Progression Of Cardiac Pathology Research Articles

NAFLD is a predictor of high risk of development and a co-factor in the progression of cardiovascular diseases

To date, nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver pathology and already at the stage of steatosis causes a high risk of developing cardiovascular diseases (CVD). Convincing evidence has been obtained that CVD is the most common cause of death in patients with NAFLD. Common risk factors (insulin resistance, abdominal obesity, dyslipidemia, hyperuricemia, chronic kidney disease and type 2 diabetes mellitus) and similar pathophysiological mechanisms (endothelial dysfunction, changes in lipid metabolism, systemic inflammation, plaque formation/instability, oxidative stress) of NAFLD and CVD, allow us to consider NAFLD not only as a key risk factor for the development of CVD, but also as a co-factor in the progression of cardiac pathology. The progression of NAFLD itself leads to a more severe course of CVD.

Gender-specific genetic and epigenetic signatures in cardiovascular disease.

Cardiac sex differences represent a pertinent focus in pursuit of the long-awaited goal of personalized medicine. Despite evident disparities in the onset and progression of cardiac pathology between sexes, historical oversight has led to the neglect of gender-specific considerations in the treatment of patients. This oversight is attributed to a predominant focus on male samples and a lack of sex-based segregation in patient studies. Recognizing these sex differences is not only relevant to the treatment of cisgender individuals; it also holds paramount importance in addressing the healthcare needs of transgender patients, a demographic that is increasingly prominent in contemporary society. In response to these challenges, various agencies, including the National Institutes of Health, have actively directed their efforts toward advancing our comprehension of this phenomenon. Epigenetics has proven to play a crucial role in understanding sex differences in both healthy and disease states within the heart. This review presents a comprehensive overview of the physiological distinctions between males and females during the development of various cardiac pathologies, specifically focusing on unraveling the genetic and epigenetic mechanisms at play. Current findings related to distinct sex-chromosome compositions, the emergence of gender-biased genetic variations, and variations in hormonal profiles between sexes are highlighted. Additionally, the roles of DNA methylation, histone marks, and chromatin structure in mediating pathological sex differences are explored. To inspire further investigation into this crucial subject, we have conducted global analyses of various epigenetic features, leveraging data previously generated by the ENCODE project.

Thyroid gland and heart: a cardiologist’s view on an endocrinological pathology. Review

The review of the literature considered the mechanism of action and the role of thyroid hormones (TH) on cardiovascular hemodynamics and, subsequently, on changes in the myocardial structure. A brief description of the genomic and non‑genomic mechanisms of thyroid hormones is provided. The mechanisms of thyroid hormones’ effects on the development of arterial and pulmonary hypertension, atrial fibrillation are highlighted. Attention is focused on the fact that congestive heart failure of the dilatation type develops against the background of hyperthyroidism. A possible connection between thyroid hyperfunction and Takotsubo stress‑induced cardiomyopathy was investigated. The impact of subclinical hyperthyroidism on the development and progression of cardiac pathology is illustrated. The mechanism of influence of hypothyroidism on the parameters of the lipid spectrum, acute phase proteins, insulin sensitivity, but not only the contractile function of the myocardium was considered. Changes in the electrical activity of the heart and its structural and functional changes were determined. Attention is focused on the importance of achieving euthyroidism in both hyperthyroidism and hypothyroidism. Stress‑induced Takotsubo cardiomyopathy is closely related to the hyperthyroid state and is often accompanied by the development of cardiogenic shock. Hyperthyroidism is associated with an increased risk of permanent atrial fibrillation and hypercoagulability. The achievement of euthyroid state can result in the reversal of left ventricular hypertrophy and decrease in the heart chamber dilatation. Even subclinical hyperthyroidism increases the risks of overall mortality and cardiovascular events, especially in the elderly persons. Patients with hypothyroidism are characterized by the development of anemia, dyslipidemia, decreased sensitivity to insulin, which is associated with endothelial dysfunction. In hypothyroidism, in contrast to hyperthyroidism, the risk of atrial fibrillation development is lower due to an increase in the arrhythmogenic threshold, but more typical disorders include sinus bradycardia, atrioventricular blocks of various degrees and prolongation of the QT interval, which are associated with the early development of impaired myocardial relaxation. For patients with thyroid pathology, the achievement of euthyroidism is mandatory to ensure cardio‑ and vasoprotection.

Immune system in development and progression of viral myocardial damage

This review demonstrates the role of the immune system in the development and progression of cardiac pathology caused byviral infection. The authors describe the role of lymphocytes (T- helper-17–Th17) in the viral persistence in myocardial tissue.They provide the information on increased level of interleukin-17A, the main Th17 cytokine in patients with dilated cardiomyopathy,which proves role of these cells in the progression of cardiac pathology. They discuss the role of T regulatory (Treg) lymphocytesin inflammatory heart disease.

Results of treatment of patients with combined atherosclerotic lesions of the cerebral and coronary arteries who underwent carotid endarterectomy at different terms before aortic-coronary bypass surgery.

