Healthy Heart Research Articles

Abstract MP56: Screening for Familial Hypercholesterolemia: School Based Programs May Be Best Alternative

Introduction: Familial Hypercholesterolemia (FH) is an autosomal dominant condition characterized by elevated cholesterol and premature development of cardiovascular (CV) disease affecting 1/200 - 1/500 individuals. Only 10% of the affected population in the United States have been identified and treated compared to 50-70% in Scandinavian countries identified through school-based or universal screening programs. Hypothesis Statement: School based programs are the best mechanism for FH screening. Methods: The Healthy Hearts and Minds Program (HHM) through UCHealth performs biometric screenings on 5th, 7th, and 10th grade students in Northern Colorado. HHM tested 10,991 5th grade students (9/2017 - 5/2022) and identified 424 students with total cholesterol levels ≥200 mg/dL (range 200-302). A buccal smear test (APOB, LDLR, PCSK9) was performed on 99 individuals with the highest total cholesterol levels to identify genetic status. A binomial logistic regression model was used for analysis. Results: Of the 99 students, six tested positive (50% male, 10.3 years, 22.8 BMI) for FH with five (40% male, 11.3 years, 17.3 BMI.) reporting a variant of indeterminate significance. A sigmoidal association between total cholesterol and predicted chance of FH was identified with the inflection point at ~270 mg/dL. Conclusions: Comprehensive school based programs are the most effective and equitable means of identifying this genetic based disease and should be supported in a collaborative manner with health care systems, industry and the community. With availability to all students, diversity, equity, and inclusion concerns are addressed and provide at risk populations with personalized health information. The results from this study suggest a school-based screening program can be effective at identifying students most at risk for FH. These results further define the relation between total cholesterol and predicted chance of FH for a school-aged population where 245 mg/dL indicates a 10.3% of testing positive for FH whereas 275 mg/dL has a 54.8% chance. Additionally, the multiplier effect documented through cascade FH testing enhances the benefit of the information to other family members, as the autosomal dominant pattern insures that 50% of members will be at risk. The individual benefit of identifying FH early is the treatability of this condition. Early use of lipid lowering agents can make the CV disease risk equal to the general population. If left untreated, CV disease occurs approximately 10 years earlier which results in increased mortality and disability, along with increased health care costs. Therefore, if elevated cholesterol is present in school children, genetic testing is warranted and treatment considered by age 8-10 years, especially if signs of abnormal vascular plaquing is identified.

Analysis of Types of Physical Activity on Active Elderly Community in Bandung City

Physical activity can improve health and reduce the risk of some diseases, and most importantly it can improve the quality of life of the elderly. The purpose of this study was to determine the level of physical activity and the type of physical activity carried out by the elderly daily in the elderly community in Bandung City. The method used is descriptive with a quantitative approach. This data collection technique used a purposive sampling technique, and the level of physical activity was measured using the International Physical Activity Questionnaire-Short Form (IPAQ-SF) questionnaire. The sample of this study was 40 people consisting of the Pasir Layung Elderly Community 20 people and the Setiabudhi Healthy Heart Community 20 people. The results of this study are that the majority of the elderly do physical activity every day, namely gymnastics as much as 75% and the majority of the elderly in this community have a high level of physical activity as much as 52%. It is proven that the elderly here have a high level of physical activity and have good physical activity.

Abstract P256: Rationale, Development, and Implementation of a Multidisciplinary Digital Lifestyle Health Education Program for Older Adults With Cardiovascular Disease and Osteoarthritis

