Persistent atrial fibrillation worsens heart rate variability, activity and heart rate, as shown by a continuous monitoring by implantable biventricular pacemakers in heart failure patients

Background: Atrial fibrillation (AF) induces loss of atrial contribution, heart rate irregularity, and fast ventricular rate.
Objectives: The objectives of the study were to accurately measure AF incidence and to investigate the mutual temporal patterns of AF and heart failure (HF) in patients indicated to cardiac resynchronization therapy.
Methods: Four hundred ten consecutive patients (70% male, age 69 ± 11) with advanced HF (NYHA = 3.0 ± 0.6), low ejection fraction (EF = 27 ± 9%), and ventricular conduction delay (QRS = 165 ± 29 ms) received a biventricular pacemaker. Enrolled patients were divided into two groups: G1 = 249 patients with no AF history, G2 = 161 patients with history of paroxysmal/persistent AF.
Results: In a median follow-up of 13 months, AF episodes longer than 5 minutes occurred in 105 of 249 (42.2%) G1 patients and 76 of 161 (47.2%) G2 patients, while AF episodes longer than one day occurred in 14 of 249 (5.6%) G1 patients and in 36 of 161 (22.4%) G2 patients. Device diagnostics monitored daily values of patient activity, night heart rate (NHR), and heart rate variability (HRV). Comparing 30-day periods before AF onset and during persistent AF, significant (P < 0.0001) changes were observed in patient activity, which decreased from 221 ± 13 to 162 ± 12 minutes, and in NHR, which increased from 68 ± 3 to 94 ± 7 bpm. HRV significantly decreased (from 75 ± 5 ms before AF onset to 60 ± 6 ms after AF termination). NHR during AF was significantly (P < 0.01) and inversely correlated (R²= 0.73) with activity, with a significant lower activity associated with NHR ≥ 88 bpm.
Conclusion: AF is frequent in HF patients. Persistent AF is associated with statistically significant decrease in patient activity and HRV and NHR increase.     

Racial variation in the prevalence of atrial fibrillation among patients with heart failure: the Epidemiology, Practice, Outcomes, and Costs of Heart Failure (EPOCH) study

OBJECTIVES: This study was designed to determine the association between race and atrial fibrillation (AF) among patients with heart failure (HF). BACKGROUND: Atrial fibrillation is known to complicate HF, but whether its prevalence varies by race, and the reasons why, are not well understood. METHODS: We identified adults hospitalized with confirmed HF within a large integrated healthcare delivery system. We obtained information on demographics, comorbidity, vital signs, medications, and left ventricular systolic function status. "Atrial fibrillation" was defined as AF or atrial flutter documented by electrocardiogram or prior physician-assigned diagnoses. We evaluated the independent relationship between race and AF using multivariable logistic regression. RESULTS: Among 1,373 HF patients (223 African Americans, 1,150 Caucasians), the prevalence of AF was 36.9% (95% confidence interval [CI] 34.3% to 39.5%). Compared with Caucasians, African Americans were younger (mean age 67 vs. 74 years, p < 0.001) and more likely to have hypertension (86.6% vs. 77.7%, p < 0.01) and prior diagnosed HF (79.4% vs. 70.7%, p < 0.01). African Americans had less prior diagnosed coronary disease, revascularization, hypothyroidism, or valve replacement. Atrial fibrillation was much less prevalent in African Americans (19.7%) than Caucasians (38.3%, p < 0.001). After adjustment for risk factors for AF and other potential confounders, African Americans had 49% lower odds of AF (adjusted odds ratio 0.51, 95% CI 0.35 to 0.76). CONCLUSIONS: In a contemporary HF cohort, AF was significantly less common among African Americans than among Caucasians. This variation was not explained by differences in traditional risk factors for AF, HF etiology and severity, and treatment.     

