Treatment Persistence in Atrial Fibrillation: The Next Major Hurdle Elaine M. Hylek1 1 Department of Internal Medicine, Boston University, Boston, Massachusetts, United States Thromb Haemost Address for correspondence Elaine M. Hylek, MD, Department of Internal Medicine, Boston University, 801 Massachusetts Avenue, 2nd Floor Suite, Boston, MA 02118, United States (e-mail: [email protected]). In the October issue of Thrombosis and Haemostasis, Geng et al reported treatment satisfaction with dabigatran versus warfarin among patients with atrial fibrillation (AF) in China.1 This time-intensive, patient-centred study with high completion rate of standardized telephone interviews provides high-quality data and key insights from the patients’ perspectives. At 6 months, 33.5% of patients had discontinued dabigatran compared with 19.2% for warfarin. The authors report no difference in the global Anti-Clot Treatment Scale (ACTS) Burdens score or the global ACTS Benefits score. Thefavourable effects of dabigatran regarding decreased concern for dietary or drug interactions and medication-related hassles were offset by the economic burden of dabigatran which is not covered by medical insurance in China. As noted by the authors, the cost of dabigatran is 70 times the cost of warfarin. Factors associated with treatment persistence included older age, longer duration of anticoagulation therapy, global ACTS Benefits score and warfarin therapy. Other important findings of this study include the overall low proportion of patients in the registry receiving anticoagulant therapy, 27%, for stroke prevention. In addition, of the 4,511 patients in the registry receiving an oral anticoagulant, only 18.5% (n ¼ 834) were ultimately enrolled in the study. Prior to propensity scorematching,warfarin-treated patients were older, had higher CHA2DS2-VASc scores, lower education level and longer duration of anticoagulation use. The investigators did not assess changes in patient satisfaction over time. One would anticipate different attitudes among patients newly starting an anticoagulant opposed to longer term users whose mere persistence is a marker of drug tolerability and patient acceptance. The reasons for medication discontinuation are also of note with 47.6% (dabigatran-treated patients) and 42.9% (warfarin-treated patients) stopping treatment for non-bleeding adverse events, and 13.1 and 11.4%, respectively, for minor bleeding. Although initiation of anticoagulation among patients with AF remains a major global challenge, treatment persistence is an increasingly recognized major clinical hurdle. Reported rates of treatment persistence vary widely, including within country, depending on the population studied and methodology used to ascertain treatment exposure. Definitions of gaps in treatment that constitute permanent discontinuation vary across studies. In addition, observational studies restricted to new users of anticoagulant treatment provide different insights and conclusions than those studies composed of switchers, restarts or patients already established on treatment. In a retrospective study conducted in Ontario, Canada, investigators used administrative data to assess treatment discontinuation defined as a gap in dabigatran or rivaroxaban prescriptions of 14 days or greater.2 The cohort was comprised of 15,857 dabigatran-treated patients and 10,119 rivaroxaban users. At 6 months, 36.4% of patients had discontinued dabigatran and 31.9% of patients had stopped rivaroxaban. In the United Kingdom, using the primary care Clinical Practice Research Datalink, patients newly starting anticoagulant therapy for incident AF were identified (12,307 vitamin K antagonist [VKA] and 914 non-VKA oral anticoagulant [NOAC]).3 Treatment persistence at 12 months for VKA was 63.6% and 79.2% for NOACs.3 In the Dresden AF Registry, 124 of 341 patients treated with dabigatran discontinued treatment during follow-up (25.8 per 100 patient-years).4 Similar to Geng et al, the main reasons for treatment discontinuation were non-bleeding side effects. Higher rates of treatment persistence were reported from a prospective study of 1,305 patients with AF in Italy. At 12 months, 15.4% of patients stopped NOAC treatment with most of the discontinuations occurring in the first 6 months.5 In the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, 1-year persistence rates for dabigatran were lower than warfarin (adjusted persistence rates: 66% [95% confidence interval [CI], 60–72] vs. 82% [95% CI, 80–84]).6 This is in contrast to a retrospective cohort analysis of a large U.S. commercial insurance database (n ¼ 64,661) of patients with AF that found 47.5% of NOAC-treated patients had a proportion of received November 9, 2018 accepted November 9, 2018 © Georg Thieme Verlag KG Stuttgart · New York DOI https://doi.org/ 10.1055/s-0038-1676101. ISSN 0340-6245. Invited Editorial Focus Downloaded by: Université Paris Sud XI. Copyrighted material. days covered of 80%, compared with 40.2% in warfarintreated patients.7 The risk of stroke with treatment discontinuation has been shown in multiple studies including several randomized trials, the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation and the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial.8,9 This risk of stroke has also been shown in clinical practice, and its association with time off treatment (1–3 months: hazard ratio [HR], 1.96, 3–6 months: HR, 2.64, 6 months: HR, 3.66; all p< 0.001).7 Given the high morbidity and mortality associated with AF-related stroke, physician and patient thresholds to discontinue treatment and physician and patient reluctance to resume an anticoagulant warrant further study.10 Geng et al found that nearly half of all discontinuations were for non-bleeding reasons. Access and out-of-pocket patient costs are major determinants of drug adherence and persistence.11,12 However, having paroxysmal versus permanent AF has also been associated with treatment discontinuation.13 Certainly the mixed messages that patients receive regarding drug safety from the media warrant clarification by the medical community. As recently demonstrated by the GARFIELD registry, progress has been made in extending appropriate treatment to patients with AF at high risk of stroke.14 Targeted educational interventions as employed in the IMPACT AF trial are proven strategies to improve global use of anticoagulants for stroke prevention in AF.15 Parallel with these efforts is increasing focus on the challenge of long-term medication persistence.16,17 Perhaps stated best by Raparelli et al, ‘A multi-level approach, including patients’ preferences, factors determining