Therapy For Ischemic Heart Disease Research Articles

Psmb8 inhibits mitochondrial fission and alleviates myocardial ischaemia/reperfusion injury by targeting Drp1 degradation

The mitochondrial dynamic imbalance is an important cause of myocardial ischaemia/reperfusion (I/R) injury and dysfunction. Psmb8, as one of the immunoproteasome catalytic subunits, is a key regulator of protein homoeostasis, inflammation and some cardiac diseases. Here, we found that the expression level and activity of Psmb8 were significantly reduced in the heart of I/R mice and in subjects with myocardial infarction (MI). Cardiomyocyte-specific Psmb8 overexpression in mice markedly ameliorated I/R-mediated cardiac injury and dysfunction, which was accompanied by reduced mitochondrial division via the downregulation of dynamin-related protein-1 (Drp1). However, Psmb8 knockout (KO) mice exhibited the opposite changes. The effects of Psmb8 on mitochondrial fission and apoptosis was confirmed in primary cardiomyocytes with overexpression or knockdown of Psmb8 in vitro. Mechanistically, Psmb8 was directly associated with Drp1 and enhanced its degradation, which subsequently suppressed I/R-mediated mitochondrial fission and cardiac injury. Conversely, knockdown of Drp1 in Psmb8-KO mice restored I/R-induced cardiac dysfunction and mitochondrial dynamic imbalance. Our study identified a new cardioprotective role of Psmb8 in cardiac I/R damage through targeting Drp1, and highlight that increasing Psmb8 activity may constitute a promising therapy for ischaemic heart disease.

New avenues in the treatment of ischemic heart disease - Stem cell therapy

Faced with the large number of patients with ischemic heart disease and high mortality rates, traditional drug treatments come with the risks of drug resistance and rebound effects after discontinuation, as well as the shortcomings of surgical treatments such as poor blood circulation and the inability to restore necrotic myocardium. This article starts from the perspective of stem cell regenerative medicine, focusing on the stem cell therapy for ischemic heart disease, and provides a comprehensive review of the types of stem cells and transplantation methods. It also includes further summaries and prospects, believing that more comprehensive and improved treatment methods will emerge in the future to benefit patients.

13-Methylpalmatine improves myocardial infarction injury by inhibiting CHOP-mediated cross-talk between endoplasmic reticulum and mitochondria

Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide, and endoplasmic reticulum stress (ERS) and mitochondrial Ca2+ overload have been involved in apoptotic cardiomyocyte death during MI. 13-Methylpalmatine (13-Me-PLT) is a natural isoquinoline alkaloid isolated from Coptis chinensis and has not been systematically studied for their potential pharmacological effects in cardiovascular diseases. We conducted the present study to elucidate whether 13-Me-PLT modulates MI pathology in animal MI and cellular hypoxic models, employing state-of-the-art molecular techniques. The results demonstrated that 13-Me-PLT preserved post-ischemic cardiac function and alleviated cardiomyocyte apoptosis. 13-Me-PLT decreased ERS and the communication between ER and mitochondria, which serves as a protective mechanism against mitochondrial Ca2+ overload and structural and functional injuries to mitochondria. Our data revealed mitigating mitochondrial Ca2+ overload and apoptosis by inhibiting CHOP-mediated Ca2+ transfer between inositol 1,4,5-trisphosphate receptor (IP3R) in ER and VDAC1 in mitochondria as an underlying mechanism for 13-Me-PLT action. Furthermore, 13-Me-PLT produced superior effects in alleviating cardiac dysfunction and apoptosis post-MI to diltiazem and palmatine. Collectively, our research suggests that the CHOP/IP3R/VDAC1 signaling pathway mediates ER-mitochondrial Ca2+ transfer and 13-Me-PLT activates this axis to maintain cellular and organellar Ca2+ homeostasis, protecting against ischemic myocardial injury. These findings may offer an opportunity to develop new agents for the therapy of ischemic heart disease.

