcased studies that highlight AIs potential to revolutionize cardiac healthcare. This article presents a review of these cutting-edge studies exploring how AI is applied in health, the outcomes of these applications, and their implications for clinical practice. The insights gained from this review will contribute to the discussion on AI's role in healthcare and its capacity to enhance outcomes.

Heart failure (HF) affects about 60 million people worldwide, making it one of the chronic conditions with the greatest health and economic impact. The primary objective was to assess the efficacy of lung ultrasound (LUS) in the management of HF in order to intervene early and reduce the rate of hospital readmissions. A systematic search was conducted on PubMed, Embase, Google Scholar, Web of Science, and Scopus, including clinical trials, meta-analysis, systematic reviews, and original articles from 2019/1/1-2023/12/31, about LUS for the assessment of HF, on an outpatient basis, for HF diagnosis or/and decompensation. There may be risk of bias because the effects are dependent on the persons delivering the intervention. The results were synthetized by PRISMA method. A total of 873 articles were identified of which 33 articles were selected: [n=19] focused on prognostic assessment of HF, [n=11] centred on multimodal diagnostic assessments, and [n=2] addressing therapeutic guidance for HF diagnosis. LUS exhibits advantages in the detection of sub-clinical congestion linked to prognostic significance in re-admission and mortality during out-patient follow-up, after hospital discharge, and in complex scenarios as the patients' homes or institutional long-term care facilities. However, there are considerable uncertainties in their interpretation and monitoring changes due to its lack of standardization. The need for an updated international consensus on the use of LUS seems obvious.

The differentiation of ESCs into cardiomyocytes in vitro is an excellent and reliable model system for studying normal cardiomyocyte development in mammals, modeling cardiac diseases, and for use in drug screening. Mouse ESC differentiation still provides relevant biological information about cardiac development. However, the current methods for efficiently differentiating ESCs into cardiomyocytes are limiting. Here, we describe a “WNT Switch” method to efficiently commit mouse ESCs into cardiomyocytes using the small molecule WNT signaling modulators CHIR99021 and XAV939 in vitro. This method significantly improves the yield of beating cardiomyocytes, reduces number of treatments, and is less laborious.

Background: We aimed to evaluate whether baseline GLS and NT-proBNP and their changes after cardiac resynchronization therapy (CRT) can predict the long-term clinical outcomes and the echocardiographic-based response to CRT (defined by 15% relative reduction in left ventricular end-systolic volume). Methods: We enrolled 143 patients with stable, ischemic heart failure (HF) undergoing CRT-D implantation. NT-proBNP and echocardiogram were obtained before and 6 months after. The patients were followed-up (median: 58 months) for HF-related deaths and/or HF hospitalizations (primary endpoint) or HF-related deaths (secondary endpoint) Results: 84 patients achieved the primary and 53 the secondary endpoint, while 104 patients were considered as CRT-responders and 39 as non-responders. At baseline, event-free patients had higher absolute GLS values (p&lt;0.001) and lower NT-proBNP serum levels (p&lt;0001) than those achieving primary endpoint. A similar pattern was observed in favor of CRT-responders vs non-responders. In Cox regression analysis, lower baseline absolute GLS value (HR=0.77;95%CI, 0.51-1.91; p=0.002), higher baseline NT-proBNP levels (HR=1.55;95%CI, 1.43-2.01;p=0.002) and diabetes (HR=1.27;95%CI, 1.12-1.98;p=0.003) were associated with lower incidence of primary endpoint. Conclusions: In HF patients undergoing CRT-D, baseline GLS and NT-proBNP concentrations may serve as prognostic factors, while they may predict the echocardiographic-based response to CRT.

This study investigates the suitability of the timestamp approach algorithm for predicting blood pressure (BP) using wearable and comfortable devices, showcasing its accuracy even with low-frequency sampled signals. Developed within the SINTEC European project, the algorithm utilizes Electrocardiogram (ECG) and Photoplethysmogram (PPG) sensors, demonstrating promising results in both laboratory and hospital settings. The research emphasizes the algorithm’s potential to transform continuous and non-invasive BP monitoring through wearable technology, offering frequent measurements with minimal discomfort. While the study shows promise, further exploration is needed, focusing on optimizing machine learning coefficients for long-term monitoring applications and addressing potential changes over time. Technological improvements, including the implementation of edge computing algorithms, hold the key to enhancing BP accuracy, denoising techniques, and integrating alarm systems for future wearable solutions. This study emphasizes the adaptability of the algorithm for diverse healthcare environments, paving the way for broader applications in convenient and reliable BP monitoring.

