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Background: Myocardial fibrosis, a hallmark of heart disease, is closely associated with macrophages, yet the genetic pathophysiology remains incompletely understood. In this study, we utilized integrated single-cell transcriptomics and bulk RNA-seq analysis to investigate the relationship between macrophages and myocardial fibrosis across omics integration., Methods: We examined and curated existing single-cell data from dilated cardiomyopathy (DCM), ischemic cardiomyopathy (ICM), myocardial infarction (MI), and heart failure (HF), and analyzed the integrated data using cell communication, transcription factor identification, high dimensional weighted gene co-expression network analysis (hdWGCNA), and functional enrichment to elucidate the drivers of macrophage polarization and the macrophage-to-myofibroblast transition (MMT). Additionally, we assessed the accuracy of single-cell data from the perspective of driving factors, cell typing, anti-fibrosis performance of left ventricular assist device (LVAD). Candidate drugs were screened using L1000FWD., Results: All four heart diseases exhibit myocardial fibrosis, with only MI showing an increase in macrophage proportions. Macrophages participate in myocardial fibrosis through various fibrogenic molecules, especially evident in DCM and MI. Abnormal RNA metabolism and dysregulated transcription are significant drivers of macrophage-mediated fibrosis. Furthermore, profibrotic macrophages exhibit M1 polarization and increased MMT. In HF patients, those responding to LVAD therapy showed a significant decrease in driver gene expression, M1 polarization, and MMT. Drug repurposing identified cinobufagin as a potential therapeutic agent., Conclusion: Using integrated single-cell transcriptomics, we identified the drivers of macrophage-mediated myocardial fibrosis in four heart diseases and confirmed the therapeutic effect of LVAD on improving HF with single-cell accuracy, providing novel insights into the diagnosis and treatment of myocardial fibrosis., (© 2024. The Author(s).)

Ischemic heart failure continues to be a highly prevalent disease among westernized countries and there is great interest in understanding the mechanisms preventing or exacerbating disease progression. The literature suggests an important role for the activation of interleukin-13 or interleukin-4 signaling in improving ischemic heart failure outcomes after myocardial infarction in mice. Dupilumab, a neutralizing antibody that inhibits the shared IL13/IL4 receptor subunit IL4Rα, is widely used for conditions such as ectopic dermatitis in humans. If global depletion of IL4Rα influences ischemic heart failure, either in mice or in humans taking dupilumab, is unknown. Here, we investigated the pathophysiological effects of global IL4Rα genetic deletion in adult mice after surgically induced myocardial infarction (MI). We also determined heart failure risk in patients with ischemic heart disease and concomitant usage of dupilumab using the collaborative patient data network TriNetX. Global deletion of IL4Rα results in exacerbated cardiac dysfunction associated with reduced capillary size after myocardial infarction in mice. In agreement with our findings in mice, dupilumab treatment significantly increased the risk of heart failure development in patients with preexisting diagnosis of ischemic heart disease. Our results indicate that systemic IL4Rα signaling is protective against heart failure development in adult mice and human patients specifically following an ischemic event. Thus, the compelling evidence presented hereby advocates for the development of a randomized clinical trial specifically investigating heart failure development after myocardial ischemia in patients taking dupilumab for another underlying condition. NEW & NOTEWORTHY A body of literature suggests a protective role for IL4Rα signaling postmyocardial infarction in mice. Here, our observational study demonstrates that humans taking the IL4Rα neutralizing antibody, dupilumab, have increased incidence of heart failure following an ischemic event. Similarly, global IL4Rα deletion in mice exacerbates heart failure postinfarct. To our knowledge, this is the first study reporting an adverse association in humans of dupilumab use with heart failure following a cardiac ischemic event.

The Wnt signaling pathway is a fundamental cellular communication system with extensive implications in various organs including the heart. In cardiac homeostasis, it governs essential processes like cellular proliferation, differentiation, and apoptosis, ensuring the heart's structural and functional integrity from embryonic stages and throughout life. Both canonical and non-canonical Wnt signaling pathways play a critical role during embryonic heart development in a region- and stage-specific manner. Canonical Wnt signaling also plays a significant role in heart diseases such as myocardial infarction and heart failure. However, the role of non-canonical Wnt signaling in heart diseases has not been fully elucidated. Wnt5a is a major ligand that activates non-canonical Wnt pathway, and recent studies start to clarify the role of the Wnt5a signaling axis in cardiac health and disease. In this review, we will briefly summarize the previous findings on the role of Wnt signaling pathways in heart development and diseases, and then focus on the role of Wnt5a signaling in heart failure progression. The multifaceted roles of the Wnt signaling pathway highlight its therapeutic potential for various types of heart diseases., (© 2024. The Author(s).)

Background and Aims: Our aim was to define reference limits for cardiac troponin T (cTnT) and N-terminal pro B-type natriuretic peptide (proBNP) that would better reflect their concentrations in older people. In addition, the incidence of acute myocardial infarctions (AMIs) was studied using these reference limits in an older population with and without previous heart diseases., Materials and Methods: A population-based study with a ten-year follow-up. The reference population was formed by 763 individuals aged over 64 years, with no diagnoses of heart or kidney diseases., Results: There was a significant increase in cTnT and proBNP concentrations with age. The 99 % reference limits for cTnT were 25 ng/L, 28 ng/l, 38 ng/l, and 71 ng/l for men in five-year-intervals starting from 64 to 69 years to 80 years and older, and 18 ng/L, 22 ng/l, 26 ng/l, and 52 ng/L for women, respectively. The 97.5 % reference limits for proBNP were 272 ng/L, 287 ng/l, 373 ng/l and 686 ng/L for men, and 341 ng/L, 377 ng/l, 471 ng/l, and 794 ng/L for women, respectively. Elevated proBNP was statistically significantly associated with future AMIs in subjects with and without a previous heart disease., Conclusions: Age-specific reference limits for cTnT and proBNP are needed to better evaluate cardiac symptoms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: To explore cardiac structural and functional parameters and myocardial sensitivity to ischemia in a rat model of chronic arthritis, pristane-induced arthritis (PIA), and to investigate the effects of a running exercise protocol on cardiac disorders related to rheumatoid arthritis (RA)., Main Methods: 3 groups of male Dark Agouti rats were formed: Controls, PIA and PIA-Exercise. The PIA-Exercise group was subjected to an individualized treadmill running protocol during the remission phase. At acute and chronic phases of PIA, cardiac structure was analyzed by histology. Cardiac function was explored in isolated hearts to measure left ventricular developed pressure (LVDP), cardiac compliance and infarct size before and after ischemia/reperfusion. Cardiac inflammation was evaluated through VCAM-1 mRNA expression by RT-qPCR. Plasma irisin levels were measured by ELISA., Key Findings: PIA rats exhibited myocardial hypertrophy fibrosis and inflammation at the 2 inflammatory phases of the model. At chronic phase only, LVDP and cardiac compliance were lower in PIA compared to controls. As compared to sedentary PIA, exercise did not change cardiac function but reduced fibrosis, inflammation, infarct size, and arthritis severity and increased irisin levels. Cardiac inflammation positively correlated with fibrosis, while irisin levels negatively correlated with cardiac inflammation and fibrosis., Significance: In the PIA model that recapitulated most cardiac disorders of RA, a daily program of treadmill running alleviated cardiac fibrosis and inflammation and improved resistance to ischemia. These data provide arguments to promote the practice of exercise in RA patients for cardiac diseases prevention., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Cardiovascular diseases (CVDs), such as heart disease and stroke, have a significant impact on life expectancy, healthy life expectancy, and medical costs in Japan. Each prefecture is currently promoting measures in accordance with the Japanese National Plan for Promotion of Measures Against Cerebrovascular and Cardiovascular Disease, which was established by the government. In recent years, the crude mortality rate of heart disease in Japan has been increasing year by year with the aging population. Meanwhile, the age-adjusted mortality rate has leveled off or shown a downward trend. In addition, the proportion of acute myocardial infarction has decreased, whereas the proportion of heart failure has increased. By contrast, both the crude and age-adjusted mortality rates of stroke have a declining trend. Nevertheless, considering the potential variations in death certificates issued for patients with myocardial infarction across different prefectures, it is crucial to determine the incidence of CVD in each prefecture for the accurate assessment of CVD trends. However, as for the incidence of CVD, not many prefectures have yet implemented registration programs. The age-adjusted incidence rate of acute myocardial infarction has been increasing in some areas and decreasing in others since 1990. The age-adjusted incidence rate of stroke has consistently declined since the 1960s. Nevertheless, the possible increase in the incidence rate of cerebral embolism and thrombotic cerebral infarction among patients with different stroke subtypes is a cause of concern. The impact of heart failure on the incidence of heart disease has increased. Therefore, relevant academic societies and prefectures must collaborate in registering the incidence of heart failure as well as myocardial infarction and implementing countermeasures., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Patient blood group (BG) is predictive for von-Willebrand-factor (VWF) and Factor VIII variation. The clinical impact of this ABO-effect on blood loss, cardiovascular complications and outcome has been described for several patient cohorts. The aim of this study was to investigate the impact of patient BG on blood loss and outcome after coronary artery bypass surgery (CABG). Patient records, intraoperative data and perioperative transfusion records of 5713 patients receiving an on-pump CABG procedure between 05/2004 and 12/2018 were analyzed. A logistic regression model for death due to perioperative myocardial ischaemia (PMI) was developed from initially 24 variables by using an univariate and multivariate selection process. BG AB patients required less blood transfusions as compared to the other blood groups, especially in case of emergency operations. However, BG AB patients also had a higher mortality which was due to secondary cardiovascular complications. The impact of blood type on the rate of cardiovascular mortality was confirmed in the logistic regression model. BG AB patients have a worse outcome after CABG surgery due to an increased incidence of fatal cardiovascular complications. As perioperative myocardial ischemia due to graft occlusion appears to be the most likely explanation, stricter anticoagulation for BG AB patients should be discussed., (© 2024. The Author(s).)

