Cardiac fibrosis in patients with atrial fibrillation: Mechanisms and clinical implications

atrial fibrillation, heart failure, cardiac fibrosisAtrial fibrillation (AF) is associated with structural, electrical and contractile remodeling of the atria. Development and progression of atrial fibrosis is the hallmark of structural remodeling in AF and is considered to be substrate for AF perpetuation. In contrast, experimental and clinical data on impact of ventricular fibrotic processes in pathogenesis of AF and its complications are controversial. Ventricular fibrosis appears to contribute to abnormalities in cardiac relaxation and contractility, and development of heart failure, a common finding in AF. Given the frequent coexistence of AF and heart failure and the fact that both conditions affect patient prognosis better understanding of mutual impact of fibrosis in AF and heart failure is of particular interest. In this review article, we provide an overview on the general mechanisms of cardiac fibrosis in AF, differences between fibrotic processes in atria and ventricles, and the clinical and prognostic significance of cardiac fibrosis in AF

Cardiac fibrosis in patients with atrial fibrillation: Mechanisms and clinical implications

atrial fibrillation, heart failure, cardiac fibrosisAtrial fibrillation (AF) is associated with structural, electrical and contractile remodeling of the atria. Development and progression of atrial fibrosis is the hallmark of structural remodeling in AF and is considered to be substrate for AF perpetuation. In contrast, experimental and clinical data on impact of ventricular fibrotic processes in pathogenesis of AF and its complications are controversial. Ventricular fibrosis appears to contribute to abnormalities in cardiac relaxation and contractility, and development of heart failure, a common finding in AF. Given the frequent coexistence of AF and heart failure and the fact that both conditions affect patient prognosis better understanding of mutual impact of fibrosis in AF and heart failure is of particular interest. In this review article, we provide an overview on the general mechanisms of cardiac fibrosis in AF, differences between fibrotic processes in atria and ventricles, and the clinical and prognostic significance of cardiac fibrosis in AF

Ventricular-arterial coupling in obstructive sleep apnea

Arterial elastance (Ea) and systolic elastance are important parameters determining effective functional interaction of heart and vessels. The aims of this study were to (1) compare arterial (arterial elastance index [EaI]) and ventricular (end-systolic elastance [Ees] and end-diastolic elastance [Eed]) elastance in subjects with obstructive sleep apnea (OSA) and patients with treated ‘high-risk’ hypertension (HHT) and (2) test whether these parameters in OSA patients can be improved by continuous positive airway pressure (CPAP) therapy. Echocardiographic parameters of cardiac and vascular stiffness (EaI, Ees, and Eed) were quantified in 28 patients with OSA (mean [standard deviation], age 51 [11] years; 79% male) and 28 treated subjects with HHT (mean [standard deviation], age 48 [12] years; 61% male). Twenty-three OSA patients were treated with CPAP for median of 26 weeks. Ea was calculated from stroke volume and systolic BP and adjusted by body area (EaI). Both study groups had preserved and comparable left ventricle contractility. There was no significant differences in EaI (P = .94), Ees (P = .5), Eed (P = .63), and arterial-ventricular interaction (P = .62) between OSA and HHT groups. After CPAP therapy, there was a significant reduction in EaI (paired t test, P = .013) and arterial-ventricular interaction (paired t test, P = .004). Ees (P = .17) and Eed (P = .66) parameters did not change significantly. OSA and HHT patients have similar parameters of elastance and ventricular-arterial coupling. CPAP treatment in OSA patients significantly improved ventricular-arterial coupling

Myocardial Strain Imaging in Resistant Hypertension.

PURPOSE OF REVIEW: Resistant hypertension (RH) is a major contributor to cardiovascular diseases and is associated with increased all-cause and cardiovascular mortality. Cardiac changes such as impaired left ventricular (LV) function, left ventricular hypertrophy (LVH), myocardial fibrosis, and enlarged left atrium (LA) are consequences of chronic exposure to an elevated blood pressure. The purpose of this review article is to demonstrate the potential benefits of using STE as a non-invasive imaging technique in the assessment of cardiac remodeling in patients with hypertension and specifically in uncontrolled and RH population. RECENT FINDINGS: It is well-recognized that conventional transthoracic echocardiography is a useful analytic imaging modality to evaluate hypertension-mediated organ damage (HMOD) and in a resistant hypertensive population. More recently two-dimensional speckle tracking echocardiography (STE) has been utilized to provide further risk assessment to this population. Recent data has shown that STE is a new promising echocardiographic marker to evaluate early stage LV dysfunction and myocardial fibrosis over conventional 2D parameters in patients with cardiovascular diseases