Background There is a considerable overlap between clinical presentation of post-COVID-19 condition (PCC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) . Many of their common symptoms can be linked to dysregulation of the autonomic nervous system (dysautonomia). This study aimed to objectively assess autonomic function in patients with PCC and in patients with ME/CFS whose disease was not related to COVID-19. Methods Synchronous recordings of an electrocardiogram, continuous dynamics of blood pressure in the digital artery using the Penaz method and ultrasound pneumotachography with the spirography function were obtained with spiroarteriocardiorhythmography method in 34 patients diagnosed with ME/CFS, in whom the onset of the disease was not associated with COVID-19, 29 patients meeting PCC definition and 32 healthy controls. Heart rate variability (HRV), systolic and diastolic blood pressure variability (RV), respiration variability were assessed at rest and in tests with fixed respiratory rates. At rest, indicators of baroreflex regulation were additionally determined (baroreflex effectiveness index and baroreflex sensitivity). Results The total power, power of very low frequency, low-frequency and high-frequency of RR interval variability at rest as well as baroreflex effectiveness index in up-ramps of arterial blood pressure and baroreflex sensitivity were significantly lower both in PCC and ME/CFS patients compared to HC. Several diagnostic prediction models for ME/CFS were developed based on HRV parameters. During slow breathing HRV parameters return to normal in PCC, but not in ME/CFS. Correlation analysis revealed a close relationship of HRV, RV parameters and baroreflex sensitivity with fatigue, but not with HADS depressive/anxiety symptoms in ME/CFS and PCC. Conclusion A similar pattern of HRV and baroreflex failure with signs of a pathological acceleration of age-dependant dysautonomia was identified in ME/CFS and PCC. The clinical, diagnostic and therapeutic implications of these findings are discussed, in light of previously described relationship between inflammation, vascular pathology, atherosclerotic cardiovascular disease and autonomic dysfunction.

Gabapentin (GBP), a GABA analogue, is primarily used as an anticonvulsant to treat partial seizures and neuropathic pain. While a majority of the side effects are associated with the nervous system, emerging evidence suggests a high risk for heart diseases in the patients taking GBP. In the present study, we used a preclinical model of rats to investigate (1) the acute cardiovascular responses to GBP (bolus i.v. injection, 50 mg/kg) and (2) the effects of chronic GBP treatment (i.p. 100 mg/kg/day x 7 days) on cardiovascular function and the myocardial proteome. Under isoflurane-anesthesia, rat blood pressure (BP), heart rate (HR), and left ventricular (LV) hemodynamics were measured using Millar pressure transducers. The LV myocardium and brain cortex were analyzed by proteomics, bioinformatics, and western blot to explore the molecular mechanisms underlying GBP-induced cardiac dysfunction. In experiment (1), we found that i.v. GBP significantly decreased BP, HR, maximal LV pressure, and maximal and minimal dP/dt, whereas it increased IRP-AdP/dt, Tau, systolic, diastolic, and cycle durations (*p < 0.05 and **p < 0.01 vs baseline; n = 4/group). In experiment (2), we found that chronic GBP treatment resulted in hypotension, bradycardia, and LV systolic dysfunction, with no change in plasma norepinephrine. In the myocardium, we identified 109 differentially expressed proteins involved in calcium pathways, cholesterol metabolism, and galactose metabolism. Particularly, we found that calmodulin, a key protein of intracellular calcium signaling, was significantly upregulated by GBP in the heart but not in the brain. In summary, we found that acute and chronic GBP treatments suppressed cardiovascular function in rats, which is attributed to abnormal calcium signaling in cardiomyocytes. These data reveal a novel side effect of GBP independent of the nervous system, providing important translational evidence to suggest that GBP can evoke adverse cardiovascular events by depression of myocardial function.

Although the frequency of myocarditis in the general population is very difficult to accurately determine due to the large number of asymptomatic cases, the incidence of this disease is increasing significantly due to better defined criteria for diagnosis and the development of modern diagnostic method. The multitude of different etiological factors, the diversity of the clinical picture and the variability of the diagnostic findings make this disease often demanding both for the selection of the diagnostic modality and for the proper therapeutic approach. The previously known most common viral etiology of this disease is today overshadowed by new findings based on immune-mediated processes, associated diseases that in their natural course can lead to myocardial involvement, but also the iatrogenic cause of myocarditis due to use of immune checkpoint inhibitors in the treatment of cancer patients. Suspecting that a patient with polymorphic and non-specific clinical signs and symptoms, changes in ECG and echocardiography has myocarditis is the starting point in the diagnostic algorithm. Cardio magnetic resonance imaging is non-invasive diagnostic gold standard for diagnosis and clinical follow-up of thses patients. Endomyocardial biopsy as an invasive method is the diagnostic choice in life-threatening patients with suspicion of fulminant myocarditis where the diagnosis has not yet established or there is no adequate response to the applied therapeutic regimen. The treatment of myocarditis is increasingly demanding and includes conservative methods of treating heart failure, immunomodulatory and immunospressive therapy, methods of mechanical circulatory support and heart transplantation. The goal of developing new diagnostic and therapeutic methods is to reduce mortality from this complex disease, which is still high.

Background: Depending on the phase of the menstrual cycle the athlete is in, some kinetic, physiological and fatigue variables will show differences. The aim of this study is to analyze whether there are changes in these variables over the course of the menstrual cycle. Methods: Eight regular female runners and triathletes performed a maximal treadmill test, as well as a submaximal test (6’ stages at 50%, 60% and 80% of maximal aerobic speed) in each of the phases of the menstrual cycle: bleeding phase (day 2.4 ± 0.7), follicular phase (day 10.4 ± 2.2) and luteal phase (day 21.8 ± 2.1). Running dynamics were measured (using RunScribe) at the end of each test, as were lactate concentration, heart rate and fatigue (evaluated on a scale of 0 to 5). Results: Higher shock (G) values were recorded in the bleeding phase and higher vertical spring stiffness (kN/m) in the follicular phase. The phase of the menstrual cycle had a significant effect on average and peak heart rate, which was significantly higher in the follicular phase. Conclusions: Higher vertical spring stiffness was observed in the follicular phase, as well as higher peak and average heart rate.