Background: Myocardial infarction (MI), stroke, peripheral arterial disease (PAD), heart failure (HF) and chronic kidney disease (CKD) are common cardiovascular renal diseases (CVRD) manifestations for type 2 diabetes. The objective was to estimate the incidence of the first occurring CVRD manifestation and cumulative hospitalization costs of each CVRD manifestation for type 2 diabetes without CVRD history., Methods: A cohort study of all type 2 diabetes free of CVRD as of January 1st 2014, was identified and followed-up for 5 years within the French SNDS nationwide claims database. The cumulative incidence of the first occurring CVRD manifestation was estimated using the cumulative incidence function, with death as a competing risk. Cumulative hospitalization costs of each CVRD manifestations were estimated from the perspective of all payers., Results: From 2,079,089 type 2 diabetes without cancer or transplantation, 76.5% were free of CVRD at baseline with a mean age of 65 years, 52% of women and 7% with microvascular complications history. The cumulative incidence of a first CVRD manifestation was 15.3% after 5 years of follow-up with a constant linear increase over time for all CVRD manifestations: The most frequent was CKD representing 40.6% of first occurred CVRD manifestation, followed by HF (23.0%), then PAD (13.5%), stroke (13.2%) and MI (9.7%). HF and CKD together reached about one patient out of ten after 5 years and represented 63.6% of first CVRD manifestations. The 5-year global cost of all CVRD hospitalizations was 3.9 billion euros (B€), i.e. 2,450€ per patient of the whole cohort, with an exponential increase over time for each specific CVRD manifestation. The costliest was CKD (2.0 B€), followed by HF (1.2 B€), then PAD (0.7 B€), stroke (0.6 B€) and MI (0.3 B€)., Conclusions/interpretation: While MI, stroke and PAD remain classic major risks of complications for CVRD-free type 2 diabetes, HF and CKD nowadays represent individually a higher risk and cost than each of these classic manifestations, and jointly represents a risk and a cost twice as high as these three classic manifestations all together. This should encourage the development of specific HF and CKD preventive strategies., (© 2024. The Author(s).)

Background: Ventricular mural thrombi are rare occurrences and form one of the common mechanical complications of myocardial infarctions. They also occur in patients with nonischemic myocardial disorders and even in those devoid of cardiac diseases. Clinical detection often depends on the size of the thrombi., Aim: This study was aimed at ascertaining the etiopathogenesis of mural thrombi with a clinicopathologic correlation., Materials and Methods: This was a 12-year retrospective observational study reviewing the autopsy records of all cases showing ventricular mural thrombi. The location, size, morphology, and histologic appearances of the thrombi were noted. The cases, depending on the etiology, were categorized into myocardial ischemic (Group 1), myocardial nonischemic (Group 2), and non-myocardial (Group 3) causes. These features were correlated with the clinical settings., Results: There were 93 cases of mural thrombi with an almost equal sex distribution and a mean age of 45.9 years. The cause was ischemic heart disease in most of the patients (Group 1, 46.2%), while 21.5% and 32.3% of patients belonged to Group 2 and Group 3, respectively. Unlike the large and dominantly left ventricular thrombi seen in Group 1, the other two groups frequently had biventricular involvement, location in the intertrabecular spaces, and a high microscopic detection. Clinical diagnosis had been made in only 3.2% of patients. Thromboembolism was noted in other organs in 34.4% of the total cases., Conclusion: Ventricular thrombi should be ruled out in patients with evidence of systemic and/or pulmonary thromboembolism, even in those without any cardiac disorders.

Kinesiophobia is a well-known barrier to positive clinical outcomes among patients with various diseases, but there remain few comprehensive studies of kinesiophobia among patients with myocardial infarction (MI). In this cross-sectional study, we investigated the presence of kinesiophobia and its relationship with clinical outcomes among 42 patients with MI who completed the Tampa Scale of Kinesiophobia Swedish Version for Heart (TSK-SV Heart) the International Physical Activity Questionnaire-Short Form (IPAQ-SF), the Six-Minute Walk Test (6MWT), the Hospital Anxiety and Depression Scale (HADS), the modified Medical Research Council (mMRC) Dyspnea Scale, the Charlson Comorbidity Index (CCI), and the MacNew Heart Disease Health-Related Quality of Life Questionnaire. The participants' mean TSK-SV Heart score was 39.24 ( SD = 6.65), and 71.4% of these patients reported a high level of kinesiophobia. The TSK-SV Heart score demonstrated a strong correlation with the IPAQ-SF, 6MWT walking distance, and mMRC score ( p < .001), and a moderate correlation with the HADS, CCI, and MacNew Heart Disease HRQoL ( p < .05). Patients with a high level of kinesiophobia had lower IPAQ-SF, 6MWT walking distance, and HRQoL and higher mMRC, CCI, and HADS scores than patients with low levels of kinesiophobia ( p < .05). Kinesiophobia was common and represented a considerable risk factor for physical-psychosocial dysfunctions in these patients with MI. To maintain functional independence and to increase physical activity level, clinicians should consider kinesiophobia from early to late-stage disease and should add a treatment focus that seeks to eliminate kinesiophobia in cardiac rehabilitation programs., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Circadian rhythms are internal 24-h intrinsic oscillations that are present in essentially all mammalian cells and can influence numerous biological processes. Cardiac function is known to exhibit a circadian rhythm and is strongly affected by the day/night cycle. Many cardiovascular variables, including heart rate, heart rate variability (HRV), electrocardiogram (ECG) waveforms, endothelial cell function, and blood pressure, demonstrate robust circadian rhythms. Many experiential and clinical studies have highlighted that disruptions in circadian rhythms can ultimately lead to maladaptive cardiac function. Factors that disrupt the circadian rhythm, including shift work, global travel, and sleep disorders, may consequently enhance the risk of cardiovascular diseases. Some cardiac diseases appear to occur at particular times of the day or night; therefore, targeting the disease at particular times of day may improve the clinical outcome. The objective of this review is to unravel the relationship between circadian rhythms and cardiovascular health. By understanding this intricate interplay, we aim to reveal the potential risks of circadian disruption and discuss the emerging therapeutic strategies, specifically those targeting circadian rhythms. In this review, we explore the important role of circadian rhythms in cardiovascular physiology and highlight the role they play in cardiac dysfunction such as ventricular hypertrophy, arrhythmia, diabetes, and myocardial infarction. Finally, we review potential translational treatments aimed at circadian rhythms. These treatments offer an innovative approach to enhancing the existing approaches for managing and treating heart-related conditions, while also opening new avenues for therapeutic development.

Background Cardiovascular complications after acute ischemic stroke (AIS) can be related to chronic/comorbid cardiac conditions or acute disruption of the brain-heart autonomic axis (stroke-heart syndrome). Women are known to be more vulnerable to certain stress-induced cardiac complications, such as Takotsubo cardiomyopathy. We investigated sex differences in cardiac troponin (cTn) elevation, cardiac events, and outcomes after AIS. Methods and Results We retrospectively analyzed consecutive patients with AIS from 5 stroke centers. Patients with AIS with elevated baseline cTn and at least 2 cTn measurements were included, while patients with acute comorbid conditions that could impact cTn levels were excluded. Poststroke acute myocardial injury was defined as the presence of a dynamic cTn pattern (rise/fall >20% in serial measurements) in the absence of acute atherosclerotic coronary disease (type 1 myocardial infarction) or cardiac death (type 3 myocardial infarction). From a total cohort of 3789 patients with AIS, 300 patients were included in the study: 160 were women (53%). Women were older, had a lower burden of cardiovascular risk factors, and more frequently had cardioembolic stroke and right insula involvement ( P values all <0.05). In multivariate analysis, women were more likely to have a dynamic cTn pattern (adjusted odds ratio, 2.1 [95% CI, 1.2-3.6]) and develop poststroke acute myocardial injury (adjusted odds ratio, 2.1 [95% CI, 1.1-3.8]). Patients with poststroke acute myocardial injury had higher 7-day mortality (adjusted odds ratio, 5.5 [95% CI, 1.2-24.4]). Conclusions In patients with AIS with elevated cTn at baseline, women are twice as likely to develop poststroke acute myocardial injury, and this is associated with higher risk of short-term mortality. Translational studies are needed to clarify mechanisms underlying sex differences in cardiac events and mortality in AIS.

