Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis.
Kotecha Dipak,Holmes Jane,Krum Henry,Altman Douglas G,Manzano Luis,Cleland John G F,Lip Gregory Y H,Coats Andrew J S,Andersson Bert,Kirchhof Paulus,von Lueder Thomas G,Wedel Hans,Rosano Giuseppe,Shibata Marcelo C,Rigby Alan,Flather Marcus D,
Lancet (London, England)
BACKGROUND:Atrial fibrillation and heart failure often coexist, causing substantial cardiovascular morbidity and mortality. β blockers are indicated in patients with symptomatic heart failure with reduced ejection fraction; however, the efficacy of these drugs in patients with concomitant atrial fibrillation is uncertain. We therefore meta-analysed individual-patient data to assess the efficacy of β blockers in patients with heart failure and sinus rhythm compared with atrial fibrillation. METHODS:We extracted individual-patient data from ten randomised controlled trials of the comparison of β blockers versus placebo in heart failure. The presence of sinus rhythm or atrial fibrillation was ascertained from the baseline electrocardiograph. The primary outcome was all-cause mortality. Analysis was by intention to treat. Outcome data were meta-analysed with an adjusted Cox proportional hazards regression. The study is registered with Clinicaltrials.gov, number NCT0083244, and PROSPERO, number CRD42014010012. FINDINGS:18,254 patients were assessed, and of these 13,946 (76%) had sinus rhythm and 3066 (17%) had atrial fibrillation at baseline. Crude death rates over a mean follow-up of 1·5 years (SD 1·1) were 16% (2237 of 13,945) in patients with sinus rhythm and 21% (633 of 3064) in patients with atrial fibrillation. β-blocker therapy led to a significant reduction in all-cause mortality in patients with sinus rhythm (hazard ratio 0·73, 0·67-0·80; p<0·001), but not in patients with atrial fibrillation (0·97, 0·83-1·14; p=0·73), with a significant p value for interaction of baseline rhythm (p=0·002). The lack of efficacy for the primary outcome was noted in all subgroups of atrial fibrillation, including age, sex, left ventricular ejection fraction, New York Heart Association class, heart rate, and baseline medical therapy. INTERPRETATION:Based on our findings, β blockers should not be used preferentially over other rate-control medications and not regarded as standard therapy to improve prognosis in patients with concomitant heart failure and atrial fibrillation. FUNDING:Menarini Farmaceutica Internazionale (administrative support grant).
Risk of stroke in chronic heart failure patients with preserved ejection fraction, but without atrial fibrillation: analysis of the CHARM-Preserved and I-Preserve trials.
Abdul-Rahim Azmil H,Perez Ana-Cristina,MacIsaac Rachael L,Jhund Pardeep S,Claggett Brian L,Carson Peter E,Komajda Michel,McKelvie Robert S,Zile Michael R,Swedberg Karl,Yusuf Salim,Pfeffer Marc A,Solomon Scott D,Lip Gregory Y H,Lees Kennedy R,McMurray John J V,
European heart journal
Aims:The incidence and predictors of stroke in patients with heart failure and preserved ejection fraction (HF-PEF), but without atrial fibrillation (AF), are unknown. We described the incidence of stroke in HF-PEF patients with and without AF and predictors of stroke in those without AF. Methods and results:We pooled data from the CHARM-Preserved and I-Preserve trials. Using Cox regression, we derived a model for stroke in patients without AF in this cohort and compared its performance with a published model in heart failure patients with reduced ejection fraction (HF-REF)-predictive variables: age, body mass index, New York Heart Association class, history of stroke, and insulin-treated diabetes. The two stroke models were compared and Kaplan-Meier curves for stroke estimated. The risk model was validated in a third HF-PEF trial. Of the 6701 patients, 4676 did not have AF. Stroke occurred in 124 (6.1%) with AF and in 171 (3.7%) without AF (rates 1.80 and 1.00 per 100 patient-years, respectively). There was no difference in performance of the stroke model derived in the HF-PEF cohort and the published HF-REF model (c-index 0.71, 95% confidence interval 0.57-0.84 vs. 0.73, 0.59-0.85, respectively) as the predictive variables overlapped. The model performed well in the validation cohort (0.86, 0.62-0.99). The rate of stroke in patients in the upper third of risk approximated to that in patients with AF (1.60 and 1.80 per 100 patient-years, respectively). Conclusions:A small number of clinical variables identify a subset of patients with HF-PEF, but without AF, at elevated risk of stroke.
