Progression Of Heart Disease Research Articles

Sex-Related Differences in Clinical Characteristics and Outcome Prediction Among Patients Undergoing Transcatheter Tricuspid Valve Intervention

BackgroundMen and women differ regarding comorbidities, pathophysiology, and the progression of valvular heart diseases. ObjectivesThis study sought to assess sex-related differences regarding clinical characteristics and the outcome of patients with severe tricuspid regurgitation (TR) undergoing transcatheter tricuspid valve intervention (TTVI). MethodsAll 702 patients in this multicenter study underwent TTVI for severe TR. The primary outcome was 2-year all-cause mortality. ResultsAmong 386 women and 316 men in this study, men were more often diagnosed with coronary artery disease (52.9% in men vs 35.5% in women; P = 5.6 × 10−6). Subsequently, the underlying etiology for TR in men was predominantly secondary ventricular (64.6% in men vs 50.0% in women; P = 1.4 × 10−4), whereas women more often presented with secondary atrial etiology (41.7% in women vs 24.4% in men, P = 2.0 × 10−6). Notably, 2-year survival after TTVI was similar in women and men (69.9% in women vs 63.7% in men; P = 0.144). Multivariate regression analysis identified dyspnea expressed as New York Heart Association functional class, tricuspid annulus plane systolic excursion (TAPSE), and mean pulmonary artery pressure (mPAP) as independent predictors for 2-year mortality. The prognostic significance of TAPSE and mPAP differed between sexes. Consequently, we looked at right ventricular–pulmonary arterial coupling expressed as TAPSE/mPAP and identified sex-specific thresholds to best predict survival; women with a TAPSE/mPAP ratio <0.612 mm/mm Hg displayed a 3.43-fold increased HR for 2-year mortality (P < 0.001), whereas men with a TAPSE/mPAP ratio <0.434 mm/mm Hg displayed a 2.05-fold increased HR for 2-year mortality (P = 0.001). ConclusionsEven though men and women differ in the etiology of TR, both sexes show similar survival rates after TTVI. The TAPSE/mPAP ratio can improve prognostication after TTVI, and sex-specific thresholds should be applied to guide future patient selection.

Health-related quality of life among transthyretin amyloid cardiomyopathy patients.

Transthyretin amyloid cardiomyopathy (ATTR CM) is a progressive and severe heart disease with physical and psychological implications. The Nordic PROACT study was conducted to investigate the health-related quality of life (HRQoL) in ATTR CM patients. The Nordic PROACT study was a cross-sectional non-interventional study conducted in 12 cardiology hospital clinics across Norway, Sweden, Finland and Denmark. Men and women aged ≥18years diagnosed with symptomatic ATTR CM were included. The investigator provided information on medical history, biomarkers, current treatment, co-morbidities and disease severity according to the New York Heart Association (NYHA) class and the National Amyloidosis Centre (NAC) staging. Patients completed the HRQoL questionnaires in the form of the Kansas City Cardiomyopathy Questionnaire (KCCQ), the EQ-5D-5L index with Visual Analog Scale (VAS), and the Major Depression Inventory (MDI). A total of 169 patients (mean ± SD age 77.7±6.2years) were included. Ninety-two per cent were men. Seventy-six per cent had wildtype ATTR CM (ATTRwt CM) and 15% had a hereditary form of ATTR CM (ATTRv CM) while 9% were genetically unclassified. Most patients were in NYHA class II (54%) and NAC stage 1 (53%). Participation in randomized clinical trials (RCT) was noted in 58% of the patients. The 169 ATTR CM patients had a mean±SD KCCQ score of 64.3±23.1 for total symptom score, 64.8±20.9 for overall summary score (OSS) and 65.1±21.5 for clinical summary score. The EQ-5D-5L total utility score was 0.8±0.2 and the EQ-5D-5L VAS score was 62.9±20.6. The vast majority (89%) did not report any signs of depression. Patients with ATTRv CM had a higher KCCQ OSS as compared with ATTRwt CM, while EQ-5D-5L utility score, EQ-5D-5L VAS and MDI were similar. Non-RCT participants had a poorer HRQoL as compared with RCT participants as reflected in lower KCCQ OSS and EQ-5D-5L VAS scores and a higher MDI score. Patients with higher NYHA classes and NAC disease stages had a poorer HRQoL as demonstrated by lower KCCQ and EQ-5D-5L scores and higher MDI scores. Correlation between KCCQ, EQ-5D-5L and MDI and the covariate NYHA class remained significant (P<0.05) after adjusting for multiple testing. KCCQ scores were lower than previously reported for patients with other heart diseases of non-ATTR CM origin. The HRQoL measures correlated well to NYHA class and NAC disease stage. The prevalence of depression appeared to be low.