Contribution of fibrosis and the autonomic nervous system to atrial fibrillation electrograms in heart failure

Background- Fibrotic and autonomic remodeling in heart failure (HF) increase vulnerability to atrial fibrillation (AF). Because AF electrograms (EGMs) are thought to reflect the underlying structural substrate, we sought to (1) determine the differences in AF EGMs in normal versus HF atria and (2) assess how fibrosis and nerve-rich fat contribute to AF EGM characteristics in HF. Methods and Results- AF was induced in 20 normal dogs by vagal stimulation and in 21 HF dogs (subjected to 3 weeks of rapid ventricular pacing at 240 beats per minute). AF EGMs were analyzed for dominant frequency (DF), organization index, fractionation intervals (FIs), and Shannon entropy. In 8 HF dogs, AF EGM correlation with underlying fibrosis/fat/nerves was assessed. In HF compared with normal dogs, DF was lower and organization index/FI/Shannon entropy were greater. DF/FI were more heterogeneous in HF. Percentage fat was greater, and fibrosis and fat were more heterogeneously distributed in the posterior left atrium than in the left atrial appendage. DF/organization index correlated closely with %fibrosis. Heterogeneity of DF/FI correlated with the heterogeneity of fibrosis. Autonomic blockade caused a greater change in DF/FI/Shannon entropy in the posterior left atrium than left atrial appendage, with the decrease in Shannon entropy correlating with %fat. Conclusions- The amount and distribution of fibrosis in the HF atrium seems to contribute to slowing and increased organization of AF EGMs, whereas the nerve-rich fat in the HF posterior left atrium is positively correlated with AF EGM entropy. By allowing for improved detection of regions of dense fibrosis and high autonomic nerve density in the HF atrium, these findings may help enhance the precision and success of substrate-guided ablation for AF.     

Atrial fibrillation in heart failure: The sword of damocles revisited

Heart failure (HF) and atrial fibrillation (AF) frequently coexist and have emerged as major cardiovascular epidemics. There is growing evidence that AF is an independent prognostic marker in HF and affects patients with both reduced as well as preserved LV systolic function. There has been a general move in clinical practice from a rhythm control to a rate control strategy in HF patients with AF, although recent data suggests that rhythm control strategies may provide better outcomes in selected subgroups of HF patients. Furthermore, various therapeutic modalities including pace and ablate strategies with cardiac resynchronisation or radio-frequency ablation have become increasingly adopted, although their role in the management of AF in patients with HF remains uncertain. This article presents an overview of the multidimensional impact of AF in patients with HF. Relevant literature is highlighted and the effect of various therapeutic modalities on prognosis is discussed. Finally, while novel anticoagulants usher in a new era in thromboprophylaxis, research continues in avariety of new pathways including selective atrial anti-arrhythmic agents and genomic polymorphisms in AF with HF.     

Novel oral anticoagulants and stroke prevention in atrial fibrillation and chronic heart failure

Heart failure (HF) and atrial fibrillation (AF) frequently coexist and share a reciprocal relationship. The presence of AF increases the propensity to HF and can worsen its severity as well as escalating the risk of stroke. Despite the proven efficacy of vitamin K antagonists and warfarin for stroke prevention in AF, their use is beset by numerous problems. These include their slow onset and offset of action, unpredictability of response, the need for frequent coagulant monitoring and serious concerns around the increased risks of intracranial and major bleeding. Three recently approved novel anticoagulants (dabigatran, rivaroxaban and apixaban) are already challenging warfarin use in AF. They have a predictable therapeutic response and a wide therapeutic range and do not necessitate coagulation monitoring. In this article, the relationship between HF and AF and the mechanisms for their compounded stroke risk are reviewed. The evidence to support the use of these three NOACs amongst patients with AF and HF is further explored.     

Prognostic significance of new atrial fibrillation and its relation to heart failure following acute myocardial infarction

BACKGROUND: New-onset atrial fibrillation (AF) after acute myocardial infarction (AMI) frequently occurs in association with postinfarction complications, particularly with heart failure (HF). AIMS: To evaluate whether postinfarction HF is associated with the subsequent development of AF and whether AF independently predicts poorer prognosis. METHODS AND RESULTS: We examined 650 patients with AMI and compared patients with AF (n=320) to those without (n=330). AF patients were classified as either early AF (n=208)-patients who developed AF within 24 h of symptom onset or late AF (n=112)-patients who had AF thereafter. We compared outcomes between these groups, adjusting for differences in baseline characteristics and postinfarction HF. Heart failure was the most important predictor of AF. In most patients, AF occurred secondary to HF. AF patients had poorer outcomes, including higher in-hospital and 7-year mortality. After multivariate adjustment, overall, AF was not an independent predictor of in-hospital [odds ratio (OR)=0.70) and 7-year [relative risk (RR)=1.14] mortality, but late AF remained an independent predictor of 7-year (RR=2.48, 95% confidence interval, 1.26-4.87) mortality. CONCLUSIONS: Heart failure mostly preceded the occurrence of new-onset atrial fibrillation after acute myocardial infarction, but only late atrial fibrillation was independently related to long-term mortality.     