The Cumulative Incidence of Stroke, Myocardial infarction, Heart Failure and Sudden Cardiac Death in Patients with Atrial Fibrillation.
Naser Nabil,Kulic Mehmed,Dilic Mirza,Dzubur Alen,Durak Azra,Pepic Esad,Smajic Elnur,Kusljugic Zumreta
Medical archives (Sarajevo, Bosnia and Herzegovina)
Introduction:Atrial fibrillation represents the most common cardiac arrhythmia in clinical practice. By year 2030, 14-17 million AF patients are anticipated in the European Union. Atrial fibrillation remains one of the major causes of stroke, heart failure, sudden death all over the world. Research Objectives:The objective of our study is to determine the cardiac and cerebrovascular events (myocardial infarction, heart failure, stroke, sudden cardiac death) and their cumulative incidence during 11 years follow up period. Patients and methods:This study includes 2352 ambulant and hospitalized patients with atrial fibrillation (AF) who were enrolled during the follow up period. All patients underwent clinical evaluation in order to determine cardiac and cerebrovascular events (myocardial infarction, heart failure, stroke, sudden cardiac death) and their cumulative incidence. Results:The results of cumulative incidence for sudden cardiac death was 1.71%, for stroke 2.56%, for myocardial infarction 1.20% and for heart failure was 5.73%. In our study the age-adjusted incidence and prevalence of AF are slightly lower in women. The study shows that the risk of death is higher in females than in males with AF. Conclusion:Despite good progress in the management of patients with atrial fibrillation (AF), this arrhythmia remains one of the major causes of stroke, heart failure, sudden death. Effective treatment of patients with atrial fibrillation includes not only rate control, rhythm control, and prevention of stroke, but also management of cardiovascular risk factors and concomitant diseases.
Atrial Fibrillation in Heart Failure US Ambulatory Cardiology Practices and the Potential for Uptake of Catheter Ablation: An National Cardiovascular Data Registry (NCDR) Research to Practice (R2P) Project.
Mathew Jehu S,Marzec Lucas N,Kennedy Kevin F,Jones Philip G,Varosy Paul D,Masoudi Frederick A,Maddox Thomas M,Allen Larry A
Journal of the American Heart Association
BACKGROUND:Atrial fibrillation (AF) and heart failure with reduced ejection fraction frequently coexist. The AATAC (Ablation versus Amiodarone for Treatment of persistent Atrial fibrillation in patients with Congestive heart failure and an implantable device) trial suggests that catheter ablation may benefit these patients. However, applicability to contemporary ambulatory cardiology practice is unknown. METHODS AND RESULTS:Using the outpatient National Cardiovascular Data Registry Practice Innovation and Clinical Excellence Registry, we identified participants meeting AATAC enrollment criteria between 2013 and 2014. Treatment with medications and procedures was assessed at registry inclusion. From 164 166 patients with AF and heart failure, 8483 (7%) patients potentially met AATAC inclusion criteria. Eligible subjects, compared to AATAC trial participants, were older (mean age, 71.2±11.4 years) and had greater comorbidity (coronary artery disease 79.2%, hypertension 82.4%, and diabetes mellitus 31.8%). AF was predominantly paroxysmal (65.5%), rather than persistent/permanent (16.7%) or new onset (17.8%), whereas all patients in the AATAC trial had persistent AF. Commonly used atrioventricular-nodal blocking agents were carvedilol (71.2%), digoxin (31.9%), and metoprolol (27.1%). Rhythm control with anti-arrhythmic drugs was reported in 29.0% of AATAC eligible patients (predominantly amiodarone [24.6%]) and 9.3% had undergone catheter ablation. Patients who underwent ablation were more likely to be younger and have less comorbidities than those who did not. CONCLUSIONS:Among the contemporary ambulatory AF/heart failure with reduced ejection fraction population, treatment is predominantly rate control with few catheter ablations. Application of AATAC findings has the potential to markedly increase the use of catheter ablation in this population, although significant differences in clinical profiles might influence ablation outcomes in practice.
Catheter Ablation for Atrial Fibrillation with Heart Failure.