Fetal pulmonary valvuloplasty for pulmonary atresia with intact ventricular septum: a single-center clinical experience.

Fetal pulmonary valvuloplasty for pulmonary atresia with intact ventricular septum: a single-center clinical experience.

Myocardial steatosis impairs left ventricular diastolic-systolic coupling in healthy humans.

Mounting evidence suggests that myocardial steatosis contributes to left ventricular diastolic dysfunction, but definitive evidence in humans is lacking due to confounding comorbidities. As such, we utilized a 48-h food restriction model to acutely increase myocardial triglyceride (mTG) content - measured by 1 H magnetic resonance spectroscopy - in 27 young healthy volunteers (13men/14 women). Forty-eight hours of fasting caused a more than 3-fold increase in mTG content (P<0.001). Diastolic function - defined as early diastolic circumferential strain rate (CSRd) - was unchanged following the 48-h fasting intervention, but systolic circumferential strain rate was elevated (P<0.001), indicative of systolic-diastolic uncoupling. Indeed, in a separate control experiment in 10 individuals, administration of low-dose dobutamine (2μg/kg/min) caused a similar change in systolic circumferential strain rate as was found during 48h of food restriction, along with a proportionate increase in CSRd, such that the two metrics remained coupled. Taken together, these data indicate that myocardial steatosis contributes to diastolic dysfunction by impairing diastolic-systolic coupling in healthy adults, and suggest that steatosis may contribute to the progression of heart disease. KEY POINTS: Preclinical evidence strongly suggests that myocardial lipid accumulation (termed steatosis) is an important mechanism driving heart disease. Definitive evidence in humans is limited due to the confounding influence of multiple underlying comorbidities. Using a 48-h food restriction model to acutely increase myocardial triglyceride content in young healthy volunteers, we demonstrate an association between myocardial steatosis and left ventricular diastolic dysfunction. These data advance the hypothesis that myocardial steatosis may contribute to diastolic dysfunction and suggest myocardial steatosis as a putative therapeutic target.

A Pilot study on thyroid status, lipid profile creatine kinase in human cardiac patients

Background: The progression of Coronary Heart Disease (CHD) is linked to a multitude of comorbidities, such as thyroid dysfunction, dyslipidemia. Objectives were to determine the thyroid and serum lipid profile, cholesterol, triglycerides and creatin kinase profile of CHD patients and to establish correlation between severity of cardiac disease with these two metabolic parameters.&#x0D; Methods: This was a prospective study conducted among 55 CHD patients over 1 year admitted in the department of cardiology, General Government Hospital, Bikaner.&#x0D; Results: There are 66% male and 36% female patients among the 55 study cases. Majority of the patients (54/55) exhibited higher T3 concentration, whereas one patient has low T4 value accompanied by 14 patients with high TSH value. Three patients have higher value of cholesterol with 17 patients of higher triglycerides levels. Among the patients eleven demonstrated higher creatine kinase values. &#x0D; Conclusions: The numbers of patients increasing with decreasing T3 and increasing thyroid stimulating hormone (TSH) proportionate to the severity of the cardiac failure. In addition, hypothyroidism is becoming more common in people with chronic cardiac disease. Serum triglycerides, LDL and HDL levels rise statistically significantly in CHD patients.&#x0D; Keywords: Dyslipidemia, CHD, Cholesterol, triglycerides, TMB.

SUBCUTANEOUS INFLIXIMAB IN REFRACTORY CROHN'S DISEASE PATIENTS AFTER THE MULTIPLE TREATMENT FAILURES - SHORT TREATMENT OUTCOMES