Heart disease is one of the principal death reasons around the world and there is a growing requirement to discover novel healing targets that have the potential to avert or manage these illnesses. On the other hand, apoptosis is a strongly controlled, cell removal procedure that has a crucial part in numerous cardiac problems, such as reperfusion injury, MI (myocardial infarction), consecutive heart failure, and inflammation of myocardium. Completely comprehending the managing procedures of cell death signaling is critical as it is the primary factor that influences patient mortality and morbidity, owing to cardiomyocyte damage. Indeed, the prevention of heart cell death appears to be a viable treatment approach for heart illnesses. According to current researches, a number of long non-coding RNAs cause the heart cells death via different methods that are embroiled in controlling the activity of transcription elements, the pathways that signals transmission within cells, small miRNAs, and the constancy of proteins. When there is too much cell death in the heart, it can cause problems like reduced blood flow, heart damage after restoring blood flow, heart disease in diabetics, and changes in the heart after reduced blood flow. Therefore, studying how lncRNAs control apoptosis could help us find new treatments for heart diseases. In this review, we present recent discoveries about how lncRNAs are involved in causing cell death in different cardiovascular diseases., Competing Interests: Declaration of Competing Interest There is no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Cardiac disorders are a leading cause of global casualties, emphasizing the need for the initial diagnosis and prevention of cardiovascular diseases (CVDs). Electrocardiogram (ECG) procedures are highly recommended as they provide crucial cardiology information. Telemedicine offers an opportunity to provide low-cost tools and widespread availability for CVD management. In this research, we proposed an IoT-based monitoring and detection system for cardiac patients, employing a two-stage approach. In the initial stage, we used a routing protocol that combines routing by energy and link quality (REL) with dynamic source routing (DSR) to efficiently collect data on an IoT healthcare platform. The second stage involves the classification of ECG images using hybrid-based deep features. Our classification system utilizes the "ECG Images dataset of Cardiac Patients", comprising 12-lead ECG images with four distinct categories: abnormal heartbeat, myocardial infarction (MI), previous history of MI, and normal ECG. For feature extraction, we employed a lightweight CNN, which automatically extracts relevant ECG features. These features were further optimized through an attention module, which is the method's main focus. The model achieved a remarkable accuracy of 98.39%. Our findings suggest that this system can effectively aid in the identification of cardiac disorders. The proposed approach combines IoT, deep learning, and efficient routing protocols, showcasing its potential for improving CVD diagnosis and management.

Competing Interests: Disclosures Dr Reynolds received National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) research grant support for ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) and ISCHEMIA EXTEND (ISCHEMIA EXTEND [Extended Follow-up]) clinical trials; in-kind research support from Abbott Vascular. Dr Hochman received NIH/NHLBI research grant support for ISCHEMIA and ISCHEMIA EXTEND clinical trials. Dr Rao reports no conflict.

Electrocardiogram (ECG) signal is an important basis for the diagnosis of arrhythmia and myocardial infarction. In order to further improve the classification effect of arrhythmia and myocardial infarction, an ECG classification algorithm based on Convolutional vision Transformer (CvT) and multimodal image fusion was proposed. Through Gramian summation angular field (GASF), Gramian difference angular field (GADF) and recurrence plot (RP), the one-dimensional ECG signal was converted into three different modes of two-dimensional images, and fused into a multimodal fusion image containing more features. The CvT-13 model could take into account local and global information when processing the fused image, thus effectively improving the classification performance. On the MIT-BIH arrhythmia dataset and the PTB myocardial infarction dataset, the algorithm achieved a combined accuracy of 99.9% for the classification of five arrhythmias and 99.8% for the classification of myocardial infarction. The experiments show that the high-precision computer-assisted intelligent classification method is superior and can effectively improve the diagnostic efficiency of arrhythmia as well as myocardial infarction and other cardiac diseases.

Cardiovascular disorders are often diagnosed using an electrocardiogram (ECG). It is a painless method that mimics the cyclical contraction and relaxation of the heart's muscles. By monitoring the heart's electrical activity, an ECG can be used to identify irregular heartbeats, heart attacks, cardiac illnesses, or enlarged hearts. Numerous studies and analyses of ECG signals to identify cardiac problems have been conducted during the past few years. Although ECG heartbeat classification methods have been presented in the literature, especially for unbalanced datasets, they have not proven to be successful in recognizing some heartbeat categories with high performance. This study uses a convolutional neural network (CNN) model to combine the benefits of dense and residual blocks. The objective is to leverage the benefits of residual and dense connections to enhance information flow, gradient propagation, and feature reuse, ultimately improving the model's performance. This proposed model consists of a series of residual-dense blocks interleaved with optional pooling layers for downsampling. A linear support vector machine (LSVM) classified heartbeats into five classes. This makes it easier to learn and represent features from ECG signals. We first denoised the gathered ECG data to correct issues such as baseline drift, power line interference, and motion noise. The impacts of the class imbalance are then offset by resampling techniques that denoise ECG signals. An RD-CNN algorithm is then used to categorize the ECG data for the various cardiac illnesses using the retrieved characteristics. On two benchmarked datasets, we conducted extensive simulations and assessed several performance measures. On average, we have achieved an accuracy of 98.5%, a sensitivity of 97.6%, a specificity of 96.8%, and an area under the receiver operating curve (AUC) of 0.99. The effectiveness of our suggested method for detecting heart disease from ECG data was compared with several recently presented algorithms. The results demonstrate that our method is lightweight and practical, qualifying it for continuous monitoring applications in clinical settings for automated ECG interpretation to support cardiologists.

