The Role for Cardiovascular Remodeling in Cardiovascular Outcomes.

PURPOSE OF REVIEW: Ischemic and non-ischemic injury to the heart causes deleterious changes in ventricular size, shape, and function. This adverse remodeling is mediated by neurohormonal and hemodynamic alterations and is reflected in non-invasive measures of left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV). These measures are closely linked to cardiovascular outcomes and have become key surrogate endpoints for evaluating the therapeutic efficacy of contemporary treatments for heart failure with reduced ejection fraction (HFrEF). In this review, we critically evaluate recent published data (2015-2016) from randomized clinical trials (RCTs) and observational studies of HFrEF therapies to assess the role of ventricular remodeling on outcomes. RECENT FINDINGS: These data highlight the benefits of certain guideline-directed medical therapies (GDMT) such as cardiac resynchronization therapy, surgical revascularization, and mechanical circulatory support on remodeling, while revealing the limitations of other therapies-routine mitral valve repair for patients with moderate ischemic mitral regurgitation and adjuncts to percutaneous coronary intervention in patients with ST elevation myocardial infarction (cyclosporine A and bioabsorbable cardiac matrix). The new angiotensin receptor blocker/neprilysn inhibitor, sacubitril/valsartan, demonstrates convincing improvements in clinical outcomes with a study of remodeling parameters to follow; the new cardiac myosin activator, omecamtiv mecarbil, demonstrates improvement in remodeling parameters without a clear early clinical benefit. The concepts and contemporary trials reviewed in this paper reinforce the value of non-invasive measures of ventricular remodeling (LVEF, LVESV, and LVEDV) as important metrics across a range of cardiovascular therapies. Global non-invasive measures of cardiovascular remodeling have roughly paralleled or preceded hard clinical outcomes. Additionally, the capacity for reverse remodeling in HFrEF with GDMT motivates continued research in the fields of implementation science, diagnostic imaging, and gene-based therapeutics.

Cardioprotective Effects of the 4-Week Aerobic Running Exercises Before Treatment with Doxorubicin in Rats.

Doxorubicin is associated with cardiotoxicity, and physical exercise seeks to minimize the toxic effects of doxorubicin through physiological cardiac remodeling, as well as the reduction of oxidative stress, evidenced by previous studies. This study aimed to analyze whether running training before treatment with doxorubicin influences tolerance to physical exertion and cardiotoxicity. Thirty-nine male Wistar rats, aged 90 days and weighing between 250 and 300 g, were divided into 4 groups: Control (C), Doxorubicin (D), Trained (T), and Trained + Doxorubicin (TD). Animals in groups T and DT were submitted to treadmill running for 3 weeks, 5 times a week at 18 m/min for 20-30 min before treatment with doxorubicin. Animals in groups D and DT received intraperitoneal injections of doxorubicin hydrochloride three times a week for two weeks, reaching a total cumulative dose of 7.50 mg/kg. Our results show an increase in total collagen fibers in the D group (p = 0.01), but no increase in the TD group, in addition to the attenuation of the number of cardiac mast cells in the animals in the TD group (p = 0.05). The animals in the TD group showed maintenance of tolerance to exertion compared to group D. Therefore, running training attenuated the cardiac damage caused by the treatment with doxorubicin, in addition to maintaining the tolerance to exertion in the rats.

Leucine Supplementation Improves Effort Tolerance of Rats With Hyperthyroidism.

Leucine is a regulator of protein metabolism in vivo and information on its action on effort tolerance of both animals and humans with hyperthyroidism is scarce. The objective of the present study was to verify the influence of leucine supplementation on the effort tolerance of Wistar rats with experimental hyperthyroidism. 40 animals were divided into four groups of ten: control (C), hormone (H), leucine (L), and hormone + leucine (HL). Hyperthyroidism was induced by daily administration of 20 µâ‹…g100 g-1 of levothyroxine sodium in aqueous suspension by gavage. Leucine was supplemented by adding 5% of the amino acid to the conventional feed. The animals' blood was collected by cardiac puncture to analyze TSH, T4, and T3 levels. The effort tolerance was determined by the swimming test with a 7% load attached to animals' tails. Statistical analysis was performed using the Shapiro-Wilk normality test, followed by the analysis of variance (ANOVA) of repeated measures of two factors (treatment × time) and Tukey post hoc, with a significance level of p < 0.05. Administering thyroid hormone increased the swimming performance of rats after 14 and 21 days, but with a drop in performance at 28 days. The HL group, on the other hand, had a significantly higher swimming performance compared to the other groups after 28 days of treatment. Leucine supplementation associated with the experimental model of hyperthyroidism improved the performance of rats in a swimming test after 28 days of treatment.

Epicardial adipose tissue and carotid artery disease: Protocol for systematic review and meta-analysis.

BACKGROUND: Atherosclerosis is now widely recognized as a multifactorial disease with outcomes that arise from complex factors such as plaque components, blood flow, and inflammation. Epicardial adipose tissue (EAT) is a metabolically active fat depot, abundant in proinflammatory cytokines, and has been correlated with the extent and severity of carotid artery disease (CD). The locations most frequently affected by carotid atherosclerosis are the proximal internal carotid artery (ie, the origin) and the common carotid artery bifurcation. Progression of atheromatous plaque at the carotid bifurcation results in luminal narrowing, often accompanied by ulceration. However, there are no systematic analyses or well-conducted meta-analyses to evaluate the relationship between EAT and CD. The aim of this study is to examine this association of EAT with CD in different ages and sex. METHODS: This systematic review and meta-analysis will be conducted using published studies that will be identified from electronic databases (ie, PubMed, EMBASE, Web of Science, and Google Scholar. Studies that (1) examined the association between EAT and CD, (2) focus on cohort, case-control and cross-sectional studies, (3) will conducted among in adults aged 40 to 70 years, (4) provided sufficient data for calculating ORs or relative risk with a 95% CI, (5) will published as original articles written in English or other languages, and (6) have been published until January 2018 will be included. Study selection, data collection, quality assessment and statistical syntheses will be conducted based on discussions among investigators. RESULTS: We propose the current protocol to evaluate the evaluation of EAT with ED. CONCLUSION: This systematic review will not need ethical approval, because it does not involve human beings. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal. ETHICS AND DISSEMINATION: Ethics approval was not required for this study because it was based on published studies. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal. TRIAL REGISTRATION NUMBER: PROSPERO (CRD42018083458).