Abstract BACKGROUND Subcutaneous administration of infliximab shows an increased benefit in terms of pharmacokinetics and pharmacodynamics effects compared to the intravenous infliximab. The practical question arises whether routine administration in refractory CD patients who have failed prior biological therapy will provide "biobetter" clinical efficacy. AIMS We propose a single center study designed to evaluate SC-IFX treatment outcomes in patients with active CD after the previous failures of other biologicals (TMAbs). Such a refractory CD cohort was chosen because there is currently insufficient appropriate medication therapy available for these patients and the identification of parameters predicting response to SC-IFX treatment could be of great benefit to some of them. PATIENTS &amp; METHODS A total of 32 CD patients were included, with the median age of 34.5 years and median CD duration of 11 years; &amp;gt;90% of them with stricturing and/or penetrating disease behavior, &amp;gt;80% with ileocolic involvement, and about 40% with the active perianal disease. Eighteen of 32 patients (56%) have failed on ≥3 previous TMAbs, the rest on 2 previous TMAbs. Twenty (62.5%) of n = 32 have had IV-IFX in past; in this sub-cohort, 85% of patients have positive anti-IFX antibodies (ATI). In ATI-positive sub-cohort, induction of SC-IFX was realized with four 120 mg SC doses weekly. Two induction IV infusions of 5 mg/kg IFX were administered in 2-week intervals in ATI-negative sub-cohort. Maintenance treatment in whole cohort consisted of 120 mg SC IFX bi-weekly. RESULTS Of the 32 patients, 7 individuals have failed the treatment during the induction phase: one because of heart disease progression, and 6 patients due to delayed hypersensitivity reactions with systemic manifestation. In 25/32 patients who continued their treatment up to W14, the initial median Harvey-Bradshaw index (HBI) of 6 (min 1, max 28) did not decrease significantly within the 14 weeks of treatment (p=0.067). However, both the serum CRP level (p=0.039) and fecal calprotectin level (p=0.027) have shown significant decrease. Median trough IFX levels have increased from 6 μg/mL at W2 to 10 μg/mL at W14 (p&amp;lt;0.001), and median ATI levels dropped from median of 38 ng/mL to 5 ng/mL (p= 0.0004). None of the patients with initial zero ATI levels have shown new ATI formation. Moreover, in 10 of 17 patients (59%) with the initial ATI positivity, ATI serum levels have decreased significantly even to the cut-off levels. The only risk factor for SC-IFX discontinuation before W14 was a high serum levels of ATIs (p &amp;lt; 0.001). CONCLUSIONS Our short-term experience with SC-IFX shows the treatment efficacy and tolerability in complicated CD patients after multiple TMAbs failures.The research gap in information about biobetters in patients with IBD must be filled and predictive factors for the response to SC-IFX must be found.

Role of myeloperoxidase in atrial fibrillation and ischemic heart disease

Atrial fibrillation and ischemic heart disease are the key problems in cardiology. Despite of numerous clinical trials and researches underlying molecular biology remains uncertain. Atrial fibrillation and ischemic heart disease are often combined. During ischemic heart disease progression myocardial tissue structure are changing which lead to structural and electrophysiological remodeling and promote atrial fibrillation. It has been shown a crucial role of oxidative stress and chronic systemic inflammation in ischemic heart disease and atrial fibrillation. Myeloperoxidase (MPO) is one of marker of oxidative stress and inflammation that located in azurophilic granules of neutrophils and monocytes. There are a numerous articles showed a relation between MPO level and cardiovascular disease. MPO is a peroxidase enzyme that is important part of immune system. During disease MPO could facilitate chronic inflammation and local tissue damage through active oxygen forms. MPO releases after lysosome conjunction with phagosome. Oxygen reductase activity of MPO lead synthesis of hypochlorous acid that play role not only in organism protection from infection agents but in matrix transformation and fibrosis. It has been shown MPO can destabilize atherosclerotic plaque and modifies low- and high-density lipoproteins that promote atherosclerosis and ischemic heart diseaseу progression. This review summarizes current data about role of MPO in atrial fibrillation and ischemic heart disease pathogenesis.

Knockdown of histone deacetylase 9 attenuates sepsis-induced myocardial injury and inflammatory response.