Empagliflozin in heart failure with preserved ejection fraction with and without atrial fibrillation

Aims

Atrial fibrillation/flutter (AF) is common in heart failure (HF) with preserved left ventricular ejection fraction (LVEF) and associated with worse outcomes. Empagliflozin reduces cardiovascular death or HF hospitalizations and slows estimated glomerular filtration rate (eGFR) decline in patients with HF and LVEF >40%. We aimed to assess the efficacy and safety of empagliflozin in improving outcomes in patients with HF and LVEF >40% with and without AF.

Methods and results

In this pre-defined secondary analysis of EMPEROR-Preserved, we compared the effects of empagliflozin versus placebo on the primary and secondary endpoints and safety outcomes, stratified by baseline AF, defined as AF reported in any electrocardiogram before empagliflozin initiation or in medical history. Among 5988 patients randomized, 3135 (52%) had baseline AF; these patients were older, with worse functional class, more previous HF hospitalizations and higher natriuretic peptides compared to those without AF (all p < 0.001). After a median of 26 months, empagliflozin reduced cardiovascular death or HF hospitalization compared to placebo to a similar extent in patients with and without AF (hazard ratio [HR] 0.78 [95% confidence interval 0.66–0.93] vs. 0.78 [0.64–0.95], interaction p = 0.96). Empagliflozin also reduced total HF hospitalizations (HR 0.73 [0.57–0.94] vs. 0.72 [0.54–0.95], interaction p = 0.94) and annual eGFR decline (difference = 1.368 vs. 1.372 ml/min/1.73 m²/year, interaction p = 0.99) consistently in patients with and without AF. There was no increase in serious adverse events with empagliflozin versus placebo in patients with and without AF.

Conclusions

In patients with HF and ejection fraction >40%, empagliflozin reduced the risk of serious HF events and slowed the eGFR decline regardless of baseline AF.     

Influence of atrial fibrillation on plasma von willebrand factor, soluble E-selectin, and N-terminal pro B-type natriuretic peptide levels in systolic heart failure

BACKGROUND: Endothelial dysfunction is present in patients with heart failure (HF) due to left ventricular systolic dysfunction, as well as in patients with atrial fibrillation (AF) who have normal cardiac function. It is unknown whether AF influences the degree of endothelial dysfunction in patients with systolic HF. METHODS: We measured levels of plasma von Willebrand factor (vWF) and E-selectin (as indexes of endothelial damage/dysfunction and endothelial activation, respectively; both enzyme-linked immunosorbent assay) in patients with AF and HF (AF-HF), who were compared to patients with sinus rhythm and HF (SR-HF), as well as in age-matched, healthy, control subjects. We also assessed the relationship of vWF and E-selectin to plasma N-terminal pro B-type natriuretic peptide (NTpro-BNP), a marker for HF severity and prognosis. RESULTS: One hundred ninety patients (73% men; mean age, 69.0 +/- 10.1 years [+/- SD]) with systolic HF were studied, who were compared to 117 healthy control subjects: 52 subjects (27%) were in AF, while 138 subjects (73%) were in sinus rhythm. AF-HF patients were older than SR-HF patients (p = 0.046), but left ventricular ejection fraction and New York Heart Association class were similar. There were significant differences in NT-proBNP (p < 0.0001) and plasma vWF (p = 0.003) between patients and control subjects. On Tukey post hoc analysis, AF-HF patients had significantly increased NT-proBNP (p < 0.001) and vWF (p = 0.0183) but not E-selectin (p = 0.071) levels when compared to SR-HF patients. On multivariate analysis, the presence of AF was related to plasma vWF levels (p = 0.018). Plasma vWF was also significantly correlated with NT-proBNP levels (Spearman r = 0.139; p = 0.017). CONCLUSIONS: There is evidence of greater endothelial damage/dysfunction in AF-HF patients when compared to SR-HF patients. The clinical significance of this is unclear but may have prognostic value.     