Effect of cardiac rehabilitation on heart rate recovery in patients with coronary artery disease

Background/Aim: It is well-established that individuals with coronary artery disease (CAD) often exhibit autonomic dysfunction and a reduction in vagal function is associated with increased mortality and morbidity. Vagally mediated heart rate recovery (HRR) can be assessed by analyzing the post-exercise heart rate (HR) decay. It is hypothesized that effective exercise-based cardiac rehabilitation (CR) can enhance post-exercise parasympathetic function. This study aims to evaluate the impact of CR on HRR and other cardiac parameters in CAD patients. Methods: This retrospective cohort study was conducted at a single center. It included patients with CAD who were referred to the CR unit and completed either 30 or 60 sessions. These patients were free from angina or angina-equivalent symptoms at the time of enrollment and were receiving guideline-directed medical therapy for ischemic heart disease. A customized CR program was implemented for each patient. To calculate HRR, the maximum HR during the exercise test and HR values at 1, 2, and 3 minutes after exercise cessation were recorded. The differences between the maximum HR and the HR values at the end of the 1st, 2nd, and 3rd minutes after exercise were designated as HRR1, HRR2, and HRR3, respectively. Results: This study enrolled 104 patients with CAD. Following CR, there was a significant improvement in functional capacity, as assessed by the 6-minute walk test (from 367.83 [56.58] to 381.61 [53.76], P=0.001), and endurance, as measured by the Cycle Ergometer Test Maximum Watts (from 63.22 [22.29] to 77.38 [19.87], P<0.001). CR also led to a noteworthy increase in HRR1, HRR2, and HRR3 (P=0.036, P=0.015, P=0.002, respectively). Conclusion: In our study, both the functional capacity and endurance of CAD patients improved significantly after CR sessions. Additionally, HRR showed a substantial increase following CR, suggesting that exercise-based CR can enhance post-exercise parasympathetic function. HRR may serve as a potential prognostic marker for predicting outcomes in CR.

Abstract We022: Depletion of Tip60 After Myocardial Infarction Induces Histone H2A.Z Deacetylation Followed by Cardiomyocyte Dedifferentiation/Cell-Cycle Activation

Myocardial infarction (MI) leads to cardiomyocyte (CM) loss, resulting in cardiac dysfunction and heart failure. Remuscularization of injured myocardium requires proliferation of surviving CMs. However, approaches aimed at inducing CM regeneration following MI have been inadequate. To this end, we are targeting the acetyltransferase Tip60 (Tat-interactive protein 60 kD), a pleiotropic tumor suppressor encoded by the Kat5 gene. Using a murine genetic model, we previously reported that disruption of Kat5 promotes CM cell-cycle re-entry, and protects against the damaging effects of MI. It is becoming increasingly recognized that pre-existing CMs must undergo dedifferentiation accompanied by reversion to glycolytic metabolism in order to resume proliferation. The site-specific acetylation of the histone variant H2A.Z at lysine K4/K7 (H2A.Zac K4/K7 ) has been shown to maintain the differentiated state in hematopoietic stem cells (HSCs), neurons, and skeletal myocytes. Here, we report that Tip60 depletion post-MI results in the near-complete absence of H2A.Zac K4/K7 in CMs. This is associated with the enrichment of differentially expressed genes (DEGs) in epithelial to mesenchymal transitioning (EMT), cytoskeletal disassembly, extracellular matrix (ECM) softening, and metabolic reprogramming. To assess therapeutic relevance, we have begun to evaluate the potential cardioprotective effects of the anti-parasitic drug pentamidine, a known Tip60 inhibitor. Systemic administration of pentamidine on days 3-16 post-MI preserved cardiac function, accompanied by CM cell-cycle activation. These data suggest that pentamidine treatment enhances remuscularization, thereby promoting the retention of post-MI function, supporting the translational promise of targeting Tip60 as an innovative therapy for ischemic heart disease.

Comprehensive macro and micro views on immune cells in ischemic heart disease.

Ischemic heart disease (IHD) is a prevalent cardiovascular condition that remains the primary cause of death due to its adverse ventricular remodelling and pathological changes in end-stage heart failure. As a complex pathologic condition, it involves intricate regulatory processes at the cellular and molecular levels. The immune system and cardiovascular system are closely interconnected, with immune cells playing a crucial role in maintaining cardiac health and influencing disease progression. Consequently, alterations in the cardiac microenvironment are influenced and controlled by various immune cells, such as macrophages, neutrophils, dendritic cells, eosinophils, and T-lymphocytes, along with the cytokines they produce. Furthermore, studies have revealed that Gata6+ pericardial cavity macrophages play a key role in regulating immune cell migration and subsequent myocardial tissue repair post IHD onset. This review outlines the role of immune cells in orchestrating inflammatory responses and facilitating myocardial repair following IHD, considering both macro and micro views. It also discusses innovative immune cell-based therapeutic strategies, offering new insights for further research on the pathophysiology of ischemic heart disease and immune cell-targeted therapy for IHD.

