Abstract 16130: Plasma Proteomic Analysis of Association Between Atrial Fibrillation, Coronary Microvascular Disease and Heart Failure

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Cevher Ozcan ◽  
GUNJAN DIXIT ◽  
John Blair
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Proteomic Analysis ◽  
Microvascular Disease ◽  
Microvascular Dysfunction ◽  
Coronary Microvascular Dysfunction ◽  
Matrix Remodeling ◽  
Label Free ◽  
Inflammatory Processes ◽  
Novel Biomarkers

Introduction: Atrial fibrillation (AF) commonly occurs in patients with heart failure with preserved ejection fraction (HFpEF). Recent studies showed a high prevalence of coronary microvascular dysfunction (CMD) in patients with HFpEF and a likely association with AF. Yet, the biomarkers and mechanisms of their association have not been characterized. Hypothesis: Plasma proteomic analysis can identify novel biomarkers of the association between AF, CMD and HFpEF, and mechanistic pathways of their association. Methods: We studied the plasma samples from the patients with AF, CMD and/or HFpEF. Liquid chromatography-mass spectrometry based untargeted and label-free quantification proteomic analysis was performed. Circulating plasma proteins were screened to determine candidate biomarkers and the mutual mechanistic pathways in these disease processes. Results: We identified 130 dysregulated proteins across the groups with the independent patient replicates. Discovery-based untargeted plasma proteomic analysis identified 35 proteins in association with AF, CMD and HFpEF candidate biomarkers of their association (Fig). SAA1, LRG1 and APOC3 were significantly elevated in the coexistence of AF, CMD and HFpEF. LCP1, PON1 and C1S were markedly downregulated in their associations. Combined downregulation of PON1 and C1S was a marker of the HFpEF and CMD. Low PON1 was associated with HFpEF. Low C1S was a marker of CMD. Reduced levels of LCP1, KLKB1 and C4A were associated with AF in patients with CMD and HFpEF. These dysregulated proteins are associated with inflammatory processes, coagulation pathways, oxidative stress, metabolism, complement system and extracellular matrix remodeling. Conclusions: Plasma proteomic profile provides biomarkers and mechanistic insight into the association of AF, CMD and HFpEF. Circulation dysregulated proteins can be clinically useful for risk stratification.

scholarly journals Prevalence and correlates of coronary microvascular dysfunction in heart failure with preserved ejection fraction: PROMIS-HFpEF

2018 ◽  
Vol 39 (37) ◽  
pp. 3439-3450 ◽  
Author(s):  
Sanjiv J Shah ◽  
Carolyn S P Lam ◽  
Sara Svedlund ◽  
Antti Saraste ◽  
Camilla Hage ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Endothelial Dysfunction ◽  
Ejection Fraction ◽  
Microvascular Dysfunction ◽  
Left Ventricular ◽  
Coronary Microvascular Dysfunction ◽  
Preserved Ejection Fraction ◽  
Transthoracic Doppler Echocardiography ◽  
Flow Reserve

Abstract Aims To date, clinical evidence of microvascular dysfunction in patients with heart failure (HF) with preserved ejection fraction (HFpEF) has been limited. We aimed to investigate the prevalence of coronary microvascular dysfunction (CMD) and its association with systemic endothelial dysfunction, HF severity, and myocardial dysfunction in a well defined, multi-centre HFpEF population. Methods and results This prospective multinational multi-centre observational study enrolled patients fulfilling strict criteria for HFpEF according to current guidelines. Those with known unrevascularized macrovascular coronary artery disease (CAD) were excluded. Coronary flow reserve (CFR) was measured with adenosine stress transthoracic Doppler echocardiography. Systemic endothelial function [reactive hyperaemia index (RHI)] was measured by peripheral arterial tonometry. Among 202 patients with HFpEF, 151 [75% (95% confidence interval 69–81%)] had CMD (defined as CFR <2.5). Patients with CMD had a higher prevalence of current or prior smoking (70% vs. 43%; P = 0.0006) and atrial fibrillation (58% vs. 25%; P = 0.004) compared with those without CMD. Worse CFR was associated with higher urinary albumin-to-creatinine ratio (UACR) and NTproBNP, and lower RHI, tricuspid annular plane systolic excursion, and right ventricular (RV) free wall strain after adjustment for age, sex, body mass index, atrial fibrillation, diabetes, revascularized CAD, smoking, left ventricular mass, and study site (P < 0.05 for all associations). Conclusions PROMIS-HFpEF is the first prospective multi-centre, multinational study to demonstrate a high prevalence of CMD in HFpEF in the absence of unrevascularized macrovascular CAD, and to show its association with systemic endothelial dysfunction (RHI, UACR) as well as markers of HF severity (NTproBNP and RV dysfunction). Microvascular dysfunction may be a promising therapeutic target in HFpEF.

