Atrial fibrillation is not associated with altered left atrial microRNA expression profile in ischemic end-stage human heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Ruppert ◽  
B Agg ◽  
A.A Sayour ◽  
S.Z Kugler ◽  
P Perge ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Mrna Expression ◽  
Mirna Expression ◽  
Left Atrial ◽  
Interstitial Fibrosis ◽  
Left Ventricular ◽  
Funding Source ◽  
Human Heart Failure ◽  
End Stage

Abstract Introduction In patients with chronic heart failure (CHF) left ventricular dysfunction results in elevated left atrial (LA) pressure, triggering pathological atrial remodelling and atrial fibrillation (AF). Nevertheless, it has been reported that some patients with CHF remain in sinus rhythm (SR) despite of the pathological structural alterations (e.g. dilation and fibrosis) of the LA. Of particular interest, data is scarce regarding the molecular explanation for the observed variability in AF development among CHF patients. Recent studies have indicated that alterations in microRNA (miRNA) expression might contribute to the pathogenesis of AF. However, the majority of previous studies focusing on miRNA expression compared healthy LA with SR to pathologically remodelled, dilated LA with AF. Consequently, whether dysregulation of miRNA expression directly contribute to AF and not only to pathological LA remodelling has not been tested before. Purpose The present study aimed to investigate miRNA expression in comparably remodelled LA from end-stage CHF patients with permanent AF (CHF-AF) or SR (CHF-SR). Methods LA samples were collected from male, non-diabetic, ischemic end-stage CHF patients undergoing heart transplantation (n=24). Patients were carefully selected to avoid any differences in age (55±2 vs. 54±2 years, CHF-AF vs. CHF-SR, n.s.), ejection fraction ([EF]: 22.5±1.8 vs. 23.3±2.5%, CHF-AF vs. CHF-SR, n.s.) LA diameters (longitudinal LA diameter: 56±4 vs. 48±5mm.; CHF-AF vs. CHF-SR, n.s.; horizontal LA diameter: 61±2 vs. 54±3, CHF-AF vs. CHF-SR, n.s.) and NYHA stage. As a molecular marker of atrial load, the mRNA expression of atrial natriuretic peptide (ANP) was measured with qRT-PCR. The extent of left atrial fibrosis was assessed on picrosirius red stained histological sections. Global LA miRNA expression profiling (including the measurement of 800 human miRNA) was carried out using a commercially available kit. Results LA mRNA expression of ANP was comparable between the AF-CHF and the SR-CHF groups, suggesting that atrial load occurred to the same level in the two experimental groups. Furthermore, no differences could be observed in the extent of atrial collagen content between the AF-CHF and the SR-CHF groups (collagen area: 20.3±1.3% vs. 23.9±3.1%, n.s.), providing evidence that fibrotic remodelling had occurred to a similar magnitude. The high-throughput miRNA measurement revealed no differences in atrial miRNA expression between the two study groups. Conclusion The present study provides evidence for the first time that AF is not associated with different LA miRNA expression in end-stage CHF patients with comparable level of LA dilatation, ANP expression (atrial load) and interstitial fibrosis. Based on these findings, the potential of miRNA-based therapeutic interventions might be limited in AF patients with ischemic end-stage CHF. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): NVKP_16-1-2016-0017

AIM2-driven inflammasome activation in chronic heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Ruppert ◽  
Z.S Onodi ◽  
P Leszek ◽  
V.E Toth ◽  
G Koncsos ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Animal Models ◽  
Left Ventricular ◽  
Inflammasome Activation ◽  
Coronary Artery Ligation ◽  
Funding Source ◽  
Human Cardiomyocytes ◽  
Pannexin 1 ◽  
End Stage

