Current Medicinal Chemistry - Volume 26, Issue 5, 2019

Background: Myocardial redox state is a critical determinant of atrial biology, regulating cardiomyocyte apoptosis, ion channel function, and cardiac hypertrophy/fibrosis and function. Nevertheless, it remains unclear whether the targeting of atrial redox state is a rational therapeutic strategy for atrial fibrillation prevention. Objective: To review the role of atrial redox state and anti-oxidant therapies in atrial fibrillation. Method: Published literature in Medline was searched for experimental and clinical evidence linking myocardial redox state with atrial fibrillation pathogenesis as well as studies looking into the role of redoxtargeting therapies in the prevention of atrial fibrillation. Results: Data from animal models have shown that altered myocardial nitroso-redox balance and NADPH oxidases activity are causally involved in the pathogenesis of atrial fibrillation. Similarly experimental animal data supports that increased reactive oxygen / nitrogen species formation in the atrial tissue is associated with altered electrophysiological properties of atrial myocytes and electrical remodeling, favoring atrial fibrillation development. In humans, randomized clinical studies using redox-related therapeutic approaches (e.g. statins or antioxidant agents) have not documented any benefits in the prevention of atrial fibrillation development (mainly post-operative atrial fibrillation risk). Conclusion: Despite strong experimental and translational data supporting the role of atrial redox state in atrial fibrillation pathogenesis, such mechanistic evidence has not been translated to clinical benefits in atrial fibrillation risk in randomized clinical studies using redox-related therapies.

Atrial fibrillation is the most common rhythm disturbance encountered in clinical practice. Although often considered as solely arrhythmic in nature, current evidence has established that atrial myopathy constitutes both the substrate and the outcome of atrial fibrillation, thus initiating a vicious, self-perpetuating cycle. This myopathy is triggered by stress-induced (including pressure/volume overload, inflammation, oxidative stress) responses of atrial tissue, which in the long term become maladaptive, and combine elements of both structural, especially fibrosis, and electrical remodeling, with contemporary approaches yielding potentially useful biomarkers of these processes. Biomarker value becomes greater given the fact that they can both predict atrial fibrillation occurrence and treatment outcome. This mini-review will focus on the biomarkers of atrial remodeling (both electrical and structural) and fibrosis that have been validated in human studies, including biochemical, histological and imaging approaches.

Background: Atrial fibrillation (AF) is associated with an increased risk of cardioembolic stroke. The risk of cardioembolism is not adequately reduced with the administration of oral anticoagulants, since a number of patients continue to experience thromboembolic events despite receiving treatment. Therefore, identification of a circulating biomarker to identify these high-risk patients would be clinically beneficial. Objective: In the present article, we aim to review the available data regarding use of biomarkers to predict cardioembolic stroke in patients with AF. Methods: We performed a thorough search of the literature in order to analyze the biomarkers identified thus far and critically evaluate their clinical significance. Results: A number of biomarkers have been proposed to predict cardioembolic stroke in patients with AF. Some of them are already used in the clinical practice, such as d-dimers, troponins and brain natriuretic peptide. Novel biomarkers, such as the inflammatory growth differentiation factor-15, appear to be promising, while the role of micro-RNAs and genetics appear to be useful as well. Even though these biomarkers are associated with an increased risk for thromboembolism, they cannot accurately predict future events. In light of this, the use of a scoring system, that would incorporate both circulating biomarkers and clinical factors, might be more useful. Conclusions: Recent research has disclosed several biomarkers as potential predictors of cardioembolic stroke in patients with AF. However, further research is required to establish a multifactorial scoring system that will identify patients at high-risk of thromboembolism, who would benefit from more intensive treatment and monitoring.

Background: Prevention of thromboembolic disease, mainly stroke, with oral anticoagulants remains a major therapeutic goal in patients with atrial fibrillation. Unfortunately, despite the high efficacy, anticoagulant therapy is associated with a significant risk of, frequently catastrophic, and hemorrhagic complications. Among different clinical and laboratory parameters related to an increased risk of bleeding, several biological markers have been recognized and various risk scores for bleeding have been developed. Objectives/Methods: The aim of the present study is to review current evidence regarding the different biomarkers associated with raised bleeding risk in atrial fibrillation. Results: Data originating from large cohorts or the recent large-scale trials of atrial fibrillation have linked numerous individual biomarkers to an increased bleeding risk. Such a relation was revealed for markers of cardiac physiology, such as troponin, BNP and NT-proBNP, markers of renal function, such as GFR and Cystatin or hepatic function, markers involving the system of coagulation, such as D-dimer and Von Willebrand factor, hematologic markers, such as low haemoglobin or low platelets, inflammatory markers, such as interleukin-6, other factors such as GDF-15 and vitamin-E and finally genetic polymorphisms. Many such biomarkers are incorporated in the bleeding risk schemata developed for the prediction of the hemorrhagic risk. Conclusions: Biomarkers were introduced in clinical practice in order to better estimate the potential risk of haemorrhage in these patients and increase the prognostic impact of clinical risk scores. In the last years this concept is gaining significant importance.