The factors associated with cerebral infarction and mortality in patients hospitalized with intracardiac thrombus are unknown. A retrospective cohort study was undertaken of nationally representative hospital admissions in the National Inpatient Sample with a diagnosis of intracardiac thrombus between 2016 to 2019. Multiple logistic regressions were used to define factors associated with cerebral infarction and in-hospital mortality. There were a total of 175,370 admissions for patients with intracardiac thrombus and 10.1% patients had cerebral infarction (n = 17,675). Intracardiac thrombus represented 4.4% of primary diagnosis for admissions while circulatory conditions (65.4%), infection (5.9%), gastrointestinal conditions (4.4%), respiratory conditions (4.4%) and cancer (2.2%) were the other prevalent primary diagnoses. All-cause mortality was higher for patients with cerebral infarction (8.5% vs 4.8%). The five factors most associated with cerebral infarction were nephrotic syndrome (OR 2.67 95%CI 1.05-6.78), other thrombophilia (OR 2.12 95%CI 1.52-2.95), primary thrombophilia (OR 1.99 95%CI 1.52-2.53), previous stroke (OR 1.61 95%CI 1.47-1.75) and hypertension (OR 1.41 95%CI 1.27-1.56). The strongest independent predictors of death were heparin induced thrombocytopenia (OR 2.45 95%CI 150-4.00), acute venous thromboembolism (OR 2.03 95%CI 1.78-2.33, p < 0.001) acute myocardial infarction (OR 1.95 95%CI 1.72-2.22), arterial thrombosis (OR 1.75 95%CI 1.39-2.20) and cancer (OR 1.57 95%CI 1.36-1.81). Patients with intracardiac thrombus are at risk of cerebral infarction and in-hospital mortality. Nephrotic syndrome, thrombophilia, previous stroke, hypertension, and heparin induced thrombocytopenia were associated with cerebral infarction, while acute venous thromboembolism, acute myocardial infarction, and cancer were predictors of mortality., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cardiac wall rupture (CWR) is a serious and often fatal complication of myocardial infarction (MI). Despite an increase in the incidence of MI in patients with systemic lupus erythematosus (SLE), cases of CWR in these patients have been reported rarely. This study reports an SLE patient with CWR and pseudoaneurysm formation and reviews previously reported cases of CWR in SLE patients. An English language literature review of from the PubMed, EMBASE, and Scopus databases on published cases of CWR in SLE, up until January 2023, was performed and analyzed. The search identified 4 patients, including the present one, 5 cases altogether. All of them were female aged 27-40 years, and 3 of them had had SLE for 10 years or more. Chest pain and dyspnea were the common presentations. All had left ventricular (LV) wall rupture. Three patients had LV wall rupture with pseudoaneurysm formation (one had MI with normal coronary artery, one myocardial necrosis secondary from small coronary artery vasculitis and one MI from uncertain cause). The other 2 patients had LV free wall rupture (one had MI with extensive coronary atherosclerosis with coronary arteritis, and the other septic myocarditis with septic coronary arteritis) and these 2 patients died before the diagnosis was made. Three patients with pseudoaneurysm received surgical correction with good clinical outcomes in all. Cardiac wall rupture is a serious and often fatal cardiac complication. Emergency diagnosis and appropriate management with an experienced cardiology team is crucial. Surgical correction is the treatment of choice. Key Points • Cardiac wall rupture, a serious and often fatal cardiac complication, has rarely been described in SLE patients. • Emergency diagnosis and appropriate management with an experienced cardiology team is crucial. Surgical correction is the treatment of choice., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Aims and Objectives: To assess the effects of intensive follow-up by primary care nurses on cardiovascular disease self-management and compliance behaviours after myocardial infarction., Background: Although cardiovascular disease prevention and cardiac rehabilitation take place in hospital settings, a nurse-led approach is necessary in primary care during the first few months after a myocardial infarction. Therefore, it is important to assess self-management of cardiovascular disease and levels of compliance with the prescribed diet, physical activity, and medication., Design: The study used a multicentre, quasi-experimental, pre-post design without a control group., Methods: Patients with acute coronary syndrome from 40 healthcare facilities were included in the study. A total of 212 patients participated in a programme including 11 interventions during the first 12-18 months after myocardial infarction. The following Nursing Outcomes Classification (NOC) outcomes were assessed at baseline and at the end of the intervention: Self-management: Cardiac Disease (1617) and Compliance Behaviour: Prescribed Diet (1622), Compliance Behaviour: Prescribed Activity (1632), and Compliance Behaviour: Prescribed Medication (1623). Marjory Gordon's functional health patterns and a self-care notebook were used in each intervention. Pre-post intervention means were compared using Student's t-tests for related samples. The results of the study are reported in compliance with the TREND Statement., Results: A total of 132 patients completed the intervention. The indicators for each NOC outcome and the variations in scores before and after the intensive follow-up showed a statistically significant improvement (p-value = 0.000). Compliance Behaviour: Prescribed Diet (pre = 3.7; post = 4.1); Compliance Behaviour: Prescribed Activity (pre = 3.9; post = 4.3); Compliance Behaviour: Prescribed Medication (pre = 3.9; post = 4.7)., Conclusion: Intensive, immediate follow-up after myocardial infarction improves compliance behaviours and self-management of heart disease. A combined self-care and family care approach should be encouraged to empower post-myocardial infarction patients. To facilitate patients' self-efficacy, the use of health education tools such as a cardiovascular self-care notebook can also be helpful., Relevance to Clinical Practice: This study highlights the benefits of intensive, protocolised, comprehensive patient follow-up in primary care during the first few months after an acute myocardial infarction (AMI). Primary care nurses train patients in cardiovascular self-care., Patient or Public Contribution: Patients were not involved in either the design or the carrying out of the study. However, at the end of the study, they participated in an evaluation process about the utility of the research study and their satisfaction with it. This process was carried out using an ad hoc survey consisting of 10 questions assessing the nursing care and follow-up inputs that were received., (© 2023 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Infection with SARS-CoV-2, the virus that causes COVID, is associated with numerous potential secondary complications. Global efforts have been dedicated to understanding the myriad potential cardiovascular sequelae which may occur during acute infection, convalescence, or recovery. Because patients often present with nonspecific symptoms and laboratory findings, cardiac imaging has emerged as an important tool for the discrimination of pulmonary and cardiovascular complications of this disease. The clinician investigating a potential COVID-related complication must account not only for the relative utility of various cardiac imaging modalities but also for the risk of infectious exposure to staff and other patients. Extraordinary clinical and scholarly efforts have brought the international medical community closer to a consensus on the appropriate indications for diagnostic cardiac imaging during this protracted pandemic. In this review, we summarize the existing literature and reference major societal guidelines to provide an overview of the indications and utility of echocardiography, nuclear imaging, cardiac computed tomography, and cardiac magnetic resonance imaging for the diagnosis of cardiovascular complications of COVID., Competing Interests: Disclosures None.

Objective: Biaxial mechanical testing is a common method for elucidation of mechanical properties of excised ventricular myocardium, especially in the context of structural remodeling that accompanies heart disease. Current imaging strategies in biaxial testing are based on optical camera imaging of the tissue surface, thus providing no information about the tissue microstructure and limiting strain measurements to two dimensions. Here, these limitations are overcome by replacing the camera with ultrasound imaging in order to measure both transmural fiber orientation and 3D tissue deformation during biaxial testing., Methods: Quasi-static biaxial mechanical testing is applied to four samples of excised porcine ventricular myocardium (two left- and two right-ventricular tissues). During testing, a rotational scan of an ultrasound linear array provides data for both backscatter tensor imaging and 3D speckle tracking, from which transmural fiber orientation and tissue deformation are computed, respectively. Ultrasound-derived fiber orientation and tissue strain are validated against histology and camera surface imaging, respectively., Discussion: Ultrasound-derived fiber angle and tissue strain exhibit good accuracy, with root-mean-square errors of 9.9° and 1.2% strain, respectively. Further investigation into the optimization of backscatter tensor imaging is warranted. Replacing the rotational scan of a linear array with volume imaging with a matrix array will improve the technique., Conclusion: Ultrasound imaging can replace the optical camera measurement during biaxial mechanical testing of ventricular myocardium in order to accurately provide measurements of transmural fiber orientation and tissue strain. In situ knowledge of transmural fiber structure and tissue deformation can enhance the inverse problem used to determine tissue mechanical properties from biaxial testing., Competing Interests: Declaration of Interest The authors have no conflicts of interest to report., (Copyright © 2023 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Cellular stress has been a key factor in the development of cardiovascular diseases. Major types of cellular stress such as mitochondrial stress, endoplasmic reticulum stress, hypoxia, and replicative stress have been implicated in clinical complications of cardiac patients. The heart is the central regulator of the body by supplying oxygenated blood throughout the system. Impairment of cellular function could lead to heart failure, myocardial infarction, ischemia, and even stroke. Understanding the effect of these distinct types of cellular stress on cardiac function is crucial for the scientific community to understand and develop novel therapeutic approaches. This review will comprehensively explain the different mechanisms of cellular stress and the most recent findings related to stress-induced cardiac dysfunction., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Johnson Rajasingh reports financial support was provided by The University of Tennessee Health Science Center. Johnson Rajasingh reports financial support was provided by National Institutes of Health. Johnson Rajasingh reports financial support was provided by American Heart Association., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective . Prompt identification and recognization of myocardial ischemia/infarction (MI) is the most important goal in the management of acute coronary syndrome. The 12-lead electrocardiogram (ECG) is widely used as the initial screening tool for patients with chest pain but its diagnostic accuracy remains limited. There is early evidence that machine learning (ML) algorithms applied to ECG waveforms can improve performance. Most studies are designed to classify MI from healthy controls and thus are limited due to the lack of consideration of ECG abnormalities from other cardiac conditions, leading to false positives. Moreover, clinical information beyond ECG has not yet been well leveraged in existing ML models. Approach. The present study considered downstream clinical implementation scenarios in the initial model design by dichotomizing study recordings from a public large-scale ECG dataset into a MI class and a non-MI class with the inclusion of MI-confounding conditions. Two experiments were conducted to systematically investigate the impact of two important factors entrained in the modeling process, including the duration of ECG, and the value of multimodal information for model training. A novel multimodal deep learning architecture was proposed to learn joint features from both ECG and patient demographics. Main results. The multimodal model achieved better performance than the ECG-only model, with a mean area under the receiver operating characteristic curve of 92.1% and a mean accuracy of 87.4%, which is on par with existing studies despite the increased task difficulty due to the new class definition. By investigation of model explainability, it revealed the contribution of patient information in model performance and clinical concordance of the model's attention with existing clinical insights. Significance. The findings in this study help guide the development of ML solutions for prompt MI detection and move the models one step closer to real-world clinical applications., (Creative Commons Attribution license.)

MiRNAs regulate both physiological and pathological heart functions. Altered expression of miRNAs is associated with cardiovascular diseases (CVDs), making miRNAs attractive therapeutic strategies for the diagnosis and treatment of heart diseases. A recent publication defined, for the first time, the term theranoMiRNA, meaning the miRNAs that may be used both for diagnosis and treatment. The use of in silico tools may be considered fundamental for these purposes, clarifying several molecular aspects, suggesting future directions for in vivo studies. This study aims to explore different bioinformatic tools in order to clarify miRNA interactions with candidate genes, demonstrating the need to use a computational approach when establishing the most probable associations between miRNAs and target genes. This study focused on the functions of miR-133a-3p, miR-21-5p, miR-499a-5p, miR-1-3p, and miR-126-3p, providing an up-to-date overview, and suggests future lines of research in the identification of theranoMiRNAs related to CVDs. Based on the results of the present study, we elucidated the molecular mechanisms that could be linked between miRNAs and CVDs, confirming that these miRNAs play an active role in the genesis and development of heart damage. Given that CVDs are the leading cause of death in the world, the identification of theranoMiRNAs is crucial, hence the need for a definition of in vivo studies in order to obtain further evidence in this challenging field of research.