Electrochemical detection of atrial natriuretic peptide-coated nanocarriers based on a molecularly imprinted polymer receptor thin film

Molecularly imprinted polymers (MIPs) are biomimetic materials of great interest in the scientific and industrial fields for the development of innovative sensing strategies. Herein, we proposed a new sensing application by developing an electrochemical sensor using molecular imprinting (MI) technology for recognition of atrial natriuretic peptide (ANP) both as a free molecule in solution and attached to nanoparticle-based drug delivery systems (DDSs), aiming to provide fast and reliable information on the cell uptake of nanoparticles (NPs). As proof of concept, poly(lactic-co-glycolic acid) (PLGA) NPs were synthesized and used as nanocarriers for ischemic heart disease therapy were synthesized and then functionalized with ANP (named here as PLGA-NPs@ANP). The MIP receptor film was prepared by electrochemical polymerization of dopamine over the working area of a gold screen-printed electrode (AuSPE), using cyclic voltammetry (CV) technique. The construction of the ANP sensor was carefully optimized to enhance its performance, including the film thickness and the procedures for effective template extraction from the MIP matrix. The MIP biosensor presented a linear response against polymeric NPs (PLGA-NPs@ANP) concentration logarithm ranging from 4.0 μg mL-1 to 100 μg mL-1, with a sensitivity of – 0.0129 mA mL μg-1 decade-1 and an LOD < 4.0 μg mL-1. Furthermore, the developed MIP receptor film was able to discriminate ANP-functionalized nanocarriers from non-functionalized NPs.

Harnessing 3D Printing and Electrospinning for Multiscale Hybrid Patches Mimicking the Native Myocardium.

Engineered cardiac tissues show potential for regenerative therapy in ischemic heart disease. Yet, selection of soft biomaterials for scaffold manufacturing is primarily influenced by empirical and compositional factors, raising concerns about arrhythmic risks due to poor electrophysiological integration. Addressing this, we developed multiscale hybrid myocardial patches mimicking native myocardium's structural and biomechanical attributes, utilizing 3D printing and electrospinning techniques. We compared three patch types: pure silicone and silicone-poly(lactic-co-glycolic acid) (PLGA) with random (S-PLGA-R) and aligned (S-PLGA-A) fibers. S-PLGA-A patches with fiber orientation angles of 95-115° are achieved by applying a secondary electrical field using two parallel aluminum enhancers. With bulk and localized moduli of 350-750 and 13-20 kPa resembling the native myocardium, S-PLGA-A patches demonstrate a sarcomere length of 2.1 ± 0.2 μm, ≥50% higher strain motions and diastolic phase, and a 50-70% slower rise of calcium handling compared to the other two patches. This enhanced maturation and improved synchronization phenomena are attributed to efficient force transmission and reduced stress concentration due to mechanical similarity and linear propagation of electrical signals. This study presents a promising strategy for advancing regenerative cardiac therapies by harnessing the capabilities of 3D printing and electrospinning, providing a proof-of-concept for their effectiveness.

Shear stress preconditioning and microbubble flow pattern modulate ultrasound-assisted plasma membrane permeabilization