Abstract Background Inflammation and cytokine release have been implicated in the pathogenesis of chronic heart failure (CHF). Of particular interest, Canakinumab, a monoclonal antibody against interleukin-1b (IL-1β), had provided benefit against cardiovascular events, suggesting that blockade of IL-1β secretion and signaling might be a promising new therapeutic target. Although, recent studies have provided evidence that inflammasome activation is the main contributor to IL-1β maturation, the role of inflammasome activation in CHF remains unknown. Objective Therefore, we aimed to assess inflammasome activation in myocardial samples from end-stage failing hearts. Methods Inflammasome activation was assessed by immunoblotting in left ventricular myocardial specimens harvested from patients with end-stage CHF. Furthermore, immunoblot measurements were also performed on translational animal models of CHF (e.g. rat models of permanent coronary artery ligation and transverse aortic constriction). Left ventricular monocyte and macrophage infiltration was detected by immunohistochemistry. To investigate the molecular background of inflammasome activation, a series of cell culture experiments were performed on AC16 human cardiomyocytes and THP-1 human monocytic cell lines. Results Out of the 4 major inflammasome sensors tested, expression of the inflammasome protein absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4) increased in human CHF while the NLRP1 and NLRP3 (NLR family, pyrin domain containing 1 and 3) inflammasome showed no change. A similar expression pattern in AIM2 and NLRC4 was also noted in CHF animal models. Furthermore, robust infiltration of Iba1+ monocytes/macrophages was observed in human failing hearts as well as in different animal models of CHF. In vitro AIM2 inflammasome activation, as induced by transfection with double-stranded DNA [poly(deoxyadenylic-deoxythymidylic)] was reduced significantly by the pharmacological blockade of pannexin-1 channels. Conclusions AIM2 and NLRC4 inflammasome activation might contribute to chronic inflammation in CHF. Our findings suggest that pannexin-1 channels might be a promising novel target to reduce inflammasome activation. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): NVKP_16-1-2016-0017

P1766Clinical impact of atrial fibrillation and heart failure in a cohort of patients with hypertrophic cardiomyopathy

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
I Esteve Ruiz ◽  
H Llamas Gomez ◽  
I M Esteve Ruiz ◽  
M J Romero Reyes ◽  
R Pavon Jimenez ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Atrial Fibrillation ◽  
Hypertrophic Cardiomyopathy ◽  
Left Atrial ◽  
Left Ventricular ◽  
Left Atrial Diameter ◽  
Myocardial Thickness ◽  
Worse Prognosis ◽  
Echocardiographic Findings

Abstract Background Atrial fibrillation (AF) and heart failure (HF) are common complications in Hypertrophic Cardiomyopathy (HCM) patients, leading to a worsening of their quality of life, need of hospitalization and prognosis. Purpose To analyze clinical variables associated with the presence of AF and HF in HCM patients. Methods HCM patients followed-up in cardiological visits from 2005 to 2017 were included and a descriptive analysis of those with AF and HF was performed. Results Out of 168 patients, 28% had reported AF. They were older than those without arrhythmia (68±15 years (yrs) vs 56±20 yrs, p<0.001) and had more comorbidities such as diabetes (27.7% vs 12.4%, p=0.02) and chronic renal disease (21.3% vs 6.6%, p=0.006). Echocardiographic findings are summarized in Table 1. In our cohort, 27.4% of the patients had HF with a functional class according to the New York Heart Association criteria ≥2. They were older than those without HF (69.3±11.6 yrs vs 55.9±20.6 yrs, p<0.001) and had higher rate of cardiovascular (CV) risk factors such as hypertension (65.2% vs 44.3%, p=0.015). The presence of HF was directly associated with the presence of AF: 52.2% of the patients with HF and 18.9% of the patients without HF developed this arrhythmia (p<0.001). HF patients associated larger left atrial diameter (48±8.1 vs 41.6±7.2mm, p<0.001), myocardial thickness (21.7±3.9 vs 19.2±5.8mm, p=0.002) and higher left ventricular outflow obstruction (LVOO) (55±32 vs 34.3±31.3mmHg, p=0.021), without any differences in the left ventricular ejection fraction. HF patients had a worse prognosis (Picture 1). Multivariate analysis showed that the presence of AF (OR 2.6, CI 95% 1.1–6.3) and LVOO (OR 4.8, CI 95% 1.5–14.8) were independent risk factors of developing HF. Table 1. Echocardiographic findings AF (n=47) Non AF (n=121) p LVOO 27.7 19 0.22 Aortic regurgitation 12.8 3.3 0.02 Mitral regurgitation 27.7 12.4 0.02 Left atrial diameter (mm) 48.8±7.2 40.7±7 <0.001 Myocardial thickness (mm) 20±5.4 19±5.2 0.02 Qualitative variables are expressed as percentages (%) and quantitative variables as mean and standard deviation (M ± SD). Picture 1. Main outcomes of HF patients Conclusions AF and HF were directly associated in our cohort, especially in elderly patients with higher comorbidities, leading to a worse prognosis with a higher hospitalization rate and CV death. This emphasizes the importance of a thorough search of both complications in order to initiate early treatment and improve the prognosis of HCM patients.

scholarly journals TRP Channels Expression Profile in Human End-Stage Heart Failure