Marrouche Nassir F,Brachmann Johannes,Andresen Dietrich,Siebels Jürgen,Boersma Lucas,Jordaens Luc,Merkely Béla,Pokushalov Evgeny,Sanders Prashanthan,Proff Jochen,Schunkert Heribert,Christ Hildegard,Vogt Jürgen,Bänsch Dietmar,
The New England journal of medicine
BACKGROUND:Mortality and morbidity are higher among patients with atrial fibrillation and heart failure than among those with heart failure alone. Catheter ablation for atrial fibrillation has been proposed as a means of improving outcomes among patients with heart failure who are otherwise receiving appropriate treatment. METHODS:We randomly assigned patients with symptomatic paroxysmal or persistent atrial fibrillation who did not have a response to antiarrhythmic drugs, had unacceptable side effects, or were unwilling to take these drugs to undergo either catheter ablation (179 patients) or medical therapy (rate or rhythm control) (184 patients) for atrial fibrillation in addition to guidelines-based therapy for heart failure. All the patients had New York Heart Association class II, III, or IV heart failure, a left ventricular ejection fraction of 35% or less, and an implanted defibrillator. The primary end point was a composite of death from any cause or hospitalization for worsening heart failure. RESULTS:After a median follow-up of 37.8 months, the primary composite end point occurred in significantly fewer patients in the ablation group than in the medical-therapy group (51 patients [28.5%] vs. 82 patients [44.6%]; hazard ratio, 0.62; 95% confidence interval [CI], 0.43 to 0.87; P=0.007). Significantly fewer patients in the ablation group died from any cause (24 [13.4%] vs. 46 [25.0%]; hazard ratio, 0.53; 95% CI, 0.32 to 0.86; P=0.01), were hospitalized for worsening heart failure (37 [20.7%] vs. 66 [35.9%]; hazard ratio, 0.56; 95% CI, 0.37 to 0.83; P=0.004), or died from cardiovascular causes (20 [11.2%] vs. 41 [22.3%]; hazard ratio, 0.49; 95% CI, 0.29 to 0.84; P=0.009). CONCLUSIONS:Catheter ablation for atrial fibrillation in patients with heart failure was associated with a significantly lower rate of a composite end point of death from any cause or hospitalization for worsening heart failure than was medical therapy. (Funded by Biotronik; CASTLE-AF ClinicalTrials.gov number, NCT00643188 .).
Progression of Device-Detected Subclinical Atrial Fibrillation and the Risk of Heart Failure.
Wong Jorge A,Conen David,Van Gelder Isabelle C,McIntyre William F,Crijns Harry J,Wang Jia,Gold Michael R,Hohnloser Stefan H,Lau C P,Capucci Alessandro,Botto Gianluca,Grönefeld Gerian,Israel Carsten W,Connolly Stuart J,Healey Jeff S
Journal of the American College of Cardiology
BACKGROUND:Long-term continuous monitoring detects short-lasting, subclinical atrial fibrillation (SCAF) in approximately one-third of older individuals with cardiovascular conditions. The relationship between SCAF, its progression, and the development of heart failure (HF) is unclear. OBJECTIVES:This study examined the relationship between progression from shorter to longer SCAF episodes and HF hospitalization. METHODS:Subjects in ASSERT (Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial) were ≥65 years old, had history of hypertension, no prior clinical AF, and an implanted pacemaker or defibrillator. We examined patients whose longest SCAF episode during the first year after enrollment was >6 min but ≤24 h (n = 415). Using time-dependent Cox models, we evaluated the relationship between subsequent development of SCAF >24 h or clinical AF and HF hospitalization. RESULTS:Over a mean follow-up of 2 years, 65 patients (15.7%) progressed to having SCAF episodes >24 h or clinical AF (incidence 8.8% per year). Older age, greater body mass index, and longer SCAF duration within the first year were independent predictors of SCAF progression. The rate of HF hospitalization among patients with SCAF progression was 8.9% per year compared with 2.5% per year for those without progression. After multivariable adjustment, SCAF progression was independently associated with HF hospitalization (hazard ratio [HR]: 4.58; 95% confidence interval [CI]: 1.64 to 12.80; p = 0.004). Similar results were observed when we excluded patients with prior history of HF (HR: 7.06; 95% CI: 1.82 to 27.30; p = 0.005) or when SCAF progression was defined as development of SCAF >24 h alone (HR: 3.68; 95% CI: 1.27 to 10.70; p = 0.016). CONCLUSIONS:In patients with a pacemaker or defibrillator, SCAF progression was strongly associated with HF hospitalization.
Prognostic implications of atrial fibrillation in heart failure with reduced, mid-range, and preserved ejection fraction: a report from 14 964 patients in the European Society of Cardiology Heart Failure Long-Term Registry.