physicians’prescribing habits and healthcare system infrastructure and support, is warranted to improve initiation and adherence of anticoagulants’.18 Conflict of Interest Research: Janssen. Advisory Board: Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, Janssen, Medtronic and Portola. Symposium: Boehringer Ingelheim and Bristol Myers Squibb/Pfizer. References 1 Geng YP, Lan DH, Liu N, et al. Patient-reported treatment satisfaction with dabigatran versus warfarin in patients with non-valvular atrial fibrillation in China. Thromb Haemost 2018;118(10): 1815–1822 2 Jackevicius CA, Tsadok MA, Essebag V, et al. Early non-persistence with dabigatran and rivaroxaban in patients with atrial fibrillation. Heart 2017;103(17):1331–1338 3 Martinez C, Katholing A, Wallenhorst C, Freedman SB. Therapy persistence in newly diagnosed non-valvular atrial fibrillation treated with warfarin or NOAC. A cohort study. Thromb Haemost 2016;115(01):31–39 4 Beyer-Westendorf J, Ebertz F, Förster K, et al. Effectiveness and safety of dabigatran therapy in daily-care patients with atrial fibrillation. Results from the Dresden NOAC Registry. Thromb Haemost 2015;113(06):1247–1257 5 Vedovati MC, Verdecchia P, Giustozzi M, et al. Permanent discontinuation of non vitamin K oral anticoagulants in real life patients with non-valvular atrial fibrillation. Int J Cardiol 2017; 236:363–369 6 Jackson LR II, Kim S, Shrader P, et al. Early therapeutic persistence on dabigatran versus warfarin therapy in patients with atrial fibrillation: results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry. J Thromb Thrombolysis 2018;46(04):435–439 7 Yao X, Abraham NS, Alexander GC, et al. Effect of adherence to oral anticoagulants on risk of stroke and major bleeding among patients with atrial fibrillation. J Am Heart Assoc 2016;5(02):e003074 8 Patel MR, Mahaffey KW, Garg J, et al; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365(10):883–891 9 Granger CB, Alexander JH, McMurray JJ, et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365(11):981–992 10 Lip G, Freedman B, De Caterina R, Potpara TS. Stroke prevention in atrial fibrillation: past, present and future. Comparing the guidelines and practical decision-making. Thromb Haemost 2017;117 (07):1230–1239 11 Weernink MGM, Vaanholt MCW, Groothuis-Oudshoorn CGM, von Birgelen C, IJzerman MJ, van Til JA. Patients’ priorities for oral anticoagulation therapy in non-valvular atrial fibrillation: a multi-criteria decision analysis. Am J Cardiovasc Drugs 2018. Doi: 10.1007/s40256-018-0293-0 12 Loewen PS, Ji AT, Kapanen A, McClean A. Patient values and preferences for antithrombotic therapy in atrial fibrillation. A narrative systematic review. Thromb Haemost 2017;117(06):1007–1022 13 Aronis KN, Thigpen JL, Tripodis Y, et al. Paroxysmal atrial fibrillation and the hazards of under-treatment. Int J Cardiol 2016; 202:214–220 14 Camm AJ, Accetta G, Ambrosio G, et al; GARFIELD-AF Investigators.Evolving antithrombotic treatment patterns for patients with newly diagnosed atrial fibrillation. Heart 2017;103(04):307–314 15 Vinereanu D, Lopes RD, Bahit MC, et al; IMPACT-AF investigators. A multifaceted intervention to improve treatment with oral anticoagulants in atrial fibrillation (IMPACT-AF): an international, cluster-randomised trial. Lancet 2017;390(10104):1737–1746 16 Hess PL, Mirro MJ, Diener HC, et al; Atrial Fibrillation Think-Tank Participants. Addressing barriers to optimal oral anticoagulation use and persistence among patients with atrial fibrillation: Proceedings, Washington, DC, December 3-4, 2012. Am Heart J 2014;168(03):239–247 17 Steffel J, Verhamme P, Potpara TS, et al; ESC Scientific Document Group. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrialfibrillation. Eur Heart J 2018;39(16):1330–1393 18 Raparelli V, Proietti M, Cangemi R, Lip GY, Lane DA, Basili S. Adherence to oral anticoagulant therapy in patients with atrial fibrillation. Focus on non-vitamin K antagonist oral anticoagulants. Thromb Haemost 2017;117(02):209–218 Thrombosis and Haemostasis Invited Editorial Focus Downloaded by: Université Paris Sud XI. Copyrighted material.
News > Medscape Medical News Most Paroxysmal AF Patients Report 'Triggers' Like Alcohol, Caffeine Intake Steve Stiles February 28, 2019 paroxysmal atrial fibrillation (AF) in a survey-based study identified at least one acute experience they believed was a trigger of individual episodes of their arrhythmia. The most commonly reported possible triggers were consumption of alcohol, caffeine intake, a bout of exercise, and a lack of sleep. Among the nearly 1300 survey respondents, women and those with a family history of AF were the likeliest to report that they had such triggers and that they had multiple triggers. Those with heart failure in addition to symptomatic paroxysmal AF were among the least likely to report that their atrial arrhythmia had triggers. One goal of the analysis was to identify potential AF triggers that are modifiable and could contribute to patient discussions and, in the case of family AF history, clarify interactions between genetic predisposition and environmental promoters, observed senior author Gregory M. Marcus, MD, MAS, University of California, San Francisco. "It's a little unsatisfying," he told theheart.org | Medscape Cardiology, that "there appears to be quite a bit of heterogeneity regarding the perceived triggers, suggesting that, for example, a catch-all recommendation may not be appropriate." For example, he noted, avoidance of caffeine seems to be an almost universal recommendation for patients with known paroxysmal AF. "But the reality is, yes, there may be some people for whom caffeine is a trigger, but almost certainly many others for whom it is not. Same thing for exercise. We don't want to discourage exercise, but certain types of exercise may be an important trigger for some people," Marcus said. "We need to better understand these more idiosyncratic relationships that may be most relevant to any one given individual." The analysis was published February 14 in Heart Rhythm, with lead author Christopher A. Groh, MD, University of California, San Francisco. Of the 1295 patients with symptomatic paroxysmal AF who responded to the survey, 74% reported experiencing at least one of the triggers on a provided list. Among that group, the most prevalent perceived triggers that were experienced "all or some of the time" were: An occasion of drinking alcohol in 35% Consuming caffeine in 28% A bout of exercise in 23% A lack of sleep in 21% Respondents also were invited to "write in" perceived triggers not on the provided list. By far the most common write-in trigger, at 20% of respondents, was stress or anxiety.