During the last few years, a significant number of studies have attempted to clarify the underlying mechanisms that lead to the presentation of atrial fibrillation (AF). Inflammation is a key component of the pathophysiological processes that lead to the development of AF; the amplification of inflammatory pathways triggers AF, and, in tandem, AF increases the inflammatory state. Indeed, the plasma levels of several inflammatory biomarkers are elevated in patients with AF. In addition, the levels of specific inflammatory biomarkers may provide information regarding to the AF duration. Several small studies have assessed the role of anti-inflammatory treatment in atrial fibrillation but the results have been contradictory. Large-scale studies are needed to evaluate the role of inflammation in AF and whether anti-inflammatory medications should be routinely administered to patients with AF.

MicroRNAs (miRNAs) are small non-coding RNAs, involved in regulation of post-transcriptional gene expression. They exert key role not only in physiology and normal development of the cardiovascular system but also in cardiovascular disease development and progression. Recent animal and human studies of tissue specific miRNAs have suggested a role in structural and electrical remodeling in atrial fibrillation (AF). Their emerging role as biomarkers and potential therapeutic targets in patients with AF is discussed in this review.

Aortic valve stenosis is one of the most common valvular heart disorders and the prevalence will rise as the population ages. Once symptomatic patients with aortic valve stenosis tend to fare worse with high mortality rates. Aortic valve replacement is indicated in these patients and besides the standard surgical replacement, a less invasive approach, transcatheter aortic valve implantation, has gained momentum and has showed promising and solid results in patients with high surgical risk. An important aspect of evaluating patients with aortic valve stenosis is the ability to choose the best possible candidate for the procedure. In addition, predicting the short and long-term clinical outcomes after the valve replacement could offer the treating physicians a better insight and provide information for optimal therapy. Biomarkers are biological parameters that can be objectively measured and evaluated as indicators of normal biological processes and are easily monitored. The aim of this review is to critically assess some of the most widely used biomarkers at present (natriuretic peptides, troponins, C-reactive protein) and provide an insight in novel biomarkers that are currently being investigated (galectin-3, growth differentiation factor-15, microRNAs) for possible diagnostic and prognostic use in aortic valve stenosis and transcatheter aortic valve implantation respectively.

Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice and an important contributor to cardiovascular morbidity and mortality. Although the exact mechanisms behind AF are not completely elucidated, the underlying pathophysiological changes have been well described. Predisposal factors for AF include the older age, the increased left atrial size, the decreased left atrial function, the presence of heart failure and left ventricular systolic dysfunction and the presence of coronary heart disease or pulmonary or mitral valve disease. In addition to these factors, emerging evidence demonstrate that myocardial strain, fibrosis and inflammation, are associated with AF as well as the pathogenesis of the arrhythmia. The natruretic peptide system including Atrial Natriuretic Peptide (ANP), Brain Natriuretic Peptide (BNP) and C-type Natriuretic Peptide (CNP) is indicative of the level of myocardial strain which may predispose to AF. As a result, the aforementioned peptides are increased in AF patients. The levels of myocardial fibrosis biomarkers, such as ST2 and Galectin-3, are elevated suggesting atrial structural abnormalities, while the increased levels of CRP and Interleukin-6 supplement the inflammatory profile of AF patients. Emerging data for the aforementioned biomarkers are discussed in the present review.

Background: Atrial fibrillation (AF) is the most frequently encountered cardiac arrhythmia globally and substantially increases the risk for thromboembolic disease. Albeit, 20% of all cases of AF remain undiagnosed. On the other hand, hypertension amplifies the risk for both AF occurrences through hemodynamic and non-hemodynamic mechanisms and cerebrovascular ischemia. Under this prism, prompt diagnosis of undetected AF in hypertensive patients is of pivotal importance. Method: We conducted a review of the literature for studies with biomarkers that could be used in AF diagnosis as well as in predicting the transition of paroxysmal AF to sustained AF, especially in hypertensive patients. Results: Potential biomarkers for AF can be broadly categorized into electrophysiological, morphological and molecular markers that reflect the underlying mechanisms of adverse atrial remodeling. We focused on P-wave duration and dispersion as electrophysiological markers, and left atrial (LA) and LA appendage size, atrial fibrosis, left ventricular hypertrophy and aortic stiffness as structural biomarkers, respectively. The heterogeneous group of molecular biomarkers of AF encompasses products of the neurohormonal cascade, including NT-pro BNP, BNP, MR-pro ANP, polymorphisms of the ACE and convertases such as corin and furin. In addition, soluble biomarkers of inflammation (i.e. CRP, IL-6) and fibrosis (i.e. TGF-1 and matrix metalloproteinases) were assessed for predicting AF. Conclusion: The reviewed individual biomarkers might be a valuable addition to current diagnostic tools but the ideal candidate is expected to combine multiple indices of atrial remodeling in order to effectively detect both AF and adverse characteristics of high risk patients with hypertension.