Zafrir Barak,Lund Lars H,Laroche Cecile,Ruschitzka Frank,Crespo-Leiro Maria G,Coats Andrew J S,Anker Stefan D,Filippatos Gerasimos,Seferovic Petar M,Maggioni Aldo P,De Mora Martin Manuel,Polonski Lech,Silva-Cardoso José,Amir Offer,
European heart journal
Aim:To investigate the characteristics long-term prognostic implications (up to ∼2.2 years) of atrial fibrillation (AF) compared to sinus rhythm (SR), between acute and chronic heart failure (HF) with reduced (HFrEF < 40%), mid-range (HFmrEF 40-49%), and preserved (HFpEF ≥ 50%) ejection fraction (EF). Methods and results:Data from the observational, prospective, HF long-term registry of the European Society of Cardiology were analysed. A total of 14 964 HF patients (age 66 ± 13 years, 67% male; 53% HFrEF, 21% HFmrEF, 26% HFpEF) were enrolled. The prevalence of AF was 27% in HFrEF, 29% in HFmrEF, and 39% in HFpEF. Atrial fibrillation was associated with older age, lower functional capacity, and heightened physical signs of HF. Crude rates of mortality and HF hospitalization were higher in patients with AF compared to SR, in each EF subtype. After multivariable adjustment, the hazard ratio of AF for HF hospitalizations was: 1.036 (95% CI 0.888-1.208, P = 0.652) in HFrEF, 1.430 (95% CI 1.087-1.882, P = 0.011) in HFmrEF, and 1.487 (95% CI 1.195-1.851, P < 0.001) in HFpEF; and for combined all-cause death or HF hospitalizations: 0.957 (95% CI 0.843-1.087, P = 0.502), 1.302 (95% CI 1.055-1.608, P = 0.014), and 1.365 (95% CI 1.152-1.619, P < 0.001), respectively. In patients with HFrEF, AF was not associated with worse outcomes in those presenting with either an acute or a chronic presentation of HF. Conclusions:The prevalence of AF increases with increasing EF but its association with worse cardiovascular outcomes, remained significant in patients with HFpEF and HFmrEF, but not in those with HFrEF.
β-blockers and risk of all-cause mortality in patients with chronic heart failure and atrial fibrillation-a meta-analysis.
Xu Tianyu,Huang Yuli,Zhou Haobin,Bai Yujia,Huang Xingfu,Hu Yunzhao,Xu Dingli,Zhang Yuhui,Zhang Jian
BMC cardiovascular disorders
BACKGROUND:Effects of β-blockers on outcomes in patients with chronic heart failure (CHF) and atrial fibrillation (AF) is still in controversy. METHODS:Searching was conducted by using keywords "atrial fibrillation", and "heart failure" in PubMed, MEDLINE and Embase databases before November 30, 2017. Prospective studies [i.e. randomized control trials (RCTs), post-hoc analysis of RCTs, prospective cohort studies and registry studies] that studied the effect of β-blockers and all-cause mortality in patients with CHF and AF were included. The analysis was stratified by study design. RESULTS:We identified 12 studies, including 6 post-hoc analysis of RCTs and 6 observational studies (including prospective registry studies and prospective cohort studies), which enrolled 38,133 patients with CHF and AF. Overall, β-blockers treatment was associated with significant decrease in all-cause mortality [Risk Ratio (RR) =0.73; 95% Confidence Interval (CI) 0.65-0.82, P < 0.001]. When stratified by study design, β-blockers treatment was associated with 34% reduction in patients with CHF and AF in observational study (RR = 0.66; 95% CI 0.58-0.76, P < 0. 001), but not in post-hoc analysis of RCT (RR = 0.87; 95% CI 0.74-1.02, P = 0.09). CONCLUSIONS:β-blockers treatment was associated with significantly decrease the risk of all-cause mortality in patients with AF-CHF and it was only seen in observational study group, but not in subgroup analysis of RCT group. Further large RCTs are required to verify the effect of β-blockers treatment on patients with CHF and AF. The main limitation of this study is the lack of individual data on patients in each study.
Heart Failure and Atrial Fibrillation, Like Fire and Fury.