Prevention of infections is crucial in solid organ transplant (SOT) candidates and recipients. These pa-tients are exposed to an increased infectious risk due to previous organ insufficiency and to pharmaco-logic immunosuppression. Besides infectious-related morbidity and mortality, this vulnerable group of patients is also exposed to the risk of acute decompensation and organ rejection or failure in the pre- and post-transplant period respectively, since antimicrobial treatments are less effective than in the immunocompetent patients. Vaccination represents a major preventive measure against specific infec-tious risks in this population but as responses to vaccines are reduced, especially in the early post-transplant period or after treatment for rejection, an optimal vaccination status should be obtained prior to transplantation whenever possible. This review reports the currently available data on the indications and modalities of vaccination in SOT adult candidates and recipients.

Background: Trans-septal endocardial left ventricle lead placement is an alternative technique used capture the left ventricular endocardially but it is use is limited due lack of evidence, practice uptake and clinical trials. we evaluated the efficiency of the procedure, post procedural complication rate, rate of thromboembolic events as well as changes in echocardiographic parameters, brain natriuretic peptide (BNP) level and the New York Heart Association (NYHA) class. Results: TSLV lead implant is safe, improves ejection fraction, LVEDV, LVESV, LVIDd. Significantly reduces NTproBNP levels and NYHA class. Stroke rate was reported only in one patient (9%), noticeably, this particular patient was on DOAC rather than anti-vitamin K antagonists. In this group, patients, who were on Warfarin , were not reported to have any thrombo-embolic events. Discussion: Trans-septal endocardial LV lead implant in patients with a failed CS approach remains a viable alternative however, there is a higher risk of stroke amongst these patients, as well as more procedure related risk of complications compared to conventional CRT. The data analysis demonstrates that patients undergoing a TSLV lead implant due to a failed trans-venous approach have more advanced heart failure, defined by their higher NYHA class compared to conventional trans-venous CRT implant groups. Their pre TSLV implant, echocardiographic parameters are also worse compared to trans-venous CRT implant group

For a subject suffering from complex post-traumatic stress disorder, a psychological intervention program was designed, monitored in real-time during psychotherapy, and evaluated quantitatively and qualitatively after psychotherapy. One male subject participated in this program under consent. The proposed intervention program was designed using cognitive behavioral therapy and stabilization treatments for body-based sensory processes in four sessions of 90 min each. During psychotherapy, a wearable heart sensor and a communication application were utilized to determine the subject’s current psychological state. After the intervention, the effect of the proposed program was analyzed qualitatively and quantitatively using the Impact of Event Scale–Revised (IES-R-K), Athens insomnia scale (AIS), and heart rate variability (HRV). After the intervention program was conducted, the subject reconstructed his traumatic events and trained himself with certain psychological techniques to decrease his negative thoughts and emotions induced by his previous traumatic events. The IES-R-K and AIS ten months after the last session were changed positively by approximately 25% compared with the subject’s state before the first session. During psychotherapy, the HRV exhibited a significant correlation with the subject’s emotional state. The proposed intervention program induced a positive change in the subject. Although the HRV was well utilized in this investigation, more sophisticated statistical analysis will be required for clinical trials.

This work deals with finding out whether the heart rate values of operators of forwarding machines during the work shift are influenced by the individual activities that the operator has to perform during timber skidding, or by the operators themselves. Furthermore, the work deals with determining the difficulty of individual activities in terms of physical load. For this purpose, the work shift of operators carrying out timber skidding was divided into individual activities: Driving, Maintenance, Forwarding, Break. During these work activities, the heart rate of each operator was taken for subsequent evaluation. The results show that the highest pulse rates of the operators were achieved during the Maintenance of the entrusted machine, while the highest pulse fluctuations in the operators were recorded during Forwarding. As part of this activity, the highest heart rate of the entire measurement process was recorded (132.0000 bpm), but also the lowest (42.0000 bpm). Furthermore, it was proven that both the operator and the activity he performs affect the pulse rate. The activities themselves did not differ from each other in only one of the six cases of comparison. Specifically, it was Driving and Forwarding.

Introduction: The choice of Cardiac Preservation Solution (CPS) for myocardial protection at the time of heart procurement remains controversial and uncertainties persist regarding its effect on the early and midterm Heart Transplantation (HTx) outcomes. Thus, we retrospectively analyzed our adult HTx performed with two different CPS, during a period of 12 years, in terms of hospital mortality, mid-term survival, inotropic score, primary graft dysfunction and rejection score. Methods: From January 2009 to December 2020, 154 adult HT were performed in our hospital. Patients were divided in two groups according to the CPS used: St. Thomas (n=75, group P 1) and HTK-Custodiol (n=79, group P 2). The choice of CPS was related to an institutional policy; from 2009 to 2015, St. Thomas solution was exclusively used, and after that, HTK-Custodiol alone. Results: There was no significant difference between the two groups in terms of preoperative and intraoperative features. Postoperatively, the Custodiol group showed significantly lower inotropic score (p&lt;0.0001), mean rejection score (p= 0.036) and 30 days mortality (p=0.0068). The use of HTK-Custodiol was the only variable that improved midterm survival (HTK-Custodiol vs St Thomas, HR= 0.20 (95% CI: 0.069 -0.6) p=0.0039). Conclusion: In our single center experience, using HTK-Custodiol as myocardial protection during heart procurement leads to improved outcomes after HTx, including postoperative inotropic score, rejection score, 30-days mortality and midterm survival.