Whether the increased atrial fibrillation (AF) risk in metabolic syndrome (MetS) patients is due to the syndrome as a whole or simply the sum of the risks of its individual component parts is still obscure. These two clinical entities share many pathophysiological links and thus distinction between a casual observation and a significant association is difficult. Biomarkers associated with pathogenesis of AF in the context of MetS have the ability to refine future risk prediction. In the present review we identify circulating substances that could be regarded as potential biomarkers for prediction of incident AF, or of cardiovascular events in the setting of AF in patients with MetS. Cardiac myocyte injury and stress markers (troponin and natriuretic peptides), markers of renal function (glomeral filtration rate, cystatin-C), and inflammation markers/mediators (interleukin- 6, CRP) are promising biomarkers of patients with AF and MetS.

Atrial fibrillation (AF) is a common cardiac arrhythmia known to incite increased thromboembolic and mortality risks, especially among patients not under anticoagulant therapy when indicated. Several routine scores exist to help stratify AF patients, such as the CHAD2DS2-VASc score and upon which physicians are based to decide whether to administer anticoagulant therapy. Being that anticoagulant regimen is a double- edged situation with both benefits and risks, decision-making process demands a definite and reliable, evidence-based set of data to rely on. Blood-based biological elements known as biomarkers are measurable indices that can provide crucial insights concerning not only underlying disease mechanisms but also prognostic and risk stratifying information. As AF is constituted by an overwhelming range of pathophysiological aspects such as inflammation, fibrosis, hypercoagulable states and myocardial damage, identifying and assessing relevant biomarkers will evidently support the clinician’s prognostication efforts. The current reviewpresents studied biomarkers with proven prognostic potential in AF as well as possible enhancement of risk-scores when incorporated to them.

Background: New onset of atrial fibrillation (AF) after cardiovascular surgery is associated with increased risk of complications and length of hospital stay. Identification of patients at high risk of post-operative AF (POAF) may help to act with preventive strategies having clinical and economic relevance. Objective: The focus of this review is to summarize findings on biomarkers of myocardial fibrosis (PICP and PIIINP), profibrotic mediators (TGF-beta1), extracellular matrix remodeling (MMP-9), myocardial stretch (BNP and NTpro-BNP), inflammation (interleukins, C-reactive protein and sCD40L), and myocardial necrosis (high-sensitivity troponin T), biomarkers, that can be used in clinical practice to stratify patients at risk for POAF. Method: We searched English-language studies on MEDLINE and PubMed. Evidence synthesis was based on cohort studies, clinical trials and meta-analysis data. International clinical practice guidelines were reviewed, as well. Results: Factors such as cardiac remodelling, atrial pressure, surgery trauma, inflammation, oxidative stress, and sympathetic/parasympathetic activation have been implicated in the development of POAF. On the basis of multifactorial mechanism underlying the onset of POAF, several studies have investigated the predictive value of some serum biomarkers. To date, there are promising preliminary data on the clinical utility of PICP, PIINP, TGF-β1 and sCD40L, whereas data on NT-proBNP, BNP, CRP, IL- 6, and hs-cTnT are controversial. Conclusion: Although some studies have shown promising results, there is a need for future larger studies with longer follow-up, before applying biomarkers as tools for POAF risk-stratification into clinical practice.

Catheter ablation for rhythm control is recommended in specific patient populations with paroxysmal, persistent, or long-standing persistent atrial fibrillation. Pulmonary vein isolation is the cornerstone of the ablative therapy for atrial fibrillation. However, relapse is still common since the single procedure efficacy of atrial fibrillation ablation was estimated to be 60-80% in paroxysmal and 50-70% in persistent atrial fibrillation. It is important to identify predictors of successful atrial fibrillation patients ablation. In the present review, we will assess the role of available biomarkers to predict responders of an initial atrial fibrillation catheter ablation. Emphasis has been given on the role of myocardial injury biomarkers, natriuretic peptides and traditional inflammatory markers. Novel inflammatory markers, oxidative stress biomarkers and microRNAs have also been examined as predictors of a successful atrial fibrillation procedure. Notably, the impact of procedural and short-term administration of steroids, as well as the role of colchicine on preventing atrial fibrillation recurrence after ablation is thoroughly presented.