Carlisle Matthew A,Fudim Marat,DeVore Adam D,Piccini Jonathan P
JACC. Heart failure
Heart failure and atrial fibrillation are 2 common cardiovascular disorders that frequently complicate one another and exert a significant detrimental effect on cardiovascular health and well-being. Both heart failure and atrial fibrillation continue to increase in prevalence as the risk factors underlying each condition become more common. This review encompasses what is currently known about the epidemiology and pathophysiology of these comorbidities along with incorporation of landmark trials that have contributed to current guidelines. The focus is on clinically relevant considerations, including the contribution of inflammation in the pathophysiology of atrial fibrillation and heart failure. We explore the emerging role of catheter ablation relative to medical therapy in the management of heart failure with reduced ejection fraction, along with indications for biventricular pacing modalities in cardiac resynchronization therapy. We discuss current guideline-directed therapies and how practice models and national recommendations will likely change based on the most recent randomized controlled trials.
Effect of catheter ablation on pre-existing abnormalities of left atrial systolic, diastolic, and neurohormonal functions in patients with chronic heart failure and atrial fibrillation.
European heart journal
The critical role of the left atrium (LA) in cardiovascular homoeostasis is mediated by its reservoir, conduit, systolic, and neurohormonal functions. Atrial fibrillation is generally a reflection of underlying disease of the LA, especially in patients with heart failure. Disease-related LA remodelling leads to a decline in both atrial contractility and distensibility along with an impairment in the control of neurohormonal systems that regulate intravascular volume. Catheter ablation can lead to further injury to the atrial myocardium, as evidenced by post-procedural troponin release and tissue oedema. The cardiomyocyte loss leads to replacement fibrosis, which may affect up to 30-35% of the LA wall. These alterations further impair atrial force generation and neurohormonal functions; the additional loss of atrial distensibility can lead to a 'stiff LA syndrome', and the fibrotic response predisposes to recurrence of the atrial arrhythmia. Although it intends to restore LA systole, catheter ablation often decreases the chamber's transport functions. This is particularly likely in patients with long-standing atrial fibrillation and pre-existing LA fibrosis, especially those with increased epicardial adipose tissue (e.g. patients with obesity, diabetes and/or heart failure with a preserved ejection fraction). Although the fibrotic LA in these individuals is an ideal substrate for the development of atrial fibrillation, it may be a suboptimal substrate for catheter ablation. Such patients are not likely to experience long-term restoration of sinus rhythm, and catheter ablation has the potential to worsen their haemodynamic and clinical status. Further studies in this vulnerable group of patients are needed.
A prospective observational survey on landiolol in atrial fibrillation/atrial flutter patients with chronic heart failure - AF-CHF landiolol survey.
Yamashita Takeshi,Nakasu Yukiko,Mizutani Hiroto,Sumitani Kenji
Journal of cardiology
BACKGROUND:Atrial fibrillation and atrial flutter occur commonly in patients with heart failure. Ultrashort-acting β-blockers, including landiolol, can rapidly control heart rate. As part of postmarketing surveillance for landiolol in Japan, a real-world drug-use survey (AF-CHF landiolol survey) was established for the treatment of atrial fibrillation and atrial flutter in patients with heart failure. We report the safety and effectiveness of landiolol from this survey, focusing on adverse events/adverse drug reactions. METHODS:Consecutive patients with cardiac dysfunction who received landiolol (continuous intravenous infusion, starting at 1μg/kg/min) for atrial fibrillation or atrial flutter in routine clinical practice in Japan were enrolled between June 2014 and May 2016. Safety variables included adverse events and adverse drug reactions (number of patients and events, incidence rate, types, seriousness). Effectiveness variables included the proportion of patients with a ≥20% decrease in heart rate. RESULTS:Data were available for 1121 patients (safety analysis set); 888 patients were evaluable for effectiveness parameters. Mean (± standard deviation) patient age was 72.5±13.5 years, 57.2% were male. Most patients (84.2%) received landiolol for atrial fibrillation. Overall, 174 adverse events occurred in 140 patients (12.5%), including 105 serious adverse events. The most common type of adverse events was cardiac (60 events). Seventy-five events in 63 patients were categorized as adverse drug reactions (5.6% of patients). Mean heart rate decreased substantially after treatment with landiolol, by ≥20% in 77.5% of patients. CONCLUSIONS:In a real-world setting in Japan, landiolol for the treatment of atrial fibrillation or atrial flutter with heart failure was acceptable without new safety concerns, and most patients achieved effective heart rate control during their arrhythmias.
Rhythm Control Versus Rate Control in Patients With Atrial Fibrillation and Heart Failure With Preserved Ejection Fraction: Insights From Get With The Guidelines-Heart Failure.