The circadian and stress-realizing systems are interconnected, and the balance of their interaction determines the state of human health. The objective of this study was to investigate the modulating effect of activating the circadian system on heart rate variability in female medical students with high anxiety while performing a cognitive task. After 20 minutes of adequate stimulation of circadian photoreceptors with a monochromatic blue light, the cognitive task performance resulted in a decrease in sympathetic impact. During the session of using Blue Sky Pro glasses, a trend of increasing heart rate variability was observed in a state of relative rest (especially in the first 5 minutes). A comparative analysis of the parameters of the letter cancellation test before and after light exposure revealed a statistically significant increase in the indexes reflecting mental productivity, work accuracy, and concentration of attention. The results suggest an essential physiological role of the human circadian system in modulating the autonomic and psycho-emotional conditions, as well as cognitive functions of individuals with high anxiety. Our findings indicate the possibility of quickly correcting the balance in human systemic regulatory mechanisms using the activation of retinal circadian photoreceptors by blue light.

Several studies have reported a relationship between autonomic dysfunction　 during tasks and Internet addiction. Changes within 24 h regarding heart rate variability (HRV) may be a more sensitive indicator than short term observations. We evaluated the influence of excessive Internet usage on HRV using a 24 h electrocardiogram (ECG) and examined acute changes during computer game tasks. A total 13 high school students and 22 young adults were recruited, and divided into excessive Internet user and non- excessive user groups based on Internet addiction test scores. The ECG was recorded continuously for 24 h by a wearable sensor and during two computer games (the Iowa gambling task and each participant’s preferred game) using a standard type ECG system. Multiple psychometric tests were also conducted. The excessive Internet user group exhibited clinically significant depressive symptoms, and higher self-reported scores for anxiety, impulsivity, autistic tendencies, and sleep problems than the non- excessive internet user group. There were weak differences within the 24 h high-frequency (HF) band power between two groups. During the Iowa gambling task, younger participants exhibited a reduced HF response, which may be related to weaker top- down self- regulatory mechanisms.

This case report examined the characteristics of body composition, sleep quality, and autonomic nerve activity in active older adults with a younger body age—calculated from age trends in body composition and basal metabolic rate. We selected two cases who had a metabolic age younger than their actual age. They had good sleep quality, low sleep quality scores, no sarco-penia, strong muscle and grip strength, and balanced autonomic nervous system activity. Fur-thermore, they were determined to be much younger than their actual age. They were compared with two other age- and sex-matched cases, who had poor sleep quality, unbalanced autonomic nervous system activity, and had a physical age closer to their actual age. Older adults with more muscle mass and higher basal metabolism were younger than their actual age, had a better sleep status, and a good balance of autonomic nervous activity in the exercise stimulation. They also had lower percentages of body- and visceral fat and higher body water. Meanwhile, the older adults with standard muscle mass and basal metabolic rate had a poor sleep status and no sympathetic hyperactivity in the exercise simulation.

Background: Anthracyclines form the backbone of many systemic chemotherapy regimens but dose-limiting cardiotoxicity can also lead to reduction in cardiac function and an increased risk of heart failure. Methods: This review was conducted in accordance with PRISMA guidelines and registered on PROSPERO (CRD42022373496). Results: 26 studies met the eligibility criteria including a total of 910 patients. Overall reduction in pooled mean left ventricular ejection fraction (LVEF) post‐anthracyclines in the placebo arms of included randomised-controlled trials was 4.6% (95% CI, 2.7 to 6.6). The trend in LVEF showed a progressive decline until approximately 180 days after which there was no significant change. Those receiving a cumulative anthracycline dose 300 mg/m2 experienced a more profound reduction. The risk of a 10% absolute decline in LVEF from baseline or decline to an LVEF below 50%, the overall pooled risk was 16% (95% CI: 11 to 21; I2 = 77%). Sensitivity analyses by baseline LVEF and trastuzumab treatment status did not yield significant differences. Conclusion: While the mean LVEF decline in patients without cardioprotective therapy was clinically small, a vulnerable subset experienced significant impairment. Further research to best identify those who benefit most from cardioprotective therapies when receiving anthracyclines are required.

Nowadays, fostered by technological progress and contextual circumstances such as economic crisis and pandemic restrictions, remote education is living a growing deployment. However, this growth generated widespread doubts about the actual effectiveness of remote/online compared to face-to-face education. The present study aimed at comparing face-to-face and remote education through a multimodal neurophysiological approach. It involved forty students at a driving school, during a real classroom, experiencing both the modalities. Wearable devices to measure brain, ocular, heart and sweating activities were employed in order to analyse the students’ neurophysiological signals to obtain insights about their cognitive dimension. In particular, four parameters were considered, the Eye Blink Rate, the Heart Rate and its Variability and the Skin Conductance Level. Also, the students filled a questionnaire at the end to obtain an explicit measure of their learning performance. Data analysis showed a higher cognitive activity, in terms of attention and mental engagement, in presence with respect to remote modality. On the other hand, students by remote felt more stressed, in particular during the first part of the lesson. Analysis of questionnaires demonstrated worst performance by remote, thus suggesting a common “disengaging” behaviour when attending remote courses, thus undermining their effectiveness. In conclusion, neuroscientific tools could help to obtain insights about mental concerns, often «blind», such as attentional decreasing and stress increasing, as well as their dynamics during the lesson itself, so allowing to define proper countermeasures to emerging issues when introducing new practices into daily life.

