Contemporary management of heart failure patients with reduced ejection fraction: the role of implantable devices and catheter ablation

Heart failure (HF) is a complex clinical syndrome characterised by significant morbidity and mortality worldwide. Evidence-based therapies for the management of HF include several well-established neurohormonal antagonists and antiarrhythmic drug therapy to mitigate the onset of cardiac arrhythmia. However, the degree of rate and rhythm control achieved is often suboptimal and mortality rates continue to remain high. Implantable cardioverter-defibrillators (ICDs), cardiac resynchronization (CRT), and combined (CRT-D) therapies have emerged as integral and rapidly expanding technologies in the management of select patients with heart failure with reduced ejection fraction (HFrEF). ICDs treat ventricular arrhythmia and are used as primary prophylaxis for sudden cardiac death, while CRT resynchronizes ventricular contraction to improve left ventricular systolic function. Left ventricular assist device therapy has also been shown to provide clinically meaningful survival benefits in patients with advanced HF, and His-bundle pacing has more recently emerged as a safe, viable, and promising pacing modality for patients with CRT indication. Catheter ablation is another important and well-established strategy for managing cardiac arrhythmia in HF, demonstrating superior efficacy when compared with antiarrhythmic drug therapy alone. In this article, we provide a comprehensive and in-depth evaluation of the role of implantable devices and catheter ablation in patients with HFrEF, outlining current applications, recent advances, and future directions in practice

The prognostic role of galectin-3 and endothelial function in patients with heart failure

Background: Heart failure (HF) is nowadays classified as HF with reduced ejection fraction (HFrEF), HF with mildly reduced EF (HFmrEF), and HF with preserved EF (HFpEF). Endothelial dysfunction (assessed by flow-mediated dilatation [FMD]), increased arterial stiffness (assessed by carotid-femoral pulse-wave velocity [PWV]), and galectin-3, a biomarker of myocardial fibrosis, have been linked to major adverse cardiovascular events (MACE) in patients with ischemic HF. Methods: In this study we prospectively enrolled 340 patients with stable ischemic HF. We assessed the brachial artery FMD, carotid-femoral PWV, and galectin-3 levels, and patients were followed up for MACE according to EF group. Results: Interestingly, the FMD values exhibited a stepwise improvement according to left ventricular ejection fraction (LVEF) (HFrEF: 4.74 ± 2.35% vs. HFmrEF: 4.97 ± 2.81% vs. HFpEF: 5.94 ± 3.46%, p = 0.01), which remained significant after the evaluation of possible confounders including age, sex, cardiovascular risk factors, and number of significantly stenosed epicardial coronary arteries (b coefficient: 0.990, 95% confidence interval: 0.166–1.814, p = 0.019). Single-vessel coronary artery disease (CAD) was more frequent in the group of HFpEF (HFrEF: 56% vs. HFmrEF: 64% vs. HFpEF: 73%, p = 0.049). PWV did not display any association with LVEF. Patients who presented MACE exhibited worse FMD values (4.51 ± 2.35% vs. 5.32 ± 2.67%, p = 0.02), and the highest tertile of galectin-3 was linked to more MACEs (36% vs. 5.9%, p = 0.01). Conclusions: Flow-mediated dilatation displayed a linear improvement with LVEF in patients with ischemic HF. Deteriorated values are associated with MACE. Higher levels of galectin-3 might be used for risk stratification of patients with ischemic HF

Olive Oil-related Anti-inflammatory Effects on Atherosclerosis: Potential Clinical Implications