Myocardial cell damage is associated with apoptosis and excessive inflammatory response in sepsis. Histone deacetylases (HDACs) are implicated in the progression of heart diseases. This study aims to explore the role of histone deacetylase 9 (HDAC9) in sepsis-induced myocardial injury. Lipopolysaccharide (LPS)-induced Sprague Dawley rats and cardiomyocyte line H9C2 were used as models in vivo and in vitro. The results showed that HDAC9 was significantly upregulated after LPS stimulation, and HDAC9 knockdown remarkably improved cardiac function, as evidenced by decreased left ventricular internal diameter end diastole (LVEDD) and left ventricular internal diameter end systole (LVESD), and increased fractional shortening (FS)% and ejection fraction (EF)%. In addition, HDAC9 silencing alleviated release of inflammatory cytokines (tumor necrosis factor-α (TNF-α), IL-6 and IL-1β) and cardiomyocyte apoptosis in vivo and in vitro. Furthermore, HDAC9 inhibition was proved to suppress nuclear factor-kappa B (NF-κB) activation with reducing the levels of p-IκBα and p-p65, and p65 nuclear translocation. Additionally, interaction between miR-214-3p and HDAC9 was determined through bioinformatics analysis, RT-qPCR, western blot and dual luciferase reporter assay. Our data revealed that miR-214-3p directly targeted the 3'UTR of HDAC9. Our findings demonstrate that HDAC9 suppression ameliorates LPS-induced cardiac dysfunction by inhibiting the NF-κB signaling pathway and presents a promising therapeutic agent for the treatment of LPS-stimulated myocardial injury.

To Explore the Influencing Factors of Pericoronary Adipose Tissue and Noninvasive Fractional Flow Reserve on the Progression of Coronary Heart Disease Based on 320-Slice Coronary CTA.

The objective of the study was to measure pericoronal adipose tissue parameters, fractional flow reserve with coronary artery computed tomographic angiography (CTA), and difference of fractional flow reserve with coronary artery CTA, by using high-performance 320-slice coronary CTA combined with semiautomatic quantitative software and explore the relationship between them and progression of coronary artery disease. According to the inclusion criteria, 118 patients with complete data were selected. According to the results of coronary angiography during follow-up review, the patients were divided into coronary artery disease progression group (n = 43) and coronary artery disease stable group (n = 75), and the clinical baseline data, pericoronal adipose tissue volume, pericoronal adipose tissue fat attenuation index, fractional flow reserve with coronary artery CTA, and difference of fractional flow reserve with coronary artery CTA were compared between the 2 groups. According to univariate and multivariate logistic regression analyses, the risk factors related to coronary artery disease progression were screened out from pericoronal adipose tissue parameters and noninvasive hemodynamic characteristics (fractional flow reserve with coronary artery CTA and difference of fractional flow reserve with coronary artery CTA). There was no significant difference in baseline clinical data between the progression group and the stable group (P >.05). The left anterior descending artery-fat attenuation index-40 mm, left anterior descending artery-fat attenuation index-70 mm, left circumflex artery-fat attenuation index-70 mm, right coronary artery-fat attenuation index-70 mm, and difference of fractional flow reserve with coronary artery CTA in the progression group were higher than those in the stable group, while fractional flow reserve with coronary artery CTA was lower than that in the stable group, and the differences were statistically significant (P <.05). After adjusting for several factors, the results showed that left anterior descending artery-fat attenuation index-40 mm (P =.002; odds ratio = 1.237; 95% CI: 1.081-1.415), right coronary artery-fat attenuation index-70 mm (P =.039; odds ratio = 1.119; 95% CI: 1.006-1.246), fractional flow reserve with coronary artery CTA (P =.001; odds ratio = 0.708; 95% CI: 0.581-0.846), and difference of fractional flow reserve with coronary artery CTA (P <.001; odds ratio = 1.846; 95% CI: 1.394-2.445) were related to the progression of coronary artery disease. Compared with the above 5 indicators, the area under curve (AUC) of the above indicators combined is larger (0.897). Quantitative pericoronal adipose tissue parameters and noninvasive hemodynamic characteristics based on 320-slice coronary CTA can be used as the basis for predicting the progression of coronary artery disease.

A review to access knowledge, attitudes, and practices among nurses of cardiac medicine for heart failure patients to prevent readmission in hospitals

This research paper conducts an in-depth evaluation in order to improve nurses' comprehension of self-care management and patient discharge education for patients with Heart Failure (HF). It also discusses the reasons and obstacles to nurses for increasing their knowledge, attitude, and practice to support improved health outcomes and reduce readmission. In order to prevent readmission and re-hospitalization through discharge training, this study aims to raise awareness about the gaps in knowledge, practice, and attitude among nurses working with patients admitted with heart failure. The study evaluates the nurses' knowledge and aids in the education that heart failure patients must receive. By using effective medication management and post-discharge instructions, heart failure symptoms and disease progression can be controlled. Therefore, effective medication management following discharge is crucial for improving the quality of life, controlling symptoms, avoiding deterioration that triggers hospital readmission, and reducing death. Additionally, it is not always possible for healthcare team members to exchange enough accurate information with one another effectively. Numerous nations have emphasised the importance of the right health practices, optimistic attitudes, and suitable education among healthcare professionals to dispel misconceptions, increase confidence in providing support, and promote effective treatment.