Background: Heart rate variability is a non-invasive, measurable, and established autonomic nervous system test. Long-term COVID-19 sequelae are unclear; however, acute symptoms have been studied. Objectives: To determine autonomic cardiac differences between long COVID-19 patients and heathy controls and evaluate associations among symptoms, comorbidities, and laboratory findings. Methods: This single-center study included long COVID-19 patients and healthy controls. The heart rate variability (HRV), a quantitative marker of autonomic activity, was monitored for 24 h using an ambulatory electrocardiogram system. HRV indices were compared between case and control groups. Symptom frequency and inflammatory markers were evaluated. The significance level of 5% (p-value 0.05) was adopted. Results: A total of 47 long COVID-19 patients were compared to 42 healthy controls. Patients averaged 43.8 (SD14.8) years old, and 60.3% were female. In total, 52.5% of patients had moderate illness. Post-exercise dyspnea was most common (71.6%), and 53.2% lacked comorbidities. COVID-19 patients had 4 times more dyslipidemia. CNP, D-dimer, and CRP levels were elevated (p-values of 0.0098, 0.0023, and 0.0015, respectively). The control group had greater SDNN24 and SDANNI (OR = 0.98 (0.97 to 0.99; p = 0.01)). Increased low-frequency (LF) indices in COVID-19 patients (OR = 1.002 (1.0001 to 1.004; p = 0.030)) and high-frequency (HF) indices in the control group (OR = 0.987 (0.98 to 0.995; p = 0.001)) were also associated. Conclusions: Patients with long COVID-19 had lower HF values than healthy individuals. These variations are associated with increased parasympathetic activity, which may be related to long COVID-19 symptoms and inflammatory laboratory findings.

Driver drowsiness is one of the leading causes of traffic accidents. This paper proposes a new method for classifying driver drowsiness using deep convolution neural networks trained by wavelet scalogram images of electrocardiogram (ECG) signals. Three different classes were de-fined for drowsiness based on video observation of driving tests performed in a simulator for manual and automated modes. The Bayesian optimization method is employed to optimize the hyperparameters of the designed neural networks, such as the learning rate and the number of neurons in every layer. To assess the results of the deep network method, Heart Rate Variability (HRV) data is derived from the ECG signals, some features are extracted from this data, and finally, random forest and k-nearest neighbors (KNN) classifiers are used as two traditional methods to classify the drowsiness levels. Results show that the trained deep network achieves balanced accuracies of about 77% and 79% in the manual and automated modes, respectively. However, the best obtained balanced accuracies using traditional methods are about 62% and 64%. We conclude that designed deep networks working with wavelet scalogram images of ECG signals significantly outperform KNN and random forest classifiers which are trained on HRV-based features.

The ryanodine receptor (RyR) is a Ca2+ release channel in the sarcoplasmic reticulum of skeletal and cardiac muscles and plays a key role in excitation-contraction coupling. The activity of the RyR is regulated by many intracellular factors such as divalent cations (Ca2+ and Mg2+), nucleotides, associated proteins, and reactive oxygen species. Since these intracellular factors change depending on the condition of the muscle, e.g., exercise, fatigue, or disease states, the RyR channel activity will be altered accordingly. In this review, we describe how the RyR channel is regulated under various conditions and discuss the possibility that the RyR acts as a sensor for change in the cellular environment of muscles.

Background: Left ventricular noncompaction (LVNC) is a genetically determined cardiomyopathy, that occurs following a disruption of endomyocardial morphogenesis. The purpose of this study was to identify the clinical characteristics and genetic profile of children with LVNC. Methods: From February 2008 to July 2020, a total of 32 children (median 11.5 years) with LVNC were prospectively enrolled and followed up for the median of 4.02 years. Diagnosis was made based on characteristic features of LVNC in echocardiography and cardiovascular magnetic resonance (CMR). Patients’ clinical symptoms, family history, ECG, Holter ECG and genetic tests were also evaluated. Results: The most common presenting symptom was heart failure (31% of children). ECG abnormalities were noted in 56% of patients. The most prominent features were ventricular arrhythmias, sinus bradycardia and paroxysmal third-degree atrioventricular block. Most of the patients (94%) met the criteria for LVNC and CMR confirmed this diagnosis in 82% of cases. The molecular etiology was found in 53% of children. Conclusion: Although heart failure and arrhythmias were very frequent in our study group, thromboembolic events and genetic syndromes were rare. For accurate and reliable assessment of children with LVNC, it is necessary to get to know their family history and detailed clinical profile.

Several performance-enhancing or ergogenic drugs have been linked to both significant adverse cardiovascular effects and increased cardiovascular risk. Even with increased scrutiny on the governance of performance-enhancing drugs (PEDs) in professional sport and heightened awareness of the associated cardiovascular risk, there are some who are prepared to risk their use to gain competitive advantage. Caffeine is the most commonly consumed drug in the world and its ergogenic properties have been reported for decades. Thus, the removal of caffeine from the World Anti-Doping Agency (WADA) list of banned substances, in 2004, has naturally led to an exponential rise in its use amongst athletes. The response to caffeine is complex and influenced by both genetic and environmental factors. Whilst the evidence may be equivocal, the ability of an athlete to train longer or at a greater power output cannot be overlooked. Furthermore, its impact on the myocardium remains unanswered. In contrast, anabolic steroids are recognised PEDs that improve athletic performance, increase muscle growth and suppress fatigue. Their use, however, comes at a cost, afflicting the individual with several side effects, including those that are detrimental to the cardiovascular system. This review addresses the effects of the two commonest PEDs, one legal, the other prohibited, and their respective effects on the heart, as well as the long-term implications.