Prognostic implication of monocytes in atrial fibrillation: The West Birmingham Atrial Fibrillation Project

BACKGROUND AND OBJECTIVES:High monocyte counts are related to adverse outcomes in cardiovascular disease. Their role in prognostication in patients with atrial fibrillation (AF) is unknown. We investigated whether monocyte counts are useful as a marker of prognosis in patients with AF. METHODS:Monocyte counts were obtained from blood samples in 881 AF patients. Study outcomes were (i) all-cause death; (ii) major adverse cardiovascular events; (iii) stroke, TIA or other systemic embolism (SSE); and (iv) major bleeding. RESULTS:Median follow up was 7.2 years; 44% of patients died, 48% developed MACE; 9% had SSE and 5% had major bleeding. On Cox regression, after adjustment for CHA2DS2-VASc score, the highest quartile of monocyte counts (i.e., ≥580 μL vs. other quartiles) was associated with increased risk of death (hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.31-2.05, p<0.001) and MACE (HR 1.58, 95% CI 1.28-1.96, p<0.001). Persistent monocyte levels ≥580 per μL during follow up were associated with further increase in risk of death (HR 1.52, 95% CI 1.10-2.11, p = 0.01) and MACE (HR 1.54, 95% CI 1.13-2.09, p = 0.006). Persistent monocyte levels ≥580 per μL during were associated with a significant increase in major bleeding events (HR 2.77, 95% CI 1.36-5.67, p = 0.005, after adjustment for HAS-BLED score). CONCLUSION:High monocyte counts independently predict the occurrence of MACE, major bleeding and mortality, but not SSE. Understanding the pathophysiological mechanisms involved would help understand the relationships between monocytes, and adverse thrombotic and bleeding outcomes in AF patients

Hypertension and Atrial Fibrillation: An Intimate Association of Epidemiology, Pathophysiology, and Outcomes

atrial fibrillation; bleeding; blood pressure; epidemiology; fibrosis; hypertension; inflammation; oxidative stress; prevention; stroke.Atrial fibrillation (AF) is the most prevalent sustained arrhythmia found in clinical practice. AF rarely exists as a single entity but rather as part of a diverse clinical spectrum of cardiovascular diseases, related to structural and electrical remodeling within the left atrium, leading to AF onset, perpetuation, and progression. Due to the high overall prevalence within the AF population arterial hypertension plays a sig¬nificant role in the pathogenesis of AF and its complications. Fibroblast proliferation, apoptosis of cardiomyocytes, gap junction remodeling, accumulation of collagen both in atrial and ventricular myocardium all accompany ageing-related structural remodeling with impact on electrical activity. The presence of hypertension also stimulates oxidative stress, systemic inflammation, rennin-angiotensin-aldosterone and sympathetic activation, which further drives the remodeling process in AF. Importantly, both hypertension and AF independently increase the risk of cardiovascular and cerebrovascular events, e.g., stroke and myo-cardial infarction. Given that both AF and hypertension often present with limited on patient wellbeing, treatment may be delayed resulting in development of complications as the first clinical manifestation of the disease. Antithrombotic prevention in AF combined with strict blood pressure control is of primary importance, since stroke risk and bleeding risk are both greater with underlying hypertension

Clinical implications of different types of dementia in patients with atrial fibrillation: Insights from a global federated health network analysis.

