Natriuretic peptides in acute coronary syndromes: A new role to predict recurrent ischemic event-related mortality?

Risk stratification in acute coronary syndromes (ACS) has been previously based on the severity of acute clinical presentation, presence of cardiovascular comorbidities, and abnormalities of ischemia-specific biomarkers, most importantly troponins. Natriuretic peptides (NPs), which become elevated upon increased myocardial wall stress, are established diagnostic and prognostic biomarkers in patients with heart failure. Recently, their prognostic potential in ACS has been reported, specifically as predictors of future new-onset heart failure or left ventricular (LV) systolic dysfunction. In the current issue of the Hellenic Journal of Cardiology, a new role of NPs is suggested in ACS as predictors of long-term mortality associated with recurrent cardiac ischemic events, specifically in patients with preserved or mid-range LV ejection fraction upon index ACS. Potential pathophysiological mechanisms that explain the association between augmented NP levels with recurrent myocardial ischemia are hypothesized including the potential of NPs to reflect augmented local and/or systemic inflammation, prothrombotic state, and vascular dysregulation. © 2018 Hellenic Society of Cardiolog

Practical considerations on the introduction of sacubitril/valsartan in clinical practice: Current evidence and early experience

The combination of neprilysin inhibitor sacubitril with the angiotensin II receptor 1 blocker valsartan is the first agent from the angiotensin receptor neprilysin inhibitors (ARNI) class authorized for clinical use in heart failure (HF) patients with reduced ejection fraction (HFrEF). Sacubitril/valsartan resulted in 20% reduction in the incidence rate of death or HF hospitalization compared to enalapril in symptomatic HFrEF patients in the seminal PARADIGM-HF trial. As a result, the recently updated European and American HF guidelines granted this agent a class IB indication for the treatment of ambulatory/chronic symptomatic HFrEF patients. However, translating the positive results of trials into true clinical benefit is often challenging. This is particularly true in the case of sacubitril/valsartan, as HF is a heterogeneous syndrome including many severely ill patients who are prone to decompensation, while this new agent comes to replace a cornerstone of current evidence-based HF therapy. In the present paper, we address a number of practical issues regarding the introduction of sacubitril/valsartan and propose an algorithm based on available evidence and early clinical experience. © 2016 Elsevier Ireland Lt

Inotropic agents in cardiogenic shock

PURPOSE OF REVIEW: Cardiogenic shock is a multifactorial and diverse entity in which inotropes are the cornerstone therapy. Although published clinical trials have focused on pharmacologic treatment of cardiogenic shock, there is lack of an established and widely accepted decision-making algorithm on the use of inotropic agents in cardiogenic shock. RECENT FINDINGS: The current review incorporates cardiogenic shock pathophysiology, inotropes and vasopressors pharmacodynamics. It emphasizes on each agent's indications, potential adverse effects, highlights special considerations and fsummarizes the recent guidelines. SUMMARY: Finally, proposes an algorithm of inotropes and vasopressors use and their potential combinations based on the clinical stage of cardiogenic shock. This algorithm can be used as a guide during the initial management of cardiogenic shock while underlying cause investigation is underway

Novel biologic mechanisms of levosimendan and its effect on the failing heart

Background: Calcium sensitizers belong to a new class of cardiac enhancers that stimulate cardiac contractility without causing intracellular calcium overload or increasing myocardial oxygen demand. Levosimendan, the most well-studied calcium sensitizer in the real clinical practice, produces greater hemodynamic and symptomatic improvement in patients with acute heart failure than traditional inotropes. Objective: To review the recent experimental and clinical evidence on novel biologic mechanisms explaining the pleiotropic effects of levosimendan on the falling heart. Methods: A systematic search of peer-reviewed publications was performed on Medline and EMBASE from January 1995 to December 2007. The results of unpublished trials were obtained from presentations at national and international meetings. Results: Levosimendan has a unique dual mechanism of action by enhancing cardiac contractility and causing peripheral vasodilatation. Immunomodulatory and antiapoptotic properties of levosimendan may be an additional biologic mechanism that prevents further cytotoxic and hemodynamic consequences of abnormal immune and neurohormonal respones in acute heart failure, leads to cardioprotection and beneficially intervenes in the progression of syndrome. Experimental data show that levosimendan exerts its cardioprotective effects through its antioxidant properties and seems to be a potent inhibitor of H2O2-induced cardiomyocyte apoptotic cell death. Clinical data demonstrate that levosimendan does not increase markers of oxidative and nitrosative stress, in contrast to placebo treatment, in advanced chronic heart failure patients. Levosimendan has also been shown to activate mitoKATP channels which are important mediators of ischemic preconditioning. Pharmacological modulation of KATP channels may prove beneficial in patients at risk of myocardial ischemia, particularly those requiring inotropic support. Conclusion: Pleiotropic effects of levosimendan appear to have important clinical and prognostic implications in acute heart failure syndromes and ischemic heart disease. © 2008 Informa UK Ltd