More than 40% of patients with a history of atrial fibrillation attend the emergency department inappropriately 1st March 2019 575 Patients with a previous diagnosis of atrial fibrillation who were assessed as attending the emergency department inappropriately did so because of fear, or as a result of advice from another person or self-monitoring, a study has found. Benedict Glover from Schulich Heart Center, Sunnybrook Health Sciences Centre (Toronto, Canada) presented the initial results of the Canadian AF-ED trial at the 24thAnnual International AF Symposium (24–26 January, Boston, USA) during a late-breaking session. The multicentre trial was conducted in Canada “to discover reasons why people with atrial fibrillation present inappropriately to emergency departments,” explained Glover. He added that the trial’s wider vision was “to try and develop a mechanism to stratify patients through other mechanisms so they don’t need to come to the emergency department with atrial fibrillation”. According to Glover, inappropriate hospitalisations and emergency department visits among people with atrial fibrillation are “a huge financial problem”. The annual cost of atrial fibrillation in the USA is more than $6.7 billion, with “75% of this related to inpatient stay”. In Canada, smaller numbers are involved, but annual hospital costs of atrial fibrillation “are approximately $815 million”. Glover stated that the researchers’ aim was to “try to reduce the hospitalisations and emergency department attendance of patients with atrial fibrillation” in Canada. The Canadian AF-ED trial was run with the Canadian Arrhythmia Network (CANet), which comprises 29 universities, each of which has two or three hospitals linked to it, 180 investigators and 24 industry partners. CANet’s 10-year goal aims to achieve “a 10% drop in sudden cardiac death, a 20% drop in hospitalisation and emergency department visits in patients with atrial fibrillation, and a 30% drop in hospitalisation and emergency department visits in patients with a history of syncope”. The study was conducted over a 14-month period and coordinated at a centre in Ontario. If a patient with a known diagnosis of atrial fibrillation was admitted or attended the emergency department in any of the participating hospitals, they were asked to enrol in the study. They were asked a series of questions about why they had attended hospital. “We tried to work out whether it was an appropriate admission or attendance or not, and then what the outcomes of the attendance were, and whether there were any alternative strategies that may have worked better,” Glover explained. Of the 356 patients recruited to the study, 71% attended because they had symptoms, such as palpitations, chest pain or shortness of breath. However, almost a third of patients did not have symptoms. Almost 10% of the patients without symptoms attended because they were scared they were going to die, have a heart attack or have a stroke. Forty per cent of those patients who were scared they were going to have a stroke were not on oral anticoagulation even though their mean CHA2DS2-VASc score was 2. Eighteen per cent of patients without symptoms attended because they had been advised to, in a third of cases by a cardiologist, while 2% attended as a result of self-monitoring. Patients assessed as having appropriate reasons to attend (n=204; 57%) required hospital admission or electrical or chemical cardioversion. Patients with symptoms were more likely to have an appropriate reason to visit the emergency department, as were those who had had multiple visits previously, and female patients. The remaining patients (n=152; 43%) would have been better managed in another setting. These patients had received previous advice from a physician or a nurse, or were not on an oral anticoagulant and were worried they were going to have a stroke, or were scared. When asked about alternative treatment strategies, most patients stated they would attend a rapid assessment outpatient atrial fibrillation clinic instead of the emergency department, while a significant number believed that smartphone applications may be of benefit. This prompted the researchers to develop the VIRTUES platform (Virtual Integrated Reliable Transformative User-driven E-health System), which is now being tested in a small pilot study in patients with atrial fibrillation. Wearable biosensor technology enables the patient to record their physiological data (such as ECG and blood pressure), which are transmitted via their cellphone to a central system linked to the hospital cardiology clinic and family practice clinic. The patient is then given feedback and advised what action to take instead of attending the emergency department. Glover concluded by stating that he hoped the VIRTUES platform would help reduce emergency department attendances by patients with atrial fibrillation in the future. He also emphasised that it was important to ensure that patients with a CHA2DS2-VASc score of 2 are anticoagulated.
Drugs & Diseases > Cardiology Atrial Fibrillation Updated: Jul 18, 2018 Author: Lawrence Rosenthal, MD, PhD, FACC, FHRS; Chief Editor: Jeffrey N Rottman, MD cardiogenic shock or devastating cerebrovascular accident (CVA). Unstable patients requiring immediate direct current (DC) cardioversion include the following: Patients with decompensated congestive heart failure (CHF) Patients with hypotension Patients with uncontrolled angina/ischemia Initial history and physical examination include the following: Documentation of clinical type of AF (paroxysmal, persistent, long-standing persistent or permanent) Assessment of type, duration, and frequency of symptoms Assessment of precipitating factors (eg, exertion, sleep, caffeine, alcohol use) Assessment of modes of termination (eg, vagal maneuvers) Documentation of prior use of antiarrhythmics and rate-controlling agents Assessment of presence of underlying heart disease Documentation of any previous surgical or percutaneous AF ablation procedures Airway, breathing, and circulation (ABCs) Vital signs (particularly heart rate, blood pressure, respiratory rate, and oxygen saturation) Evaluation of head and neck, lungs, heart, abdomen, lower extremities, and nervous system See Clinical Presentation for more detail. Diagnosis Findings from 12-lead electrocardiography (ECG) usually confirm the diagnosis of AF and include the following: Typically irregular ventricular rate (QRS complexes) Absence of discrete P waves, replaced by irregular, chaotic F waves Aberrantly conducted beats after long-short R-R cycles (ie, Ashman phenomenon) Heart rate (typically 110-140 beats/min, rarely >160-170 beats/min) Preexcitation Left ventricular hypertrophy Bundle-branch block or intraventricular conduction delay Acute or prior myocardial infarction (MI) Transthoracic echocardiography (TTE) is helpful for the following applications: To evaluate for valvular heart disease To evaluate atrial and ventricular chamber and wall dimensions To estimate ventricular function and evaluate for ventricular thrombi To estimate pulmonary systolic pressure (pulmonary hypertension) To evaluate for pericardial disease Transesophageal echocardiography (TEE) is helpful for the following applications: To evaluate for atrial thrombus (particularly in the left atrial appendage) To guide cardioversion (if thrombus is seen, cardioversion should be delayed) See Workup for more detail.
Perspective > theheart.org on Medscape > Trials and Fibrillations with Dr John Mandrola > ACC 2019 COMMENTARY A Sobering Breakthrough in AF Care John M. Mandrola, MD Alcohol-AF trial, presented here at ACC.19, will do two things: Bolster common-sense advice with evidence and create difficult decisions for patients and doctors alike. Recruiting for Alcohol AF Researchers screened patients with AF at six hospitals for randomization to a trial of alcohol abstinence or continued usual intake. Obviously, to be enrolled, patients had to drink moderate amounts of alcohol. The trial planned for 1-year follow-up but had to be shortened to 6 months because of "challenges" in adherence. The average alcohol intake of enrolled patients was 16 drinks per week. Perhaps you can see the challenge? Voskoboinik said the researchers screened nearly 700 patients and ended up with 70 patients in each arm. He made clear that these were highly motivated patients—an important point for translating results of the trial. Enrolled patients look like those we see in an AF clinic: average age 61, average CHADSVASC score of 1.5, about two thirds with paroxysmal AF and about one third having undergone AF ablation. Results On average, alcohol intake markedly decreased in the abstinence arm, but only 43 of 70 (61%) patients achieved complete abstinence; most (86%) cut their intake by more than 70%. Even so, the first primary endpoint, time to AF recurrence, was prolonged by 37% in the abstinence arm (P = .004). The second co-primary endpoint, mean AF burden, was also significantly reduced, and 46 patients in the abstinence group vs 25 in the control arm had 0% AF burden (P = .01). Other good things happened: Body mass index and blood pressure were significantly reduced in the abstinence arm. The researchers used MRI to document statistically significant decreases in left atrial (LA) area and increases in LA emptying fraction in the abstinence arm. They concluded that moderate alcohol consumption of more than 10 (standard) drinks per week is a potentially modifiable risk factor for AF. Abstinence (or a good attempt at it) was associated with reduction of AF burden, AF recurrence rates, reduction in AF symptoms, and improvement in weight loss and blood pressure. Comments What struck me most about Voskoboinik was his humility. In our interview and from the podium, he repeatedly and clearly noted the limitations of the study: It is not yet published, the patients were highly selected and motivated, not all patients had implantable loop recorders, and alcohol abstinence was confirmed mostly by self-report. If more clinical scientists displayed this degree of humility about their work, science might have less issues with trust. I look forward to the full paper, but plausibility and concordance with previous studies suggest these findings represent a true causal effect. Observational data strongly associate alcohol intake—in a dose-dependent manner—with AF.[1] Alcohol exerts pro-fibrillatory autonomic,[2] electrical, The findings of lower BP in the abstinence arm also aligns well with a recent systematic review showing that decreasing alcohol intake in people who drank more than two drinks per day was associated with significant blood pressure reduction.[5] And one hardly needs a reference to confirm that lower intake of carbohydrate-laden beverages would induce weight loss. Voskoboinik concluded that reducing alcohol intake should be considered as part of the lifestyle intervention in moderate drinkers with AF. I would go further. When this paper is published, it will create a bit of a moral challenge. If the doctor and patient know that reduction of alcohol may eliminate AF, should that not be a mandatory first step before expensive and risky drugs or procedures are used? Given the vast inequities of access to healthcare, what would it say if we were ablating people so that they can continue drinking alcohol without experiencing AF?