scholarly journals Untangling the pathophysiologic link between coronary microvascular dysfunction and heart failure with preserved ejection fraction

2021 ◽  
Author(s):  
Aish Sinha ◽  
Haseeb Rahman ◽  
Andrew Webb ◽  
Ajay M Shah ◽  
Divaka Perera
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Obstructive Coronary Artery Disease ◽  
Microvascular Disease ◽  
Microvascular Dysfunction ◽  
Common Finding ◽  
Coronary Microvascular Dysfunction ◽  
Preserved Ejection Fraction ◽  
Flow Reserve ◽  
Artery Disease

Abstract Coronary microvascular disease (CMD), characterized by impaired coronary flow reserve (CFR), is a common finding in patients with stable angina. Impaired CFR, in the absence of obstructive coronary artery disease, is also present in up to 75% of patients with heart failure with preserved ejection fraction (HFpEF). Heart failure with preserved ejection fraction is a heterogeneous syndrome comprising distinct endotypes and it has been hypothesized that CMD lies at the centre of the pathogenesis of one such entity: the CMD–HFpEF endotype. This article provides a contemporary review of the pathophysiology underlying CMD, with a focus on the mechanistic link between CMD and HFpEF. We discuss the central role played by subendocardial ischaemia and impaired lusitropy in the development of CMD–HFpEF, as well as the clinical and research implications of the CMD–HFpEF mechanistic link. Future prospective follow-up studies detailing outcomes in patients with CMD and HFpEF are much needed to enhance our understanding of the pathological processes driving these conditions, which may lead to the development of physiology-stratified therapy to improve the quality of life and prognosis in these patients.

scholarly journals Label-free proteomic analysis of serum exosomes from paroxysmal atrial fibrillation patients

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Hanwen Ni ◽  
Wenqi Pan ◽  
Qi Jin ◽  
Yucai Xie ◽  
Ning Zhang ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Protein Folding ◽  
Protein Content ◽  
Complement System ◽  
Proteomic Analysis ◽  
Surface Composition ◽  
Label Free ◽  
Healthy Donors ◽  
Variable Surface ◽  
Serum Exosomes

Abstract Background Atrial fibrillation (AF) is the most common cardiac heterogeneous rhythm disorder. It represents a major cause of mortality and morbidity, mainly related to embolic events and heart failure. Mechanisms of AF are complex and remain incompletely understood. Recent evidence suggests exosomes are membrane-coated objects released by many cell-types. Their presence in body fluids and the variable surface composition and content render them attractive as a mechanism for potential biomarkers. However, the content of serum exosomes of AF patients has not been fully delineated. Methods In this work, the serum exosomes from AF patients and healthy donors were used to compare changes in the exosome protein content. Exosomes were isolated from serum of AF patients and healthy donors and their purity was confirmed by Western blotting assays and transmission electron microscopy (TEM). Label-free LC–MS/MS quantitative proteomic analysis was applied to analyze protein content of serum exosomes. Results A total of 440 exosomal protein groups were identified, differentially expressed proteins were filtrated with fold change ≥ 2.0 (AF/controls protein abundance ratio ≥ 2 or ≤ 0.5) and p value less than 0.05 (p < 0.05), significantly changed in abundance group contains 39 elevated proteins and 18 reduced proteins, while consistent presence/absence expression profile group contains 40 elevated proteins and 75 reduced proteins. Bioinformatic analysis of differential exosomal proteins confirmed the significant enrichment of components involved in the anticoagulation, complement system and protein folding. Parallel-Reaction Monitoring Relative Quantitative Analysis (PRM) further suggested that AF related to complement system and protein folding. Conclusions These results revealed the composition and potential function of AF serum exosomes, thus providing a new perspective on the complement system and protein folding to AF.

scholarly journals Beyond Natriuretic Peptides for Diagnosis and Management of Heart Failure

2017 ◽  
Vol 63 (1) ◽  
pp. 211-222 ◽  
Author(s):  
Nasrien E Ibrahim ◽  
James L Januzzi
Keyword(s):  
Heart Failure ◽  
Renal Dysfunction ◽  
Complex Disease ◽  
Disease Process ◽  
Clinical Information ◽  
Matrix Remodeling ◽  
Injury Death ◽  
Societal Burden ◽  
Myocardial Stretch ◽  
Novel Biomarkers

