Doxorubicin-related cardiotoxicity: review of fundamental pathways of cardiovascular system injury.

Over the years, advancements in the field of oncology have made remarkable strides in enhancing the efficacy of medical care for patients with cancer. These modernizations have resulted in prolonged survival and improved the quality of life for these patients. However, this progress has also been accompanied by escalation in mortality rates associated with anthracycline chemotherapy. Anthracyclines, which are known for their potent antitumor properties, are notorious for their substantial cardiotoxic potential. Remarkably, even after 6 decades of research, a conclusive solution to protect the cardiovascular system against doxorubicin-induced damage has not yet been established. A comprehensive understanding of the pathophysiological processes driving cardiotoxicity combined with targeted research is crucial for developing innovative cardioprotective strategies. This review seeks to explain the mechanisms responsible for structural and functional alterations in doxorubicin-induced cardiomyopathy.

MicroRNA-155 and exosomal microRNA-155: Small pieces in the cardiovascular diseases puzzle.

MicroRNAs (miRs, miRNAs) are known to have a part in various human illnesses, such as those related to the heart. One particular miRNA, miR-155, has been extensively studied and has been found to be involved in hematopoietic lineage differentiation, immunity, viral infections, inflammation, as well as vascular remodeling. These processes have all been connected to cardiovascular diseases, including heart failure, diabetic heart disease, coronary artery disease, and abdominal aortic aneurysm. The impacts of miR-155 depend on the type of cell it is acting on and the specific target genes involved, resulting in different mechanisms of disease. Although, the exact part of miR-155 in cardiovascular illnesses is yet not fully comprehended, as some studies have shown it to promote the development of atherosclerosis while others have shown it to prevent it. As a result, to comprehend the underlying processes of miR-155 in cardiovascular disorders, further thorough study is required. It has been discovered that exosomes that could be absorbed by adjacent or distant cells, control post-transcriptional regulation of gene expression by focusing on mRNA. Exosomal miRNAs have been found to have a range of functions, including participating in inflammatory reactions, cell movement, growth, death, autophagy, as well as epithelial-mesenchymal transition. An increasing amount of research indicates that exosomal miRNAs are important for cardiovascular health and have a major role in the development of a number of cardiovascular disorders, including pulmonary hypertension, atherosclerosis, acute coronary syndrome, heart failure, and myocardial ischemia-reperfusion injury. Herein the role of miR-155 and its exosomal form in heart diseases are summarized.

A Comparison of the Clinical Outcomes of Minimum and Maximum Hematocrit Levels During Cardiopulmonary Bypass (CPB) in Low-risk Patients Undergoing Coronary Artery Bypass Graft Surgery (CABG): A Cross-sectional Study.

Background: This study investigated the clinical outcomes at the minimum and maximum levels of hematocrit (HCT) during cardiopulmonary bypass (CPB) in low-risk patients undergoing coronary artery bypass graft (CABG) surgery. Materials and Methods: In this cross-sectional study, 85 patients who underwent CABG with an ejection fraction of greater than 35% were selected. Based on the HCT range during CPB, patients were divided into two groups: minimum HCT: HCT = 16-18% and maximum HCT: HCT = 25-27%. Then the operation outcomes, amount of drainage, and transfusion were recorded and compared between these groups. Results: In the middle tube 8 h after surgery and left tube 24 h after surgery, the amount of drainage in the minimum HCT group with mean of 71.00 ± 130.9 and 60.65 ± 71.23, respectively, was significantly lower than the maximum HCT group with mean of 101.5 ± 246.50 and 123.76 ± 93.17, respectively (P value < 0.05). The incidence of cognitive disorders in the maximum HCT group was significantly higher than in the minimum HCT group (11.1% vs. 0%, P value = 0.041). Also, the mean transfusion of packed red blood cell (PRBC) and fresh frozen plasm (FFP) during CPB in the maximum HCT group, with mean of 346.7 ± 86.22 and 396.1 ± 21.05, respectively, were significantly higher than the minimum HCT group with mean of 178.8 ± 80.91 and 136.8 ± 46.77, respectively (P value < 0.05). After CPB, there was no significant difference in transfusion products (P value > 0.05). Conclusion: According to the results of this study, patients undergoing CABG surgery with maximum HCT level versus minimum HCT level during CPB, need more packed cells and fresh frozen plasma products transfusion, which will be associated with the complication of cognitive impairment.

Methotrexate & rheumatoid arthritis associated atherosclerosis: A narrative review of multidisciplinary approach for risk modification by the international board of experts.