Introduction: Cardiovascular disease (CVD) is the leading cause of death worldwide. Globally, osteoarthritis (OA) affects 654 million. In 2018, of the 1.2 million Australians who had CVD, half also had arthritis, with the most common form in Australia being OA. Ongoing pain and physical limitations from OA can affect lifestyle choices, contributing to the shared risk factor profile of CVD and OA (physical inactivity, overweight/obesity, poor diet, high medication use). This contributes further to the burden of both diseases including reduced 6-minute walk (6MW) performance, which is directly related to increased CVD mortality. This project outlines the rationale for and development of a multidisciplinary digital lifestyle health education program for the treatment and secondary prevention of CVD and its common comorbidity of OA. Methods: This study is a cross-sectional analysis of older adults in Sydney. Class was classified based on the Australian socioeconomic index for areas. Conditions were defined according to Australian national guidelines. Medical history, body mass index (BMI), waist measurement, muscle strength, and 6MW measurements were assessed. Differences between those with and without OA were determined via one-way analysis of variance. Simple linear regressions assessed potential relationships. Results: In a cohort of 532 adults; n=341 (64.1%) had diagnosed CVD; 48.4% of which had OA (mean age 66±12 years; 73.3% female). Socioeconomic index was deemed high. In the OA cohort mean BMI and waist were above healthy heart recommendations according to the World Health Organisation. There were no significant differences between those with OA and those without for cardiovascular risk factors of body weight, BMI, waist measurement, blood pressure, 6MW, or muscle strength. However, in those with CVD and OA, the relationship between age and 6MW was stronger and age accounted for more of the variance in performance (r=-0.44; r 2 =0.19; p<0.001) than those without OA (r=-0.37; r 2 =0.17; p<0.001), indicating a greater reduction in walking ability in those with OA as they get older. Conclusion: With 6MW performance being related to CVD mortality, interventions are needed to improve health and fitness in this cohort. International guidelines for CVD and OA recommend treatment should prioritise lifestyle changes, including a healthy diet, regular physical activity, and interventions that address all risk factors. Lifestyle LIFEMAP will assess the efficacy of a widely translatable multidisciplinary digital evidence-based 10-module lifestyle, food, exercise, medication, and park prescription education program for adults with the comorbidity of CVD and OA. We expect this program to improve knowledge, and healthy lifestyle choices, thereby improving physical activity and health outcomes in this highly vulnerable population.

Sex-and age-related variations in myocardial tissue composition of the healthy heart: a native T1 mapping cohort study.

Cardiovascular diseases manifest differently in males and females, potentially influenced by inherent sex- and age-related differences in myocardial tissue composition. Such inherent differences are not well-established in the literature. With this study using cardiac magnetic resonance (CMR) native T1 mapping, we aim to determine the effect of sex and age on myocardial tissue composition in healthy individuals. CMR native T1 mapping was performed in 276 healthy individuals (55% male, age 8---84 years) on a 1.5 Tesla scanner using a MOLLI 5(3)3 acquisition scheme. Additionally, 30 healthy participants (47% male, age 24-68 years) underwent a 1-year follow-up CMR to assess the longitudinal changes of native T1. Mean native T1 values were 1000 ± 22 ms in males and 1022 ± 23 ms in females [mean difference (MD) = 22 ms, 95% confidence interval (CI) (17, 27)]. Female sex was associated with higher native T1 in multivariable linear regression adjusting for age, heart rate, left ventricular mass index, and blood T1 [β=10 ms, 95% CI (3.4, 15.8)]. There was no significant interaction between sex and age (P = 0.27). Further, age was not associated with native T1 [β=0.1 ms, 95% CI (-0.02, 0.2)], and native T1 did not change during a 1-year period [MD -4 ms, 95% CI (-11, 3)]. Female sex was associated with higher native T1; however, there was no association between age and native T1. Additionally, there was no evidence of an interaction between sex and age. Our findings indicate intrinsic sex-based disparities in myocardial tissue composition.

Stressing heart cells to study disease

Tension across heart muscle cells in 3D engineered tissues prompts distinct electrical changes in healthy and diseased heart cells.

3D models of the cardiac conduction system in healthy neonatal human hearts

Iatrogenic damage to the cardiac conduction system (CCS) remains a significant risk during congenital heart surgery. Current surgical best practice involves using superficial anatomical landmarks to locate and avoid damaging the CCS. Prior work indicates inherent variability in the anatomy of the CCS and supporting tissues. This study introduces high-resolution, 3D models of the CCS in normal pediatric human hearts to evaluate variability in the nodes and surrounding structures. Human pediatric hearts were obtained with an average donor age of 2.7 days. A pipeline was developed to excise, section, stain, and image atrioventricular (AVN) and sinus nodal (SN) tissue regions. A convolutional neural network was trained to enable precise multi-class segmentation of whole-slide images, which were subsequently used to generate high- resolution 3D tissue models. Nodal tissue region models were created. All models (10 AVN, 8 SN) contain tissue composition of neural tissue, vasculature, and nodal tissues at micrometer resolution. We describe novel nodal anatomical variations. We found that the depth of the His bundle in females was on average 304 μm shallower than those of male patients. These models provide surgeons with insight into the heterogeneity of the nodal regions and the intricate relationships between the CCS and surrounding structures.