Rheumatic Heart Disease Secondary Prophylaxis Prescribing Patterns and Outcomes

Background: Rheumatic heart disease (RHD) is a leading cause of heart disease in children and young adults in developing countries and is considered a significant cause of cardiovascular diseases. Antimicrobial prophylaxis is recommended as secondary prevention for heart complications caused by recurrent acute rheumatic fever. Objective: Our study aims to describe the prescribing patterns of RHD antibiotic secondary prophylaxis among eligible patients and highlight the frequency of valvular heart disease complications requiring intervention. Materials and Methods: A single-center retrospective study was conducted at a tertiary hospital in Saudi Arabia. The study included all patients 5 years old and above diagnosed with rheumatic heart fever and/or RHD and eligible for secondary prevention between January 2009 and December 2018. The primary outcome is the frequency of RHD secondary prophylaxis prescribed for eligible patients. Results: Among 806 patients who were screened, 272 patients were eligible for inclusion. A total of 194 (71.3%) were female, and 146 (53.67%) were older than 40. RHD secondary prophylaxis prescribing adherence was found in only 14 of 272 (5.14%). A total of 185 of 272 (68%) patients had at least one cardiac-related intervention during the follow-up period. Valvular heart disease progression was found in 72 of 185 (38.9%) after a primary intervention. Overall mortality was 30 (11%). Conclusion: Our study found low prescribing adherence to RHD secondary prevention among eligible patients in an area with a high disease prevalence. A larger sample size is needed to confirm these findings.

Integrated analysis of miRNA-mRNA regulatory network and functional verification of miR-338-3p in coronary heart disease.

Coronary heart disease is a cardiovascular disease with high morbidity and mortality. Although great progress has been made in treatment, the prognosis is still very poor. Therefore, this project aims to screen potential diagnostic markers and therapeutic targets related to the progression of coronary heart disease. A total of 94 overlapping differentially expressed mRNAs and 70 differentially expressed miRNAs were identified from GSE20681, GSE12288, GSE49823, and GSE105449. Through a series of bioinformatics methods and experiment, we obtained 5 core miRNA-mRNA regulatory pairs, and selected miR-338-3p/RPS23 for functional analysis. Moreover, we found that RPS23 directly targets miR-338-3p by dual luciferase assay, western, and qPCR. And the expression of miR-338-3p and RPS23 is negatively correlated. The AUC value of miR-338-3p is 0.847. Downregulation of miR-338-3p can significantly inhibit the proliferation and migration of HUVEC. On the contrary, overexpression of miR-338-3p promoted the proliferation and migration of HUVEC. In addition, the interference of RPS23 expression can reverse the regulation of miR-338-3p on HUVEC proliferation. In conclusion, miR-338-3p/RPS23 may be involved in the progression of coronary heart disease, and miR-338-3p may be a diagnostic biomarker and therapeutic target for coronary heart disease.