Rheumatoid arthritis (RA) is an idiopathic, autoimmune connective tissue disorder that primarily affects the synovial joints, causing symmetric, erosive-deforming polyarthritis. It is also associated with extra-articular manifestations, particularly cardiovascular (CV) diseases (CVD). CV risk modification in RA remains unsolved despite recent advances in the management of RA. RA is an independent risk factor for atherosclerosis. RA and atherosclerosis share similar pathophysiological features (such as the pro-inflammatory cascade activation including interleukin-6) and risk factors (such as microflora dysbacteriosis and smoking). Patients with RA experience an exacerbation of atherogenesis, with atheromas destabilization, endothelial dysfunction, vasculitis, and hypercytokinemia. Consequently, the inflammatory response associated with RA is the basis for CVD development. The treat-to-target strategy not only improved RA control but also had a favorable effect on the morpho-functional state of the CV system in patients living with RA. Thus, disease-modifying antirheumatic drugs (DMARDs) - in particular methotrexate - may have a beneficial effect on the prevention of CV events in RA. It must be mentioned that RA is a serious multi-system disease, not only because of a window period during which the course of RA can be reversed, but also due to early damage to the heart and blood vessels. For this reason, a thorough cardiological assessment must be performed for all patients with RA, regardless of sex, age, disease stage, and disease activity score.

Diabetic Cardiomyopathy: 2023 Update by the International Multidisciplinary Board of Experts.

Diabetes mellitus (DM) is considered by many the pandemic of the 21st century and is associated with multiple organ damages. Among these, cardiovascular complications are responsible for an incredible burden of mortality and morbidity in Western Countries. The study of the pathological mechanisms responsible for the cardiovascular complications in DM patients is key for the development of new therapeutic strategies. The metabolic disorders caused by hyperglycemia, insulin resistance, and dyslipidemia, results in a cascade of pathomorphological changes favoring the atherosclerotic process and leading to myocardial remodeling. Parallel to this, oxidative stress, calcium overload, mitochondrial dysfunction, activation of protein kinase C signaling pathways, myocardial lipomatosis, and low-grade inflammation of the myocardium - are the main pathways responsible for the diabetic cardiomyopathy development. This review aims to appraise and discuss the pathogenetic mechanisms behind the diabetic cardiomyopathy development.

Determination of Shock Index and Age Shock Index Cut-Off Points in Patients with ST-Segment Elevation Myocardial Infarction: SEMI-CI Study

Abstract Background Shock index (SI) and age shock index (ASI) are less frequently used for assessment of major adverse cardiovascular events (MACE) among patients with ST-segment elevation myocardial infarction (STEMI), and their reported cut-off points are controversial. Objectives We aimed to define proper cut-off value of these indices for MACE prediction among Iranian patients with STEMI. Methods This study was in the context of the ST-Elevation Myocardial Infarction Cohort in Isfahan (SEMI-CI) study. SI and ASI were calculated by division of heart rate (HR) over systolic blood pressure (SBP) and age multiplied by SI, respectively, in 818 subjects with STEMI. Receiver operating characteristic (ROC) curve analysis was used to determine optimal SI and ASI cut-off values. Chi-square test, independent t test, and analysis of variance were employed for nominal and numerical variables, as appropriate, with consideration of p values < 0.05. MACE was defined as a composite of non-fatal reinfarction, heart failure (HF), recurrent percutaneous intervention (PCI), rehospitalization for cardiovascular diseases, and all-cause mortality. Results Mean age was 60.70 ± 12.79 years (males: 81.7%). Area under curve (AUC) values from ROC curve analysis for SI and ASI were 0.613 (95% confidence interval [CI]: 0.569 to 0.657, p < 0.001) and 0.672 (95% CI: 0.629 to 0.715, p < 0.001), respectively. Optimal SI and ASI cut-offs were 0.61 (sensitivity: 61%, specificity: 56%) and 39.5 (sensitivity: 65%, specificity: 66%), respectively. Individuals with SI ≥ 0.61 or within the highest quartile (SI ≥ 0.75) had significantly higher frequency of one-year MACE compared to the reference group (34.7% versus 22.2%, p < 0.001 and 42.4% versus 20.6%, p < 0.05, respectively). Similar relations were observed in terms of ASI values (ASI ≥ 39.5 versus ASI < 39.5: 43.6% versus 17.3%, p < 0.001, ASI Q4 ≥ 47.5 versus ASI Q1 ≤ 28.8: 49% versus 16.6%, p < 0.05). Conclusions SI and ASI cut-off values of 0.61 and 39.5 could reliably predict MACE occurrence among Iranian patients with STEMI.

Possibilities of dapagliflozin-induced cardioprotection on doxorubicin + cyclophosphamide mode of chemotherapy-induced cardiomyopathy.