Cardiovascular diseases (CVDs) have been the leading cause of death worldwide during the past several decades. Cell loss is the main problem that results in cardiac dysfunction and further mortality. Cell therapy aiming to replenish the lost cells is proposed to treat CVDs especially ischemic heart diseases which lead to a big portion of cell loss. Due to the direct injection's low cell retention and survival ratio, cell therapy using biomaterials as cell carriers has attracted more and more attention because of their promotion of cell delivery and maintenance at the aiming sites. In this review, the three main factors involved in cell therapy for myocardial tissue regeneration: cell sources (somatic cells, stem cells, and engineered cells), chemical components of cell carriers (natural materials, synthetic materials, and electroactive materials), and categories of cell delivery materials (patches, microspheres, injectable hydrogels, nanofiber and microneedles, etc.) are systematically summarized. An introduction of the methods including magnetic resonance/radionuclide/photoacoustic and fluorescence imaging for tracking the behavior of transplanted cells in vivo is also included. Current challenges of biomaterials-based cell therapy and their future directions are provided to give both beginners and professionals a clear view of the development and future trends in this area., (© 2023 Wiley-VCH GmbH.)

Objectives: Exposure to ionizing radiation may increase the risk of circulatory diseases, including heart disease. A limited number of cohort studies of underground miners have investigated these associations. We previously reported a positive but non-statistically significant association between radon progeny and heart disease in a cohort of Newfoundland fluorspar miners. In this study, we report updated findings that incorporate 15 additional years of follow-up., Methods: The cohort included 2050 miners who worked in the fluorspar mines from 1933 to 1978. Statistics Canada linked the personal identifying data of the miners to Canadian mortality data to identify deaths from 1950 to 2016. We used previously derived individual-level estimates of annual radon progeny exposure in working-level months. Cumulative exposure was categorized into quantiles. We estimated relative risks and their 95% confidence intervals using Poisson regression for deaths from circulatory, ischemic heart disease and acute myocardial infarction. Relative risks were adjusted for attained age, calendar year, and the average number of cigarettes smoked daily., Results: Relative to the Newfoundland male population, the standardized mortality ratio for circulatory disease in this cohort was 0.82 (95% CI 0.74-0.91). Those in the highest quantile of cumulative radon progeny exposure had a relative risk of circulatory disease mortality of 1.03 (95% CI 0.76-1.40) compared to those in the lowest quantile. The corresponding estimates for ischemic disease and acute myocardial infarction were 0.99 (95% CI 0.66-1.48), and 1.39 (95% CI 0.84-2.30), respectively., Conclusions: Our findings do not support the hypothesis that occupational exposure to radon progeny increases the risk of circulatory disease., (© 2022. The Authors.)

Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic that has affected nearly 600 million people to date across the world. While COVID-19 is primarily a respiratory illness, cardiac injury is also known to occur. Cardiovascular magnetic resonance (CMR) imaging is uniquely capable of characterizing myocardial tissue properties in-vivo, enabling insights into the pattern and degree of cardiac injury. The reported prevalence of myocardial involvement identified by CMR in the context of COVID-19 infection among previously hospitalized patients ranges from 26 to 60%. Variations in the reported prevalence of myocardial involvement may result from differing patient populations (e.g. differences in severity of illness) and the varying intervals between acute infection and CMR evaluation. Standardized methodologies in image acquisition, analysis, interpretation, and reporting of CMR abnormalities across would likely improve concordance between studies. This consensus document by the Society for Cardiovascular Magnetic Resonance (SCMR) provides recommendations on CMR imaging and reporting metrics towards the goal of improved standardization and uniform data acquisition and analytic approaches when performing CMR in patients with COVID-19 infection., (© 2023. The Author(s).)

Background: Low-dose colchicine significantly reduces the risk of cardiovascular events in patients with chronic coronary disease. An increase of non-cardiovascular death raised concerns about its safety. This study reports cause-specific mortality and baseline predictors of mortality in the Low-Dose Colchicine 2 (LoDoCo2) trial., Methods: Patients with chronic coronary disease were randomly allocated to colchicine 0.5 mg once daily or placebo on a background of optimal medical therapy. Cause-specific mortality data were analysed, stratified by treatment status. Multivariate analyses were performed to examine the predictors of mortality as well as cardiovascular and non-cardiovascular death., Results: After a median 28.6 months follow-up, 133 out of 5522 participants (2.4%) died. Forty-five deaths were cardiovascular (colchicine versus placebo: 20 [0.7%] versus 25 [0.9%], HR, 0.80; 95% CI, 0.44-1.44), while eighty-eight deaths were non-cardiovascular (53 [1.9%] versus 35 [1.3%]; HR, 1.51; 95% CI, 0.99-2.31). Forty-eight deaths were due to cancer (26 [0.9%] versus 22 [0.8%]), thirteen end-stage pulmonary disease (9 [0.3%] versus 4 [0.1%]), eight infection (4 [0.1%] versus 4 [0.1%]), five dementia (4 [0.1%] versus 1 [0.0%]) and five related multiple organ failure (3 [0.1%] versus 2 [0.1%]). Multivariable analysis demonstrated age > 65 years was the only independent baseline characteristic associated with non-cardiovascular death (HR, 3.65; 95% CI, 2.06-6.47)., Conclusions: During the LoDoCo2 trial, assignment to colchicine was not associated with an adverse effect on any specific causes of death. Most deaths were related to non-cardiovascular causes, underscoring the importance of comorbidities as drivers of all-cause mortality in patients with chronic coronary disease., Competing Interests: Declaration of Competing Interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aim      To study the nosological structure of male mortality in 5-year age groups (15-85+) and the contribution of cardiac causes to all-cause mortality in 2020; to discuss the correctness of statistical recording of causes of cardiac death.Material and methods  Data source: Center for Demographic Research of the Russian School of Economy http://demogr.nes.ru / index.php / ru / demogr&#95;indicat / agreement. The selected indexes were all-cause death, causes of the class of circulatory diseases (CD) according to the International Classification of Diseases, Tenth Revision (ICD-10) (class IX, codes I00-I99), and cardiac causes of death (codes I00-I40, I70, I67.4, Q20-28) in 5-year age groups.Results Proportions of CD and cardiac causes in the male all-cause mortality were almost identical in the age groups younger than 30 years. Then the proportion of cardiac deaths remained almost unchanged (30-34 %) in contrast to the rapid growth of the CD proportion (to 51 % with a maximum at 75-79 years). Until the age of 45 years, more than 50% of cardiac deaths were caused by heart defects and cardiomyopathies and more than 25% by acute forms of ischemic heart disease (IHD); in older groups, their proportions decreased but the mortality increased. In the age groups younger than 50 years, the mortality from "Other forms of acute IHD" (ICD codes I20, I24.1-9 counted as one line) was higher than the mortality from myocardial infarction (MI); after 50 years, the MI mortality became higher. The combined proportion of two groups in the mortality from cardiac causes was maximal at the age of 20-24 years (31 %), then it decreased to a minimum of 9 % at the age of 85+. The mortality from and the proportions of chronic forms of IHD (more than 50% of which have no clear criteria for diagnosis and death), arterial hypertension, "Myocardial degeneration" (ICD code I51.5), and "Pulmonary heart and pulmonary circulation disorders" (ICD codes I26-I28) rapidly grow with increasing age. Existing approaches to recording the causes of death do not allow assessment of the contribution and mortality rates from a number of cardiac diseases.Conclusion      Mortality reduction programs should provide more accurate recording of the causes of death and take into account age-related features of the nosological structure of cardiac mortality.