FEATURES OF THE COURSE OF ARTERIAL HYPERTENSION IN PATIENTS AFTER COVID-19

Introduction. Arterial hypertension (AH) is one of the most common comorbidities in patients with COVID-19. A number of studies have revealed a more severe course of COVID-19 (coronavirus disease (CVD) in patients with hypertension. The problem of studying the association between AH and COVID-19 is also very relevant from an etiopathogenetic point of view, since, both in the development of COVID-19 and in the pathogenesis of AH, one of the key places is occupied by the components of the renin-angiotensin-aldosterone system (RAAS) and, first of all, turn, angiotensin-converting enzyme-2 (ACE-2) and angiotensin II (AII). It has been established that the penetration of the SARS-CoV-2 virus into the body occurs by binding to the RAAS enzyme - ACE-2. This leads to a decrease in the level of ACE-2 and to an increase in the level of AII, which initiates a cytokine storm, damage to the lungs and contributes to the development of severe CVD. On the other hand, AII is one of the most powerful vasoconstrictor factors and plays an extremely important role in the mechanisms of development and progression of hypertension. However, despite the already long period of the COVID-19 pandemic, the features of the course of hypertension in patients who have had this disease have not been adequately studied. The problem of clinical and pathogenetic relationships between AH and COVID-19 remains relevant in 2022, after the start of a new wave of COVID-19 with the dominant Omicron strain. Aim: study of the features of the course of hypertension in patients after COVID-19. Materials and methods. 82 patients with AH were examined before and 6-12 weeks after COVID-19 disease. Among the examined patients, 68 patients (83%) had moderate COVID-19, 14 patients (17%) had severe COVID-19. All patients before and after infection with COVID-19 underwent a general clinical laboratory and instrumental examination. Results. A significant negative impact of COVID-19 on the nature of the course of hypertension was revealed: an increase in the severity of hypertension, the frequency of cardiac arrhythmias, the frequency and severity of heart failure, a decrease in kidney function, destabilization of existing type 2 diabetes and development of new cases of diseases, progression of lipid metabolism disorders and coronary heart disease. A significant contribution to the worsening of the course of AH after CVD is made by the formation of «ongoing symptomatic COVID-19» and astheno-depressive syndrome. Taking into account current data, COVID-19 can directly lead to a worsening of hypertension due to a decrease in ACE-2 levels and an increase in the production of AII, which plays a key role in the pathogenesis of hypertension. Conclusions. Postponed COVID-19 significantly worsens the course of hypertension, which increases the overall risk of complications and indicates the need for timely initiation of adequate comprehensive treatment. Key words: coronavirus disease -19- COVID-19, arterial hypertension, renin- angiotensin- aldosterone system, angiotensin converting enzyme-2, angiotensin ІІ.

Stages of Valvular Heart Disease Among Older Adults in the Community: The Atherosclerosis Risk in Communities Study.

Limited data exist on American College of Cardiology/American Heart Association valvular heart disease (VHD) stage prevalence, progression, and association with incident cardiovascular diseases in late life. Participants in the ARIC study (Atherosclerosis Risk in Communities), a prospective community-based cohort study, underwent protocol echocardiography at ARIC visits 5 (2011-2013) and 7 (2018-2019), and their aortic stenosis, aortic regurgitation, mitral stenosis, and mitral regurgitation stage were defined according to American College of Cardiology/American Heart Association guidelines. The overall VHD stage prevalence at visit 5 was measured. The associations between VHD stages and incident adjudicated death, heart failure, coronary heart disease, stroke, and atrial fibrillation were assessed with Cox proportional hazard models adjusted for age, sex, race, hypertension, diabetes, prior myocardial infarction, heart failure, body mass index, study center, systolic blood pressure, estimated glomerular filtration rate, and low-density lipoprotein at visit 5. Longitudinal changes in VHD stage prevalence over ≈6 years were estimated with inverse probability of attrition weights to account for participant attrition. Among 6118 ARIC participants, the mean±SD age was 76±5 years, 42% were male, and 22% reported Black race. Stage A VHD was present in 39%, stage B in 17%, and stage C/D in 1.1%;, 0.7% had previously undergone valve replacement or repair. A graded association was observed between stage A, B, and C/D VHD and risk of all-cause mortality, incident heart failure, incident atrial fibrillation, and incident coronary heart disease, but not incident stroke. Similar findings were observed for stages of each valvular lesion individually. During the 6.6 years (interquartile range, 6.1-7.0 years) between visits 5 and 7 (mean age, 81±4 years), the prevalence of freedom from VHD stage decreased from 43% to 24%, whereas the prevalence of stage C/D VHD increased from 1% to 7%. Subclinical VHD is common in older adults, with 39% at risk (stage A) and 17% with progressive VHD (stage B), and is independently associated with risk of incident cardiovascular events. VHD stages progress over 6 years in late life, with a several-fold increase in prevalence of severe VHD (stage C/D), highlighting the public health importance of interventions to mitigate VHD progression.

Cellular mechanisms and molecular pathways linking bitter taste receptor signalling to cardiac inflammation, oxidative stress, arrhythmia and contractile dysfunction in heart diseases.