RATIONALE: The global burden of cardiovascular (CV) and oncological diseases continues to increase. In this regard, the prevention of CV diseases (CVD) before and after cancer treatment is an urgent and unsolved problem in medicine. For this reason, our research group aimed to investigate the possibility of dapagliflozin-related cardioprotection, using an experimental model of chronic Doxorubicin (Adriamycin) + Cyclophosphamide (AC)-mode of chemotherapy-induced cardiomyopathy. OBJECTIVE: The redox balance, lipid metabolism, endothelial dysfunction, and myocardial damage parameters were measured to evaluate the pathways of dapagliflozin-induced stabilization of CV homeostasis. METHODS: For this study, 80 inbred Wistar rats were randomly assigned to four equally sized groups. A model of chronic cardiotoxicity was attained by using doxorubicin and cyclophosphamide co-administration. In the case, the markers of redox-balance, cholesterol metabolism, endothelial dysfunction, myocardial alteration, and morphological examination were assessed. RESULTS: For all parameters, statistically significant deviations were obtained, emphasizing the sequel of AC-mode chemotherapy-related detergent effect on CV system (group 2). Moreover, the data obtained from dapagliflozin-treated groups (group 3) showed that this strategy provide limitation of lipid peroxidation, cholesterol metabolism and endothelial function normalization, with subsequent morphological preservation of myocardium. CONCLUSION: Dapagliflozin has a broad spectrum of pleiotropic influences, namely cholesterol-lowering, anti-inflammatory, and endothelium-stabilizing properties. These properties provide a favorable environment for the prevention of chemotherapy-related cardiomyopathy.

HIV-Related Atherosclerosis: State-of-the-Art-Review.

The infection caused by the Human Immunodeficiency Virus (HIV) has spread rapidly across the globe, assuming the characteristics of an epidemic in some regions. Thanks to the introduction of antiretroviral therapy into routine clinical practice, there was a considerable breakthrough in the treatment of HIV, that is now HIV is potentially well-controlled even in low-income countries. To date, HIV infection has moved from the group of life-threatening conditions to the group of chronic and well controlled ones and the quality of life and life expectancy of HIV+ people, with an undetectable viral load is closer to that of an HIV- people. However, unsolved issues still persist. For example: people living with HIV are more prone to the age-related diseases, especially atherosclerosis. For this reason, a better understanding of the mechanisms of HIV-associated destabilization of vascular homeostasis seems to be an urgent duty, that may lead to the development of new protocols, bringing the possibilities of pathogenetic therapies to a new level. The purpose of the article was to evaluate the pathological aspects of HIV-induced atherosclerosis.

The Association of Thyroid-Stimulating Hormone (TSH) Levels and Lipid Profile in Euthyroid Patients with Familial Hypercholesterolemia.

Previous studies reported a relationship between thyroid-stimulating hormone (TSH) and low-density lipoprotein cholesterol (LDL-C) levels. In this study, we aim to evaluate the impact of TSH levels on lipid profile in patients with familial hypercholesterolemia (FH) and euthyroid state. Patients were selected from the Isfahan FH registry. The Dutch Lipid Clinic Network (DLCN) criteria are used to detect FH. Patients were classified into no FH, possible FH, probable FH, and definite FH groups based on the DLCN scores. Patients with any cause of secondary hyperlipidemia, including hypothyroidism, were excluded from this study. The study group consisted of 103 patients with possible FH, 25 patients with definite FH, and 63 individuals with no FH. The mean TSH and LDL-C levels among participants were 2.10 ± 1.22 mU/l and 142.17 ± 62.56 mg/dl, respectively. No positive or negative correlation was found between serum TSH and total cholesterol (P value = 0.438), high-density lipoprotein cholesterol (P = 0.225), triglycerides (P value = 0.863), and LDL-C (P value = 0.203). We found no correlation between serum TSH levels and lipid profiles in euthyroid patients with FH.

Cardiac Sarcoidosis: A Contemporary Concept of Forgotten Granulomatosis.

Sarcoidosis is a complex multisystem inflammatory granulomatous disease that can affect any organ, with a wide range of clinical presentations. A significant number of patients with systemic sarcoidosis may also have cardiac involvement. Clinical manifestations of cardiac sarcoidosis can include various rhythm and conduction disturbances, as well as heart failure. The structure of sarcoid granulomas is similar to that of tuberculous granulomas, but in contrast, they lack caseous necrosis. Tissue changes in sarcoidosis tissues depend on the stage of development of the disease, progressing from pathological process: macrophage-lymphocytic infiltration to epithelioid cell granuloma formation, and fibrosis. Granulomas can be found in any part of the myocardium, with the most common locations being the free wall of the left ventricle, the basal part of the interventricular septum, and the interatrial septum. Vasculopathy of the pulmonary circulation and coronary arteries is often observed. Advancements in diagnostic imaging techniques, such as computer tomography and magnetic resonance imaging, have facilitated the verification of cardiac sarcoidosis. This article presents an analysis of updated information on cardiac sarcoidosis by a multidisciplinary working group.

