Coronary Artery Disease and Cancer: Treatment and Prognosis Regarding Gender Differences

Cardiovascular disease and cancer remain the leading causes of hospitalization and mortality in high-income countries. Survival after myocardial infarction has improved but there is still a difference in clinical outcome, mortality, and developing heart failure to the disadvantage of women with myocardial infarction. Most major cardiology trials and registries have excluded patients with cancer. As a result, there is only very limited information on the effects of coronary artery disease in cancer patients. In particular, the outcomes in women with cancer and coronary artery disease and its management remain empiric. We reviewed studies of over 27 million patients with coronary artery disease and cancer. Our review focused on the most important types of cancer (breast, colon, lung, prostate) and hematological malignancies with particular attention to sex-specific differences in treatment and prognosis.

Origin of congenital coronary arterio-ventricular fistulae from anomalous epicardial and myocardial development

Coronary Artery Fistulae (CAFs) are cardiac congenital anomalies consisting of an abnormal communication of a coronary artery with either a cardiac chamber or another cardiac vessel. In humans, these congenital anomalies can lead to complications such as myocardial hypertrophy, endocarditis, heart dilatation and failure. Unfortunately, despite their clinical relevance, the aetiology of CAFs remains unknown. In this work, we have used two different species (mouse and avian embryos) to experimentally model CAFs morphogenesis. Both conditional Itga4 (alpha 4 integrin) epicardial deletion in mice and cryocauterisation of chick embryonic hearts disrupted epicardial development and ventricular wall growth, two essential events in coronary embryogenesis. Additional transcriptomics and in vitro analyses were performed to better understand how arterio-ventricular connections are originated in the embryonic heart. Our results suggest myocardial discontinuities in the developing heart promote the formation of endocardial pouch-like structures resembling human CAF. The structure of these CAF-like anomalies was compared with histopathological data from a paediatric heart CAF, showing histomorphological and immunochemical similarities, including an accumulation of smooth muscle positive cells in the pouch-like structure wall. In vitro experiments showed the abnormal contact between the epicardium and the endocardium may promote the precocious differentiation of epicardial cells to smooth muscle. Our results suggest that myocardial discontinuities in the embryonic ventricular wall promote the early contact of the endocardium with epicardial-derived coronary progenitors at the cardiac surface, leading to ventricular endocardial extrusion, precocious differentiation of coronary smooth muscle cells, and the formation of pouch-like aberrant coronary-like structures in direct connection with the ventricular lumen. Our results may provide relevant information for the early diagnosis of these congenital anomalies and the molecular mechanisms that regulate their embryogenesis.

Recapitulating human cardio-pulmonary co-development using simultaneous multilineage differentiation of pluripotent stem cells

The extensive crosstalk between the developing heart and lung is critical to their proper morphogenesis and maturation. However, there remains a lack of models that investigate the critical cardio-pulmonary mutual interaction during human embryogenesis. Here, we reported a novel stepwise strategy for directing the simultaneous induction of both mesoderm-derived cardiac and endoderm-derived lung epithelial lineages within a single differentiation of human induced pluripotent stem cells (hiPSCs) via temporal specific tuning of WNT and nodal signaling in the absence of exogenous growth factors. Using 3D suspension culture, we established concentric cardio-pulmonary micro-Tissues (mTs), and expedited alveolar maturation in the presence of cardiac accompaniment. Upon withdrawal of WNT agonist, the cardiac and pulmonary components within each dual-lineage mT effectively segregated from each other with concurrent initiation of cardiac contraction. We expect that our multilineage differentiation model will offer an experimentally tractable system for investigating human cardio-pulmonary interaction and tissue boundary formation during embryogenesis.

Modern treatment of patients with arterial hypertension and chronic coronary syndrome

Approximately 1,2 billion people worldwide suffer from arterial hypertension. Among these patients, less than half receive effective treatment. Poor blood pressure control contributes to the development of complications such as stroke or coronary artery disease. A patient with such complications automatically becomes a patient at very high cardiovascular risk, and thus requires personalized and effective treatment, not only of hypertension, but also of its complications. Despite the advancement of the disease, lifestyle modification and correct choice of pharmacotherapy can protect the patient from developing heart failure and prevent acute cardiovascular events.