Heart diseases and related complications constitute a leading cause of death and socioeconomic threat worldwide. Despite intense efforts and research on the pathogenetic mechanisms of these diseases, the underlying cellular and molecular mechanisms are yet to be completely understood. Several lines of evidence indicate a critical role of inflammatory and oxidative stress responses in the development and progression of heart diseases. Nevertheless, the molecular machinery that drives cardiac inflammation and oxidative stress is not completely known. Recent data suggest an important role of cardiac bitter taste receptors (TAS2Rs) in the pathogenetic mechanism of heart diseases. Independent groups of researchers have demonstrated a central role of TAS2Rs in mediating inflammatory, oxidative stress responses, autophagy, impulse generation/propagation and contractile activities in the heart, suggesting that dysfunctional TAS2R signalling may predispose to cardiac inflammatory and oxidative stress disorders, characterised by contractile dysfunction and arrhythmia. Moreover, cardiac TAS2Rs act as gateway surveillance units that monitor and detect toxigenic or pathogenic molecules, including microbial components, and initiate responses that ultimately culminate in protection of the host against the aggression. Unfortunately, however, the molecular mechanisms that link TAS2R sensing of the cardiac milieu to inflammatory and oxidative stress responses are not clearly known. Therefore, we sought to review the possible role of TAS2R signalling in the pathophysiology of cardiac inflammation, oxidative stress, arrhythmia and contractile dysfunction in heart diseases. Potential therapeutic significance of targeting TAS2R or its downstream signalling molecules in cardiac inflammation, oxidative stress, arrhythmia and contractile dysfunction is also discussed.

Autonomic Nervous System Regulation of Epicardial Adipose Tissue: Potential Roles for Regulator of G Protein Signaling-4.

The epicardial adipose tissue (EAT) or epicardial fat is a visceral fat depot in the heart that contains intrinsic adrenergic and cholinergic nerves, through which it interacts with the cardiac sympathetic (adrenergic) and parasympathetic (cholinergic) nervous systems. These EAT nerves represent a significant source of several adipokines and other bioactive molecules, including norepinephrine, epinephrine, and free fatty acids. The production of these molecules is biologically relevant for the heart, since abnormalities in EAT secretion are implicated in the development of pathological conditions, including coronary atherosclerosis, atrial fibrillation, and heart failure. Sympathetic hyperactivity and parasympathetic (cholinergic) derangement are associated with EAT dysfunction, leading to a variety of adverse cardiac conditions, such as heart failure, diastolic dysfunction, atrial fibrillation, etc.; therefore, several studies have focused on exploring the autonomic regulation of EAT as it pertains to heart disease pathogenesis and progression. In addition, Regulator of G protein Signaling (RGS)-4 is a protein with significant regulatory roles in both adrenergic and muscarinic receptor signaling in the heart. In this review, we provide an overview of the autonomic regulation of EAT, with a specific focus on cardiac RGS4 and the potential roles this protein plays in this regulation.

The effect of a game-based mobile app 'MyHeartMate' to promote lifestyle change in coronary disease patients: a randomized controlled trial.

Secondary prevention reduces coronary heart disease (CHD) progression. Traditional prevention programs including cardiac rehabilitation are under-accessed, which smartphone apps may overcome. To evaluate the effect of a game-based mobile app intervention (MyHeartMate) to improve cardiovascular risk factors and lifestyle behaviours. Single-blind randomized trial of CHD patients in Sydney, 2017-2021. Intervention group were provided the MyHeartMate app for 6 months. Co-designed features included an avatar of the patient's heart and tokens earned by risk factor work (tracking, challenges, and quizzes). The control group received usual care. Primary outcome was self-reported physical activity [metabolic equivalents (METs), Global Physical Activity Questionnaire] and secondary outcomes included lipid levels, blood pressure (BP), body mass index, and smoking. Pre-specified sample size was achieved (n = 390), age 61.2 ± 11.5 years; 82.5% men and 9.2% current smokers. At 6 months, adjusted for baseline levels, the intervention group achieved more physical activity than control (median difference 329 MET mins/wk), which was not statistically significant (95% CI -37.4, 696; P = 0.064). No differences occurred between groups on secondary outcomes except for lower triglyceride levels in the intervention [mean difference -0.3 (95% CI -0.5, -0.1 mmoL/L, P = 0.004)]. Acceptability was high: 94.8% of intervention participants engaged by tracking exercise or BP and completing missions; 26.8% continued to engage for ≥30 days. Participants (n = 14) reported the app supported tracking behaviours and risk factors, reinforcing and improving self-care confidence, and decreasing anxiety. A game-based app proved highly acceptable for patients with CHD but did not improve risk factors or lifestyle behaviours other than triglyceride levels.