Atrial fibrillation: A preventable lifestyle disease! .entryAuthor" data-author-container-selector=".NLM_contrib-group"> Martin HalleMark Haykowsky First Published September 5, 2018 Editorial https://doi.org/10.1177/2047487318796625 Article information 1 In the publication of the journal,2 the group from the K.G. Jebsen Center for Exercise in Medicine at Trondheim University leading the investigation have addressed an important issue in preventive cardiology, the role of obesity and physical activity on the incidence of atrial fibrillation. The topic is not new and has been investigated before in different regions of the world.3–5 However, the HUNT investigation provides important data, particularly on a detailed questionnaire of the frequency, duration and intensity of physical activity per week. Results of the HUNT3 survey assessing data between 2006 and 2008 and follow-up until the end of 2015 clearly confirm the notion that obesity is a risk factor for atrial fibrillation and flutter, whereas high physical activity has preventive potential. In detail, overweight and obesity were associated with an 18% and 59% higher risk of atrial fibrillation, respectively, when compared to the population with normal body mass index between 18 and 25 kg/m2. However, data also show that obesity seems to be more important than physical inactivity. Although data reveal that active obese individuals have a 22% lower risk of atrial fibrillation than sedentary obese subjects, these data were not significant. Therefore, the conclusion of the Norwegian authors ‘our results suggest that obese individuals are likely to benefit the most from being physically active concerning AF risk’ should be extended also addressing weight reduction as an important intervention strategy. Nonetheless, increasing physical activity has to be included in a weight reduction programme in order to extend maintenance successfully, but weight reduction seems to be at least as important from a pathophysiological perspective. The mechanisms for the deleterious influence of obesity on the pathophysiology of atrial fibrillation are multifactorial,6 as also explained by the authors. They are mediated by obesity itself as well as obesity-associated cardiovascular risk factors. Present over several decades this risk factor profile eventually leads to myocardial changes, including disturbances of the atrial conduction pathways and autonomic control, leading to a significantly increased incidence of atrial fibrillation as observed in the HUNT study (4% incidence per 1000 person-years).2 Two different strains of pathophysiology can be distinguished, ‘pressure overload’ and ‘metabolic overload’ (Figure 1). On the one hand arterial hypertension (pressure overload) is the leading risk factor for the development of atrial fibrillation, even independently of obesity. However, it is particularly prevalent in overweight and obese individuals, leading to myocardial remodeling over time inducing ventricular diastolic dysfunction, left ventricular hypertrophy, mitral valve regurgitation and left atrial enlargement (Figure 1), which will eventually lead to disturbances in sinus node, adjacent atrial and pulmonary vein electrical conduction. On the other hand, obesity-associated metabolic disorders such as insulin resistance or type 2 diabetes not only favour systemic inflammation, but also favour the deposition of epicardial fat tissue leading to increased local myocardial inflammation, a significant pathophysiology for the development of atrial fibrosis and conduction disturbances.7 Figure 1. Pathophysiology of obesity on the development of atrial fibrillation, role of pressure and metabolic overload. LV: left ventricle. In contrast, regular physical activity and exercise training has been shown to improve numerous pathophysiological factors for the development of atrial fibrillation (Figure 2). It has been shown to improve endothelial function,8 reduce arterial hypertension,9improve diastolic dysfunction,10 reduce left atrial volume10 (pathophysiology of ‘pressure overload’), improve insulin resistance, reduce hepatic fat tissue and may even reduce epicardial fat11 and local myocardial inflammation (pathophysiology of ‘metabolic overload’). Beyond prevention of the first event of atrial fibrillation, these beneficial effects have also been observed in obese patients after experiencing their first event of atrial fibrillation.12,13 Reduction of obesity as well as improvement of physical fitness by regular physical activity is capable of reducing the subsequent events by 35% over the subsequent 5 years.12 However, this was only observed in those patients who had improved their ‘pressure overload’ as well as ‘metabolic overload’ including diastolic dysfunction.14 Figure 2. Physiological mechanisms of lifestyle intervention by exercise and weight reduction on pathophysiological pathways of the development of atrial fibrillation. HF: heart failure; EF: ejection fraction. A distinctly different pathophysiology of atrial fibrillation evolves in elite endurance athletes when exercise is performed at high volumes over a long period of time.15Then cardiac remodeling with atrial fibrosis may be induced by volume and pressure overload leading to electrical disturbances of the sinus node and atrial electrical conductance.16 Recent epidemiological data from the Copenhagen City Heart Study extend this to the general population showing that higher intensities of occupational exercise may increase the risk for atrial fibrillation.17 Nonetheless, the overall data including the HUNT cohort confirm the concept that obesity and sedentary lifestyles are significant risk factors for atrial fibrillation whereas moderate intensity exercise particularly in obesity significantly reduces the incidence of atrial fibrillation as well as recurrent events (Figure 3). Figure 3. Atrial fibrillation risk relationship between age and lifestyle factors. MTS: metabolic syndrome. With the increasing epidemic of obesity and physical inactivity as well as an aging population, the incidence of atrial fibrillation and stroke will increase even further. Lifestyle intervention measures have to start as early as possible to avoid the deterioration of myocardial pathophysiology (Figures 1 and 2). In obese individuals with metabolic disturbance, arterial hypertension and increased inflammatory state, weight reduction and increasing physical activity have to be particularly addressed. Data from the HUNT3 study as well as lifestyle intervention programs including weight loss and exercise training have revealed an additive effect of both measures.2,3,12,13In addition, intervention has to be long term in order to improve the functional as well as the structural myocardial pathophysiology and reduce first events or recurrent episodes of atrial fibrillation.12,18 Therefore, general practitioners, cardiologists as well as diabetologists need to integrate advice for lifestyle measures particularly for obese patients into their daily medical routine, and stakeholders such as health insurance companies need to find ways of reimbursement for physicians, nutritionists and exercise specialists. Prevention is not only cheaper than treatment,19 it reduces the disease burden for each individual. It is a definite time for action!