Perceived Health Behaviors and Learning Needs of Patients with Myocardial Infarction

Introduction: - Myocardial infarction is one of the foremost cardiovascular disease causes of mortality and morbidity worldwide. The prevention of this disease requires continuous monitoring and rehabilitative management. It can be achieved by the health promotion of patients using effective, planned educational programs and lifestyle modification by the patient. Patients perceived that their learning needs were unmet and that the information provided was too general. Hence, assessing the healthy heart habits performed by the patient and the patient’s preference regarding learning needs is crucial. The descriptive study is intended to identify the perceived health behaviors and learning needs of patients with myocardial infarction for the first time. Methodology: A quantitative descriptive design was used in this present study. The study included 102 newly diagnosed patients with MI carefully chosen by the non-probability convenience selection method. Information was collected using a patient profile (socio-demographic data, clinical data, and clinical parameters), a Modified cardiac health behavior scale (MCHBS), and a Cardiac patient's learning needs inventory (CPLNI). Results: -The present study result showed that subjects with MI for the first time had a high level of perceived learning needs of 164.11 + 22.28, with symptoms management was 27.61 + 3.763, medication information was 23.15 + 3.010, diet information was 23.12 + 3.148 were the areas perceived as high learning need information among the subjects. Only 11 (10.8%) subjects had a high perception of cardiac health behavior, among which were controlling risk habits and was 14.53 + 3.16. Medication adherence was only 6.76 + 1.89, perception of the subjects regarding dietary management was 19.47 + 4.15, and blood pressure control was 5.09 + 2.13 as considered essential in maintaining a healthy heart. Interestingly, the findings show that subjects with the perception of higher learning needs showed a negatively weak correlation with a lesser perception of health behavior, which is not a statistically significant level at p >0.05. The study highlighted that exercise, habits, and RBS had a statistically significant association with perceived health behavior (χ2= 18.52, p <0.001), (χ2=20.133, p =0.013), (χ2=9.067, p=0.037) respectively. Also, the exposure of subjects to mass media (χ2 =15.01, p<0.05), diversional activities practiced (χ2 =19.08, p <0.01), perception about the prognosis (χ2=7.22, p<0.02), habits (χ2= 13.68, p<0.03) level had a statistically significant association with the perceived learning needs. Conclusion: - Patients’ health behaviors practices and learning needs will change according to their perceptions. Determining the learning needs will help to guide the patient to achieve good cardiac health behaviors practice, subsequently reducing the reoccurrence of myocardial infarction.

Diet quality and cardiovascular disease risk among breast cancer survivors in the Pathways Study.

Women with breast cancer are at higher risk of cardiovascular disease (CVD) compared with women without breast cancer. Whether higher diet quality at breast cancer diagnosis lowers this risk remains unknown. We set out to determine if higher diet quality at breast cancer diagnosis was related to lower risk of CVD and CVD-related death. This analysis included 3415 participants from the Pathway Study, a prospective cohort of women diagnosed with invasive breast cancer at Kaiser Permanente Northern California between 2005 and 2013 and followed through December 31, 2021. Scores from 5 diet quality indices consistent with healthy eating were obtained at the time of breast cancer diagnosis. Scores were categorized into ascending quartiles of concordance for each diet quality index, and multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. P values were 2-sided. The Dietary Approaches to Stop Hypertension diet quality index was associated with lower risk of heart failure (HR = 0.53, 95% CI = 0.33 to 0.87; Ptrend = .03), arrhythmia (HR = 0.77, 95% CI = 0.62 to 0.94; Ptrend = .008), cardiac arrest (HR = 0.77, 95% CI = 0.61 to 0.96; Ptrend = .02), valvular heart disease (HR = 0.79, 95% CI = 0.64 to 0.98; Ptrend = .046), venous thromboembolic disease (HR = 0.75, 95% CI = 0.60 to 0.93; Ptrend = .01), and CVD-related death (HR = 0.70, 95% CI = 0.50 to 0.99; Ptrend = .04), when comparing the highest with lowest quartiles. Inverse associations were also found between the healthy plant-based dietary index and heart failure (HR = 0.60, 95% CI = 0.39 to 0.94; Ptrend = .02), as well as the alternate Mediterranean dietary index and arrhythmia (HR = 0.74, 95% CI = 0.60 to 0.93; Ptrend = .02). Among newly diagnosed breast cancer patients, higher diet quality at diagnosis was associated with lower risk of CVD events and death.