Protein acetylation is a reversible central mechanism to control gene expression and cell signaling events. Current evidence suggests that pharmacological inhibitors for protein deacetylation have already been used in various disease conditions. Accumulating reports showed that several compounds that enhance histone acetylation in cells are in both the preclinical and clinical development stages targeting non-communicable diseases, which include cancerous and non-cancerous especially cardiovascular complications. These compounds are, in general, enzyme inhibitors and target a family of enzymes- called histone deacetylases (HDACs). Since HDAC inhibitors have shown to be helpful in preclinical models of cardiac complications, further research on developing novel compounds with high efficacy and low toxicity may be essential for treating cardiovascular diseases. In this review, we have highlighted the roles of HDAC and its inhibitors in cardiac complications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: The objective of this study was to identify undertreated subgroups of patients with heart failure who would benefit from better perioperative optimization., Summary of Background Data: Patients with heart failure have increased risks of postoperative cardiac complications after noncardiac surgery., Methods: In this analysis of hospital registry data of 130,677 patients undergoing noncardiac surgery, the exposure was preoperative history of heart failure. The outcome, cardiac complications, was defined as a composite of myocardial infarction, cardiac arrest, acute heart failure, and mortality within 30 postoperative days., Results: History of heart failure (n = 10,256; 7.9%) was associated with increased risk of cardiac complications [8.1% vs 1.1%; adjusted odds ratio, 2.28 (95% CI, 2.02-2.56); P < 0.001). Patients with heart failure and who carried a lower risk profile had increased risks of postoperative cardiac complications secondary to heart failure [adjusted absolute risk difference, 1.7% (95% CI, 1.4%-2.0%, lower risk); P < 0.001 vs 0.5% (95% CI, -0.6% to 1.6%, higher risk); P = 0.38]. Patients with heart failure and lower risk received a lower level of health care utilization preoperatively, and less frequently received anti-heart failure medications (59% vs 72% and 61% vs 82%; both P < 0.001). These preventive therapies significantly decreased the risk of cardiac complications in patients with heart failure., Conclusions: In patients with heart failure who have a lower preoperative risk profile, clinicians often make insufficient attempts to optimize their clinical condition preoperatively. Preoperative preventive treatment reduces the risk of postoperative cardiac complications in these lower-risk patients with heart failure., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Myocardial infarction (MI) refers to myocardial ischemic necrosis that is caused by coronary artery disease. Notably, crocin has protective effects on the heart. The present study aimed to i) investigate the protective effect of crocin, an active ingredient in Gardenia jasminoides Ellis and Crocus sativus L., on myocardial ischemia and ii) to verify the interaction between crocin and kelch repeat and BTB domain‑containing protein 7 (KBTBD7), which is a novel member of the BTB‑kelch protein family. In the present study, the left anterior descending coronary artery was ligated to establish a myocardial ischemia‑reperfusion injury (MIRI) model in rats and the protective effect of crocin on rat myocardial tissue was observed. The levels of the inflammatory cytokines, interleukin (IL)‑1β, IL‑6 and tumor necrosis factor α (TNFα), in the sham, MI model, MI + crocin (100 mg/kg) and MI + crocin (200 mg/kg) groups were compared in the rat myocardial tissue. The TUNEL assay was used to detect apoptosis of myocardial cells. In addition, RAW264.7 cells were stimulated with the inflammatory factors recombinant mouse high mobility group box 1 (rmHMGB1) and recombinant mouse heat shock protein 60 (rmHSP60). The inhibitory effect of crocin on inflammatory cytokine levels was observed using ELISA. Western blotting was used to detect the inhibitory effect of crocin on KBTBD7. The inhibitory effect of KBTBD7 knockdown on MAPK and nuclear factor (NF)‑κB signaling pathways was also analyzed. The expression levels of IL‑1β, IL‑6 and TNFα were significantly decreased in the crocin‑treated groups compared with in the model group. Crocin significantly reduced the apoptosis of myocardial cells and significantly inhibited the release of inflammatory cytokines induced by rmHMGB1 and rmHSP60. KBTBD7 was determined to be a target of crocin. Knockdown of KBTBD7 significantly inhibited p38 and NF‑κB signaling pathways. Furthermore, the results demonstrated that KBTBD7 knockdown significantly reduced the production of inflammatory cytokines induced by rmHMGB1 and rmHSP60. KBTBD7 knockdown also significantly reduced p38 and NF‑κB signaling in the rmHMGB1‑ and rmHSP60‑treated groups. The present study demonstrated the potential protective effect of crocin on MIRI in rats. The underlying mechanism may be through direct inhibition of KBTBD7, thereby inhibiting excessive inflammatory responses and myocardial cell apoptosis following myocardial infarction.

Familial hypercholesterolaemia (FH) is under-recognized and under-treated in Europe leading to significantly higher risk for premature heart disease in those affected. As treatment beginning early in life is highly effective in preventing heart disease and cost-effective in these patients, screening for FH is crucial. It has therefore now been recognized by the European Commission Public Health Best Practice Portal as an effective strategy. Model programmes exist in Europe to identify young individuals with FH, which are based on cascade screening of first-degree relatives of affected individuals, universal screening for high cholesterol, opportunistic screening of high-risk individuals, or a combination of the above approaches. Recommendations presented herein to improve identification of FH emphasize that every country should have an FH screening programme. These programmes should be adapted from existing strategies to best fit the individual country's healthcare system, governments should provide financial support for these programmes and related care, and further research to optimize care and implementations should be conducted., Competing Interests: Conflict of interest: S.S.G. is a consultant at Esperion Therapeutics. A.W. reports research support for pharmaceutical trials of lipid-modifying agents from Amgen, Regeneron, Novartis, and Silence Therapeutics. T.F. was supported by the Ministry of Health of the Czech Republic [grant NU20-02-00261], by the project National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES, ID Project No. LX22NPO5104) - Funded by the European Union – Next Generation EU, and received honoraria from Sanofi, Amgen, and Novartis, outside the submitted work. M.D. is a Chief Executive of FH Europe. N.B. is a senior advisor with FH Europe. K.K.R. reports grants and personal fees from Amgen, Sanofi/Regeneron, Pfizer, AstraZeneca, Medicines Company, Kowa, Novartis, Lilly, Algorithm, Boehringer Ingelheim, MSD, Abbvie, Silence Therapeutics, Bayer, Daiichi Sankyo, Esperion, Abbott, New Amsterdam, Resverlogix, outside the submitted work. R.D.S. has received honoraria related to consulting, research, and/or speaker activities from: Abbott, Amgen, Aché, Astra Zeneca, Esperion, EMS, GETZ Pharma, Kowa, Libbs, Merck, MSD, Novo-Nordisk, Novartis, PTC Therapeutics, Pfizer, Roche, and Sanofi. L.T. has received honoraria from Abbott, Actelion, Amgen, Bayer, Daiichi Sankyo, MSD, Mylan, Novartis, Novo Nordisk, Sanofi, Servier, Pfizer, and Recorda. K.I.D. reports grants from Pfizer, Amgen, Merck Sharp & Dohme, Sanofi-Aventis, Daichii Sankyo, and Regeneron, and personal fees from Bayer, outside the submitted work. N.P. reports grants from AMGEN, SHIRE, ALEXION, Nutricia, NHC, Biocodex, and NHS. U.G., J.S., M.H., I.G.-I., F.J.P., and M.G. have no conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: Myocardial injury after non-cardiac surgery has been defined as myocardial injury due to ischaemia, with or without additional symptoms or ECG changes occurring during or within 30 days after non-cardiac surgery and mainly diagnosed based on elevated postoperative cardiac troponin (cTn) values. In patients undergoing thoracic surgery for lung resection, only postoperative cTn elevations are seemingly not enough as an independent predictor of cardiovascular complications. After lung resection, troponin elevations may be regulated by mechanisms other than myocardial ischaemia. The combination of perioperative natriuretic peptide measurement together with high-sensitivity cTns may help to identify changes in ventricular function during thoracic surgery. Integrating both cardiac biomarkers may improve the predictive value for cardiovascular complications after lung resection. We designed our cohort study to evaluate perioperative elevation of both high-sensitivity troponin I (hs-TnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients undergoing lung resection and to establish a risk score for major cardiovascular postoperative complications., Methods and Analysis: We will conduct a prospective, multicentre, observational cohort study, including 345 patients undergoing elective thoracic surgery for lung resection. Cardiac biomarkers such as hs-TnI and NT-proBNP will be measured preoperatively and at postoperatively on days 1 and 2. We will calculate a risk score for major cardiovascular postoperative complications based on both biomarkers' perioperative changes. All patients will be followed up for 30 days after surgery., Ethics and Dissemination: All participating centres were approved by the Ethics Research Committee. Written informed consent is required for all patients before inclusion. Results will be disseminated through publication in peer-reviewed journals and presentations at national or international conference meetings., Trial Registration Number: NCT04749212., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cardiovascular diseases (CVD) remain a substantial global health problem and the leading cause of death worldwide. Although many conventional small-molecule treatments are available to support the cardiac function of the patient with CVD, they are not effective as a cure. Among potential targets for gene therapy are severe cardiac and peripheral ischemia, heart failure, vein graft failure, and some forms of dyslipidemias. In the last three decades, multiple gene therapy tools have been used for heart diseases caused by proteins, plasmids, adenovirus, and adeno-associated viruses (AAV), but these remain as unmet clinical needs. These gene therapy methods are ineffective due to poor and uncontrolled gene expression, low stability, immunogenicity, and transfection efficiency. The synthetic modified mRNA (modRNA) presents a novel gene therapy approach which provides a transient, stable, safe, non-immunogenic, controlled mRNA delivery to the heart tissue without any risk of genomic integration, and achieves a therapeutic effect in different organs, including the heart. The mRNA translation starts in minutes, and remains stable for 8-10 days (pulse-like kinetics). The pulse-like expression of modRNA in the heart induces cardiac repair, cardiomyocyte proliferation and survival, and inhibits cardiomyocyte apoptosis post-myocardial infarction (MI). Cell-specific (cardiomyocyte) modRNA translation developments established cell-specific modRNA therapeutics for heart diseases. With these laudable characteristics, combined with its expression kinetics in the heart, modRNA has become an attractive therapeutic for the treatment of CVD. This review discusses new developments in modRNA therapy for heart diseases.

