Abstract 284: Disruption of Nrf2 Promotes Atrial Remodeling and Fibrillation on Aging

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Naser Abu-Rmaileh ◽  
Sankaranarayanan Kannan ◽  
Kensuke Tsushima ◽  
Kevin Whitehead ◽  
E Dale Abel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Atrial Fibrillation ◽  
Ventricular Dysfunction ◽  
The United States ◽  
Exercise Stress ◽  
Ros Generation ◽  
Atrial Remodeling ◽  
Fibrotic Process ◽  
Mouse Atrium

Background: Heart failure is a leading health problem with over 500,000 new cases and 275,000 deaths annually in the United States. Recent reports indicate that atrial fibrillation (AF) is linked to various forms of ventricular dysfunction (VD). Over 2 million Americans have AF, which is more prevalent in people over 65 years of age. However, the molecular “cause and effect” relationship between AF and VD has not been elucidated. We hypothesize that abrogation of nuclear erythroid-2 like factor-2 (Nrf2), a master antioxidant transcriptional regulator, induces atrial remodeling and fibrillation on aging. Methods: Age and sex matched WT and Nrf2-/- mice were used in this study. Atrial mass, remodeling, antioxidants and molecular redox signaling were studied at 2 and >20 months of age. Echocardiography, immunoblotting, quantitative real-time PCR and immunofluorescence (fibrosis) analyses were performed in the atrial tissue. Results: At 2 months of age, WT and Nrf2-/- mice had comparable levels of ROS in the atrium. On aging, the ROS levels were significantly increased in atria of Nrf2- null when compared to wild-type (WT) mice at 20 months of age. While decreased Nrf2-antioxidant signaling in response to increased ROS generation in atria of Nrf2- null mice was observed, ventricular function appeared to be normal at 20 months of age. However, upon endurance exercise stress (EES), hypertrophy markers including ANF, BNF, PLN and SERCA2A were significantly (p<0.05) altered in Nrf2- null when compared to age-matched WT mice. Further, activation of fibrotic process was evident in the Nrf2- null mouse atrium as indicated by significantly (p<0.05) increased markers of tissue remodeling (i.e. MMP2/9) on aging. These results indicating an early onset of atrial hypertrophy/remodeling due to age-induced oxidative stress, which cause AF in Nrf2- null mice. Age-dependent decline in Nrf2 and sustained progression of AF could lead to ventricular dysfunction and heart failure. Conclusion: Our findings indicate that atria are primary targets to age-associated oxidative stress and exhibit fibrosis, which promotes atrial fibrillation and remodeling. Thus, activation of Nrf2 signaling to prevent oxidative stress could be a potential therapeutic target for AF.

scholarly journals Echocardiography in Patients with Atrial Fibrillation - What Should the Internist Doctor Know?

2020 ◽  
Vol 17 (4) ◽  
pp. 49-60
Author(s):  
Maria-Luiza Toplicianu-Dimitriu ◽  
Ioan Tiberiu Nanea
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrial ◽  
Structural Changes ◽  
Excess Mortality ◽  
Ventricular Dysfunction ◽  
Imaging Technique ◽  
Left Ventricular ◽  
Clinical Impact ◽  
Atrial Remodeling ◽  
Routine Imaging

AbstractAtrial fibrillation (AF) is the most common cardiac arrhythmia, with an increasing prevalence and an enormous clinical impact due to the high stroke rate, left ventricular dysfunction and excess mortality. The occurrence and maintenance of AF is favored by both the degree of left atrial (LA) dilation and the association of fibrotic lesions of the myocardium. The LA is a marker of adverse cardiovascular events in patients with AF. Atrial remodeling can be electrical (shortening atrial refractory), structural (altering geometry and altering collagen content) and contractile (loss of contractility). Cardiac imaging plays a central role in the clinical management of this arrhythmia. Echocardiography represents the routine imaging technique used in patients with AF, with a role in detecting LA dysfunction and cardiac structural changes that predispose to this arrhythmia, also having the ability to predict the maintenance of sinus rhythm after cardioversion and after ablation.