Statins and prevention of atrial fibrillation in patients with heart failure

Statins are highly effective and widely used lipid-lowering agents in clinical practice, that also display a number of pleiotropic properties beyond cholesterol lowering. Several trials have demonstrated that they reduce cardiovascular morbidity and mortality in both primary and secondary prevention. Atrial fibrillation (AF) and heart failure (HF) represent 2 world-wide epidemics. Recent evidence suggests that statins may have beneficial effects on cardiovascular outcomes in patients with HF, and specifically in the prevention of AF. The anti-arrhythmic mechanisms of statins regarding AF prevention in HF patients are not fully understood but are possibly related to their pleiotropic effects including anti-inflammatory, antioxidant, atrial remodeling attenuation, ion channel stabilization, and autonomic nervous system regulation.     

High morbidity in myocardial infarction and heart failure patients after gastric cancer surgery

AIM: To evaluate to morbidity and mortality differences between 4 underlying heart diseases, myocardial infarction (MI), angina pectoris (Angina), heart failure (HF), and atrial fibrillation (AF), after radical surgery for gastric cancer. METHODS: We retrospectively collected data from 221 patients of a total of 15167 patients who underwent radical gastrectomy and were preoperatively diagnosed with a history of Angina, MI, HF, or AF in 8 hospitals. RESULTS: We find that the total morbidity rate is significantly higher in the MI group (44%) than the Angina (15.7%), AF (18.8%), and HF (23.1%) groups (P < 0.01). Moreover, we note that the risk for postoperative cardiac problems is higher in patients with a history of HF (23.1%) than patients with a history of Angina (2.2%), AF (4.3%), or MI (6%; P = 0.01). The HF and MI groups each have 1 case of cardiogenic mortality. CONCLUSION: We conclude that MI patients have a higher risk of morbidity, and HF patients have a higher risk of postoperative cardiac problems than Angina or AF.     

Impact of atrial fibrillation in heart failure with normal ejection fraction: a clinical and echocardiographic study

BackgroundThe clinical significance of atrial fibrillation (AF) in heart failure with normal ejection fraction (HFNEF) remains undetermined.Methods and ResultsWe compared the clinical and echocardiographic characteristics among 238 patients hospitalized for HF. Using the cutoff of left ventricular EF of 50%, there were 146 patients with HFNEF (AF = 42) and 92 with systolic HF (AF = 30). When compared among HFNEF, the New York Heart Association (NYHA) class (2.61 ± 0.51 versus 2.21 ± 0.46; P < .05), 6-minute walk distance (279.7 ± 66.0 versus 338.0 ± 86.1 m; P < .01), quality of life score (26.1 ± 14.3 versus 19.5 ± 10.3; P < .05), and previous HF hospitalization were significantly worse in the AF group. These variables were significantly better in HFNEF than systolic HF with sinus rhythm, but the differences were not detected among those with AF. Patients with HFNEF and AF were associated with more severe diastolic dysfunction when compared to sinus rhythm. With a median follow-up of 10.5 months, the proportion of HFNEF patients in AF with recurrent HF hospitalization or death was significantly higher than those in sinus rhythm (28.6% versus 10.6%; P < .01). Both AF and restrictive diastolic dysfunction were independent predictors of HF hospitalization or death in HFNEF.ConclusionPatients with HFNEF and AF were associated with more severe diastolic dysfunction and worse clinical outcomes than those in sinus rhythm.     

Relationship between device-detected subclinical atrial fibrillation and heart failure in patients with cardiac resynchronization therapy defibrillator