The recent and exciting success of anti-inflammatory therapies for ischemic heart disease (e.g. atherosclerosis) is hindered by the lack of site-specific and targeted therapeutic deposition. Microbubble-mediated focused ultrasound, which uses circulating, lipid-encapsulated intravascular microbubbles to locally enhance endothelial permeability, offers an exciting approach. Atherosclerotic plaques preferentially develop in regions with disturbed blood flow, and microbubble-endothelial cell membrane interactions under such flow conditions are not well understood. Here, using an acoustically-coupled microscopy system, endothelial cells were sonicated (1 MHz, 20 cycle bursts, 1 ms PRI, 4 s duration, 300 kPa peak-negative pressure) under perfusion with Definity™ bubbles to examine microbubble-mediated endothelial permeabilization under a range of physiological conditions. Endothelial preconditioning under prolonged shear influenced physiology and the secretome, inducing increased expression of pro-angiogenesis analytes, decreasing levels of pro-inflammatory ones, and increasing the susceptibility of ultrasound therapy. Ultrasound treatment efficiency was positively correlated with concentrations of pro-angiogenic cytokines (e.g. VEGF-A, EGF, FGF-2), and negatively correlated with pro-inflammatory chemokines (e.g. MCP-1, GCP-2, SDF-1). Furthermore, ultrasound therapy under non-reversing pulsatile flow (∼4–8 dyne/cm2, 0.5–1 Hz) increased permeabilization up to 2.4-fold compared to shear-matched laminar flow, yet treatment under reversing oscillatory flow resulted in more heterogeneous modulation. This study provides insight into the role of vascular physiology, including endothelial biology, into the design of a localized ultrasound drug delivery system for ischemic heart disease.

Approaches to therapy Amlodipine/Indapamide/Perindopril therapy of high arterial hypertension in ischemic heart disease patients with chronic kidney disease stage 1-3 after coronary stenting

Introduction: Acute coronary syndrome, chronic forms of ischemic heart disease (IHD) and postinfarction cardiosclerosis are the main causes of morbidity and mortality in the world, including Russia. In the XXI century, there is an increase in comorbid pathology, especially in the combination of IHD with arterial hypertension, diabetes, chronic obstructive pulmonary disease and chronic kidney disease. Patients with IHD and chronic kidney disease have a higher incidence of coronary events and complications. The frequency of coronary events and complications indicates the need to improve the diagnosis and treatment of this group of patients. diagnosis and treatment of this group of patients. The aim of the study was to analyze the dynamics of vascular stiffness, pulmonary hypertension (PH), diastolic heart dysfunction and endothelial dysfunction indices in patients with different variants of ischemic heart disease combined with chronic kidney disease (CKD) stage 1-3 using complex therapy of combined hypotensive drug Amlodipine/Indapamide/Perindopril three months after coronary stenting and to compare them with the group of patients on conservative therapy only. Materials and Methods: 85 patients with different forms of IHD, arterial hypertension (AH) on the background of CKD 1-3 stages, as well as data of 42 patients with IHD, AH without renal pathology were analyzed. The first group – IHD, postinfarction cardiosclerosis, CKD stage 1-3 (33 patients); the second group – acute coronary syndrome with ST-segment elevation, Myocardial infarction (MI) (30 patients); the third group – ACS without ST-segment elevation, Unstable angina (UA) (22 patients). Results: The highest indices of vascular stiffness (Pulse wave velocity (PWV), Augmentation index (AI), CAVI, Central Systolic Blood Pressure (SBPao), central arterial pulse pressure (PP)) were registered in combination of ACS with ST-segment elevation and CKD 1-3 stages. These indices are markers of IHD progression in these patients; they also have increased pulmonary hypertension and diastolic dysfunction of the heart, endothelial dysfunction with vasodilation insufficiency in 88% of cases, which even without hemodynamically significant coronary artery stenoses according to coronary CT angiography data leads to the development of ACS with ST-segment elevation and ACS without ST-segment elevation with MI. Amlodipine/Indapamide/Perindopril was prescribed to all patients due to high arterial hypertension on admission against the background of basic therapy of IHD and coronary stenting. Coronary CT angiography in patients with comorbid renal pathology does not lead to aggravation of chronic kidney disease after 3 months, on the contrary; in this group of patients the most pronounced decrease of arterial stiffness (AS), AI, SBPao, PP with elevation of glomerular filtration rate (GFR) and decrease of creatinine in blood occurs in comparison with the group of patients who did not undergo coronary stenting, they were only on conservative therapy. Conclusion: Prescription of three component drug Amlodipine/Indapamide/Perindopril on the background of baseline therapy especially in combination with surgical vascularization of the heart is justified.

Oral mitochondrial transplantation using nanomotors to treat ischaemic heart disease.