Kelly Jacob P,DeVore Adam D,Wu JingJing,Hammill Bradley G,Sharma Abhinav,Cooper Lauren B,Felker G Michael,Piccini Jonathan P,Allen Larry A,Heidenreich Paul A,Peterson Eric D,Yancy Clyde W,Fonarow Gregg C,Hernandez Adrian F
Journal of the American Heart Association
Background Limited data exist to guide treatment for patients with heart failure with preserved ejection fraction and atrial fibrillation, including the important decision regarding rate versus rhythm control. Methods and Results We analyzed the Get With The Guidelines-Heart Failure (GWTG-HF) registry linked to Medicare claims data from 2008 to 2014 to describe current treatments for rate versus rhythm control and subsequent outcomes in patients with heart failure with preserved ejection fraction and atrial fibrillation using inverse probability weighted analysis. Rhythm control was defined as use of an antiarrhythmic medication, cardioversion, or AF ablation or surgery. Rate control was defined as use of any combination of β-blocker, calcium channel blocker, and digoxin without evidence of rhythm control. Among 15 682 fee-for-service Medicare patients, at the time of discharge, 1857 were treated with rhythm control and 13 825 with rate control, with minimal differences in baseline characteristics between groups. There was higher all-cause death at 1 year in the rate control compared with the rhythm control group (37.5% and 30.8%, respectively, <0.01). The lower 1-year all-cause death in the rhythm control group remained after risk adjustment (adjusted hazard ratio, 0.86; 95% CI, 0.75-0.98; =0.02). Conclusions Rhythm control in patients aged 65 and older with heart failure with preserved ejection fraction and AF was associated with a lower risk of 1 year all-cause mortality. Future prospective randomized studies are needed to explore this potential benefit.
Persistent atrial fibrillation in heart failure with preserved ejection fraction: Prognostic relevance and association with clinical, imaging and invasive haemodynamic parameters.
Schönbauer Robert,Duca Franz,Kammerlander Andreas A,Aschauer Stefan,Binder Christina,Zotter-Tufaro Caroline,Koschutnik Matthias,Fiedler Lukas,Roithinger Franz Xaver,Loewe Christian,Hengstenberg Christian,Bonderman Diana,Mascherbauer Julia
European journal of clinical investigation
BACKGROUND:Atrial fibrillation (AF) is a frequent finding in HFpEF. However, its association with invasive haemodynamics, imaging parameters and outcome in HFpEF is not well established. Furthermore, the relevance of AF subtype with regard to outcome is unclear. This study sought to investigate the prognostic impact of paroxysmal and persistent AF in a well-defined heart failure with preserved ejection fraction (HFpEF) population. MATERIALS AND METHODS:Between 2010 and 2016, 254 HFpEF patients were prospectively enrolled. All patients underwent echocardiography as well as left and right heart catheterization. Patients without contraindications underwent CMR including T1 mapping. Follow-up and outcome data were collected. Patients with significant coronary artery disease were excluded. RESULTS:A total of 153 patients (60%) suffered from AF, 119 (47%) had persistent and 34 (13%) had paroxysmal AF. By multiple logistic regression analysis, persistent AF was independently associated with NT-proBNP (P = .003), NYHA functional class (P = .040), left and right atrial size (P = .022 and <.001, respectively), cardiac output (P = .002) and COPD (P = .034). After a median follow-up of 23 months (interquartile range 5-48), 92 patients (36%) reached the primary end point defined as hospitalization for heart failure or cardiovascular death. By multivariate Cox regression analysis, only persistent AF (P = .005) and six-minute walk distance (P = .011) were independently associated with the primary end point. CONCLUSIONS:Sixty percent of our HFpEF patients suffered from AF. Persistent but not paroxysmal AF was strongly associated with event-free survival and was independently related to NYHA functional class, serum NT-proBNP, atrial size, cardiac ouput and presence of COPD.
Atrial fibrillation in heart failure: what should we do?
Kotecha Dipak,Piccini Jonathan P
European heart journal
Heart failure (HF) and atrial fibrillation (AF) are two conditions that are likely to dominate the next 50 years of cardiovascular (CV) care. Both are increasingly prevalent and associated with high morbidity, mortality, and healthcare cost. They are closely inter-related with similar risk factors and shared pathophysiology. Patients with concomitant HF and AF suffer from even worse symptoms and poorer prognosis, yet evidence-based evaluation and management of this group of patients is lacking. In this review, we evaluate the common mechanisms for the development of AF in HF patients and vice versa, focusing on the evidence for potential treatment strategies. Recent data have suggested that these patients may respond differently than those with HF or AF alone. These results highlight the clear clinical need to identify and treat according to best evidence, in order to prevent adverse outcomes and reduce the huge burden that HF and AF are expected to have on global healthcare systems in the future. We propose an easy-to-use clinical mnemonic to aid the initial management of newly discovered concomitant HF and AF, the CAN-TREAT HFrEF + AF algorithm (Cardioversion if compromised; Anticoagulation unless contraindication; Normalize fluid balance; Target initial heart rate <110 b.p.m.; Renin-angiotensin-aldosterone modification; Early consideration of rhythm control; Advanced HF therapies; Treatment of other CV disease).