Partnership As An Effort To Care For Hypertension Through A Healthy Lifestyle

Kelurahan Sukamerindu as the location of community service. This is because Kelurahan Suka Merindu is classified as slums, densely populated, cases of hyprtension and diabetes mellitus are high compared to other villages. Lurah, health devices and cadres actively participate in health programs. The purpose of community service activities is the implementation of case discovery activities, management and prevention of hypertensive patients in Bengkulu. Community service activities are carried out by registration and blood pressure checks, which are attended by 42 people. Furthermore, gymnastics activities in the form of healthy heart exercises, elderly exercises and Germas exercises, from the results of measurement of blood pressure found one grade hypertension with blood pressure 140-159 /90-99 mmHg as many as 15 people (35.7%). Counseling activities carried out by the lecture method followed by discussion and question and answer. Through community service activities, they know how to prevent hypertension through watermelon juice and know the benefits and can consume their own juice at home. Health socialization and promotion about the prevention and prevention of hypertension must be continued and can be an example for other villages and can be developed against the prevention and prevention of other non -communicable diseases, especially diabetes mellitus.

Fibroblast mediated dynamics in diffusively uncoupled myocytes: a simulation study using 2-cell motifs

In healthy hearts myocytes are typically coupled to nearest neighbours through gap junctions. Under pathological conditions such as fibrosis, or in scar tissue, or across ablation lines myocytes can uncouple from their neighbours. Electrical conduction may still occur via fibroblasts that not only couple proximal myocytes but can also couple otherwise unconnected regions. We hypothesise that such coupling can alter conduction between myocytes via introduction of delays or by initiation of premature stimuli that can potentially result in reentry or conduction blocks. To test this hypothesis we have developed several 2-cell motifs and investigated the effect of fibroblast mediated electrical coupling between uncoupled myocytes. We have identified various regimes of myocyte behaviour that depend on the strength of gap-junctional conductance, connection topology, and parameters of the myocyte and fibroblast models. These motifs are useful in developing a mechanistic understanding of long-distance coupling on myocyte dynamics and enable the characterisation of interaction between different features such as myocyte and fibroblast properties, coupling strengths and pacing period. They are computationally inexpensive and allow for incorporation of spatial effects such as conduction velocity. They provide a framework for constructing scar tissue boundaries and enable linking of cellular level interactions with scar induced arrhythmia.

Biomechanical Remodeling of Aortic Valve Interstitial Cells During Calcified Lesion Formation In Vitro.

Healthy aortic heart valves are essential to the regulation of unidirectional blood flow. Calcific aortic valve disease (CAVD) is an actively progressive disease that involves the disorganization of valve cells and accumulation of calcium deposits on the aortic valve leaflets. CAVD involves disruption of cell environment homeostasis that prior cell culture models have found difficult to portray and model. As it is still poorly understood how tissue stiffening associates with lesion formation, here, we implement a novel 3D culture platform to characterize the relationship between mechanical stress and tissue remodeling and analyze how the application of pro-osteogenic stimulation dysregulates the native ability of valve cells to organize its matrix. Through a temporal study of macroscopic remodeling, we determine that aortic valve interstitial neo-tissues undergo varying stiffness and mechanical stress, demonstrate greater myofibroblastic gene expression, and show greater remodeling activity in the outer surface of the neo-tissue in a banding pattern when cultured in osteogenic growth medium. In human aortic valve interstitial cells cultured in osteogenic growth medium, we observed an increase in stress but significant decreases in myofibroblastic gene expression with the addition of growth factors. In summary, we are able to see the interplay of biochemical and biomechanical stimuli in valvular remodeling by using our platform to model dynamic stiffening of valve interstitial neo-tissues under different biochemical conditions.