Chagas cardiomyopathy is associated with a high susceptibility to T. cruzi infection in monocyte-derived macrophages and a predominance of CD4+CD45RO+ T-cells with immunoregulatory patterns

The pathogenesis of Chronic Chagas Cardiomyopathy (CCC) is still not fully understood, and the persistence of the parasite in tissues seems to be essential for the onset and progression of heart disease, tissue destruction, and chronic inflammation. It is clear that the polarity found between the asymptomatic (IND) and cardiac clinical forms refers mainly to the mechanisms involved in the regulation of the host's immune response. Thus, to elucidate aspects of the susceptibility of host phagocytes to T. cruzi infection, the present study explored novel aspects of innate immune response, integrating data on susceptibility to infection and intracellular replication, using monocyte-derived macrophages from CCC patients, together with memory CD4+ T-cells (CD45RO+). The isolation of PBMC was conducted by means of in vitro infection assay with T. cruzi trypomastigotes and flow cytometry analysis of the intracytoplasmic cytokine production by CD4+T-cells. Our findings indicated that monocytes derived from individuals with CCC are more susceptible to the infection and replication of intracellular amastigotes. Moreover, the stimulation of CD4+ T-cells from CCC patients, together with T. cruzi trypomastigotes, induces a predominance of a regulatory response over a type 1 response, demonstrated by an increase in IL-10 production and a reduction in the IFN-γ and IFN-γ/IL-10. Suppression of the function of monocyte-derived macrophages, from CCC patients, to control trypomastigote infection and intracellular replication sheds light on a potential susceptibility of these cells isolated from peripheral blood, which may reflect the ineffectiveness of parasite control by phagocytes in cardiac tissues, which can subsequently result in serious heart disease.

Development of Myocardial Infarction in Rat Model of Diet-Induced Hypercholesterolaemia

The evidence of hypercholesterolaemia (HC) being a significant contributor to the progression of ischemic heart diseases (IHDs), particularly myocardial infarction (MI) is steadily increasing globally [1]. However, data on the establishment of MI-associated diet-induced HC rat model are lacking.&#x0D; &#x0D; Hence, this study aimed to establish an MI-associated diet-induced HC rat model, allowing a better understanding of the pathological changes of this rat model. A total of 6 male Sprague Dawley rats weighing 200-250 were randomly allotted into 2 groups; Control and HC-MI. Control rats were fed with standard pellet, while HC rats were fed with a self-made high-cholesterol diet (HCD) for 10 weeks. The recipe for the HCD was adopted from a previous study [2] with slight modification. At the end of 10th week, MI was induced with the administration of isoprenaline (85 mg/kg, s.c) for 2 consecutive days [3].&#x0D; &#x0D; In this study, 10 weeks of HCD significantly increased body mass index (BMI), triglyceride, and total cholesterol but not fasting blood glucose level in the HC group compared to the control group, suggestive of obese and HC state (Figure 1). MI was also evident by prominent observation of myocardial necrosis accompanied by infiltration of inflammatory cells in cardiac histology, although cardiac troponin T was not significantly elevated (Figure 2). Although liver function test showed significant elevation of AST but not ALT, but liver histological observation showed the presence of mixed steatosis and ballooning degeneration, suggestive of non-alcoholic fatty liver disease development (Figure 3). Nonetheless, kidney function test revealed a significant creatinine elevation but not urea level (Figure 4).&#x0D; &#x0D; Collectively, these findings suggest that supplementation of HCD for 10 weeks together with administration of isoprenaline successfully developed a rat model of HC with MI as shown across elevated systemic cholesterol level, BMI, and myocardial necrosis. This study provides useful data on the establishment of the model which could be used in the future.

Left Atrial Myocardium in Arterial Hypertension.

Arterial hypertension affects ≈ 1 billion people worldwide. It is associated with increased morbidity and mortality and responsible for millions of deaths each year. Hypertension mediates damage of target organs including the heart. In addition to eliciting left ventricular hypertrophy, dysfunction and heart failure, hypertension also causes left atrial remodeling that may culminate in atrial contractile dysfunction and atrial fibrillation. Here, we will summarize data on the various aspects of left atrial remodeling in (essential) hypertension gathered from studies on patients with hypertension and from spontaneously hypertensive rats, an animal model that closely mimics cardiac remodeling in human hypertension. Analyzing the timeline of remodeling processes, i.e., distinguishing between alterations occurring in prehypertension, in early hypertension and during advanced hypertensive heart disease, we will derive the potential mechanisms underlying left atrial remodeling in (essential) hypertension. Finally, we will discuss the consequences of these remodeling processes for atrial and ventricular function. The data imply that left atrial remodeling is multifactorial, starts early in hypertension and is an important contributor to the progression of hypertensive heart disease, including the development of atrial fibrillation and heart failure.