Abstract 12427: Racial Disparities in Hospitalization for Atrial Fibrillation: The Nationwide Inpatient Sample 2001-09

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Gene F Kwan ◽  
Danielle M Enserro ◽  
Allan J Walkey ◽  
Renda S Wiener ◽  
Emelia J Benjamin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Racial Differences ◽  
Nationwide Inpatient Sample ◽  
The United States ◽  
Census Bureau ◽  
Outcome Data ◽  
Hospitalization Rates ◽  
Increased Risk ◽  
Modifiable Factors

Introduction: Racial differences in atrial fibrillation (AF) prevalence and disparities in treatment are well established; however, racial differences in outcomes among patients hospitalized with AF are less clear. We assessed racial differences in complications related to AF in a representative sample of AF hospitalization in the United States. Methods: We identified adults (≥ 40 years) with a principal diagnosis of AF and length of stay (LOS) among survivors of 1-30 days using weighted national estimates from the Nationwide Inpatient Sample. We excluded patients undergoing cardiac surgery or with missing covariates. Annual AF hospitalization rates by race were calculated using the total US population obtained from the US Census Bureau. We used multivariable regression models (covariates listed in Table) to examine associations of race with heart failure and hospital mortality among patients admitted with AF. Results: 2,244,036 AF hospitalizations (85% White, 6.7% Black, 5.0% Hispanic and 1.4% Asian/Pacific Islander) were analyzed from 2001-09. Hospitalization and outcome data by year are summarized in the table. Across all studied years, Blacks had lower AF hospitalization rates than Whites. Yet in all study years, mean LOS was longer for Blacks (range 4.2-4.6 days) than Whites (range 3.4-3.6 days). Blacks consistently had increased risk of in-hospital heart failure (Odds Ratio [OR] ranged from 1.5 [1.4, 1.7] to 1.7 [1.6, 1.9] across years) and death (OR, 1.5 [1.1, 2.1] to 2.3 [1.7, 3.0]) compared with Whites after adjustment for comorbidities. Conclusions: Although Blacks have lower incidence of hospitalizations for AF, they experience higher risk of heart failure, longer LOS, and greater mortality compared with Whites hospitalized with AF. Further public health investigation is warranted to examine the causes for disparities in outcomes among Blacks with AF and identify modifiable factors that may improve outcomes of Blacks with AF.

3057Relation of atrial remodeling to circulating biomarkers of myocardial fibrosis and apoptotic microparticles in patients with atrial fibrillation and heart failure with preserved ejection fraction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M S Dzeshka ◽  
E Shantsila ◽  
V A Snezhitskiy ◽  
G Y H Lip
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Ejection Fraction ◽  
Matrix Metalloproteinase ◽  
Myocardial Fibrosis ◽  
Univariate Analysis ◽  
Volume Index ◽  
Atrial Remodeling ◽  
Preserved Ejection Fraction ◽  
Circulating Biomarkers