The quality of life of patients after surgical interventions in those of with combined atherosclerotic lesions of the cerebral and coronary arteries remains a topical issue of modern medicine. The purpose of the study: to analyze the results of treatment of patients with combined atherosclerotic lesions of the cerebral and coronary arteries in the temporal aspect, who underwent carotid endarterectomy as the first stage of treatment. The results of treatment of 112 patients were analyzed. All patients underwent simultaneous cerebral and coronary angiography. After the operation, if new neurological symptoms appeared or a cardiological pathology progressed, the angiographic study was performed again, and the results of this study were used to decide on further tactics. Treatment results were evaluated 30 days, 5 and 10 years after ACBS. With the revealed indications for ACBS, hemodynamically significant stenoses of the operated carotid artery were found in 10.7% of patients. Stenoses of other cerebral vessels that required surgical correction (opposite ICA, VA) in 7.1%. These patients had cerebral artery stenting before ACBS. In 9.8% of patients, indications were found for stenting of cerebral and coronary arteries, which were performed in one session. In 5.4%, only coronary artery stenting was performed. In the remaining 75 patients without indicated surgical correction of cerebral arteries ACBS was performed. So, in 3-5 years after CEE, ACBS was performed in 35 patients, later than in 5 years – in 40 patients. In the postoperative period, ACBS TIA was registered only in 4%, ischemic stroke – in 5.3%. The total lethality rate is 4%. The 10-year survival rate after myocardial revascularization was 46% [CI 95% 58%; 34%]. the most intensive decrease in survival function was registered during the first 5 years of follow-up (5-year survival rate 60% [71%; 48%]. Carotid endarterectomy is an effective method of treating atherosclerotic stenosis of the ICA and a method of preventing neurological complications in patients with combined atherosclerotic lesions of the cerebral and coronary arteries with the progression of cardiac pathology.

Abstract 285: Glycogen Receptor Antagonism Ameliorates Progression of Heart Failure

Glucagon is an important hormone for glycemic control with counter-balancing function vs. insulin, and treatment of glucagon receptor antibody is shown to be efficacious for type I and type II diabetes. It was reported recently that systemic treatment of glucagon aggravated myocardial injury and pathological remodeling in heart in a glucagon receptor dependent manner, while cardiomyocyte specific inactivation of glucagon receptor protected heart from ischemic injury and remodeling, implicating the therapeutic potential of targeting glucagon receptor for heart failure. In this report, we investigated the functional outcome of glucagon receptor antagonist treatment in mice following myocardial infarction (MI) and pressure-overload using a humanized monoclonal glucagon receptor antagonist antibody REMD2.59. Mice treated with REMD2.59 after myocardial infarction showed significantly reduced scar sizes, blunted cardiac hypertrophy and fibrotic remodeling, and attenuated contractile dysfunction at four weeks after myocardial infarction comparing to mice treated with vehicle as controls. In contrast, treatment of glucagon aggravated these pathological manifestations triggered by myocardial infarction. Furthermore, treatment with REMD2.59 at the onset of pressure-overload significantly suppressed the development of cardiac hypertrophy and chamber dilation with marked preservation of cardiac systolic and diastolic function. More remarkably, initiation of REMD2.59 treatment two weeks after pressure-overload significantly blunted the progression of cardiac pathology with remarkable recovery of hypertrophic gene induction. These results provide the first in vivo proof-of-concept evidence that glucagon receptor antagonism is a potentially efficacious therapy to block both onset and progression of heart failure.

The role of mineral and bone disorders in the development and progression of cardiac and renal pathology in patients with type 1 diabetes mellitus of long duration

AimsThe objective of our study was to evaluate the role of mineral and bone metabolism disorders associated with chronic kidney disease (MBD-CKD) in the development and progression of cardiac and renal pathology in patients with type 1 diabetes mellitus (T1DM) of long duration. MethodsWe investigated 96 patients with T1DM of long duration, with CKD at different stages (0–5), including patients on hemodialysis (HD) and with kidney transplantation (KT). Along with overall clinical examination, we assessed markers of MBD (calcium, phosphorus, parathormone, vitamin D, fibroblast growth factor (FGF) 23) and levels of cardiac injury marker (atrial natriuretic peptide, NT-proBNP). Multispiral computer tomography with Agatston index calculation was also included. ResultsDecreased kidney function was associated with increased of levels phosphorus, parathormone, FGF 23, and vitamin D deficiency, with the highest deviation from the reference ranges seen in patients on HD with a very high risk of cardiovascular events. In KT patients with satisfactory graft function, these parameters were at the same levels as in patients with CKD stages 0–4. Progression of cardiovascular pathology was accompanied by elevation of NT-proBNP levels as CKD duration increased, decreased glomerular filtration rate, and were correlated with the main parameters of mineral homeostasis. The severity of coronary arteries calcification was associated with patient age and duration of T1DM and arterial hypertension. ConclusionsDevelopment and progression of kidney dysfunction is accompanied by MBD, a significant factor in progression of cardiac pathology, which remains a major cause of mortality in this patient population.