Cognitive impairment in heart failure: clinical implications, tools of assessment, and therapeutic considerations

Cognitive impairment (CI) is an important comorbidity in patients with heart failure (HF). Its prevalence parallels the severity of heart failure, while it is an independent prognostic marker of adverse events. Various factors contribute to cognitive decline in HF, influencing self-care. There are no standardized screening methods for the diagnosis and management of these patients. The aim of the present manuscript is to provide an overview of the impact of cognitive impairment in HF, describe the utility of assessment tools and imaging methods for the evaluation of CI, and propose a comprehensive diagnostic and management approach. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature

Possible mechanisms of direct cardiovascular impact of GLP-1 agonists and DPP4 inhibitors

Diabetes mellitus is a leading cause of cardiovascular morbidity and mortality worldwide. Traditional antidiabetic therapies targeting hyperglycemia reduce diabetic microvascular complications but have minor effects on macrovascular complications, including cardiovascular disease. Instead, cardiovascular complications are improved by antidiabetic medications (metformin) and other therapies (statins, antihypertensive medications) ameliorating insulin resistance and other associated metabolic abnormalities. Novel classes of antidiabetic drugs have proven efficacious in improving glycemia, while at the same time exert beneficial effects on pathophysiologic mechanisms of diabetes-related cardiovascular disease. In the present review, we will present current evidence of the cardiovascular effects of two new classes of antidiabetic medications, glucagon-like peptide 1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP4) inhibitors, focusing from mechanistic preclinical and clinical investigation to late-phase clinical testing. © 2018, Springer Science+Business Media, LLC, part of Springer Nature

Prognostic significance of p53, bax and bcl-2 gene expression in patients with laryngeal carcinoma

Aim: This study was designed to examine the prognostic significance of the coexpression of three genes (bax, bcl-2 and p53) which play a critical role in the apoptotic mechanisms in patients with squamous cell laryngeal carcinoma.(1-3) Materials and Methods: The immunohistochemical expression of bcl-2, bax and p53 genes was retrospectively examined in 38 patients with squarrous cell laryngeal carcinoma and in five controls (necrotomic tissue). Tissue specimens were obtained both during the diagnostic biopsy and at the time of surgery. Clinicopathological and survival data were correlated with the staining results. Results: Bcl-2 protein expression (P=0.0472), stage (P=0.0087) and lymph-node involvement (P=0.0488) were found to be independent prognostic factors. Increased bcl-2 protein expression correlated with a better 5-year survival (P=0.0472). Patients who were bcl-2(-)/p53(-) (n=25) or bax(+)/bcl-2(-) (n = 13) had a significantly worse overall survival (P=0.0305 andP=0.0482, respectively). Similarly, patients who were bax(+)/bcl-2(-)/p53(-) (n = 11) also had a worse 5-year survival compared with the rest of the group (P=0.0088). Changes that were noticed in bax and p53 protein expression from the time of biopsy until the time of surgery did not correlate with a significant increase in the overall survival. Conclusions: The expression of bcl-2 gene appears to be an independent prognostic factor for patients with laryngeal carcinoma. The coexpression of the genes studied can be used to determine aggressive clinical phenotypes. (C) 2001 Harcourt Publishers Ltd