BioLearner: A Machine Learning-Powered Smart Heart Disease Risk Prediction System Utilizing Biomedical Markers

Heart disease kills more people around the world than any other disease, and it is one of the leading causes of death in the UK, triggering up to 74,000 deaths per year. An essential part in the prevention of deaths by heart disease and thus heart disease itself is the analysis of biomedical markers to determine the risk of a person developing heart disease. Lots of research has been conducted to assess the accuracy of detecting heart disease by analyzing biomedical markers. However, no previous study has attempted to identify the biomedical markers which are most important in this identification. To solve this problem, we proposed a machine learning-based intelligent heart disease prediction system called BioLearner for the determination of vital biomedical markers. This study aims to improve upon the accuracy of predicting heart disease and identify the most essential biological markers. This is done with the intention of composing a set of markers that impacts the development of heart disease the most. Multiple factors determine whether or not a person develops heart disease. These factors are thought to include Age, history of chest pain (of different types), fasting blood sugar of different types, heart rate, smoking, and other essential factors. The dataset is analyzed, and the different aspects are compared. Various machine learning models such as [Formula: see text] Nearest Neighbours, Neural Networks, Support Vector Machine (SVM) are trained and used to determine the accuracy of our prediction for future heart disease development. BioLearner is able to predict the risk of heart disease with an accuracy of 95%, much higher than the baseline methods.

Higher Long-term Visit-to-Visit Variability in Fasting Plasma Glucose Predicts New-Onset Heart Failure in the General Population

Background: Previous studies suggested an adverse association between higher fasting blood glucose (FBG) and heart failure. However, FBG values fluctuate continuously over time, the association between FBG variability and the risk of heart failure is uncertain.Aims: We investigated the relationship between visit-to-visit variability in FBG and the risk of new-onset heart failure.Methods and Results: This was a population-based cohort study using the Kailuan dataset, which comprises of medical claims and a biennially health checkup information from a Chinese cohort. A total of 98 554 individuals (mean age: 53.63 years) who had at least two health checkups with FBG measurement between 2006 and 2012 without preexisting heart failure were included. FBG variability was calculated using the variability independent of the mean, coefficient of variation, standard deviation, and average successive variability (ARV). Participants were divided into quartiles of ARV. Cox regression was used to identify heart failure. Over a mean follow-up of 6.27 years, 1218 individuals developed heart failure. The incidence of heart failure was 1.97 per 1000 person-years. After adjusting for baseline FBG and other potential confounders, individuals in the highest quartile of the ARV of FBG had 32.6% higher risk of developing heart failure compared to those in the lowest quartile (hazard ratio, 1.326; 95% confidence interval, 1.120-1.570). This association remained significant in patients with or without prevalent hypertension. In subgroup analyses, individuals who were younger (<65 years), without diabetes mellitus or chronic kidney disease, and with a body mass index<25 kg/m2 experienced a higher risk of heart failure.Conclusions: Our data demonstrated that high FBG variability is independently associated with the development of new-onset heart failure. Future studies should explore whether measures to reduce variability can lead to improve clinical outcomes. Trial registration: Chinese Clinical Trial Register, ChiCTR-TNRC-11001489. Registered on 24-08-2011.

Social relationships and the risk of incident heart failure: Results from a prospective population-based study of older men