A newly identified novel coronavirus named as severe acute respiratory syndrome-related coronavirus2 (SARS‐CoV 2) has given rise to the global pandemic. SARS-CoV2 which causes coronavirus disease 2019 (COVID-19), is a positive-stranded RNA virus with nucleocapsid. It binds to host angiotensin-converting enzyme2 (ACE2) receptor through surface glycoprotein (S protein). These ACE 2 receptors are attached to the cell membranes of many organs. Thus, COVID-19 does not only result in acute respiratory distress syndrome but also affects multiple organ systems, requiring a multidisciplinary approach to manage this disease. COVID-19 can damage the myocardial cells and result in fulminant myocarditis, acute cardiac injury, cardiomyopathy, heart failure, cardiogenic shock, or arrhythmia. COVID-19 seeds harmful immune response through cytokine storm leading to indirect organ damage. In this literature review, the available data is comprehended regarding cardiovascular complications in COVID-19, and the correlation of biomarkers with the disease activity is discussed. This literature review also highlights the important treatment options and outcomes of the individual study.

The use of machine learning techniques in predictive health care is on the rise with minimal data used for training machine-learning models to derive high accuracy predictions. In this paper, we propose such a system, which utilizes Heart Rate Variability (HRV) as features for training machine learning models. This paper further benchmarks the usefulness of HRV as features calculated from basic heart-rate data using a window shifting method. The benchmarking has been conducted using different machine-learning classifiers such as artificial neural network, decision tree, k-nearest neighbour and naive bays classifier. Empirical results using MIT-BIH Arrhythmia database shows that the proposed system can be used for highly efficient predictability of abnormality in heartbeat data series.

Objective: We determined, in stable ambulatory heart failure with preserved ejection fraction (HFpEF) subjects and matched controls, the capability of a novel blood based cardiac-specific cBIN1 Score (CS) to diagnose heart failure and prognosticate future hospitalization. Background: Heart failure (HF) poses a costly health care burden worldwide with rising prevalence. Abnormal calcium signaling is intrinsic to HF pathophysiology and correlates with reduced expression of a cardiac membrane scaffolding protein, cardiac bridging integrator 1 (cBIN1). We hypothesize that CS, a numerical score derived from plasma cBIN1 concentration, is a diagnostic and prognostic biomarker of HF. Methods: Plasma cBIN1 is quantified by an ELISA test, and CS is calculated as the natural log of the normalized reciprocal of plasma cBIN1 concentration. We determined CS among 52 clinically stable individuals with HFpEF (LVEF ≥ 50%) (mean age 57 ± 15 years old, 63% men) and 104 age and sex matched volunteers with no known history of HF. We obtained plasma concentrations of NT-proBNP, a marker of volume status, as comparison. Baseline co-morbidities and one year longitudinal clinical information were obtained through electronic medical records. Results: Median CS is 0 (IQR -0.4 – 0.6) in the control cohort and is increased to 1.8 in the HFpEF cohort (IQR 1.5 – 2.3, p < 0.0001). For HFpEF diagnosis, CS has a receiver operating characteristic (ROC) area under the curve (AUC) of 0.94 (95% CI 0.95 – 0.99) and NT-proBNP of 0.89 (95% CI 0.83 – 0.95). Kaplan-Meier analysis of one year cardiovascular hospitalizations reveals that HFpEF patients with CS ≥ 1.8 have a hazard ratio (HR) of 4.0 (95% CI 1.4 – 11.2, p=0.009). Combining CS ≥ 1.8 with NT-proBNP ≥ 300 pg/mL, increases HR to 21.4 (95% CI 2.7 – 171.6, p=0.004). Conclusions: In a cohort of stable ambulatory HF patients with cardiomyopathies of multiple etiologies and preserved ejection fraction, a positive CS correlates with worsening myocardial health and predicts future hospitalization. CS, a marker of cardiac muscle health, provides a novel index to informing the management of stable ambulatory HF patients.

Objective: We determined, in stable ambulatory heart failure with reduced ejection fraction (HFrEF) subjects and matched controls, the capability of a novel blood based cardiac-specific cBIN1 Score (CS), which assesses the health of cardiac muscle, to identify patients with known heart failure (HF) and to prognosticate future hospitalization. Background: Limited clinical tools are available in assessing cardiac muscle health in stable ambulatory patients. Cardiac bridging integrator 1 (cBIN1) is a cardiomyocyte t-tubule membrane scaffolding protein which regulates calcium signaling in cardiomyocytes, decreases in failing muscle, and is present in plasma in levels that correlate with cardiac content. We hypothesize that CS, a normalized index of plasma cBIN1 concentration, can function as a diagnostic and prognostic biomarker of HF. Methods: Plasma cBIN1 concentration is measured by an ELISA test, and CS is calculated as the natural log of the ratio of a constant population mean cBIN1 to measured cBIN1 concentration. We determined CS among 125 clinically stable individuals with HFrEF (LVEF ≤ 40%) (mean age 56 ± 10 years old, 79% men) and 125 age, sex matched volunteers with no known history of HF. We obtained plasma concentrations of NT-proBNP, a marker of volume status, as comparison. Baseline co-morbidities and 18-month longitudinal clinical information were obtained through electronic medical records. Results: CS follows a normal distribution with a median of 0 in the control population and median is significantly increased among HFrEF patients to 1.8 (IQR 1.4 – 2.1, p < 0.0001). CS diagnosed HFrEF with a receiver operating characteristic (ROC) area under the curve (AUC) of 0.93 (AUC is 0.98 for NT-proBNP, and combined CS and NT-proBNP AUC is 0.99). Unlike NT-proBNP, CS does not correlate with body mass index (BMI) in either the control or HFrEF population (Pearson’s r = -0.15, p = 0.12; Pearson’s r = 0.003, p = 0.97, respectively). NT-proBNP significantly correlates with renal function (Pearson’s r = -0.37, p = 0.001), while CS also has no correlation (Pearson’s r = 0.03, p = 0.71). During an 18-month follow-up, a high CS ≥ 1.8 at the initial visit predicted future cardiovascular hospitalizations (38% vs. 21%, p = 0.04, hazard ratio 2.0). NT-proBNP did not predict future cardiovascular hospitalizations. Conclusions: Plasma cBIN1 based CS is insensitive to BMI and renal function and differentiates myocardial health between patients with HFrEF versus matched controls. An abnormally high CS reflected poor intrinsic myocardial health and can predict future 18-month cardiac hospitalization in stable ambulatory patients.