Iron interactions with the cardiovascular system were proposed about half a century ago, yet a clear-cut understanding of this micronutrient and its intricacies with acute and chronic events is still lacking. In chronic heart failure, patients with decreased iron stores appear to benefit from intravenous administration of metallic formulations, whereas acute diseases (e.g., myocardial infarction, stroke) are barely studied in randomized controlled trials in humans. However, proof-of-concept studies have indicated that the dual redox characteristics of iron could be involved in atherosclerosis, necrosis, and ferroptosis. To this end, we sought to review the currently available body of literature pertaining to these temporal profiles of heart diseases, as well as the pathophysiologic mechanism by which iron enacts, underlining key points related to treatment options., (Copyright © 2022 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Myocardial ischemia with no obstructive coronary arteries (INOCA) is a chronic coronary syndrome condition that is increasingly being recognized as a substantial contributor to adverse cardiovascular mortality and outcomes, including myocardial infarction and heart failure with preserved ejection fraction (HFpEF). While INOCA occurs in both women and men, women are more likely to have the finding of INOCA and are more adversely impacted by angina, with recurrent hospitalizations and a lower quality of life with this condition. Abnormal epicardial coronary vascular function and coronary microvascular dysfunction (CMD) have been identified in a majority of INOCA patients on invasive coronary function testing. CMD can co-exist with obstructive epicardial coronary artery disease (CAD), diffuse non-obstructive epicardial CAD, and with coronary vasospasm. Epicardial vasospasm can also occur with normal coronary arteries that have no atherosclerotic plaque on intravascular imaging. While all predisposing factors are not clearly understood, cardiometabolic risk factors, and endothelium dependent and independent mechanisms that increase oxidative stress and inflammation are associated with microvascular injury, CMD and INOCA. Cardiac autonomic dysfunction has also been implicated in abnormal vasoreactivity and persistent symptoms. INOCA is under-recognized and under-diagnosed, partly due to the heterogenous patient populations and mechanisms. However, diagnostic testing methods are available to guide INOCA management. Treatment of INOCA is evolving, and focuses on cardiac risk factor control, improving ischemia, reducing atherosclerosis progression, and improving angina and quality of life. This review focuses on INOCA, relations to HFpEF, available diagnostics, current and investigational therapeutic strategies, and knowledge gaps in this condition., Competing Interests: Declaration of competing interest Mehta, Levit, Malas, Huang, Waheed: none; Bairey Merz: iRhythm and fees paid to CSMC - Abbott and Sanofi., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Internationally, stroke and cardiac rehabilitation clinicians agree that current cardiac rehabilitation models are a suitable secondary prevention program for people following a transient ischaemic attack (TIA) or mild stroke. There is strong evidence for exercise-based cardiac rehabilitation in people with heart disease, however, the evidence for cardiac rehabilitation post-TIA or stroke is limited. Here we will explore the effectiveness and implementation of an integrated (TIA, mild stroke, heart disease) traditional exercise-based cardiovascular rehabilitation (CVR) program for people with TIA or mild stroke over 6-months., Methods: This type 1 effectiveness-implementation hybrid study will use a 2-arm single-centre assessor-blind randomised controlled trial design, recruiting 140 participants. Adults who have had a TIA or mild stroke in the last 12-months will be recruited by health professionals from hospital and primary healthcare services. Participants will be assessed and randomly allocated (1:1) to the 6-week CVR program or the usual care 6-month wait-list control group. Distance completed in the 6-min walk test will be the primary effectiveness outcome, with outcomes collected at baseline, 6-weeks (complete CVR) and 6-months in both groups. Other effectiveness outcome measures include unplanned cardiovascular disease-related emergency department and hospital admissions, daily minutes of accelerometer moderate-to-vigorous physical activity, body mass index, waist circumference, blood pressure, quality of life, anxiety and depression. Implementation outcomes will be assessed using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework, including a cost-effectiveness analysis. Semi-structured interviews will be conducted with participants and CVR program health professionals, investigating the acceptability, value, and impact of the CVR program. Qualitative analyses will be guided by the Consolidated Framework for Implementation Research., Discussion: Few studies have assessed the effectiveness of cardiac rehabilitation for people with TIA and mild stroke, and no studies appear to have investigated the cost-effectiveness or implementation determinants of such programs. If successful, the CVR program will improve health outcomes and quality of life of people who have had a TIA or mild stroke, guiding future research, policy, and clinical practice, reducing the risk of repeat heart attacks and strokes for this population., Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621001586808 , Registered 19 November 2021., (© 2022. The Author(s).)

This study determined the association between respiratory symptoms and death from cardiovascular (CV) diseases during 45 years in a pooled sample of four cohorts of random samples of the Norwegian population with 95,704 participants. Respiratory symptoms were assessed using a modification of the MRC questionnaire on chronic bronchitis. We analyzed the association between respiratory symptoms and specific cardiovascular deaths by using Cox regression analysis with age as the time variable, accounting for cluster-specific random effects using shared frailty for study cohort. Hazard ratios (HR) for death were adjusted for sex, highest attained education, smoking habits, occupational air pollution, and birth cohort. Overall, 12,491 (13%) of participants died from CV diseases: 4,123 (33%) acute myocardial infarction, 2,326 (18%) other ischemic heart disease, 2,246 (18%) other heart diseases, 2,553 (20%) cerebrovascular diseases, and 1,120 (9%) other vascular diseases. The adjusted HR (95% confidence interval) for CV deaths was 1.9 (1.7-2.1) in men and 1.5 (1.2-1.9) in women for "yes" to the question "Are you breathless when you walk on level ground at an ordinary pace?". The same item response showed an adjusted HR for death from acute myocardial infarction of 1.8 (1.5-2.1), other ischemic heart disease 2.2 (1.8-2.7), other heart diseases 1.5 (1.1-1.9), cerebrovascular disease 1.8 (1.5-2.3), and other circulatory diseases 1.7 (1.2-2.4). The adjusted HR for CV death was 1.3 (1.2-1.4) when answering positive to the question" Are you more breathless than people of your own age when walking uphill?". However, positive answers to questions on cough, phlegm, wheezing and attacks of breathlessness were after adjustments not associated with early CV deaths. The associations between CV deaths and breathlessness were also present in never smokers. Self-reported breathlessness was associated with CV deaths and could be an early marker of CV deaths., Competing Interests: The authors have declared that no competing interests exist.

Heart disease, including coronary artery disease, myocardial infarction, heart failure, cardiac hypertrophy, and cardiomyopathies, is the leading causes of death worldwide. The Hippo pathway is a central controller for organ size and tissue growth, which plays a pivotal role in determining cardiomyocytes and nonmyocytes proliferation, regeneration, differentiation, and apoptosis. In this review, we summarize the effects of the Hippo pathway on heart disease and propose potential intervention targets. Especially, we discuss the molecular mechanisms of the Hippo pathway involved in maintaining cardiac homeostasis by regulating cardiomyocytes and nonmyocytes function in the heart. Based on this, we conclude that the Hippo pathway is a promising therapeutic target for cardiovascular therapy, which will bring new perspectives for their treatments., (© 2021 Federation of European Biochemical Societies.)

Objective: To characterize myocardial injury and cardiovascular complications and their predictors in severe and critical COVID-19 patients admitted to the intensive care unit., Methods: This was an observational cohort study of severe and critical COVID-19 patients admitted to the intensive care unit. Myocardial injury was defined as blood levels of cardiac troponin above the 99th percentile upper reference limit. Cardiovascular events considered were the composite of deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction, acute limb ischemia, mesenteric ischemia, heart failure and arrhythmia. Univariate and multivariate logistic regression or Cox proportional hazard models were used to determine predictors of myocardial injury., Results: Of 567 patients with severe and critical COVID-19 admitted to the intensive care unit, 273 (48.1%) had myocardial injury. Of the 374 patients with critical COVID-19, 86.1% had myocardial injury, and also showed more organ dysfunction and higher 28-day mortality (56.6% versus 27.1%, p < 0.001). Advanced age, arterial hypertension and immune modulator use were predictors of myocardial injury. Cardiovascular complications occurred in 19.9% of patients with severe and critical COVID-19 admitted to the intensive care unit, with most events occurring in patients with myocardial injury (28.2% versus 12.2%, p < 0.001). The occurrence of an early cardiovascular event during intensive care unit stay was associated with higher 28-day mortality compared with late or no events (57.1% versus 34% versus 41.8%, p = 0.01)., Conclusion: Myocardial injury and cardiovascular complications were commonly found in patients with severe and critical forms of COVID-19 admitted to the intensive care unit, and both were associated with increased mortality in these patients.