BackgroundAtrial fibrillation (AF) associates with higher Alzheimer's disease (AD) and vascular dementia risks but the clinical implications have been scarcely investigated. We examined the association between AD or vascular dementia and adverse outcomes in AF patients.MethodsCohort study between January 2000 and 2017. AF patients were divided into two groups according to vascular dementia or AD, and balanced using propensity score matching (PSM). During 4-years of follow-up, incident intracranial hemorrhages (ICH), the composite of ischemic stroke/transient ischemic attack (TIA), hospitalizations, and all-cause deaths, were recorded.ResultsTwo thousand three hundred seventy-seven AF patients with dementia (1225 with vascular dementia, and 1152 with AD) were identified. Following a PSM, 615 patients were included in each cohort (i.e., 1:1) and all variables were well-matched. After PSM, 22 (3.6%) patients with vascular dementia and 55 (8.1%) patients with AD had incident ICH during follow-up (hazard ratio [HR]: 2.22, 95% confidence interval [CI]: 1.33-3.70, log-rank p = 0.002). Overall, 237 (38.5%) patients with vascular dementia and 193 (31.4%) patients with AD, developed an ischemic stroke/TIA. The risk of ischemic stroke/TIA was 1.32-fold higher in vascular dementia (HR: 1.32, 95% CI: 1.09-1.59, log-rank p = 0.003). The risk of rehospitalization (HR: 1.14, 95% CI: 1.01-1.31), and mortality (HR: 1.25, 95% CI: 1.01-1.58) were also higher among AF patients with vascular dementia compared to AD.ConclusionsThe two forms of dementia in AF patients are associated with different prognosis, with AD being associated with a higher risk of ICH, and vascular dementia with a higher risk of stroke/TIA, hospitalization, and mortality

Microparticles: major transport vehicles for distinct microRNAs in circulation

AIMS: Circulating microRNAs (miRNAs) have attracted major interest as biomarkers for cardiovascular diseases. Since RNases are abundant in circulating blood, there needs to be a mechanism protecting miRNAs from degradation. We hypothesized that microparticles (MP) represent protective transport vehicles for miRNAs and that these are specifically packaged by their maternal cells. METHODS AND RESULTS: Conventional plasma preparations, such as the ones used for biomarker detection, are shown to contain substantial numbers of platelet-, leucocyte-, and endothelial cell-derived MP. To analyse the widest spectrum of miRNAs, Next Generation Sequencing was used to assess miRNA profiles of MP and their corresponding stimulated and non-stimulated cells of origin. THP-1 (monocytic origin) and human umbilical vein endothelial cell (HUVEC) MP were used for representing circulating MP at a high purity. miRNA profiles of MP differed significantly from those of stimulated and non-stimulated maternal THP-1 cells and HUVECs, respectively. Quantitative reverse transcription-polymerase chain reaction of miRNAs which have been associated with cardiovascular diseases also demonstrated significant differences in miRNA profiles between platelets and their MP. Notably, the main fraction of miRNA in plasma was localized in MP. Furthermore, miRNA profiles of MP differed significantly between patients with stable and unstable coronary artery disease. CONCLUSION: Circulating MP represent transport vehicles for large numbers of specific miRNAs, which have been associated with cardiovascular diseases. miRNA profiles of MP are significantly different from their maternal cells, indicating an active mechanism of selective 'packaging' from cells into MP. These findings describe an interesting mechanism for transferring gene-regulatory function from MP-releasing cells to target cells via MP circulating in blood

CD4+ T cell surface alpha enolase is lower in older adults

To identify novel cell ageing markers in order to gain insight into ageing mechanisms, we adopted membrane enrichment and comparison of the CD4+ T cell membrane proteome (purified by cell surface labelling using Sulfo-NHS-SS-Biotin reagent) between healthy young (n=9, 20-25y) and older (n=10; 50-70y) male adults. Following two-dimensional gel electrophoresis (2DE) to separate pooled membrane proteins in triplicates, the identity of protein spots with age-dependent differences (p1.4 fold difference) was determined using liquid chromatography-mass spectrometry (LC-MS/MS). Seventeen protein spot density differences (ten increased and seven decreased in the older adult group) were observed between young and older adults. From spot intensity analysis, CD4+ T cell surface α-enolase was decreased in expression by 1.5 fold in the older age group; this was verified by flow cytometry (n=22) and qPCR with significantly lower expression of cellular α-enolase mRNA and protein compared to young adult CD4+ T cells (p<0.05). In an independent age-matched case-control study, lower CD4+ T cell surface α-enolase expression was observed in age-matched patients with cardiovascular disease (p<0.05). An immune-modulatory role has been proposed for surface α-enolase and our findings of decreased expression suggest that deficits in surface α-enolase merit investigation in the context of immune dysfunction during ageing and vascular disease