T h e n e w e ng l a nd j o u r na l o f m e dic i n e n engl j med nejm.org 1 The authors’ full names, academic degrees, and affiliations are listed in the Appendix. Address reprint requests to Dr. Crijns at the Department of Cardiology, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, the Netherlands, or at [email protected]. *A complete list of investigators in the RACE 7 ACWAS trial is provided in the Supplementary Appendix, available at NEJM.org. Drs. Pluymaekers and Dudink contributed equally to this article. This article was published on March 18, 2019, at NEJM.org. DOI: 10.1056/NEJMoa1900353 Copyright © 2019 Massachusetts Medical Society. BACKGROUND Patients with recent-onset atrial fibrillation commonly undergo immediate restoration of sinus rhythm by pharmacologic or electrical cardioversion. However, whether immediate restoration of sinus rhythm is necessary is not known, since atrial fibrillation often terminates spontaneously. METHODS In a multicenter, randomized, open-label, noninferiority trial, we randomly assigned patients with hemodynamically stable, recent-onset (<36 hours), symptomatic atrial fibrillation in the emergency department to be treated with a wait-and-see approach (delayed-cardioversion group) or early cardioversion. The wait-and-see approach involved initial treatment with rate-control medication only and delayed cardioversion if the atrial fibrillation did not resolve within 48 hours. The primary end point was the presence of sinus rhythm at 4 weeks. Noninferiority would be shown if the lower limit of the 95% confidence interval for the between-group difference in the primary end point in percentage points was more than -10. RESULTS The presence of sinus rhythm at 4 weeks occurred in 193 of 212 patients (91%) in the delayed-cardioversion group and in 202 of 215 (94%) in the early-cardioversion group (between-group difference, -2.9 percentage points; 95% confidence interval [CI], -8.2 to 2.2; P=0.005 for noninferiority). In the delayed-cardioversion group, conversion to sinus rhythm within 48 hours occurred spontaneously in 150 of 218 patients (69%) and after delayed cardioversion in 61 patients (28%). In the earlycardioversion group, conversion to sinus rhythm occurred spontaneously before the initiation of cardioversion in 36 of 219 patients (16%) and after cardioversion in 171 patients (78%). Among the patients who completed remote monitoring during 4 weeks of follow-up, a recurrence of atrial fibrillation occurred in 49 of 164 patients (30%) in the delayed-cardioversion group and in 50 of 171 (29%) in the earlycardioversion group. Within 4 weeks after randomization, cardiovascular complications occurred in 10 patients and 8 patients, respectively. CONCLUSIONS In patients presenting to the emergency department with recent-onset, symptomatic atrial fibrillation, a wait-and-see approach was noninferior to early cardioversion in achieving a return to sinus rhythm at 4 weeks. (Funded by the Netherlands Organization for Health Research and Development and others; RACE 7 ACWAS ClinicalTrials.gov number, NCT02248753.) A BS TR AC T Early or Delayed Cardioversion in Recent-Onset Atrial Fibrillation N.A.H.A. Pluymaekers, E.A.M.P. Dudink, J.G.L.M. Luermans, J.G. Meeder, T. Lenderink, J. Widdershoven, J.J.J. Bucx, M. Rienstra, O. Kamp, J.M. Van Opstal, M. Alings, A. Oomen, C.J. Kirchhof, V.F. Van Dijk, H. Ramanna, A. Liem, L.R. Dekker, B.A.B. Essers, J.G.P. Tijssen, I.C. Van Gelder, and H.J.G.M. Crijns, for the RACE 7 ACWAS Investigators* Original Article The New England Journal of Medicine Downloaded from nejm.org on March 18, 2019. For personal use only. No other uses without permission. Copyright © 2019 Massachusetts Medical Society. All rights reserved. 2 n engl j med nejm.org T h e new engl and jour na l o f medic i ne Patients with recent-onset, symptom atic atrial fibrillation commonly undergo immediate restoration of sinus rhythm bymeans of pharmacologic or electrical cardioversion.1-3 However, it is questionable whether immediate restoration of sinus rhythm is necessary, since atrial fibrillation often terminates spontaneously.4-9 Alternatively, a wait-and-see approach that includes the administration of rate-control medication and delayed cardioversion only if necessary may avoid hospitalization and overtreatment. Therefore, we conducted a multicenter, randomized trial, RACE 7 ACWAS (Rate Control versus Electrical Cardioversion Trial 7–Acute Cardioversion versus Wait and See), to find out whether a wait-and-see approach would be noninferior to early cardioversion for obtaining sinus rhythm. Me thods Trial Oversight We conducted this noninferiority trial in the cardiology departments of 15 hospitals in the Netherlands, including 3 academic hospitals, 8 nonacademic teaching hospitals, and 4 nonteaching hospitals. The trial was initiated by the investigators and coordinated by the Maastricht University Medical Center. The trial was approved by the institutional review board at the medical center; the review board at each of the participating sites approved the protocol (available with the full text of this article at NEJM.org). A detailed overview of the trial design has been reported previously.10 All the patients provided written informed consent. Staff members of the independent Clinical Trial Center Maastricht performed the trial monitoring and data management. The trial was supported by the Netherlands Organization for Health Research and Development–Health Care Efficiency Research Program and Maastricht University Medical Center. Boehringer Ingelheim provided some devices for remote monitoring of patients by electrocardiography (ECG) but had no role in the design or execution of the trial; company representatives did not review the protocol or the manuscript. Investigators from the Department of Cardiology affiliated with the Heart and Vascular Center at the Maastricht University Medical Center designed the trial, collected and managed the data, and performed the statistical analyses. The writing committee wrote the manuscript, and all the steering committee members made the decision to submit it for publication. The authors had unrestricted access to the data and vouch for the accuracy and completeness of the data and analyses and for the fidelity of the trial to the protocol. Patients From October 2014 through September 2018, we enrolled adults (≥18 years of age) who had presented to the emergency department with hemodynamically stable, symptomatic, recent-onset (<36 hours), first-detected or recurrent atrial fibrillation, without signs of myocardial ischemia or a history of persistent atrial fibrillation (for the purpose of this trial defined as lasting for >48 hours). All the patients qualified as being candidates for either a wait-and-see approach or early cardioversion. Previous cardioversion did not exclude a patient from the trial. Details regarding the inclusion and exclusion criteria are provided in Table S1 in the Supplementary Appendix, available at NEJM.org. Randomization and Treatment Patients were randomly assigned in a 1:1 ratio to the wait-and-see approach (delayed-cardioversion group) or to standard care of early cardioversion (early-cardioversion group). Randomization was performed with the use of a centralized Web-based system. Patients and attending physicians were aware of the trial-group assignments. The wait-and-see approach consisted of the administration of rate-control medication, including intravenous or oral β-adrenergic–receptor blocking agents, nondihydropyridine calciumchannel blockers, or digoxin. These medications were given in increasing doses to obtain relief of symptoms and a heart rate of 110 beats per minute or less.11 Patients were discharged when their condition was determined to be clinically stable. An outpatient clinic visit was planned for the next day, as close as possible to 48 hours after the onset of symptoms. At this visit, the heart rhythm was reassessed on a 12-lead ECG. If atrial fibrillation was still present, patients were referred to the emergency department for delayed cardioversion. Early cardioversion consisted of pharmacologic cardioversion, preferably with flecainide. Electrical cardioversion was performed in patients with contraindications to pharmacologic cardioversion and in patients with previous or current unsuccessful pharmacologic cardioversion. Patients were The New England Journal of Medicine Downloaded from nejm.org on March 18, 2019. For personal use only. No other uses without permission. Copyright © 2019 Massachusetts Medical Society. All rights reserved. n engl j med nejm.org 3 Early or Delayed Cardioversion in Atrial Fibrillation discharged when their condition was determined to be clinically stable. In patients with a high risk of stroke who had not received previous anticoagulation, such treatment was initiated before or immediately after cardioversion.1,12 Transesophageal echocardiography was not performed in any patient. Long-term oral anticoagulation was continued in accordance with the current guidelines based on the patient’s score on the CHA 2DS2–VASc scale.1,2,12,13 This scale is used to evaluate the presence of congestive heart failure, hypertension, diabetes, and stroke or transient ischemic attack according