Abstract Introduction Left atrial (LA) remodeling is a mainstay for atrial fibrillation (AF) occurrence. AF further promotes structural changes in LA, as fibrosis and stretching, followed by AF progression to its permanent form. Many profibrotic pathways have been studied, and circulating microparticles (MPs) may have a role. MPs are extracellular submicron anucleoid phospholipid vesicles released from different cells. Annexin V-binding (AnV+) MPs were suggested as a marker of apoptosis. Purpose To evaluate association of circulating biomarkers of myocardial fibrosis and MPs subsets with LA remodeling in patients with AF and heart failure with preserved ejection fraction. Methods We studied 274 patients (median age 62 years, 37% females). Paroxysmal AF was diagnosed in 150 patients (55%) and non-paroxysmal AF (persistent or permanent) in 124 (45%). Median CHA2DS2-VASc score was 3 in males and 4 in females. Patients with valvular AF, recent (<6 months) thromboembolic or hemorrhagic event, advanced chronic kidney or hepatic dysfunction, malignancy or active inflammatory disorders were excluded. Transthoracic echocardiography was performed. LA maximum volume index (LAVi) was measured as an index of LA structural remodeling in AF. Average values from ten consecutive cardiac cycles were calculated. Blood levels of galectin 3, interleukin-1 receptor-like 1 (ST2), transforming growth factor beta 1 (TGF-β1), procollagen type III aminoterminal propeptide (PIIINP), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), angiotensin II and aldosterone were assayed as surrogate biomarkers of myocardial fibrosis with ELISA. Using microflow cytometry (Figure), numbers of platelet-derived (CD42b+), monocyte-derived (CD14+), endothelial (CD144+), and apoptotic MPs (AnV+) were quantified in plasma samples. Linear regression was used to reveal parameters associated with LAVi. Raw data were normalized with Box-Cox transformation. Results Median LAVi in studied patients was 48 (39–59) ml/m2 and increased from patients with paroxysmal AF (42 [35–51] ml/m2) to persistent AF (53 [43–62] ml/m2) and permanent AF (57 [46–69] ml/m2), p<0.001. On univariate analysis male gender (β=0.11, p=0.04); history of hypertension (β=0.18, p=0.03); AF type, i.e. progression from paroxysmal to permanent (β=0.38, p<0.001); AnV+ MPs (β=0.19, p=0.005); ST2 (β=0.15, p=0.02); and early mitral inflow velocity (E)/early mitral annular diastolic velocity (E/E') averaged for LV septal and lateral basal regions (β=0.18, p=0.005) were associated with LAVi. Using stepwise multivariate regression AnV+ MPs (β=0.14, p=0.03); AF type (β=0.35, p<0.001); and E/E' ratio (β=0.11, p=0.04) remained significant predictors of LAVi (adjusted for age and gender). Apoptotic MPs detection with microFCM Conclusion Level of circulating apoptotic MPs is associated with LAVi in AF patients with HFpEF, and may be involved in remodeling process or could represent surrogate markers of myocardial damage in AF. Acknowledgement/Funding ESC Research Grant, EHRA Academic Research Fellowship Programme

scholarly journals Impact of Left Ventricular Function and Heart Failure Symptoms on Outcomes Post Ablation of Atrial Fibrillation in Heart Failure

2020 ◽  
Vol 13 (10) ◽  
Author(s):  
Christian Sohns ◽  
Konstantin Zintl ◽  
Yan Zhao ◽  
Lilas Dagher ◽  
Dietrich Andresen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
New York ◽  
Ventricular Dysfunction ◽  
Heart Association ◽  
Left Ventricular ◽  
Pharmacological Therapy ◽  
York Heart Association Class ◽  
Association Class ◽  
New York Heart Association

Background: Recent data demonstrate promising effects on left ventricular dysfunction and left ventricular ejection fraction (LVEF) improvement following ablation for atrial fibrillation (AF) in patients with heart failure. We sought to study the relationship between LVEF, New York Heart Association class on presentation, and the end points of mortality and heart failure admissions in the CASTLE-AF study (Catheter Ablation for Atrial Fibrillation With Heart Failure) population. Furthermore, predictors for LVEF improvement were examined. Methods: The CASTLE-AF patients with coexisting heart failure and AF (n=363) were randomized in a multicenter prospective controlled fashion to ablation (n=179) versus pharmacological therapy (n=184). Left ventricular function and New York Heart Association class were assessed at baseline (after randomization) and at each follow-up visit. Results: In the ablation arm, a significantly higher number of patients experienced an improvement in their LVEF to >35% at the end of the study (odds ratio, 2.17; P <0.001). Compared with the pharmacological therapy arm, both ablation patient groups with severe (<20%) or moderate/severe (≥20% and <35%) baseline LVEF had a significantly lower number of composite end points (hazard ratio [HR], 0.60; P =0.006), all-cause mortality (HR, 0.54; P =0.019), and cardiovascular hospitalizations (HR, 0.66; P =0.017). In the ablation group, New York Heart Association I/II patients at the time of treatment had the strongest improvement in clinical outcomes (primary end point: HR, 0.43; P <0.001; mortality: HR, 0.30; P =0.001). Conclusions: Compared with pharmacological treatment, AF ablation was associated with a significant improvement in LVEF, independent from the severity of left ventricular dysfunction. AF ablation should be performed at early stages of the patient’s heart failure symptoms.