Abstract BACKGROUND Heart failure (HF) is a complex syndrome with an enormous societal burden in terms of cost and morbidity and mortality. Natriuretic peptide (NP) testing is now widely used to support diagnosis, prognostication, and management of patients with HF, but NPs come with limitations, including vulnerability to the presence of obesity, atrial fibrillation, and renal dysfunction, for example. Beyond the NPs, novel biomarkers may supplement traditional clinical and laboratory testing to improve understanding of the complex disease process of HF, and possibly to personalize care for those affected through better individual phenotyping. CONTENT In this review we discuss novel biomarkers by dividing them into categories based on major pathophysiologic pathways they represent including myocardial stretch/stress, cardiac extracellular matrix remodeling, cardiomyocyte injury/death, oxidative stress, inflammation, neurohumoral activation, and renal dysfunction. SUMMARY Given the limitations of NPs, along with the complex physiology in HF, it is logical to consider utilization of novel biomarkers providing orthogonal biological and clinical information. Several novel HF biomarkers have shown promise but have substantial expectations to meet before being used clinically. Nonetheless, it is reasonable to expect the future lies in the application of multibiomarker panels for the improvement in management of HF and the personalization of care.

Imaging of microvascular disease

2021 ◽  
pp. 481-494
Author(s):  
Paolo G. Camici ◽  
Ornella Rimoldi
Keyword(s):  
Myocardial Ischaemia ◽  
Imaging Techniques ◽  
Microvascular Disease ◽  
Microvascular Dysfunction ◽  
Microvascular Function ◽  
Coronary Microvascular Dysfunction ◽  
Maximal Increase ◽  
Asymptomatic Subjects ◽  
Coronary Microvascular Function

Beside obstructive disease of the epicardial coronary arteries dysfunction of the coronary microvasculature has emerged in the past 20 years as an additional mechanism of myocardial ischaemia. The coronary microvasculature cannot be directly visualized in vivo, therefore, both invasive and non-invasive techniques, have been developed to assess parameters that depend directly on coronary microvascular function. Studies at the microcirculatory level entail the use of vasodilators to obtain near-maximal vasodilation. The ratio of the maximal increase of blood flow above its resting value the coronary flow reserve (CFR) allows to gain an insight into the integrated circulatory function. The diagnostic accuracy of imaging techniques can be exploited to detect impairments of myocardial perfusion in asymptomatic subjects with cardiovascular risk factors. The assessment of the coronary microvascular function has provided novel details on the pathophysiological role of coronary microvascular dysfunction in the development of myocardial ischaemia bearing also important prognostic implications.

Coronary Microcirculation in Heart Failure with Preserved Systolic Function

2018 ◽  
Vol 24 (25) ◽  
pp. 2960-2966
Author(s):  
Zorana Vasiljevic ◽  
Gordana Krljanac ◽  
Marija Zdravkovic ◽  
Ratko Lasica ◽  
Danijela Trifunovic ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Microvascular Dysfunction ◽  
Left Ventricular ◽  
Coronary Microcirculation ◽  
Left Ventricular Ejection ◽  
Coronary Microvascular Dysfunction ◽  
Fractional Flow ◽  
Flow Reserve

Background: The Heart Failure with Preserved Ejection Fraction (HFpEF) is defined as the preserved left ventricular ejection fraction (LVEF) with the signs of heart failure, elevated natriuretic peptides, and either the evidence of the structural heart disease or diastolic dysfunction. The importance of this form of heart failure was increased after studies where the mortality rates and readmission to the hospital were founded similar as in patients with HF and reduced EF (HFrEF). Coronary microvascular ischemia, cardiomyocyte injury and stiffness could be important factors in the pathophysiology of HFpEF. Methods: The goal of this work is to analyse the relationship of HFpEF and coronary microcirculation in previous studies. Results: The useful diagnostic marker of coronary microcirculation in HFpEF may be the parameters measured by transthoracic echocardiography (TTE), the coronary flow reserve (CFR), as well as fractional flow reserve (FFR) and quantitative myocardial contrast echocardiography (MCE). Cardiac magnetic resonance (CMR) imaging represents the diagnostic gold standard in HFpEF. Coronary microvascular dysfunction in the absence of obstructive coronary artery disease (CAD) is poorly understood and may be more prevalent amongst women than men. Troponin level may be important in risk stratification of HEpEF patients. Conclusion: There are no precise answers with respect to the pathophysiological mechanism, nor are there any precise practical clinical assessment of and diagnostic method for coronary microvascular dysfunction and diastolic dysfunction. In accordance with that, there is no well-established treatment for HFpEF.

Sign in / Sign up

Export Citation Format

Share Document