Medicina ◽  
2019 ◽  
Vol 55 (7) ◽  
pp. 380 ◽  
Author(s):  
Martin Dragún ◽  
Andrea Gažová ◽  
Ján Kyselovič ◽  
Michal Hulman ◽  
Marek Máťuš
Keyword(s):  
Heart Failure ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Left Ventricular ◽  
Mrna Levels ◽  
Human Heart Failure ◽  
Systematic Analysis ◽  
Tissue Samples ◽  
End Stage Heart Failure ◽  
End Stage

Objectives: Many studies indicate the involvement of transient receptor potential (TRP) channels in the development of heart hypertrophy. However, the data is often conflicted and has originated in animal models. Here, we provide systematic analysis of TRP channels expression in human failing myocardium. Methods and results: Left-ventricular tissue samples were isolated from explanted hearts of NYHA III-IV patients undergoing heart transplants (n = 43). Quantitative real-time PCR was performed to assess the mRNA levels of TRPC, TRPM and TRPV channels. Analysis of functional, clinical and biochemical data was used to confirm an end-stage heart failure diagnosis. Compared to myocardium samples from healthy donor hearts (n = 5), we detected a distinct increase in the expression of TRPC1, TRPC5, TRPM4 and TRPM7, and decreased expression of TRPC4 and TRPV2. These changes were not dependent on gender, clinical or biochemical parameters, nor functional parameters of the heart. We detected, however, a significant correlation of TRPC1 and MEF2c expression. Conclusions: The end-stage heart failure displays distinct expressional changes of TRP channels. Our findings provide a systematic description of TRP channel expression in human heart failure. The results highlight the complex interplay between TRP channels and the need for deeper analysis of early stages of hypertrophy and heart failure development.

scholarly journals Game changer? A sporting indication to implant a left atrial appendage closure device in a rugby player with atrial fibrillation: a case report

2020 ◽  
Vol 4 (1) ◽  
pp. 1-5
Author(s):  
Andre Briosa e Gala ◽  
Andrew Cox ◽  
Michael Pope ◽  
Timothy Betts
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Left Atrial ◽  
Left Atrial Appendage ◽  
Left Ventricular ◽  
Atrial Appendage ◽  
Rugby Player ◽  
Management Options ◽  
Left Atrial Appendage Occlusion ◽  
Occlusion Device

Abstract Background Caring for athletes with cardiac disease requires an approach that caters to the specific needs of the athlete. Case summary A 27-year-old professional rugby player was admitted with decompensated heart failure and atrial fibrillation (AF). Transthoracic echocardiogram showed features in keeping with a dilated cardiomyopathy with severe left ventricular (LV) systolic impairment. He made good progress on evidence-based heart failure medication and his LV systolic function returned to normal. He failed to maintain sinus rhythm with cardioversion and remained in persistent AF. He then suffered a transient ischaemic attack despite appropriate anticoagulation. At 1-year follow-up, he was asymptomatic and against medical advice continued to play competitive rugby whilst taking rivaroxaban. He subsequently underwent implantation with a percutaneous left atrial appendage occlusion device, allowing him to discontinue anticoagulation, reduce his bleeding risk and resume his career, whilst simultaneously lowering the thromboembolic risk. Discussion Counselling should include different management options aimed at minimizing the risks to athletes if they to return to competitive sports. Left atrial appendage occlusion devices are a suitable AF-related stroke prevention strategy in athletes competing in full-contact sports.

scholarly journals Transitioning from Preclinical to Clinical Heart Failure with Preserved Ejection Fraction: A Mechanistic Approach

2020 ◽  
Vol 9 (4) ◽  
pp. 1110 ◽  
Author(s):  
Antoni Bayes-Genis ◽  
Felipe Bisbal ◽  
Julio Núñez ◽  
Enrique Santas ◽  
Josep Lupón ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Ejection Fraction ◽  
Right Ventricular ◽  
Left Atrial ◽  
Interstitial Fibrosis ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Ventricular Ejection Fraction