scholarly journals Association of left atrial pressure with late gadolinium enhancement extent in patient who underwent catheter ablation for atrial fibrillation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Seung-Young Roh ◽  
Dae In Lee ◽  
Sung Ho Hwang ◽  
Kwang-No Lee ◽  
Yong-soo Baek ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Late Gadolinium Enhancement ◽  
Catheter Ablation ◽  
Left Atrial ◽  
Independent Predictor ◽  
Atrial Remodeling ◽  
Clinical Parameters ◽  
Gadolinium Enhancement ◽  
Cmr Imaging

Abstract Atrial remodeling with fibrosis has been well-described in patients with atrial fibrillation (AF). We hypothesized that the left atrial (LA)-late gadolinium enhancement (LGE) extent on cardiac magnetic resonance (CMR) imaging is associated with LA pressure and can be a marker for suitable candidates for non-paroxysmal AF ablation. A total of 173 AF patients with an LA-LGE area on CMR imaging were enrolled. The clinical parameters, including invasively measured LA pressure, were compared between the patients with extensive LA-LGE (E-LGE, LGE extent ≥ 20%, n = 78) and those with small LA-LGE (S-LGE, LGE extent < 20%, n = 95). The E-LGE group had higher peak LA pressures than the S-LGE group (23 versus 19 mmHg, p < 0.001). The E-LGE group had more patients with non-paroxysmal AF (non-PAF) (51% vs. 34%), heart failure (9% vs. 0%), and higher NT pro-B-type natriuretic peptide (472 vs. 265 pg/ml) (all p < 0.05). LA pressure ≥ 21 mmHg was an independent predictor of E-LGE (OR = 2.218; p = 0.019). In the paroxysmal AF (PAF) subgroup, freedom from atrial arrhythmia after catheter ablation was not different (81% vs 86%, log-rank p = 0.529). However, in the non-PAF subgroup, it was significantly higher in the S-LGE group than in the E-LGE group (81% vs 55%, log-rank p = 0.014). Increased LA pressure was related to the LA-LGE extent. LA-LGE was a good predictor of outcome after catheter ablation, but only in patients with non-PAF.

scholarly journals Left ventricular dysfunction in atrial fibrillation and heart failure risk

2020 ◽  
Vol 7 (6) ◽  
pp. 3694-3706
Author(s):  
Jen‐Yuan Kuo ◽  
Sheng‐Hsiung Chang ◽  
Kuo‐Tzu Sung ◽  
Po‐Ching Chi ◽  
Jo‐Nan Liao ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Left Ventricular Dysfunction ◽  
Ventricular Dysfunction ◽  
Left Ventricular ◽  
Failure Risk

Sudden Cardiac Death and Heart Failure

2009 ◽  
Vol 20 (4) ◽  
pp. 356-365
Author(s):  
Brenda S. Thompson
Keyword(s):  
Heart Failure ◽  
Sudden Cardiac Death ◽  
Left Ventricular Dysfunction ◽  
Cardiac Death ◽  
Ventricular Dysfunction ◽  
Treatment Guidelines ◽  
Systolic Dysfunction ◽  
The United States ◽  
Left Ventricular ◽  
Current Evidence

Ischemic heart disease and dilated cardiomyopathy are among the most common cardiovascular disease processes associated with heart failure that can lead to lethal arrhythmias and sudden cardiac death (SCD). With the increasing incidence of heart failure in the United States, many patients are now at risk for SCD. Nurses should understand the pathophysiology, current treatment guidelines, and the rationale for these therapies to effectively manage systolic dysfunction and to mitigate the risk of SCD. Nurses are more involved than ever with this patient population and play a key role as members of the heart failure disease management team. As a result, nurses are uniquely positioned to improve survival and reduce SCD in individuals diagnosed with left ventricular dysfunction. The purpose of this article is to increase the awareness of the risk of sudden death in patients with left ventricular dysfunction. Current evidence-based practice guidelines with rationale are reviewed.

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