BackgroundAtrial fibrillation (AF) is a leading preventable cause of heart failure (HF) for which early detection and treatment is critical. Subclinical‐AF is likely to go untreated in the routine care of patients with cardiac resynchronization therapy defibrillator (CRT‐D).HypothesisThe hypothesis of our study is that subclinical‐AF is associated with HF hospitalization and increasing an inappropriate therapy.MethodsWe investigated 153 patients with an ejection fraction less than 35%. We divided into three groups, subclinical‐AF (n = 30), clinical‐AF (n = 45) and no‐AF (n = 78). We compared the baseline characteristics, HF hospitalization, and device therapy among three groups. The follow‐up period was 50 months after classification of the groups.ResultsThe average age was 66 ± 15 years and the average ejection fraction was 26 ± 8%. Inappropriate therapy and biventricular pacing were significantly different between subclinical‐AF and other groups (inappropriate therapy: subclinical‐AF 13% vs clinical‐AF 8.9% vs no‐AF 7.7%: P = .04, biventricular pacing: subclinical‐AF 81% vs clinical‐AF 85% vs no‐AF 94%, P = .001). Using Kaplan‐Meier method, subclinical‐AF group had a significantly higher HF hospitalization rate as compared with other groups. (subclinical‐AF 70% vs clinical‐AF 49% vs no‐AF 38%, log‐rank: P = .03). In multivariable analysis, subclinical‐AF was a predictor of HF hospitalization.ConclusionsSubclinical‐AF after CRT‐D implantation was associated with a significantly increased risk of HF hospitalization. The loss of the biventricular pacing and increasing an inappropriate therapy might affect the risk of HF hospitalization.     

Atrial fibrillation in heart failure patients: prevalence in daily practice and effect on the severity of symptoms. Data from the ALPHA study registry

BACKGROUND: Estimates of the prevalence of atrial fibrillation (AF) in heart failure (HF) originate from patients enrolled in clinical trials. AIMS: To assess the prevalence and clinical correlates of AF among HF patients in everyday clinical practice from HF patients screened for the T-wave ALternans in Patients with Heart fAilure (ALPHA) study; to investigate the correlation between AF and functional status. METHODS AND RESULTS: Consecutive patients (N=3513) seen at nine Heart Failure Clinics were studied; 21.4% were in AF. AF prevalence was greater with increasing age (OR 1.04/year, p<0.001) in non-ischaemic cardiomyopathy (OR 2.34, p<0.001) and with increasing NYHA class (p<0.0001). Multiple logistic regression predictors of AF were age >70 years (OR 2.35), NYHA class II III or IV vs class I (OR 1.8, 4.4 and 3.1) and non-ischaemic cardiomyopathy (OR 3.2). A logistic model indicated that AF was associated with a 2.5 OR of being in NYHA class III-IV vs I-II while accounting for age, gender, left ventricular ejection fraction (LVEF), and aetiology of HF. CONCLUSIONS: The prevalence of AF in HF patients exceeds 20%, and increases with age and functional class. The presence of AF leads to a more severe NYHA class, indicating that AF contributes to the severity of heart failure.     

缺血性心力衰竭患者心房颤动与血清尿酸水平的关联性

目的 探讨缺血性心力衰竭（HF）患者心房颤动（AF）与血清尿酸（SUA）水平的关联性。方法 连续性收集于2012年10月~2014年10月就诊于佛山市中医院的缺血性HF患者363例,根据心电图或者病史记录将患者分为AF组和无AF组,比较两组间基线特征及SUA与AF的相关性。结果 363例患者中,共有78例患者患有AF,285例患者为正常窦性心律。与无AF患者相比,AF患者的SUA水平显著提高〔(64±21) vs.(57±19) mg/L,P<0.01〕。同时,AF组患者的年龄更大〔(71±8) vs.(66±11)岁,P<0.01〕。此外,AF患者的超声心动图指标,包括左室射血分数、左房内径、左心室舒张末期内径以及左心室舒张末期容积,同样显著高于窦性心律正常的患者。多因素回归分析显示,校正相关影响因素后,SUA水平仍为AF的独立相关因素(OR=1.27,95% CI,1.06-1.52,P≤0.01)。结论 SUA水平是缺血性HF患者AF的独立相关因素。     

心力衰竭犬心房组织MMP-2和TIMP-1、2的基因表达及其与心房扩大及心房颤动的关系

目的探讨心力衰竭(简称心衰)犬心房组织基质金属蛋白酶-2(MMP-2)及其组织抑制因子1、2(TIMP-1、2)的基因表达及其与心房扩大及心房颤动(简称房颤)发生维持的关系。方法选健康成年杂种犬14只随机分为心室快速起搏致心衰组和对照组,采用Burst刺激诱发房颤,逆转录-聚合酶链式反应技术和免疫组化方法检测两组左右心房组织MMP-2和TIMP-1、2的mRNA和蛋白表达,采集心房标本前超声心动图测定左右心房收缩末期面积。结果心衰组左室射血分数下降、房颤的诱发和维持时间增加,左右心房均扩大。MMP-2的mRNA和蛋白表达在左右心房中均上调;TIMP-2的mRNA在左右心房中无明显改变,但MMP-2/TIMP-2的mRNA和蛋白的比值在左右心房中均升高(P<0.01);TIMP-1的mRNA和蛋白表达在左右心房中均下调。心衰组,房颤持续时间与左房面积呈正相关。结论心房组织MMP-2和TIMP-1、2的基因表达改变以及MMP-2/TIMP-2表达失衡可能是心衰时心房扩大及房颤发生与维持的分子机制之一。     