Atrial Fibrillation Begets Heart Failure and Vice Versa: Temporal Associations and Differences in Preserved Versus Reduced Ejection Fraction.
Santhanakrishnan Rajalakshmi,Wang Na,Larson Martin G,Magnani Jared W,McManus David D,Lubitz Steven A,Ellinor Patrick T,Cheng Susan,Vasan Ramachandran S,Lee Douglas S,Wang Thomas J,Levy Daniel,Benjamin Emelia J,Ho Jennifer E
BACKGROUND:Atrial fibrillation (AF) and heart failure (HF) frequently coexist and together confer an adverse prognosis. The association of AF with HF subtypes has not been well described. We sought to examine differences in the temporal association of AF and HF with preserved versus reduced ejection fraction. METHODS AND RESULTS:We studied Framingham Heart Study participants with new-onset AF or HF between 1980 and 2012. Among 1737 individuals with new AF (mean age, 75±12 years; 48% women), more than one third (37%) had HF. Conversely, among 1166 individuals with new HF (mean age, 79±11 years; 53% women), more than half (57%) had AF. Prevalent AF was more strongly associated with incident HF with preserved ejection fraction (multivariable-adjusted hazard ratio [HR], 2.34; 95% confidence interval [CI], 1.48-3.70; no AF as referent) versus HF with reduced ejection fraction (HR, 1.32; 95% CI, 0.83-2.10), with a trend toward difference between HF subtypes (P for difference=0.06). Prevalent HF was associated with incident AF (HR, 2.18; 95% CI, 1.26-3.76; no HF as referent). The presence of both AF and HF portended greater mortality risk compared with neither condition, particularly among individuals with new HF with reduced ejection fraction and prevalent AF (HR, 2.72; 95% CI, 2.12-3.48) compared with new HF with preserved ejection fraction and prevalent AF (HR, 1.83; 95% CI, 1.41-2.37; P for difference=0.02). CONCLUSIONS:AF occurs in more than half of individuals with HF, and HF occurs in more than one third of individuals with AF. AF precedes and follows HF with both preserved and reduced ejection fraction, with some differences in temporal association and prognosis. Future studies focused on underlying mechanisms of these dual conditions are warranted.
Type of Atrial Fibrillation and Outcomes in Patients With Heart Failure and Reduced Ejection Fraction.
Mogensen Ulrik M,Jhund Pardeep S,Abraham William T,Desai Akshay S,Dickstein Kenneth,Packer Milton,Rouleau Jean L,Solomon Scott D,Swedberg Karl,Zile Michael R,Køber Lars,McMurray John J V,
Journal of the American College of Cardiology
BACKGROUND:Atrial fibrillation (AF) is common in heart failure (HF), but the outcome by type of AF is largely unknown. OBJECTIVES:This study investigated outcomes related to type of AF (paroxysmal, persistent or permanent, or new onset) in 2 recent large trials in patients with HF with reduced ejection fraction. METHODS:The study analyzed patients in the PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure) and ATMOSPHERE (Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure) trials. Multivariable Cox regression models were used to estimate hazard ratios (HRs) for outcomes related to AF type. RESULTS:Of 15,415 patients, 5,481 (35.6%) had a history of AF at randomization, and of these, 1,645 (30.0%) had paroxysmal AF. Compared with patients without AF, patients with paroxysmal AF at randomization had a higher risk of the primary composite endpoint of cardiovascular death or HF hospitalization (HR: 1.20; 95% confidence interval [CI]: 1.09 to 1.32; p < 0.001), HF hospitalization (HR: 1.34; 95% CI: 1.19 to 1.51; p < 0.001), and stroke (HR: 1.34; 95% CI: 1.02 to 1.76; p = 0.037), whereas the corresponding risks in patients with persistent or permanent AF were not elevated. Neither type of AF was associated with higher mortality. New onset AF was associated with the greatest risk of adverse outcomes: primary endpoint (HR: 2.21; 95% CI: 1.80 to 2.71), HF hospitalization (HR: 2.11; 95% CI: 1.58 to 2.81), stroke (HR: 2.20; 95% CI: 1.25 to 3.88), and all-cause mortality (HR: 2.26; 95% CI: 1.86 to 2.74), all p values < 0.001, compared with patients without AF. Anticoagulants were used less often in patients with paroxysmal (53%) and new onset (16%) AF than in patients with persistent or permanent AF (71%). CONCLUSIONS:Among HF patients with a history of AF, those with paroxysmal AF were at greater risk of HF hospitalization and stroke than were patients with persistent or permanent AF, underlining the importance of anticoagulant therapy. New onset AF was associated with increased risk of all outcomes. (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255) (Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure [ATMOSPHERE]; NCT00853658).