Background Limited social relationships, particularly in older adults, has been implicated as a risk factor for cardiovascular disease. However, little is known about the associations between poor social relationships and heart failure incidence. Methods Prospective study of socially representative men aged 60-79 years drawn from general practices in 24 British towns and followed up for a maximum of 18 years. 3698 participants with no previous diagnosis of heart failure were included. Information on social relationships was based on a combination of marital status, living circumstances, and social contacts with friends and family. These provided information on contact frequency, contact satisfaction, and a social relationship score (low to high) combining frequency and satisfaction with contact. Heart failure included both incident non-fatal heart failure and death from heart failure. Results Among 3698 participants, 330 developed heart failure. Men with low compared to high frequency of contact with family and friends had an increased risk of incident heart failure (hazard ratio (HR) 1.59, 95%CI 1.15-2.18); this remained statistically significant after adjustment for social class, behavioural and biological risk factors. Low compared to high scores for satisfaction with contacts was associated with increased risk of heart failure (adjusted HR = 1.54; 95%CI 1.14-2.07). Lower social relationship scores (combining frequency and satisfaction with contact) were associated with greater risk of incident heart failure (adjusted HR = 1.38, 95%CI 1.02-1.87). Marital status and living alone were not significantly associated with heart failure. Conclusion Weaker social relationships appear to increase the risk of developing heart failure in older age. Further research is needed to investigate pathways underlying these associations and to test whether interventions to strengthen social relationships can reduce the risk of heart failure.

Do Dipeptidyl Peptidase-4 Inhibitors Increase the Risk of Heart Failure in Patients with Type 2 Diabetes?

: Dipeptidyl peptidase-4 inhibitors (DDP-4Is) or gliptins have been extensively studied in recent years. These studies have shown the safety and efficacy of gliptins in managing hyperglycemia in diabetic patients. However, there is ongoing debate on whether DDP-4Is are associated with a higher risk for developing heart failure. It is expected that long-term data from patients who are currently prescribed DDP-4Is will provide a clearer understanding of their potential benefits. This should also help guide the development of future guidelines. The focus of this perspective is on associations between the “use of DPP-4Is” and “increased risk of heart failure”. Thus, we examine several key publications and reviews on clinical trials on this class of oral antidiabetic medications. For this communication, the pertinent literature has been critically analyzed to provide an evidence-based overview of the evolving concept of DPP-4Is-induced risk of heart failure.

Insights to Heart Development and Cardiac Disease Models Using Pluripotent Stem Cell Derived 3D Organoids

Medical research in the recent years has achieved significant progress due to the increasing prominence of organoid technology. Various developed tissue organoids bridge the limitations of conventional 2D cell culture and animal models by recapitulating in vivo cellular complexity. Current 3D cardiac organoid cultures have shown their utility in modelling key developmental hallmarks of heart organogenesis, but the complexity of the organ demands a more versatile model that can investigate more fundamental parameters, such as structure, organization and compartmentalization of a functioning heart. This review will cover the prominence of cardiac organoids in recent research, unpack current in vitro 3D models of the developing heart and look into the prospect of developing physiologically appropriate cardiac organoids with translational applicability. In addition, we discuss some of the limitations of existing cardiac organoid models in modelling embryonic development of the heart and manifestation of cardiac diseases.

Exercise During Childhood Protects Against Cardiac Dysfunction Later in Life

Cardiovascular disease continues to be a major cause of morbidity and mortality, particularly in aging populations. Exercise is amongst the most cardioprotective interventions identified to date, with early in life exercise such as during the juvenile period potentially imparting even more cardioprotective outcomes due to the plasticity of the developing heart. To test the hypothesis that juvenile exercise would impart later in life cardioprotection, we exercised juvenile male and female mice via voluntary wheel running from 3-5 weeks of age and then exposed them to cardiac stress by isoproterenol (ISO) at 4-6 and 18 months of age in adulthood and older age, respectively. We compared cardiac function and remodeling to sedentary control animals, sedentary animals who received ISO, and adult and aged mice that exercised for two weeks immediately before ISO exposure. Juvenile mice engaged in voluntarily wheel running, with male mice running 1.3 ± 0.8 km and female mice 2.8 ± 1.0 km a day. Echocardiography suggested that these juvenile animals underwent running-induced cardiac remodeling as evidenced by higher ejection fraction and stroke volume compared to sedentary controls. Exercise in the juvenile period attenuated ISO-induced cardiac hypertrophy and remodeling later in life compared to sedentary animals and those that exercised immediately before ISO administration. The mechanisms by which early versus late exercise is protective in adult and aged mice are under investigation. Further ongoing work will identify the adaptations induced by exercise in the juvenile heart that may help improve cardiac aging.