Automated Detection of Rheumatic Heart Disease via Unsegmented Heart Sound Analysis

Rheumatic Heart Disease (RHD) remains a significant cause of morbidity and mortality in many parts of the world, particularly in low-resource settings. Early detection and intervention are critical to mitigating its progression and reducing associated complications. This paper presents an automated approach for the detection of RHD utilizing unsegmented heart sound analysis through deep learning techniques. By leveraging Spectro-temporal representations of raw heart sound signals, our proposed method aims to capture subtle yet discriminative patterns indicative of RHD pathology. The deep learning model is trained on a dataset comprising a diverse range of heart sounds, including those from both RHD-positive and RHD-negative individuals. Through rigorous evaluation of unseen data, our approach demonstrates promising performance in accurately distinguishing between RHD and healthy heart sounds. Furthermore, the proposed methodology offers the potential for scalable and cost-effective screening in resource-limited settings, thereby facilitating early identification and management of RHD cases. This work contributes to the advancement of computer-aided diagnostic tools for cardiovascular diseases, with implications for improving healthcare outcomes and reducing the burden of RHD globally. Key Words: Rheumatic Heart Disease, Heart Sound Analysis, Deep Learning, Automated Detection, Unsegmented Signals, Spectro-Temporal Representation, Cardiovascular Disease.

Healthy hearts

Knowledge and actions reap benefits for our patients, ourselves.

Secreted Protein Profiling of Human Aortic Smooth Muscle Cells Identifies Vascular Disease Associations.

Smooth muscle cells (SMCs), which make up the medial layer of arteries, are key cell types involved in cardiovascular disease, the leading cause of mortality and morbidity worldwide. In response to microenvironment alterations, SMCs dedifferentiate from a contractile to a synthetic phenotype characterized by an increased proliferation, migration, production of ECM (extracellular matrix) components, and decreased expression of SMC-specific contractile markers. These phenotypic changes result in vascular remodeling and contribute to the pathogenesis of cardiovascular disease, including coronary artery disease, stroke, hypertension, and aortic aneurysms. Here, we aim to identify the genetic variants that regulate ECM secretion in SMCs and predict the causal proteins associated with vascular disease-related loci identified in genome-wide association studies. Using human aortic SMCs from 123 multiancestry healthy heart transplant donors, we collected the serum-free media in which the cells were cultured for 24 hours and conducted liquid chromatography-tandem mass spectrometry-based proteomic analysis of the conditioned media. We measured the abundance of 270 ECM and related proteins. Next, we performed protein quantitative trait locus mapping and identified 20 loci associated with secreted protein abundance in SMCs. We functionally annotated these loci using a colocalization approach. This approach prioritized the genetic variant rs6739323-A at the 2p22.3 locus, which is associated with lower expression of LTBP1 (latent-transforming growth factor beta-binding protein 1) in SMCs and atherosclerosis-prone areas of the aorta, and increased risk for SMC calcification. We found that LTBP1 expression is abundant in SMCs, and its expression at mRNA and protein levels was reduced in unstable and advanced atherosclerotic plaque lesions. Our results unravel the SMC proteome signature associated with vascular disorders, which may help identify potential therapeutic targets to accelerate the pathway to translation.

In situ monolayer patch clamp of acutely stimulated human iPSC-derived cardiomyocytes promotes consistent electrophysiological responses to SK channel inhibition

Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) represent an in vitro model of cardiac function. Isolated iPSC-CMs, however, exhibit electrophysiological heterogeneity which hinders their utility in the study of certain cardiac currents. In the healthy adult heart, the current mediated by small conductance, calcium-activated potassium (SK) channels (ISK) is atrial-selective. Functional expression of ISK within atrial-like iPSC-CMs has not been explored thoroughly. The present study therefore aimed to investigate atrial-like iPSC-CMs as a model system for the study of ISK. iPSCs were differentiated using retinoic acid (RA) to produce iPSC-CMs which exhibited an atrial-like phenotype (RA-iPSC-CMs). Only 18% of isolated RA-iPSC-CMs responded to SK channel inhibition by UCL1684 and isolated iPSC-CMs exhibited substantial cell-to-cell electrophysiological heterogeneity. This variability was significantly reduced by patch clamp of RA-iPSC-CMs in situ as a monolayer (iPSC-ML). A novel method of electrical stimulation was developed to facilitate recording from iPSC-MLs via In situ Monolayer Patch clamp of Acutely Stimulated iPSC-CMs (IMPASC). Using IMPASC, > 95% of iPSC-MLs could be paced at a 1 Hz. In contrast to isolated RA-iPSC-CMs, 100% of RA-iPSC-MLs responded to UCL1684, with APD50 being prolonged by 16.0 ± 2.0 ms (p < 0.0001; n = 12). These data demonstrate that in conjunction with IMPASC, RA-iPSC-MLs represent an improved model for the study of ISK. IMPASC may be of wider value in the study of other ion channels that are inconsistently expressed in isolated iPSC-CMs and in pharmacological studies.