Mitochondrial transplantation is an important therapeutic strategy for restoring energy supply in patients with ischaemic heart disease (IHD); however, it is limited by the invasiveness of the transplantation method and loss of mitochondrial activity. Here we report successful mitochondrial transplantation by oral administration for IHD therapy. A nitric-oxide-releasing nanomotor is modified on the mitochondria surface to obtain nanomotorized mitochondria with chemotactic targeting ability towards damaged heart tissue due to nanomotor action. The nanomotorized mitochondria are packaged in enteric capsules to protect them from gastric acid erosion. After oral delivery the mitochondria are released in the intestine, where they are quickly absorbed by intestinal cells and secreted into the bloodstream, allowing delivery to the damaged heart tissue. The regulation of disease microenvironment by the nanomotorized mitochondria can not only achieve rapid uptake and high retention of mitochondria by damaged cardiomyocytes but also maintains high activity of the transplanted mitochondria. Furthermore, results from animal models of IHD indicate that the accumulated nanomotorized mitochondria in the damaged heart tissue can regulate cardiac metabolism at the transcriptional level, thus preventing IHD progression. This strategy has the potential to change the therapeutic strategy used to treat IHD.

Finding the right balance on the challenging path to clinical translation of anti-inflammatory therapies for ischemic heart disease.

Finding the right balance on the challenging path to clinical translation of anti-inflammatory therapies for ischemic heart disease.

The Current State of Extracellular Matrix Therapy for Ischemic Heart Disease.

The extracellular matrix (ECM) is a three-dimensional, acellular network of diverse structural and nonstructural proteins embedded within a gel-like ground substance composed of glycosaminoglycans and proteoglycans. The ECM serves numerous roles that vary according to the tissue in which it is situated. In the myocardium, the ECM acts as a collagen-based scaffold that mediates the transmission of contractile signals, provides means for paracrine signaling, and maintains nutritional and immunologic homeostasis. Given this spectrum, it is unsurprising that both the composition and role of the ECM has been found to be modulated in the context of cardiac pathology. Myocardial infarction (MI) provides a familiar example of this; the ECM changes in a way that is characteristic of the progressive phases of post-infarction healing. In recent years, this involvement in infarct pathophysiology has prompted a search for therapeutic targets: if ECM components facilitate healing, then their manipulation may accelerate recovery, or even reverse pre-existing damage. This possibility has been the subject of numerous efforts involving the integration of ECM-based therapies, either derived directly from biologic sources or bioengineered sources, into models of myocardial disease. In this paper, we provide a thorough review of the published literature on the use of the ECM as a novel therapy for ischemic heart disease, with a focus on biologically derived models, of both the whole ECM and the components thereof.

Induced Pluripotent Stem Cell-Derived Cardiomyocytes Therapy for Ischemic Heart Disease in Animal Model: A Meta-Analysis.

Ischemic heart disease (IHD) poses a significant challenge in cardiovascular health, with current treatments showing limited success. Induced pluripotent derived-cardiomyocyte (iPSC-CM) therapy within regenerative medicine offers potential for IHD patients, although its clinical impacts remain uncertain. This study utilizes meta-analysis to assess iPSC-CM outcomes in terms of efficacy and safety in IHD animal model studies. A meta-analysis encompassing PUBMED, ScienceDirect, Web of Science, and the Cochrane Library databases, from inception until October 2023, investigated iPSC therapy effects on cardiac function and safety outcomes. Among 51 eligible studies involving 1012 animals, despite substantial heterogeneity, the iPSC-CM transplantation improved left ventricular ejection fraction (LVEF) by 8.23% (95% CI, 7.15 to 9.32%; p < 0.001) compared to control groups. Additionally, cell-based treatment reduced the left ventricle fibrosis area and showed a tendency to reduce left ventricular end-systolic volume (LVESV) and end-diastolic volume (LVEDV). No significant differences emerged in mortality and arrhythmia risk between iPSC-CM treatment and control groups. In conclusion, this meta-analysis indicates iPSC-CM therapy's promise as a safe and beneficial intervention for enhancing heart function in IHD. However, due to observed heterogeneity, the efficacy of this treatment must be further explored through large randomized controlled trials based on rigorous research design.

Adipose-Derived Mesenchymal Stem Cell Therapy for Ischemic Heart Disease: Safe but Not Effective?