Background and Objective: Atherosclerosis is characterized by a chronic low-grade inflammatory process which can result in atherothrombosis and a number of cardiovascular diseases (CVD). It is believed to be caused by multiple processes that involve inflammation and immunity. Mediterranean Diet (MedD) has been discovered to possess anti-inflammatory properties and associated with a reduction in the CVD risk and mortality. Its main component, extra-virgin olive oil (EVOO), is believed to be largely responsible for these effects and therefore, has been investigated in various studies. The present review article aims to summarize the available literature on the anti-inflammatory and cardio-protective effects of EVOO. Methods: A search based on the key concepts “olive oil”, “atherosclerosis”, “inflammation” and “cardiovascular disease” was performed to retrieve relevant studies and articles on the association between the consumption of EVOO and the levels of inflammatory biomarkers as well as CVD incidence and mortality from online databases; Pubmed, Embase and Cochrane Library. Results: Consumption of EVOO is associated with a reduction in inflammatory biomarkers and molecules implicated in atherosclerosis as well as CVD incidence and mortality as well as other complications such as heart failure and atrial fibrillation. Moreover, these anti-inflammatory and cardioprotective effects of EVOO are mostly attributable to its high content of polyphenol molecules. Conclusion: Currently available evidence supports the anti-inflammatory and cardio-protective roles of EVOO. However, there is limited amount of available randomized controlled trials especially lacking those investigating the use of EVOO as secondary prevention, heterogeneity of study design, limited generalization to wide population groups, and inability to determine the minimum intake of EVOO required to clinically achieve the anti-inflammatory and cardioprotective effects. Therefore, more high-quality randomized controlled trials still need to be carried out to overcome these challenges to further assess the health benefits of EVOO consumption and potentially translate it into clinical practice as primary or secondary prevention of atherosclerosis-related conditions

The Role of Matrix Metalloproteinases in Essential Hypertension

The matrix metalloproteinases/tissue inhibitors of metalloproteinases system is involved in the regulation of extracellular matrix metabolism, which plays a crucial role with regards to maintenance of tissue integrity. During the occurrence of vascular pathologies including hypertension, the balance between proteases and their inhibitors is temporally destroyed. Even though there are conflicting data in the literature regarding the expression pattern of the vascular matrix metalloproteinase system, the occurring extracellular matrix turnover leads to the change of arterial mechanical properties. For example, hypertension plays crucial role in the formation of cardiovascular remodeling which seems to be characterized by an increase in extracellular matrix. Changes in arterial stiffness, a predictor for cardiovascular morbidity and mortality, are determined by alterations in vascular extracellular matrix due to hemodynamic, genetic, or other factors. It has become increasingly evident that blockade of the renin-angiotensin-aldosterone system and other pharmacological strategies, seem to be particularly effective in reducing vascular stiffness and collagen content in human and animal models. However, the relationship between extracellular matrix metabolism and the effects of therapy in hypertensive patients needs to be further explored in larger trials over a longer period of time

Genetic testing and antiplatelet treatment: Still way to go?

Despite medical and technical advancements stent thrombosis continued to poses a significant risk in patients after drug eluting stent (DES) implantation and clopidogrel resistance has been recognized as an important determinant of this risk. Novel antiplatelets such as prasugrel and ticagrelor can be used in cases of clopidogrel resistance however bleeding complications remain the Achilles’ heel of antiplatelet therapy. Several genetic polymorphisms affect the clopidogrel absorption and bio-activation in the active form of the drug. CYP2C19 is responsible for most of the clopidogrel bio-transformation and loss of function as well as, gain of function polymorphisms of this enzyme has been recognized. Early studies have linked CYP2C19 genetic polymorphisms with clinical events, although, these findings were not confirmed by later studies. However, when the estimated thrombotic risk is high a combination of genetic information and functional platelet tests should be essential for clinicians to access clopidogrel effectiveness and to recommend alternative antiplatelet management. (C) 2015 Elsevier Ireland Ltd. All rights reserved

From Atherosclerosis to Acute Coronary Syndromes: The Role of Soluble CD40 Ligand

The binding of CD40 ligand (CD40L) to CD40 stimulates inflammatory processes including the release of proinflammatory cytokines and the expression of adhesion molecules implying a role in atherosclerosis. Patients exhibiting hypercholesterolemia, unstable angina, or acute myocardial infarction present with increased CD40L levels. Novel data suggest that elevated soluble CD40L levels not only represent a risk factor for cardiovascular disease but also predict future adverse events, especially in patients with acute coronary syndromes (ACS). Examination of the potential role of the genetic variability on CD40/CD40L genes in ACS, as regards the regulation of CD40L, appears to be of great interest. Moreover, several therapeutic approaches such as statins, antihypertensive agents, and antiplatelet agents have been suggested as potential modulators of CD40L levels anticipating a positive impact on the outcomes of patients with ACS. Whether specific agents target the CD40/CD40L system as well as its pathogenic role in ACS remains to be elucidated by large-scale studies in the future. (Trends Cardiovasc Med 2010;20:153-164) (C) 2010, Elsevier Inc. All rights reserved