The role of resonance frequency in slow-paced breathing: Systematic review

Introduction&#x0D; A healthy heart does not beat like a metronome because it shows characteristics of complex non-linear oscillations and mathematical chaos, together with the existence of resonance in the cardiorespiratory system (Shaffer et al., 2014). On one swing, the inhalation causes an increase of the heart rate, while the opposite effect is during exhaling, thus having variability properties in the inter-beat intervals. By utilizing this effect of respiratory sinus arrhythmia, resonance frequency (RF) gives insight into the respiratory rate at which this resonance is amplified in the heart rate, blood pressure, and respiration systems (Shaffer &amp; Meehan, 2020). The aim of this systematic review was to examine the effects of resonance frequency in Slow-Paced Breathing (SPB) studies, as well as the relation between RF and anthropological measures of gender, height, and age.&#x0D; Methods&#x0D; We systematically reviewed the literature regarding the role of resonance frequency in the SPB research using the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) evidence-based reporting checklist and a Participants, Index Test, Comparison, Outcomes, and Study Design (PICOS) framework (PROSPERO Registration Number CRD42021253009). We included SPB studies with experimental and quasi-experimental designs, conducted on healthy populations that determined individual RF in the breathing protocols, with no specific criteria on gender, age restrictions, or publication year. Additionally, interventions combining RF SPB with biofeedback monitoring were included. Outcomes of the included studies included any psychological or physiological findings. Altogether, 17 studies (n = 810 participants) were assessed for risk of bias with The Joanna Briggs Institute Critical Appraisal Checklist (Moola et al., 2015).&#x0D; Results&#x0D; Overall, positive effects on psychological constructs like attention control, executive functioning, sleep quality, psychological relaxation, mindful awareness, self-compassion, vigor, self-efficacy, mood, depression, anxiety, and stress have been reported. Physiologically, RF breathing caused a more coherent heart rhythm pattern with high amplitude oscillation, while lowering systolic pressure, decreasing HF power, HR beats per minute, a-amylase and cortisol stress biomarkers, and increasing the average baroreflex gain, SpO2, and LF power. The scarcity of reported data and analysis concerning the effects of anthropological data do not give a strong claim to the existence of height, gender, and age influences, but there is a notion that height and RF are negatively correlated, while men have lower RF than women.&#x0D; Discussion/Conclusion&#x0D; We conclude the overall beneficial effects of RF breathing on psychological and physiological systems. Namely, improved attention control, executive functioning, sleep quality with fewer disturbances, and psychological relaxation, increased mindful awareness, self-compassion, vigor, and self-efficacy; less worrying and a decrease in total mood disturbance, depression, anxiety, and stress were observed. On a physiological level, RF breathing caused a lowering of systolic pressure, a decrease of HF power, HR beats per minute, a-amylase, and cortisol stress biomarkers, while increasing the average baroreflex gain, SpO2, and LF power through a more coherent heart rhythm pattern with high amplitude oscillation. In regard to the anthropological measures, scarcely reported data suggests the RF is related to the blood volume and the perfusion of the arterial tree, hence men are supposedly having a lower resonance frequency than women, and RF being negatively correlated with height. While these findings are in overall support for RF breathing, they are not ubiquitous, and thus warrants more experimental evidence to test the aforementioned effects. Besides limitations on technical levels and methodological inconsistencies among reviewed studies (e.g., differences in RF determination protocols, operationalization variables and inhale/exhale ratio), one of the major obstacles in the review process was the insufficient gathering and reporting data on some important RF aspects (i.e. no report on detected RF distribution among participants and their anthropological data, control of transient characteristics and lifestyle choices that influence HRV). Finally, future studies should empirically replicate reviewed studies and test the RF biofeedback model in a laboratory and natural setting.&#x0D; References&#x0D; Shaffer, F., McCraty, R., &amp; Zerr, C. L. (2014). A healthy heart is not a metronome: An integrative review of the heart’s anatomy and heart rate variability. Frontiers in Psychology, 5, Article 1040. https://doi.org/10.3389/fpsyg.2014.01040&#x0D; Shaffer, F., &amp; Meehan, Z. M. (2020). A practical guide to resonance frequency assessment for heart rate variability niofeedback. Frontiers in Neuroscience, 14, Article 570400. https://doi.org/10.3389/fnins.2020.570400&#x0D; Moola, S., Munn, Z., Sears, K., Sfetcu, R., Currie, M., Lisy, K., Tufanaru, C., Qureshi, R., Mattis, P., &amp; Mu, P. (2015). Conducting systematic reviews of association (etiology): The Joanna Briggs Institute’s approach. International Journal of Evidence-Based Healthcare, 13(3), 163–169. https://doi.org/10.1097/XEB.0000000000000064