Adipose-Derived Mesenchymal Stem Cell Therapy for Ischemic Heart Disease: Safe but Not Effective?

Rebuilding the myocardial microenvironment to enhance mesenchymal stem cells-mediated regeneration in ischemic heart disease.

Mesenchymal stem cells (MSCs) are naturally-derived regenerative materials that exhibit significant potential in regenerative medicine. Previous studies have demonstrated that MSCs-based therapy can improve heart function in ischemia-injured hearts, offering an exciting therapeutic intervention for myocardial ischemic infarction, a leading cause of worldwide mortality and disability. However, the efficacy of MSCs-based therapies is significantly disturbed by the myocardial microenvironment, which undergoes substantial changes following ischemic injury. After the ischemic injury, blood vessels become obstructed and damaged, and cardiomyocytes experience ischemic conditions. This activates the hypoxia-induced factor 1 (HIF-1) pathway, leading to the rapid production of several cytokines and chemokines, including vascular endothelial growth factor (VEGF) and stromal-derived factor 1 (SDF-1), which are crucial for angiogenesis, cell migration, and tissue repair, but it is not sustainable. MSCs respond to these cytokines and chemokines by homing to the injured site and participating in myocardial regeneration. However, the deteriorated microenvironment in the injured myocardium poses challenges for cell survival, interacting with MSCs, and constraining their homing, retention, and migration capabilities, thereby limiting their regenerative potential. This review discusses how the deteriorated microenvironment negatively affects the ability of MSCs to promote myocardial regeneration. Recent studies have shown that optimizing the microenvironment through the promotion of angiogenesis can significantly enhance the efficacy of MSCs in treating myocardial infarction. This approach harnesses the full therapeutic potential of MSCs-based therapies for ischemic heart disease.

Role of long non-coding RNA Zeb2os in protection of the injured heart

Abstract Heart failure due to ischemic heart disease is one of the leading causes of death worldwide. Terminated vasculature and cardiomyocyte apoptosis due to myocardial infarction are critical events in infarct healing. Therefore, identifying factors that can enhance cardiac repair by restoring the capillary network and inhibiting cardiomyocyte death is of great significance. Accumulating evidence implies that long non-coding RNAs (lncRNAs) are potent regulators of cardiac development and disease. Our preliminary data show the potential cardioprotective function of the long non-coding RNA Zeb2 opposite strand (Zeb2os). This lncRNA overlaps and is antisense to ZEB2 at the 5' splice site of an intron within the 5' UTR. Zeb2os was shown to prevent splicing of the intron containing an internal ribosome entry site (IRES) that increases translation of the ZEB2 transcript. In line with the known function of ZEB2, Zeb2os has pro-angiogenic and anti-apoptotic functions in different organs. However, its role in the heart still has to be determined. Our results show that Zeb2os expression is decreased in cultured cardiomyocytes subjected to H2O2-mediated oxidative stress, which correlates with increased apoptosis and reduced antioxidant defence of cardiac muscle cells. AAV6-mediated overexpression of Zeb2os in hiPSC-derived cardiomyocytes protects from H2O2-induced apoptosis, suggesting it may have cardioprotective activity, possibly through regulating Zeb2 translation. Additionally, systemic AAV9-mediated delivery of Zeb2os to the mouse heart enhanced angiogenesis by increasing the number of proliferating endothelial cells. Moreover, RNA-sequencing of Zeb2os overexpressing hearts at baseline implicated Zeb2os in the regulation of numerous genes related to response to hypoxia. In conclusion, we uncovered/identified Zeb2os as a new potential cardioprotective factor with pro-angiogenic and anti-apoptotic properties. We are currently investigating the effect of AAV9-mediated delivery of Zeb2os in a mouse model of cardiac ischemia to understand further its protective role in the injured heart, which is an essential step towards the development of improved therapies for ischemic heart disease.