Comparing biomarker profiles of patients with heart failure: atrial fibrillation vs. sinus rhythm and reduced vs. preserved ejection fraction.
Santema Bernadet T,Kloosterman Mariëlle,Van Gelder Isabelle C,Mordi Ify,Lang Chim C,Lam Carolyn S P,Anker Stefan D,Cleland John G,Dickstein Kenneth,Filippatos Gerasimos,Van der Harst Pim,Hillege Hans L,Ter Maaten Jozine M,Metra Marco,Ng Leong L,Ponikowski Piotr,Samani Nilesh J,Van Veldhuisen Dirk J,Zwinderman Aeilko H,Zannad Faiez,Damman Kevin,Van der Meer Peter,Rienstra Michiel,Voors Adriaan A
European heart journal
Aims:The clinical correlates and consequences of atrial fibrillation (AF) might be different between heart failure with reduced vs. preserved ejection fraction (HFrEF vs. HFpEF). Biomarkers may provide insights into underlying pathophysiological mechanisms of AF in these different heart failure (HF) phenotypes. Methods and results:We performed a retrospective analysis of the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF), which was an observational cohort. We studied 2152 patients with HFrEF [ejection fraction (EF < 40%)], of which 1419 were in sinus rhythm (SR) and 733 had AF. Another 524 patients with HFpEF (EF ≥50%) were studied, of which 286 in SR and 238 with AF. For the comparison of biomarker profiles, 92 cardiovascular risk markers were measured (Proseek® Olink Cardiovascular III panel). The circulating risk marker pattern observed in HFrEF was different than the pattern in HFpEF: in HFrEF, AF was associated with higher levels of 77 of 92 (84%) risk markers compared to SR; whereas in HFpEF, many more markers were higher in SR than in AF. Over a median follow-up of 21 months, AF was associated with increased mortality risk [multivariable hazard ratio (HR) of 1.27; 95% confidence interval (CI) 1.09-1.48, P = 0.002]; there was no significant interaction between heart rhythm and EF group on outcome. Conclusion:In patients with HFrEF, the presence of AF was associated with a homogeneously elevated cardiovascular risk marker profile. In contrast, in patients with HFpEF, the presence of AF was associated with a more scattered risk marker profile, suggesting differences in underlying pathophysiological mechanisms of AF in these HF phenotypes.
Atrial fibrillation ablation in heart failure.
Richter Sergio,Di Biase Luigi,Hindricks Gerhard
European heart journal
This review summarizes the rationale and current scientific evidence for catheter ablation in patients with atrial fibrillation and concomitant heart failure, puts it in context with recent practice recommendations, and discusses emerging technologies and future directions.
Heart failure with preserved ejection fraction, atrial fibrillation, and the role of senile amyloidosis.
van den Berg Maarten P,Mulder Bart A,Klaassen Sebastiaan H C,Maass Alexander H,van Veldhuisen Dirk J,van der Meer Peter,Nienhuis Hans L A,Hazenberg Bouke P C,Rienstra Michiel
European heart journal
Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are very common conditions, particularly in the elderly. However, the mechanisms underlying the two disorders, including their intricate interaction have not been fully resolved. Here, our aim is to review the evidence on the role of the two types of senile amyloidosis in this connection. Two types of senile amyloidosis can be identified: wild-type transthyretin (TTR)-derived amyloidosis (ATTRwt) and isolated atrial amyloidosis (IAA). ATTRwt is an underlying condition that is being increasingly recognized in patients with HFpEF and often accompanied by AF. IAA is an established cause of AF, adding to the mechanism problem. New diagnostic and therapeutic possibilities have emerged that may facilitate clinical management of (senile) amyloidosis, which in turn may have implications for the management of HFpEF and AF.