to the patient’s age and sex, along with the presence of vascular disease, including peripheral arterial disease, previous myocardial infarction, and aortic atheroma. Scores range from 0 to 9, with higher scores indicating greater risk. If complications occurred during emergency department treatments, patients were admitted to the hospital. The need to initiate or intensify drugs for rate and rhythm control was assessed at each contact with patients. Follow-up For all the patients, a visit to the outpatient clinic was scheduled at 4 weeks. The ECG result that was used to assess the primary end point was obtained during this visit. Furthermore, a complete medical history that included a review of symptomatic recurrences, medication use, complications, and hospital admissions was taken. Depending on the availability of devices, patients used ECG telemetry (MyDiagnostick, Applied Biomedical Systems)14 three times daily or in case of symptoms until the 4-week visit to detect recurrences. (Devices could not be provided to 102 patients because of a lack of availability.) If patients had serious symptoms, they could visit the emergency department or the outpatient clinic. An overview of the trial design is provided in Figure S1 in the Supplementary Appendix. End Points The primary end point was the presence of sinus rhythm on ECG recorded at the 4-week trial visit. All ECGs were centrally assessed for the presence of sinus rhythm by the first two authors. Secondary end points included the duration of the index visit at the emergency department, emergency department visits related to atrial fibrillation, cardiovascular complications, and time until recurrence of atrial fibrillation. Cardiovascular complications were defined as events leading to an emergency department visit or hospital admission and included heart failure, ischemic stroke, transient ischemic attack, unstable angina or acute coronary syndrome, symptomatic bradycardia or tachycardia, or hypotension. At the 4-week follow-up visit, we assessed the patients’ quality of life using the Atrial Fibrillation Effect on Quality-of-Life questionnaire (AFEQT), with scores ranging from 0 to 100 and higher scores indicating a better quality of life.15 All secondary end points of the trial are listed in Table S2 in the Supplementary Appendix. Statistical Analysis The primary end-point analysis was designed to test whether a wait-and-see approach was noninferior to early cardioversion, as determined by the percentage of patients who were in sinus rhythm at 4 weeks after the index visit. Noninferiority would be shown if the lower limit of the 95% confidence interval for the between-group difference in the primary end point in percentage points was more than -10 (i.e., the difference between the percentage in the delayed-cardioversion group minus the percentage in the early-cardioversion group). This estimation is equivalent to onesided noninferiority testing with an alpha of 0.025. A noninferiority margin of 10 percentage points was considered acceptable, given the natural variation in the presence of sinus rhythm, the generally low effect of the absence of sinus rhythm on prognosis of the patient, and the availability of good treatment options should treatment be necessary. Using PASS (Power Analysis and Sample Size) software, version 14, we determined that an enrollment of 412 patients would provide a power of 90% to determine noninferiority, assuming that at least 90% of the patients in the two groups had met the primary end point.16 To allow for attrition, we aimed to enroll 437 patients. In the primary analysis, we included all the patients who had undergone randomization, except for 10 patients who had withdrawn consent or been lost to follow-up (Fig. 1). We used the method of Farrington and Manning to calculate the 95% confidence interval for the betweengroup difference in the primary end point.16 In post hoc sensitivity analyses that included all the patients who had undergone randomization, the results were similar to those in the primary analysis (Table S3 in the Supplementary Appendix).17,18 The New England Journal of Medicine Downloaded from nejm.org on March 18, 2019. For personal use only. No other uses without permission. Copyright © 2019 Massachusetts Medical Society. All rights reserved. 4 n engl j med nejm.org T h e new engl and jour na l o f medic i ne The time until recurrent atrial fibrillation was analyzed in a subgroup of 335 patients in whom telemetric monitoring had been performed. We performed a Kaplan–Meier analysis to calculate the time until recurrence of atrial fibrillation and used the Cox proportional-hazards method to calculate hazard ratios with 95% confidence intervals. We used the chi-square test or Fisher’s ex Figure 1. Screening, Randomization, and Follow-up. In the delayed-cardioversion group, patients received rate-control medication and were discharged when their con dition was determined to be clinically stable. An outpatient clinic visit was planned for the next day, as close as pos sible to 48 hours after the onset of symptoms of atrial fibrillation (AF). At this visit, the heart rhythm was reas sessed on 12-lead electrocardiography (ECG). If atrial fibrillation was still present, patients were referred to the emergency department for delayed cardioversion. In the early-cardioversion group, patients underwent immediate pharmacologic or electrical cardioversion, depending on their medical history. SSS denotes sick sinus syndrome, and WPW Wolff–Parkinson–White syndrome. 2581 Were excluded (could have multiple reasons) 1285 Had duration of AF >36 hr 677 Had history of persistent AF 548 Were enrolled in another clinical trial or were withdrawn by physician 392 Had signs of hemodynamic instability 260 Were asymptomatic 119 Had signs of myocardial infarction 91 Had history of syncope, SSS, or WPW 67 Had heart rate <70 beats per minute 954 Were not enrolled 366 Declined to participate 361 Had administrative reason 227 Had spontaneous conversion 2 Were lost to follow-up 2 Withdrew 3 Were lost to follow-up 3 Withdrew 212 Were included in primary analysis and underwent ECG at 4 wk 215 Were included in primary analysis and underwent ECG at 4 wk 1125 Were eligible 3706 Patients from 2 centers with systematic screening log were assessed for eligibility 171 Were enrolled 266 from 13 centers with no systematic screening log were enrolled 437 Underwent randomization 218 Were assigned to delayed-cardioversion group 3 Underwent early cardioversion 219 Were assigned to early-cardioversion group 5 Did not undergo early cardioversion The New England Journal of Medicine Downloaded from nejm.org on March 18, 2019. For personal use only. No other uses without permission. Copyright © 2019 Massachusetts Medical Society. All rights reserved. n engl j med nejm.org 5 Early or Delayed Cardioversion in Atrial Fibrillation act test to compare categorical variables and the independent t-test or the Hodges–Lehmann test to compare continuous variables. There was no prespecified plan to adjust for multiple comparisons. Results for secondary end points are reported with 95% confidence intervals without P values. The calculations were not adjusted for multiple comparisons, and inferences drawn from the intervals may not be reproducible. All statistical analyses were performed with IBM SPSS software, version 25. R esult s Patients Of the 437 patients who had undergone randomization, 218 were assigned to the delayed-cardioversion group and 219 to the early-cardioversion group (Table 1). The mean (±SD) age was 65±11 years; 176 patients (40%) were female, and 192 (44%) had a first episode of atrial fibrillation. Palpitations were the most common symptom (87%), followed by exercise-induced fatigue (26%). An increased risk of stroke, as reflected by a CHA 2DS2-VASc score of 2 or higher, was seen in 279 patients (64%). At enrollment, 175 patients (40%) were taking oral anticoagulant drugs, and in 127 patients (29%) anticoagulation was initiated during the index visit (Table S4 in the Supplementary Appendix). The distribution of stroke risk and implementation of anticoagulant therapy are shown in Figure S2 in the Supplementary Appendix. A screening log was kept in two of the trial centers. Of the 3706 patients who had undergone screening, 2581 (70%) were excluded. The most common reasons for exclusion were a duration of atrial fibrillation of more than 36 hours and a history of persistent atrial fibrillation (Fig. 1). End Points The primary end point of the presence of sinus rhythm on the ECG recorded at the 4-week visit occurred in 193 of 212 patients (91%) in the delayed-cardioversion group and in 202 of 215 (94%) in the early-cardioversion group (between-group difference, -2.9 percentage points; 95% confidence interval [CI], -8.2 to 2.2; P=0.005 for noninferiority) (Fig. 2A). Almost all the patients were discharged home after the index presentation, with only very few admitted to the hospital (3 patients in the delayedcardioversion group and 5 in the early-cardioversion group). Visits to the emergency department because of a recurrence of atrial fibrillation were made by 14 of 212 patients (7%) in the delayedcardioversion group and in 14 of 215 patients (7%) in the early-cardioversion group.