Mental Stress and Cardiovascular Disease

As our understanding of the multifactorial etiology of cardiovascular (CV) disorders evolves, the important role of behavioral and psychological factors in the development, prevention, and management of cardiac disease is increasingly appreciated. The link between mental stress and adverse cardiac events has been long recognized. A growing body of epidemiological observations has demonstrated that acute emotional stress may trigger angina, myocardial infarction (MI), or sudden death, whereas chronic exposure to stress contributes to the pathobiology of coronary artery disease (CAD). Experimental models have enabled quantification of the cardiac effects of psychological factors and allowed for detailed investigation of the underlying mechanisms. Of clinical relevance, interventions that reduce stress or improve stress management appear to be protective against CV events in addition to their efficacy in improving patient well-being and psychological parameters. Robust evidence supports the concept that acute mental stress may trigger an acute cardiac event or even sudden cardiac death. Epidemiological reports indicate that the incidence of acute coronary syndromes rises sharply in the setting of natural disasters such as hurricanes, earthquakes, and tsunamis. Similar to these infrequent, extreme scenarios, acute behavioral and emotional stressors encountered in everyday life (eg, anger or conflict) have also been implicated as potential triggers of myocardial ischemia and MI, malignant arrhythmia, and sudden cardiac death in patients with CAD. Consistent with the observations related to acute stress, chronic stressful conditions including occupation stressors, social relationships, and environmental stimuli have been linked to the development and progression of cardiac pathology, particularly CAD. The association between anxiety and CAD was initially demonstrated in patients with psychiatric disorders, but similar associations have also been found in general populations. Large-scale, community-based studies and prospective investigations have demonstrated a strong, dose-dependent association between anxiety disorders and cardiac death, particularly among men. The INTERHEART study demonstrated a 2-fold increase in the incidence of MI in relation to chronic stressors, even after adjusting for established risk factors such as age, gender, and smoking. The association between mental stress and CV risk appears to be comparable with, or even stronger than, the wellestablished risk conferred by hypercholesterolemia. In the Framingham study, relative risks were 1.3 for total cholesterol levels between 200 and 239 mg/dL and 1.9 for total cholesterol levels >240 mg/dL. Notably, risk gradients in relation to psychological stressors are comparable to the risk gradient of elevated cholesterol. Evidence exists that the association between mental stress and CV morbidity and mortality may in part be mediated by increased exposure to organic risk factors. Individuals exposed to psychological stressors are prone to unhealthy lifestyle behaviors including smoking, changes in dietary habits, increased intake of calories, decreased physical activity, manifestation of the so-called type-A personality, increased alcohol intake, higher coffee intake, and adverse changes in sleeping habits. These unfavorable behavioral responses may in part be responsible for the documented link between anxiety and CAD. Mental stress, however, also exerts direct effects on CV pathophysiology, characterized by marked sympathetic nervous system activation and release of catecholamines and corticosteroids. These neuroendocrine responses increase heart rate and blood pressure (BP), promote endothelial dysfunction, provoke vasoconstriction in atherosclerotic coronary arteries, and favor platelet activation and hypercoagulation. Together these pathobiological responses favor a proatherogenic and prothrombotic milieu that may contribute to the development and progression of atherosclerosis in the long-term and may increase myocardial oxygen demand and thus cause

Unplanned Hospital Readmissions After HeartMate II Implantation: Frequency, Risk Factors, and Impact on Resource Use and Survival

The purpose of this study was to identify potential areas for quality improvement and cost containment. We investigated readmissions after HeartMate II left ventricular assist device (LVAD) implantation by characterizing their type, temporal frequency, causative factors, and resource use and survival after readmission. The HeartMate II LVAD provides enhanced survival and quality of life to end-stage heart failure patients. Whether these improved outcomes are accompanied by a similar reduction in unplanned hospital readmissions is largely unknown. From October 2004 to January 2010, 118 patients received a HeartMate II, of whom 92 were discharged on device support. Subsequent readmissions were analyzed using prospectively maintained clinical and financial databases. Forty-eight patients (52%) had 177 unplanned hospital readmissions, 87 non-LVAD- and 90 LVAD-associated. Reasons for non-LVAD-associated readmissions included medical management of comorbidities and progression ofcardiac pathology (n= 48), neuropsychiatric/psychosocial issues (n= 22), and infections (n= 17). Those for LVAD-associated readmissions included device component infection (n= 51), management of nontherapeutic anticoagulation or device malfunction (n= 22), and bleeding (n= 15). Cumulative incidence of unplanned readmissions was higher (p< 0.0001) for destination therapy than bridge-to-transplant patients (9/patient vs. 4/patient at 24 months). Cumulative hospital days overall were 25 and 42 at 12 and 18 months, respectively, and the costs were 18% and 29% of initial implantation costs. Increased number of unplanned readmissions was predictive of mortality. Unplanned readmissions are common during HeartMate II support and negatively affect resource use and survival. Refining patient selection, especially in destination therapy patients, reducing infectious and bleeding complications, and increasing awareness about these devices might reduce unnecessary readmissions.