Role of tissue biomechanics in the formation and function of myocardial trabeculae in zebrafish embryos.

Cardiac trabeculae are uneven ventricular muscular structures that develop during early embryonic heart development at the outer curvature of the ventricle. Their biomechanical function is not completely understood, and while their formation is known to be mechanosensitive, it is unclear whether ventricular tissue internal stresses play an important role in their formation. Here, we performed imaging and image-based cardiac biomechanics simulations on zebrafish embryonic ventricles to investigate these issues. Microscopy-based ventricular strain measurements show that the appearance of trabeculae coincided with enhanced deformability of the ventricular wall. Image-based biomechanical simulations reveal that the presence of trabeculae reduces ventricular tissue internal stresses, likely acting as structural support in response to the geometry of the ventricle. Passive ventricular pressure-loading experiments further reveal that the formation of trabeculae is associated with a spatial homogenization of ventricular tissue stiffnesses in healthy hearts, but gata1 morphants with a disrupted trabeculation process retain a spatial stiffness heterogeneity. Our findings thus suggest that modulating ventricular wall deformability, stresses, and stiffness are among the biomechanical functions of trabeculae. Further, experiments with gata1 morphants reveal that a reduction in fluid pressures and consequently ventricular tissue internal stresses can disrupt trabeculation, but a subsequent restoration of ventricular tissue internal stresses via vasopressin rescues trabeculation, demonstrating that tissue stresses are important to trabeculae formation. Overall, we find that tissue biomechanics is important to the formation and function of embryonic heart trabeculation. KEY POINTS: Trabeculations are fascinating and important cardiac structures and their abnormalities are linked to embryonic demise. However, their function in the heart and their mechanobiological formation processes are not completely understood. Our imaging and modelling show that tissue biomechanics is the key here. We find that trabeculations enhance cardiac wall deformability, reduce fluid pressure stresses, homogenize wall stiffness, and have alignments that are optimal for providing load-bearing structural support for the heart. We further discover that high ventricular tissue internal stresses consequent to high fluid pressures are needed for trabeculation formation through a rescue experiment, demonstrating that myocardial tissue stresses are as important as fluid flow wall shear stresses for trabeculation formation.

Pre-intervention myocardial stress is a good predictor of aortic valvoluplasty outcome for fetal critical aortic stenosis and evolving HLHS.