Translation, Cultural Adaptation, Validation, and Reliability of Persian-Revised Heart Failure Compliance Questionnaire.

Background: Compliance with health-related behaviors is a dilemma among heart failure (HF) patients. The present study aimed to assess the validity and reliability of a Persian translation of the revised heart failure compliance questionnaire (RHFCQ) in Iranian HF sufferers. Methods: This methodological study was performed on outpatient HF individuals referred to a heart clinic in Isfahan, Iran. The forward-backward translation method was used for translation. Twenty subjects were invited to express their opinions on the provided items concerning simplicity and understandability. Twelve experts were invited to rate the items regarding the content validity index (CVI). Cronbach's α was used to evaluate internal consistency. The patients were asked to complete the questionnaire for the second time after 2 weeks to investigate test-retest reliability using the intraclass correlation coefficient (ICC). Results: There were no obvious difficulties during the translation and assessment of the simplicity and comprehensiveness of the questionnaire items. The CVI of the items ranged from 0.833 to 1.000. Totally, 150 patients (age: 64.60±15.00 y, males: 58.0%) filled in the questionnaire twice with no missing data. The highest and lowest compliance rates were attributed to alcohol and exercise domains, respectively (83.00±7.70% and 45.55±12.00%, respectively). Cronbach's α was 0.629. After the omission of 3 items related to smoking and alcohol cessation, Cronbach's α rose to 0.655. The ICC showed an acceptable value of 0.576 (95% CI, 0.462 to 0.673). Conclusion: The modified Persian RHFCQ is a simple and meaningful tool with acceptable moderate reliability and good validity for assessing compliance in Iranian HF patients.

Cardiogenic Shock and Guillain-Barré Syndrome as the First Manifestations of Pheochromocytoma.

Febrile congestive heart failure is a rare first manifestation of pheochromocytoma. Herein, the case of a 31-year-old female with febrile congestive heart failure and subsequent cardiogenic shock is presented. After intensive care unit (ICU) admission and further evaluating the right adrenal mass observed in abdominal ultrasonography, the diagnosis of pheochromocytoma was confirmed. Then, she was scheduled for the right adrenalectomy. Before surgery, she complained of acute-onset progressive muscle weakness in the lower limbs, followed by the upper limbs. After further investigation, she was diagnosed with Guillain-Barré syndrome and treated with intravenous immunoglobulin (IVIG). She recovered well after the right adrenalectomy, and during the subsequent 18 months, the follow-up did not reveal any complications, and left ventricular function recovered to normal.

Pulmonary Vascular Capacitance as a Predictor of Vasoreactivity in Idiopathic Pulmonary Arterial Hypertension Tested by Adenosine.

BACKGROUND: Acute pulmonary vasoreactivity testing has been recommended in the diagnostic work-up of patients with idiopathic pulmonary arterial hypertension (IPAH). Pulmonary arteriolar capacitance (Cp) approximated by stroke volume divided by pulmonary pulse pressure (SV/PP) is considered as an independent predictor of mortality in patients with IPAH. OBJECTIVES: We sought to evaluate any differences in baseline and adenosine Cp between vasoreactive and non-vasoreactive IPAH patients tested with adenosine. PATIENTS AND METHODS: Fourteen patients with IPAH and a vasoreactive adenosine vasoreactivity testing according to the ESC guidelines were compared with 24 IPAH patients with nonreactive adenosine test results. RESULTS: There were no statistical significant differences between the two groups regarding NYHA class, body surface area, heart rate, and systemic blood pressure during right heart catheterization. Hemodynamic study showed no statistical significant differences in cardiac output/Index, mean pulmonary artery pressure, pulmonary vascular resistance, and baseline Cp between the two groups. There was a statistical significant but weak increase in adenosine Cp in vasoreactive group compared to non-reactive group (P = 0.04). Multivariable analysis showed an association between Cp and vasoreactivity (Beta = 2, P = 0.04, OR = 0.05 (95%CI = 0.003 - 0.9). CONCLUSIONS: Cp could be considered as an index for the prediction of vasoreactivity in patients with IPAH. Prediction of long-term response to calcium channel blockers in patients with IPAH and a positive vasoreactive test by this index should be addressed in further studies.