The Myval is a balloon-expandable transcatheter heart valve (THV) devel-oped by Meril Life Sciences Pvt. Ltd. that has innovative operator-friendly de-sign which aids to improve deliverability and features precise deployment. Vari-ous clinical studies demonstrate its effectiveness and safety, making it a promis-ing choice in valvular interventions. Myval has been successfully utilized as a transcatheter aortic valve implanta-tion (TAVI) device in cases with conduction disturbances, bicuspid aortic valve anatomy, non-calcified aortic regurgitation, dysfunctional stenosed right ventric-ular outflow tract (RVOT) conduits, pulmonary valve replacement, mitral valve replacement, Vave-in-valve and Valve-in-ring implantation procedures. Myval’s diverse sizes are also of key importance in complex cases of large and complex annuli anatomy. Further long-term studies are needed to consolidate these results. Its introduction signifies a significant advancement in cardiology, aiming to enhance patient outcomes and quality of life. In the present review, we provide an update on new-generation Myval THVs and review the available clinical data published till date with an emphasis on diverse use in specific clinical scenarios.

Background/Objectives: Heart failure (HF) is a chronic disease with a steadily increasing prevalence, high mortality, social and economic costs. Furthermore, every hospitalisation for acute HF is associated with worsening prognosis and reduced life expectancy. In order to prevent hospitalisations, it would be useful to have instruments that can predict them well in advance. Methods: We performed a review on remote monitoring of heart failure through implantable devices.; Results: Precise multi-parameter algorithms, available for ICD and CRT-D patients, have been created, which also use artificial intelligence and are able to predict a new heart failure event more than 30 days in advance. There are also implantable pulmonary artery devices that can predict hospitalisations and reduce the impact of heart failure. proper organisation of transmission and alerts management is crucial for clinical success in using these tools. Conclusions: The full implementation of remote monitoring of implantable devices and in particular the use of new algorithms for the prediction of acute heart failure episodes represents a huge challenge but also a huge opportunity.

The study´s goals were to determine the health status of a group of heart transplant recipients (HTR) and their level of physical activity and to compare the health status among them and with a group of healthy sedentary individuals. Fifty-four HTR and eighteen S were assigned to four groups, according to their level of physical activity (determined with The International Physical Activity Questionnaire); patients with a low, a moderate and a high level of physical activity (HTRL, HTRM and HTRH, respectively) and sedentary individuals (S). Participants underwent a basic blood analysis and several tests to assess their cardiovascular, neuromuscular, functional mobility condition and their quality of life. The S and HTRH were very similar in terms of BP, HR and blood analysis while HTRM and HTRL differed from both S and HTRH in these parameters. Regarding the cardiovascular, neuromuscular, functional mobility, and quality of life variables assessed in this study, HTRH showed the best results across all of them, followed by S, HTRM, and HTRL. It is suggested that the weekly level of physical activity of HTR should be high, what might help them to enhance their health and quality of life.

Heart failure (HF) is a syndrome characterized by signs and symptoms resulting from structural or functional cardiac abnormalities, confirmed by elevated natriuretic peptides or evidence of congestion. HF patients are classified according to left ventricular ejection fraction (LVEF). Worsening HF (WHF) is associated with increased short- and long-term mortality, re-hospitalization, and healthcare costs. Standard treatment of HF includes angioten-sin-converting enzyme inhibitors, angiotensin receptor-neprilysin inhibitors, mineralocorti-coid-receptor antagonists, beta-blockers, and sodium-glucose co-transporter 2 inhibitors. To manage systolic HF by reducing mortality and hospitalizations in patients experiencing WHF, treatment with vericiguat, a direct stimulator of soluble guanylate cyclase (sGC), is indicated. This drug acts by stimulating sGC enzymes, part of the nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) signaling pathway, regulating the cardiovascular system by catalyzing cGMP synthesis in response to NO. cGMP acts as a second messenger, triggering various cellular effects. Deficiencies in cGMP production, often due to low NO availability, are implicated in cardiovascular diseases. Vericiguat stimulates sGC directly, bypassing the need for a functional NO-sGC-cGMP axis, thus preventing myocardial and vascular dysfunction associated with de-creased sGC activity in heart failure. Approved by the FDA in 2021, vericiguat administration should be considered, in addition to the four pillars of HFrEF therapy, in symptomatic patients with LVEF < 45% following a worsening event. Cardiac rehabilitation represents an ideal setting where there is more time to implement therapy with vericiguat and incorporate a greater num-ber of medications for the management of these patients. This review covers vericiguat's metab-olism, molecular mechanisms, and drug-drug interactions.