Abstract 18313: Sex Disparities in Optimal Medical Therapy for Ischemic Heart Disease

Background: Despite secondary prevention guidelines recommending optimal medical therapy (OMT) forischemic heart disease (IHD), which includes antiplatelets, statins, renal-angiotensin aldosterone inhibitors (RAASi), and β-blockers, significant sex disparities in OMT utilization have been observed. However, theimpact of national efforts on narrowing this gap in contemporary cohorts remains uncertain. Methods: Using data from the National Health and Nutrition Examination Survey cycles 2011-2020, we examined the distribution and trends of OMT medication classes and combinations used in the preceding 30 days (verified through containers in most cases) among adult men and women with self-reported IHD (myocardial infarction or coronary artery disease). Results: Among 1905 adults included (40.6% women, mean age 65.4years), women had significantlylower proportions of OMT use across all medication classes- antiplatelets (68% vs. 77.7%), statins (57.2% vs. 73.9%), RAASi (45.6% vs. 59.0%), and β-blockers (51.2% vs. 61.1%); as well as combinations such as aspirin+statins (47.4% vs. 64.1%) and all four medications (17.5% vs. 32.5%). After adjusting forsociodemographic and clinical factors, the odds of using antiplatelets (OR 0.71 95%CI 0.52-0.94), statins (OR 0.62, 0.40-0.96), and RAASi (OR 0.56, 0.38-0.84) were significantly lower among women than men,whereas β-blocker use was comparable. Moreover, between 2011 to 2020, fewer women consistentlyreported using statins, RAASi, β-blockers, antiplatelets+statins, and all four medications in each survey cycle. Conclusion: This nationally representative study reveals persistent sex disparities in OMT utilization forIHD, with women receiving suboptimal treatment compared to men. These findings emphasize the urgentneed for novel targeted interventions to address and mitigate the sex disparities in OMT utilization foreffective IHD prevention.

Prediction of therapy for ischemic heart disease from PPG signals using fuzzy GRU network

BackgroundCardiac morbidity like ischemic heart disease (IHD) causes global mortality. Diagnosis of IHD requires coronary angiograms — an invasive, sophisticated, and expensive procedure. However, non-invasive methods could not gain much confidence in swift diagnosis of IHD patients. These potential issues provided the research motivation for diagnosing IHD priorly in this pilot study. ObjectiveA computer-aided technique, as an alternate method to fasten and ease IHD detection and categorization, has been suggested in this cohort study. Here, the classification was conducted by a sandwich model of GRU and fuzzy logic in a deep GRU Fuzzy network. MethodsIn this work, photoplethysmography (PPG) signals were acquired from 355 IHD patients. Gabor–Winger transform was used to derive signal features using statistical identities. Analysis was done with a Fuzzy GRU Network comprising GRU and BiGRU layers with fuzzy layers. An algorithm was designed with a Rete network and three membership functions to deduce fuzzy inference. Then, Choquet Integral was used for defuzzification. ResultsThe proposed network predicted results with 0.85 accuracy, 0.86 recall, 0.84 precision, 0.86 sensitivity, 0.78 Micro-averaged F1-score, and 0.84 specificity. The network architecture was validated using ablation and comparative studies. The PRC and ROC curves gave the highest values of 0.91 AP and 0.90 AUC, respectively for this network. A state-of-the-art study was done to show the superiority of the technique. ConclusionThis computer-aided model using PPG might become a tool in predicting the type of therapy for IHD patients which will provide a non-invasive, inexpensive, and fast mode of diagnosis.

Cardiac Stem Cell–Derived Treatment for Ischemic Heart Disease: A Review

Current first-line pharmacologic therapies for ischemic heart disease (ISD) have proven largely ineffective, leading to the exploration of alternative treatments. Various stem cell–like/progenitor cell lineages have been studied, especially c-kit+ cardiac stem cells (CSCs) due to their true stem cell origin and differentiation capabilities. These CSCs reside in the heart after birth and possess regenerative potential, providing a means of maintaining and repairing myocardial tissue. Previous studies have demonstrated the therapeutic potential of CSCs for patients with ISD. However, counterarguments have focused on the inflammatory state present in diseased hearts, which may limit the benefits of c-kit+ CSCs. Nonetheless, we argue that a thorough examination of the literature supports the potential of c-kit+ CSCs as a safe and effective therapeutic approach for restoring lost cardiac tissue and function in patients with ISD. Though promising, we believe further scientific inquiry is necessary to discern the exact mechanisms by which c-kit+ CSCs function, which could pay dividends in the approach to treating ISD.