Prevalence and prognostic significance of atrial fibrillation in outpatients with heart failure due to left ventricular systolic dysfunction

INTRODUCTION: Atrial fibrillation (AF) is common in patients with heart failure (HF) due to left ventricular systolic dysfunction (LVSD), with conflicting prognostic data. The aim of our study was to assess the prevalence and incidence of AF in patients with HF and to determine the prognostic impact of baseline AF and the development of new onset AF. METHODS AND RESULTS: We included 1019 outpatients with HF due to LVSD; follow-up time ranged from 3 to 64 months. At baseline 26.4% of patients had AF. Of the 284 patients with a follow-up ECG and baseline SR, 18.7% developed new onset AF. Patients with AF were older (p<0.001), more often male (p=0.04), and more likely to have a history of stroke (p=0.03), but were less likely to have IHD (p<0.001). Baseline rhythm was independent of LVEF and NYHA-class. Baseline AF was associated with increased all-cause mortality (HR 1.38; CI 1.07-1.78, p=0.01) and all-cause mortality/hospitalisation (HR 1.43; CI 1.22-1.68, p<0.001). When adjusted for baseline covariates, baseline AF was independently associated with an increased risk of experiencing the combined endpoint (HR 1.29; CI 1.05-1.58; p=0.02), but did not predict all-cause mortality. By multivariable analyses, new-onset AF was associated with increased risk of all-cause mortality/hospitalisation (HR 1.45; CI 1.05-2.00; p=0.02). CONCLUSION: In outpatients with HF due to LVSD, AF is a common co-morbidity, which adversely affects morbidity and mortality outcomes.     

Prevention of atrial fibrillation onset by beta-blocker treatment in heart failure: a meta-analysis.

AIMS: Atrial fibrillation (AF) is an important morbidity-mortality risk factor, especially in patients with heart failure (HF). Beta-blockers reduce morbidity and mortality in HF. The study was designed to estimate the preventive efficacy of beta-blocker treatment on AF occurrence in patients with HF. METHODS AND RESULTS: A systematic review of the literature was performed to identify all clinical trials evaluating beta-blockers' efficacy in HF. Eligible studies had to be randomized, placebo-controlled and providing information on the incidence of AF during follow-up among those with sinus rhythm at baseline. A total of seven studies which included 11 952 patients receiving a background treatment with angiotensin-converting enzyme-inhibitors could be found. Overall, beta-blockers significantly reduced incidence of onset of AF from 39 to 28 per 1000 patient-years: relative risk reduction=27% (95% confidence interval 14-38, P<0.001); heterogeneity test: P=0.096. A same trend of efficacy was observed in all trials except the SENIORS study. In this trial which included aged patients (>70 years) with systolic or diastolic HF, a higher prevalence of AF at baseline (35%) was observed compared with the mean baseline prevalence (13%). CONCLUSION: Beta-blockers appear to effectively prevent occurrence of AF in patients with systolic HF.     

The management of atrial fibrillation in heart failure

Opinion statement The development of atrial fibrillation (AF) can greatly complicate the course of heart failure (HF). Although recent trials have indicated the nonsuperiority of a rhythm control strategy in the general population with AF, this may not apply to patients with HF. We feel strongly that AF be treated aggressively in patients with HF, defaulting toward an initial rhythm control strategy, to avoid the hemodynamic detriment of irregular rapid ventricular response and the development of tachycardia-related myopathy. The index episode is treated with cardioversion and antiarrhythmic therapy. If significant benefit is demonstrated, the rhythm control strategy is maintained, to the point of catheter ablation for AF if necessary. If there is no change in cardiac performance or symptoms after cardioversion, strict rate control is enforced, to the point of atrioventricular node ablation and pacing if necessary.