Athlete’s heart is characterised by structural, functional, and electrical remodelling. During an exercise session, the heart increases the use of oxygen, which is associated with decreased vascular resistance in the lungs’ circulation. Left ventricular hypertrophy is an echocardiographic modification especially met in endurance athlete’s heart. Moreover, left atrial dilatation represents another important characteristic of endurance athletes. Electrical modulation in the athletic heart induces neurological modifications leading to sinus arrhythmia, bradycardia, early repolarisation, and first-grade atrioventricular (AV) blocks. Athletes' nutritional status involves the assimilation of macronutrients such as proteins, carbohydrates, and fats. Depending on the duration of physical exercise, ATP can be obtained in aerobic or anaerobic conditions. This systematic review aims to find correlations between different evaluative methods of cardiac adaptation and present the metabolism in performance athletes.

Heart sounds and murmurprovidecrucial diagnosis information for valvular heart diseases (VHD). Phonocardiogram (PCG) combined with modern digital processing techniques, provides a complementary tool for clinicians. This article proposes a benchmark different time-frequency representations, which are spectogram, mel-spectogram and cochleagram for obtaining images, in addition to the use of two interpolation techniques to improve the quality of the images, which are Bicubic and Lanczos. Deep features are extracted from a pre-trained model called VGG16 and for feature reduction the Boruta algorithm is applied. To evaluate the models and obtain more precise results, nested cross-validation is used. The best results achieved in this study were for coclegram with 99.2% accuracy and mel-spectogram representation with the bicubic interpolation technique which reached 99.4% accuracy, both having support vector machine (SVM) as classifier 10 algorithm. Overall, this study highlights the potential of time-frequency representations of PCG 11 signals combined with modern digital processing techniques and machine learning algorithms for 12 accurate diagnosis of VHD.

Pregnancy is a complex biological process which is associated with significant metabolic and hemodynamic changes of the maternal body which allow a normal fetal growth. The inability to adapt to these changes can affect the cardiovascular health. During pregnancy, women may experience mood swings, anxiety and emotional ambivalence. These symptoms can lead to stress and have a negative impact on the mental well-being of expectant mothers. It is crucial to know the aspects that can influence the development of cardiovascular problems among pregnant women in order to manage these cases properly. The current narrative review explores and summarizes the evidence regarding the impact of stress and anxiety on cardiovascular health in pregnant women. Understanding the physiological adaptations that the body undergoes throughout pregnancy is crucial for educating and supporting individuals as well as healthcare professionals. This enables them to recognize any risk factors or pathological conditions that may exacerbate pregnant women's health. In order to reduce maternal morbidity and mortality from cardiovascular disease, a psychological and cardiovascular risk factor screening that is done either before or during pregnancy may be able to identify situations that call for particular medical and/or psychological therapies.

Obesity is invariably accompanied by autonomic dysfunction, although data in pediatric populations are conflicting. We conducted a systematic review and meta-analysis of 12 studies (totaling 1102 participants) comparing obese and normal-weight subjects (5-18 years of age), defined as body mass index &gt;95th or &lt;85th percentile, respectively. Using a random-effects model, we report the standardized mean differences (SMD) of sympathetic and vagal indices, calculated by heart rate variability. Autonomic dysfunction was present in the obese group, based on the average SMD in the standard deviation of sinus intervals (at -0.5340), and on the ratio of low (LF) to high (HF) frequency spectra (at 0.5735). There was no difference in sympathetic activity, but the heterogeneity among the relevant studies weakens this result. SMD in HF (at 0.5876), in the root mean square of successive differences between intervals (at -0.6333), and in the number of times successive intervals exceeded 50ms divided by the total number of intervals (at -0.5867) indicated lower vagal activity in the obesity group. Thus, autonomic dysfunction is present in obese children and adolescents, attributed to lower vagal activity. Further studies on autonomic function are needed in various pediatric cohorts, placing emphasis on sympathetic activity.

Background: Catheter ablation (CA) benefits atrial fibrillation (AF) patients with heart failure (HF). Brain natriuretic peptide (BNP), a marker of left-ventricular pressure load, may serve as a potential surrogate for predicting quality of life (QOL) in broader range of patients. Methods: Within the multicenter KiCS-AF registry, 491 AF patients underwent CA without clinical HF (e.g. documented history of HF, left ventricular ejection fraction ≤40%, or BNP levels ≥100 pg/mL). Participants, aged 61±10 years, were categorized by baseline BNP quartiles. Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) questionnaire assessments were assessed at baseline and 1 year. Results: Lower baseline BNP correlated with reduced AFEQT scores. Post-CA, all groups showed significant AFEQT score improvements. Lower BNP group displayed notable enhancements (18.2±1.2, 15.0±1.1, 12.6±1.2, 13.6±1.2, p<0.005), especially in symptom and treatment concern areas. Even those with normal BNP levels (≤18.4 pg/ml) exhibited significant QOL improvements. Comparing PAF and non-PAF groups, the PAF group, especially with higher BNP levels, showed greater AFEQT score improvements. Conclusion: This study establishes BNP as a predictive marker for QOL enhancement in non-HF patients undergoing CA for AF. BNP levels represent AF stages, with individuals in earlier stages, especially within normal BNP levels, experiencing greater QOL improvement.