Atrial fibrillation type and renal dysfunction as important predictors of left atrial thrombus. Heart. 2019 Apr 30. pii: heartjnl-2018-314492. doi: 10.1136/heartjnl-2018-314492. [Epub ahead of print] Kapłon-Cieślicka A1, Budnik M1, Gawałko M1, Peller M1, Gorczyca I2, Michalska A2, Babiarz A1, Bodys A1, Uliński R1, Żochowski M1, Scisło P1, Kochanowski J1, Filipiak KJ1, Opolski G1. Author information Abstract OBJECTIVE: We aimed to identify predictors of left atrial appendage (LAA) thrombus in patients with atrial fibrillation (AF) and to enhance the prognostic value of the CHA2DS2-VASc score. METHODS: Derivation cohort included 1033 consecutive AF patients referred for catheter ablation or direct current cardioversion, in whom transoesophageal echocardiography (TOE) was performed prior to the procedure. Logistic regression analysis was used to identify predictors of LAA thrombus on TOE. Receiver operating characteristic (ROC) curves were constructed to compare the newly developed score with the CHA2DS2 and CHA2DS2-VASc scores in the derivation and the validation (n=320) cohort. RESULTS: On TOE, LAA thrombus was present in 59 (5.7%) patients in the derivation cohort. Aside from variables encompassed by the CHA2DS2-VASc score, LAA thrombus predictors included AF type (persistent/'permanent' vs paroxysmal) and renal dysfunction. These predictors were incorporated into the CHA2DS2-VASc score. In ROC analysis, area under the curve (AUC) for the new score (CHA2DS2-VASc-RAF score) was significantly higher (0.81) than those for the CHA2DS2 and CHA2DS2-VASc scores (0.71 and 0.70, respectively). In the validation cohort, the CHA2DS2-VASc-RAF score also performed significantly better (AUC of 0.88) than the CHA2DS2 and CHA2DS2-VASc scores (AUC of 0.63 and 0.60, respectively). CONCLUSION: In real-world AF patients with majority on oral anticoagulation, LAA thrombus was found in approximately 6%. Two variables not included in the CHA2DS2-VASc score (AF type and renal dysfunction) proved strong, independent predictors of LAA thrombus and might improve thromboembolic risk stratification. © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ. KEYWORDS: atrial fibrillation; cardiac risk factors and prevention PMID: 31040170 DOI: 10.1136/heartjnl-2018-314492
Frequent drinking is a more important risk factor for new-onset atrial fibrillation than binge drinking: a nationwide population-based study https://doi.org/10.1093/europace/euz256 Published: 17 October 2019 PDF Cite Permissions Icon Permissions atrial fibrillation ethanol alcohol drinking binge drinking Issue Section: Clinical Research What’s new? Weekly alcohol intake which is calculated by (drinking session per week) * (amount of alcohol consumed per drinking session) is a significant risk factor for new-onset atrial fibrillation (AF). According to our analysis, drinking session per week was the strongest risk factor for new-onset AF. However, consuming large amount of alcohol per drinking session, which is often called as binge drinking, was not associated with new-onset AF. Drinking small amount of alcohol frequently may not be a good strategy to prevent new-onset AF. Introduction Atrial fibrillation (AF) is the most frequent tachyarrhythmia, and its consequences are not limited to symptoms but also extend to deleterious cardiovascular events, including ischaemic stroke.https://nhiss.nhis.or.kr/). The current study included patients who underwent a national health check-up in 2009. The screening period was from January 2002 to December 2008. The follow-up period was from the date of national health check-up to the date of diagnosis of new-onset or December 2017 if no new-onset AF was detected. Patients were excluded if they had already been diagnosed with AF during the screening period, had missing data regarding alcohol consumption, or if they were younger than 20 years old. For this study, we obtained the health questionnaire data regarding alcohol consumption. Since diagnostic codes related to AF were also retrieved, we were able to analyse the association between alcohol consumption pattern and risk of new-onset AF using a large number of patients with a sufficient follow-up duration. Definitio
http://www.jgc301.com; [email protected] | Journal of Geriatric CardiologyJournal of Geriatric Cardiology (2019) 16: 671675 ©2019 JGC All rights reserved; www.jgc301.com Research Article Open Access Simple hematological predictors of AF recurrence in patients undergoing atrial fibrillation ablation George Bazoukis1,#, Konstantinos P Letsas1, Konstantinos Vlachos1, Athanasios Saplaouras1, Dimitrios Asvestas1, Konstantinos Tyrovolas1, Aikaterini Rokiza1, Eirini Pagkalidou2, Gary Tse3,4, Stavros Stavrakis5, Antonios Sideris1, Michael Efremidis11Department of Cardiology, Electrophysiology Laboratory, Evangelismos General Hospital of Athens, Athens, Greece 2Department of Hygiene and Epidemiology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece 3Department of Medicine and Therapeutics, Faculty Of Medicine, Chinese University of Hong Kong, Hong Kong, China; 4Li Ka Shing Institute of Health Sciences, Faculty Of Medicine, Chinese University of Hong Kong, Hong Kong, SAR, China 5Department of Medicine, Cardiovascular Section, Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA Abstract Backgound Red cell distribution width (RDW) and neutrophil-to-lymphocyte ratio (NLR) are simple hematologic indices that have been used to predict adverse outcomes in different clinical settings. The aim of our study is to determine whether RDW and NLR can predict atrial fibrillation (AF) recurrence in patients undergoing AF ablation. Methods Consecutive patients, without known hematological disor-ders, who underwent AF catheter ablation between January 2014 and April 2017 were enrolled into this study. Blood samples were taken one day before and five hours after the ablation procedure. Results A total of 346 patients (224 males (65%), mean age: 59 ± 11 years old) were included. After a mean follow up of 26.2 ± 12.1 months, 80 (23.1%) patients experienced late AF recurrence (defined as any recurrence after the blanking period of three months), while 97 (28%) patients experienced early AF recurrence during the blanking period. Univariate analysis showed that early arrhythmia recurrence, type of AF and NLR after the procedure were significantly associated with late AF recur-rence, while early arrhythmia recurrence and NLR remained significant in multivariate analysis. RDW was not associated with late AF re-currence. None of the parameters above predicted early arrhythmia recurrence. Conclusions Simple and inexpensive hematological indices such as NLR should be evaluated for their ability to predict AF recurrence in patients undergoing catheter ablation in larger prospective studies. J Geriatr Cardiol 2019; 16: 671675. doi:10.11909/j.issn.1671-5411.2019.09.008 Keywords: Atrial fibrillation; Neutrophils; Radiofrequency ablation 1 IntroductionHematological indices such as red cell distribution width (RDW) and neutrophil-to-lymphocyte ratio (NLR) have been associated with incident atrial fibrillation (AF).