Cell death is a crucial event underlying cardiac ischemic injury, pathological remodeling, and heart failure. Unlike apoptosis, necrosis had long been regarded as a passive and unregulated process. However, recent studies demonstrate that a significant subset of necrotic cell death is actively mediated through regulated pathways - a process known as "regulated necrosis". As a form of regulated necrosis, necroptosis is mediated by death receptors and executed through the activation of receptor interacting protein kinase 3 (RIPK3) and its downstream substrate mixed lineage kinase-like domain (MLKL). Recent studies have provided compelling evidence that necroptosis plays an important role in myocardial homeostasis, ischemic injury, pathological remodeling, and heart failure. Moreover, it has been shown that genetic and pharmacological manipulations of the necroptosis signaling pathway elicit cardioprotective effects. Important progress has also been made regarding the molecular mechanisms that regulate necroptotic cell death in vitro and in vivo. In this review, we discuss molecular and cellular mechanisms of necroptosis, potential crosstalk between necroptosis and other cell death pathways, functional implications of necroptosis in heart disease, and new therapeutic strategies that target necroptosis signaling., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Coronary artery embolism (CAE) is a rare, non-atherosclerotic cause of acute myocardial infarction (MI). Atrial fibrillation (AF) is the most frequent cause of CAE, and can be associated with multiple embolisms, particularly in the brain., Aims: To characterize CAE-related myocardial injury, assess the proportion of cardiocerebral infarction and characterize brain injuries associated with dual embolism., Methods: In this prospective study, patients with CAE-associated MI underwent (1) cardiac magnetic resonance imaging (MRI) to assess the extent of infarct transmurality and myocardial necrosis size and (2) brain MRI to assess the proportion of simultaneous cardiocerebral infarction. We screened 1401 consecutive patients with de novo acute MI from January 2019 to June 2021. CAE was diagnosed based on clinical, angiographic and diagnostic imaging criteria., Results: Overall, 29/1401 patients presented with CAE (2.1%), of whom 21 underwent cardiac and cerebral MRI. Of these, nine (43%) had an ischaemic stroke, and AF was the leading cause of CAE in 14 patients (67%). Multiple CAE were common at coronary angiography (33%). Four patients (19%) had left atrial appendage thrombus - 4/9 patients (44%) with a stroke but 0/12 patients without a stroke. On cardiac MRI, the median (interquartile range) number of segments with acute infarction was 3 (0-11) in patients with stroke and 3 (1-6) in those without. Most acute ischaemic strokes (78%) were localized in the superficial sylvian territory and only 2/21 patients (10%) had stroke sequelae., Conclusion: MI-related to CAE was associated with infarctions of average size but multiple locations. Systematic brain MRI revealed that 33% of cases were associated with a stroke, which was generally asymptomatic. Further studies are required to better characterize the pathophysiology, clinical course and prognostic value of CAE. Moreover, optimal management strategies remain to be determined., (Copyright © 2022. Published by Elsevier Masson SAS.)

Background: Cardiac troponin (cTn) T and cTnI are considered cardiac specific and equivalent in the diagnosis of acute myocardial infarction. Previous studies suggested rare skeletal myopathies as a noncardiac source of cTnT. We aimed to confirm the reliability/cardiac specificity of cTnT in patients with various skeletal muscle disorders (SMDs)., Methods: We prospectively enrolled patients presenting with muscular complaints (≥2 weeks) for elective evaluation in 4 hospitals in 2 countries. After a cardiac workup, patients were adjudicated into 3 predefined cardiac disease categories. Concentrations of cTnT/I and resulting cTnT/I mismatches were assessed with high-sensitivity (hs-) cTnT (hs-cTnT-Elecsys) and 3 hs-cTnI assays (hs-cTnI-Architect, hs-cTnI-Access, hs-cTnI-Vista) and compared with those of control subjects without SMD presenting with adjudicated noncardiac chest pain to the emergency department (n=3508; mean age, 55 years; 37% female). In patients with available skeletal muscle biopsies, TNNT/I1-3 mRNA differential gene expression was compared with biopsies obtained in control subjects without SMD., Results: Among 211 patients (mean age, 57 years; 42% female), 108 (51%) were adjudicated to having no cardiac disease, 44 (21%) to having mild disease, and 59 (28%) to having severe cardiac disease. hs-cTnT/I concentrations significantly increased from patients with no to those with mild and severe cardiac disease for all assays (all P <0.001). hs-cTnT-Elecsys concentrations were significantly higher in patients with SMD versus control subjects (median, 16 ng/L [interquartile range (IQR), 7-32.5 ng/L] versus 5 ng/L [IQR, 3-9 ng/L]; P <0.001), whereas hs-cTnI concentrations were mostly similar (hs-cTnI-Architect, 2.5 ng/L [IQR, 1.2-6.2 ng/L] versus 2.9 ng/L [IQR, 1.8-5.0 ng/L]; hs-cTnI-Access, 3.3 ng/L [IQR, 2.4-6.1 ng/L] versus 2.7 ng/L [IQR, 1.6-5.0 ng/L]; and hs-cTnI-Vista, 7.4 ng/L [IQR, 5.2-13.4 ng/L] versus 7.5 ng/L [IQR, 6-10 ng/L]). hs-cTnT-Elecsys concentrations were above the upper limit of normal in 55% of patients with SMD versus 13% of control subjects ( P <0.01). mRNA analyses in skeletal muscle biopsies (n=33), mostly (n=24) from individuals with noninflammatory myopathy and myositis, showed 8-fold upregulation of TNNT2 , encoding cTnT (but none for TNNI3 , encoding cTnI) versus control subjects (n=16, P Wald <0.001); the expression correlated with pathological disease activity ( R =0.59, P t-statistic <0.001) and circulating hs-cTnT concentrations ( R =0.26, P t-statistic =0.031)., Conclusions: In patients with active chronic SMD, elevations in cTnT concentrations are common and not attributable to cardiac disease in the majority. This was not observed for cTnI and may be explained in part by re-expression of cTnT in skeletal muscle., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03660969.

For at least a few centuries, if not millennia, psychological stress has been popularly believed to contribute to heart disease. Does psychological stress really contribute to heart disease? Are anecdotal, patient, and lay press reports that angina, heart attack, and even cardiac death are caused by stress based on fact, or are they just folklore? In this review, the study data supporting associations between stress and cardiovascular risk, as well as potential mechanisms by which psychological stress might contribute to heart disease and precipitate myocardial ischemia and infarction, are critically reviewed and summarized., (Published by Elsevier Inc.)

Ginkgolides are terpenoids peculiar to Ginkgo biloba, which have protective properties against cardiac diseases. This study aims to explore whether ginkgolide A (GA) could improve cardiac dysfunction of MI mice, and whether it could alleviate cardiac remodeling via binding to matrix metalloproteinase-9 (MMP9) to attenuate inflammation. Cardiac remodeling in mice induced by left coronary artery ligation were used in the in vivo model, and angiotensin (Ang) II-induced cardiac fibroblasts (NRCFs) and cardiomyocytes (NRCMs) isolated from neonatal rats were used in in vitro fibrosis and hypertrophy models, respectively. Cardiac dysfunction and fibrosis in MI mice were alleviated by GA treatment. Upregulations of collagen I (Col I), collagen III (Col III) and fibronectin in NRCFs, and enhanced levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and beta-myosin heavy chain (β-MHC) in NRCMs were inhibited by GA treatment. A total of 100 potential targets were found in 5 databases (TCMSP, BATMAN-TCM, PharmMapper, ETCM and SWISS Target). According to Protein Data Bank database GA could form hydrogen bonds between LYS65, GLU157, ASN17, ARG109, ARG106 of MMP9 protein, a target of GA. The regulatory role of GA in downregulating Col I, Col III, fibronectin in NRCFs, and enhancing levels of ANP, BNP and β-MHC in NRCMs were reversed by MMP9 overexpression, so as the downregulation of IL-1β, IL-6 and TNF-α in Ang II-induced NRCFs and NRCMs. GA could alleviate cardiac dysfunction and remodeling via binding to MMP9 to attenuate inflammation. Therefore, GA is a potential drug for cardiac remodeling therapy., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Rheumatoid Arthritis (RA) is among the most prevalent and impactful rheumatologic chronic autoimmune diseases (AIDs) worldwide. Within a framework that recognizes both immunological activation and inflammatory pathways, the exact cause of RA remains unclear. It seems however, that RA is initiated by a combination between genetic susceptibility, and environmental triggers, which result in an auto-perpetuating process. The subsequently, systemic inflammation associated with RA is linked with a variety of extra-articular comorbidities, including cardiovascular disease (CVD), resulting in increased mortality and morbidity. Hitherto, vast evidence demonstrated the key role of non-coding RNAs such as microRNAs (miRNAs) in RA, and in RA-CVD related complications. In this descriptive review, we aim to highlight the specific role of miRNAs in autoimmune processes, explicitly on their regulatory roles in the pathogenesis of RA, and its CV consequences, their main role as novel biomarkers, and their possible role as therapeutic targets.