To better understand heart failure with preserved ejection fraction (HFpEF), we need to better characterize the transition from asymptomatic pre-HFpEF to symptomatic HFpEF. The current emphasis on left ventricular diastolic dysfunction must be redirected to microvascular inflammation and endothelial dysfunction that leads to cardiomyocyte remodeling and enhanced interstitial collagen deposition. A pre-HFpEF patient lacks signs or symptoms of heart failure (HF), has preserved left ventricular ejection fraction (LVEF) with incipient structural changes similar to HFpEF, and possesses elevated biomarkers of cardiac dysfunction. The transition from pre-HFpEF to symptomatic HFpEF also involves left atrial failure, pulmonary hypertension and right ventricular dysfunction, and renal failure. This review focuses on the non-left ventricular mechanisms in this transition, involving the atria, right heart cavities, kidneys, and ultimately the currently accepted driver—systemic inflammation. Impaired atrial function may decrease ventricular hemodynamics and significantly increase left atrial and pulmonary pressure, leading to HF symptoms, irrespective of left ventricle (LV) systolic function. Pulmonary hypertension and low right-ventricular function are associated with the incidence of HF. Interstitial fibrosis in the heart, large arteries, and kidneys is key to the pathophysiology of the cardiorenal syndrome continuum. By understanding each of these processes, we may be able to halt disease progression and eventually extend the time a patient remains in the asymptomatic pre-HFpEF stage.

Abstract 1346: Rac1 GTPase Activtiy is Associated with Atrial Fibrosis and Fibrillation

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Oliver Adam ◽  
Daniel Lavall ◽  
Hans-Joachim Schäfers ◽  
Michael Böhm ◽  
Ulrich Laufs
Keyword(s):  
Atrial Fibrillation ◽  
Nadph Oxidase ◽  
Left Atrial ◽  
Ventricular Hypertrophy ◽  
Interstitial Fibrosis ◽  
Left Ventricular ◽  
Collagen Content ◽  
Atrial Fibrosis ◽  
Nadph Oxidase Activity ◽  
Rac1 Gtpase

Patients with atrial fibrillation (AF) are characterized by increased atrial fibrosis. The underlying signal transduction is incompletely understood. We hypothesized that activation of Rac1 GTPase contributes to increased fibrosis and atrial fibrillation via activation of NADPH oxidase and production of reactive oxygen species. Methods and Results: Samples of the left atrial appendage were analyzed in 8 patients with AF undergoing mitral valve surgery and 7 patients with sinus rhythm (SR) matched for atrial diameter. Despite same size of the atria, collagen content was significantly higher in AF compared to SR (14.9±2.1% vs. 8.5±1.3%). Expression analysis showed that AF was associated with upregulation of connective tissue growth factor (CTGF). Atria of patients with AF were characterized by significant upregulation of Rac1 total protein expression (Western blot), Rac1 activity (PAK pull-down assays) and a 20-fold upregulation of NADPH oxidase activity compared to SR (2225±500%). In order to test whether Rac1 plays a causal role in the pathogenesis in AF, transgenic mice with cardiac overexpres-sion (αMHC promoter) of Rac1 (RacET) were compared to wildtype (WT) and WT undergoing transaortic constriction (TAC, 360 μm). After 16 months, echocardiography showed similar left ventricular hypertrophy in RacET and TAC. RacET but not TAC exhibited atrial enlargement; 75% of RacET but no WT or TAC showed AF. Interstitial collagen content was significantly increased in the atria of RacET (44±1% of area vs 19±5% in WT). In contrast, interstitial fibrosis in TAC atria did not significantly differ from WT (31±6%). In the left ventricle, both RacET and TAC mice showed an elevated collagen content compared to the control group (WT 9±2%, RacET 29±3%; TAC 24±4%). In all mice, atrial collagen content exceeded ventricular collagen. All effects are significant with p<0.05. Conclusion: Left atria of patients with AF exhibit upregulation of Rac1, increased NADPH oxidase activity and interstitial fibrosis. Cardiac-specific overexpression of Rac1 in mice results atrial fibrosis and fibrillation independent of left ventricular hypertrophy. Rac1-GTPase mediated activation of left atrial NADPH-oxidase may represent a novel target for the prevention of atrial fibrosis.

Timing and degree of left atrial stunning and reverse functional remodeling following electrical cardioversion in patients with recent onset atrial fibrillation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Arvanitis ◽  
A.K Johansson ◽  
M Frick ◽  
H Malmborg ◽  
S Gerovasileiou ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ejection Fraction ◽  
Left Atrial ◽  
Left Ventricular ◽  
Reverse Remodeling ◽  
Funding Source ◽  
Recent Onset ◽  
Functional Remodeling ◽  
Onset Atrial Fibrillation ◽  
Electric Cardioversion