[1–6]RDW reflects variability in the size of circulating erythro-cytes and is a marker of anisocytosis,[7] while NLR is a sys-temic inflammatory marker with prognostic significance for cardiovascular diseases.[8] Specifically, a high neutrophil count reflects subclinical inflammation, and a reduced lym-phocyte count reflects physiologic stress and poor general health. As a result, the NLR provides information on both #Correspondence to: George Bazoukis, MD, MSc, Department of Cardi-ology, General Hospital of Athens “Evangelismos”, Ipsilantou 47, Athens, Greece. E-mail: [email protected] Received: November 18, 2018 Revised: December 31, 2018 Accepted: January 30, 2019 Published online:September 28, 2019 the inflammatory status and the stress response.[9] In light of the well-characterized association between inflammation and AF,[10] a number of studies have evaluated the role of corticosteroids in preventing AF recurrence after AF cathe-ter ablation.[11–14] Specifically, the STEROID-AF study showed that oral corticosteroids have significant effect in lowering certain cytokines, but this was not translated to better outcomes following AF ablation.[11] Another random-ized controlled trial reported that low dose corticosteroids administered for a short period, shortly after AF ablation may have a beneficial role in prevention of immediate and mid-term follow-up AF recurrences.[12] In addition, peripro-cedural short-term moderate intensity steroid therapy re-duced early arrhythmia recurrence but it was not effective in preventing late AF recurrence following AF ablation.[13]These findings highlight the possible association between inflammation and AF recurrence in patients undergo cathe-ter ablation. Furthermore, there is an increased interest in 672 Bazoukis G, et al. Hematological predictors of atrial fibrillation recurrence Journal of Geriatric Cardiology| [email protected]; http://www.jgc301.comfinding simple predictors for identifying patients who are at higher risk of AF recurrence and who might benefit from adjunctive antiarrhythmic medications post-ablation. There-fore, we investigated the values of RDW, NLR and other simple hematological indices for predicting AF recurrence in patients undergoing AF ablation in our center. 2Methods 2.1Patients and ablation procedure This retrospective cohort study included consecutive pa-tients undergoing AF catheter ablation between January 2014 and April 2017 in our center. The exclusion criteria were those with known hematological disorders. Catheter ablation was performed under intravenous sedation with midazolam and remifentanyl by two experienced operators (Efremidis M and Letsas KP). The ablation procedure has been described in full details elsewhere.[15] In brief, after the three-dimensional geometry of the left atrium was obtained using CARTO (Biosense Webster, Inc.), wide circumferen-tial lesions for isolation of large atrial areas around both ipsilateral pulmonary veins (PVs) were applied using a 3.5 mm-tip ablation catheter (Thermo Cool Navi-Star and Smart Touch, Biosense Webster, Inc.). The endpoint of the ablation was the absence or dissociation of potentials in the isolated area as documented by the circular mapping cathe-ter (Lasso, BiosenseWebster, Inc.) placed within each of the PVs. In addition, exit block was confirmed by pacing around the circular mapping catheter from within each PV. Entrance and exit block of the PVs were evaluated 30 min after the initial isolation. The patients were anticoagulated using acenocoumarol with a target international normalized ratio of 2.0–3.0 or direct oral anticoagulants at least four weeks before and three months after the procedure. We rou-tinely received blood samples from all patients who under-went AF catheter ablation one day before and about five hours after the ablation procedure. We measured a complete blood count, creatinine and troponin levels. All patients in our institution underwent routine fol-low-up post-ablation, as per our institution’s protocol. Spe-cifically, patients were evaluated every week at the dedi-cated arrhythmia outpatient clinic of our institution for the first month after the procedure. Patients had follow-up visits with a 24-h Holter electrocardiogram at 1, 3, 6, 9, 12 months and for every 6 months thereafter or whenever they developed symptoms consistent with recurrent AF. Antiar-rhythmic drugs, except amiodarone, were discontinued five days before the ablation procedure and were re-initiated on the next day only in patients with non-paroxysmal AF for three months after the procedure. Amiodarone was discon-tinued for four weeks before the procedure to allow enough time for wash out while non-paroxysmal AF patients were reloaded after the procedure.[16] The study was approved by the Hospital’s Ethics Committee. 2.2Statistical analysis Continuous variables are presented as mean ± SD, while categorical ones are presented as absolute and relative fre-quencies (percentages). Continuous variables were tested for normal distribution using the Kolmogorov-Smirnov test. Continuous variables with and without normal distribution were compared using Student’s t-test or the Mann-Whitney U test, respectively. Pearson’s chi-square or Fisher’s exact test were used to test for any associations between two categorical variables. We examined univariate models and multivariate models with forward selection of variables per likelihood ratio criteria by using binary logistic regression analysis. Variables with a univariate P-value < 0.2 were included in the multivariable model (Hosmer-Lemeshow). Receiving operating characteristics curve (ROC) was per-formed to assess the best cutoff value of significant contin-ues variables to predict AF recurrence. Analyses were per-formed with SPSS (version 17.0, SPSS Inc., Chicago, IL, USA) and all reported P-values are two-tailed. Dou-ble-sided P-values less than 0.05 were considered as indica-tive of statistical significance. 3Results A total of 346 patients (224 males (65%), mean age: 59 ± 11 years), who were followed for a mean period of 26.2± 12.1 months, were included. The indication for AF ablation was symptomatic AF (paroxysmal AF: 216 (62%), persis-tent AF: 121 (35%), long standing persistent AF: 9 (3%)) refractory to antiarrhythmic drugs. During follow-up, 80 (23%) patients experienced late AF recurrence (defined as any recurrence after the blanking period of three months), while 97 (28%) patients experienced early AF recurrence during the blanking period. Of the different hematological indices studied, only NLR after ablation was significantly associated with late AF recurrence during after ablation (P = 0.035). By contrast, RDW before or after ablation procedure was not significantly associated with late arrhythmia recur-rence. Other factors significantly associated with late recur-rence of AF were early arrhythmia recurrence (P = 0.023), type of AF (P = 0.0009) and procedure time (0.041) (Table 1). Multivariate analysis was performed, including variables with P < 0.2 on univariate analysis. This revealed early ar-rhythmia recurrence (OR = 1.94, 95% CI: 1.11–3.41, P = 0.02) and NLR post-ablation (OR = 1.1, 95% CI: 1.01–1.20,