Fetal critical aortic stenosis with evolving hypoplastic left heart syndrome (CAS-eHLHS) causes biomechanical and functional aberrations, leading to a high risk of progression to hypoplastic left heart syndrome (HLHS) at birth. Fetal aortic valvuloplasty (FAV) can resolve outflow obstruction and may reduce progression risk. However, it is currently difficult to accurately predict which patients will respond to the intervention and become functionally biventricular (BV) at birth, as opposed to becoming functionally univentricular (UV). This prediction is important for patient selection, parental counselling, and surgical planning. Therefore, we investigated whether biomechanics parameters from pre-FAV image-based computations could robustly distinguish between CAS-eHLHS cases with BV or UV outcomes in a retrospective cohort. To do so we performed image-based finite element biomechanics modelling of nine CAS-eHLHS cases undergoing intervention and six healthy fetal control hearts, and found that a biomechanical parameter, peak systolic myofibre stress, showed a uniquely large difference between BV and UV cases, which had a larger magnitude effect than echocardiography parameters. A simplified equation was derived for quick and easy estimation of myofibre stress from echo measurements via principal component analysis. When tested on a retrospective cohort of 37 CAS-eHLHS cases, the parameter outperformed other parameters in predicting UV versus BV outcomes, and thus has a high potential of improving outcome predictions, if incorporated into patient selection procedures. Physiologically, high myocardial stresses likely indicate a healthier myocardium that can withstand high stresses and resist pathological remodelling, which can explain why it is a good predictor of BV outcomes. KEY POINTS: Predicting the morphological birth outcomes (univentricular versus biventricular) of fetal aortic valvuloplasty for fetal aortic stenosis with evolving HLHS is important for accurate patient selection, parental counselling and management decisions. Computational simulations show that a biomechanics parameter, pre-intervention peak systolic myofibre stress, is uniquely robust in distinguishing between such outcomes, outperforming all echo parameters. An empirical equation was developed to quickly compute peak systolic myofibre stress from routine echo measurements and was the best predictor of outcomes among a wide range of parameters tested.

Cardio Protective Approach of Unani Dietotherapy with Special Reference to Avicenna’s Risaala Adwiyah Al Qalbiyah

Background and Objective: The present paper will enlighten the role of different types of diets in maintaining a healthy heart, as mentioned by Ibn Sina in his valuable work “Risaala adwiyah al Qalbiyah”. Owing to an increased trend of dietotherapy in the current era, this paper is an attempt to enhance the same (particularly the cardio-protective diets). Methodology: Risaala adwiyah al Qalbiyah is an important work of Ibn Sina focusing on the maintenance of heart health. For the current study, we have selected a total of thirteen nutraceuticals out of sixty-three that can be taken in the routine diet to avail of their benefits and avoid the risk of cardiovascular diseases, which are at their peak at present. To meet this need, a thorough literature survey of classical literature was conducted to collect all the necessary and relevant information. These medicines/diets were looked upon for their proven benefits by searching them with their botanical names using modern search engines like PubMed, Google Scholar and Research Gate to provide an evidence-based edge to the current work. Results: The specific diets mentioned by Ibn Sina have proved to possess potential effects in preventing cardiovascular diseases and thus promoting cardiac health. Conclusion: Dietotherapy plays a primary role in achieving the principal goal of the Unani system of medicine (the preservation of health and prevention of diseases). Food items mentioned in this paper can be added to the routine to get the benefits from their cardio-protective action and avoid the risk of highly increasing cardiovascular diseases.

It's a Trap! Aldolase-Prescribed C4 Deoxyradiofluorination Affords Intracellular Trapping and the Tracing of Fructose Metabolism by PET.

Fructose metabolism has been implicated in various diseases, including metabolic disorders, neurodegenerative disorders, cardiac disorders, and cancer. However, the limited availability of a quantitative imaging radiotracer has hindered its exploration in pathology and diagnostic imaging. Methods: We adopted a molecular design strategy based on the catalytic mechanism of aldolase, a key enzyme in fructolysis. We successfully synthesized a radiodeoxyfluorinated fructose analog, [18F]4-fluoro-4-deoxyfructose ([18F]4-FDF), in high molar activity. Results: Through heavy isotope tracing by mass spectrometry, we demonstrated that C4-deoxyfluorination of fructose led to effective trapping as fluorodeoxysorbitol and fluorodeoxyfructose-1-phosphate invitro, unlike C1- and C6-fluorinated analogs that resulted in fluorolactate accumulation. This observation was consistent invivo, where [18F]6-fluoro-6-deoxyfructose displayed substantial bone uptake due to metabolic processing whereas [18F]4-FDF did not. Importantly, [18F]4-FDF exhibited low uptake in healthy brain and heart tissues, known for their high glycolytic activity and background levels of [18F]FDG uptake. [18F]4-FDF PET/CT allowed for sensitive mapping of neuro- and cardioinflammatory responses to systemic lipopolysaccharide administration. Conclusion: Our study highlights the significance of aldolase-guided C4 radiodeoxyfluorination of fructose in enabling effective radiotracer trapping, overcoming limitations of C1 and C6 radioanalogs toward a clinically viable tool for imaging fructolysis in highly glycolytic tissues.