Abstract Background Atrial fibrillation (AF) results in left atrial electrical, structural and functional remodeling. Restoration of sinus rhythm hallmarks the beginning of reverse remodeling, the extent of which may depend on the type of AF. Purpose The aim of the study was to assess resumption of left atrial function after electric cardioversion in patients with recent onset AF and to explore the association between reverse remodeling and the type of atrial fibrillation. Methods Patients with AF duration &lt;48 hours were prospectively included. Trans-thoracic echocardiography was performed prior, immediately after (2–4 hours) and 7–10 days following CV. Left atrial volume index (LAVI), left atrial global longitudinal strain during reservoir (LAGLS-res), conduit (LAGLS-cond) and contractile (LAGLS-contr) phases, left atrial ejection fraction (LAEF) and left ventricular ejection fraction (LVEF) were measured. Results Forty-three patients (84% males) aged 55±9.6 years, (mean±SD), with median CHA2DS2-VASc score 1 (interquartile range 0–1) were included. Repeated measure analysis of variance revealed a statistically significant overall change for LAGLS-res F(2,78)=55.4, p&lt;0,001, LAGLS-cond F(2,78)=23.3, p&lt;0,001, LAGLS-contr F(2,78)=39.7, p&lt;0,001, LAEF F(2,80)=28.5, p&lt;0.001 and LVEF F(2,80)=8.4, p&lt;0.001. At 7–10 days, LAGLS-contr 12±4%, LAEF 53±9% and LVEF 60±6 (mean±SD) return within normal reference intervals. Notably left atrial recovery seems to precede left ventricular recovery. No statistical significant interaction with the type of atrial fibrillation could be shown. Conclusion Left atrial functional reverse remodeling occurs within ten days after successful electric cardioversion of patients with recent onset atrial fibrillation. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Swedish Heart-Lung Foundation, Correvio International Sárl (Geneva Switzerland), Selanders Stiftelse

Abstract 17226: Increased Risk of Heart Failure Associated With Left Atrial Remodeling Without Known Atrial Fibrillation

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Jodi Edwards ◽  
Jiming Fang ◽  
Jeff S Healey ◽  
Kathy Yip ◽  
Lisa Mielniczuk ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Left Atrial ◽  
Left Ventricular ◽  
Administrative Databases ◽  
Risk Scores ◽  
Atrial Remodeling ◽  
Left Atrial Remodeling ◽  
Lv Dysfunction ◽  
Increased Risk

Background: Atrial fibrillation (AF) significantly increases risk for heart failure (HF) and independently increases mortality and adverse in-hospital outcomes in HF patients. Validated clinical risk scores (ARC2H) can predict HF in patients with AF, but are limited in application as AF is frequently clinically silent or undetected. However, AF may be preceded by significant preclinical remodeling (left atrial enlargement (LAE) or excessive atrial ectopy (EAE)). Whether LAE and EAE are associated with HF prior to AF is unclear. Method(s): We analyzed consecutive adults >65 years with outpatient echocardiography or Holter at 11 Ontario community cardiology clinics (2010-2017). Exclusions were history of AF, anticoagulation, pacemaker/ICD/ILR, and prosthetic valve. Using linked administrative databases, we assessed 5-year rates of HF (primary) and incident AF and death (secondary) associated with LAE and EAE and among subgroups (M vs. F; <75 vs. >75; CHADS-VASC 0-2 vs. 3-6). Competing risks cox proportional hazards estimated adjusted hazard of HF for severe LAE: >47mm (M);>52mm (F)) or increased APBs/hour (EAE: >30) or both LAE and EAE, adjusting for age, vascular comorbidities and left ventricular (LV) dysfunction. Results: In 28,261 adults (mean 73+/-6 years), direct age-adjusted survival was reduced for those with severe LAE and EAE. 5-year rates of HF were increased for severe (8.8%) vs. moderate (3.5%) and mild (1.4%) LAE and for those with excessive (3.8%) vs. normal (2.5%) ectopy. For both LAE and EAE, those >75 and with a CHADS score 3-6 showed marked increases in HF at 5 years compared to <75 (LAE: 10.6% vs. 7.9%; EAE: 4.3% vs. 1.9%) and CHADS score 0-2 (LAE:21.4% vs. 6.6%; EAE: 8.9% vs. 2.4%). Severe LAE increased hazard of HF 2-fold (HR=2.07; p<.0001), and incident AF over 3-fold (HR= 3.43; p<.0001) and EAE increased hazard of HF (HR=1.31; p<.0001) and incident AF (HR=1.13; p<.0001). Those with both LAE and EAE showed an over 3-fold increased hazard of HF (HR=3.28; p<.0014). Conclusions: Severe LAE and EAE without known AF are associated with increased risk of HF and AF after adjusting for LV dysfunction, particularly for those >75 and with high vascular burden. These data have implications for risk stratification, AF screening, and trials for HF prevention in individuals with left atrial remodeling.

Sign in / Sign up

Export Citation Format

Share Document